Container for injectable drug

Abstract

To provide a container for an injectable medicament readily equipped with volumetric measurement means.SOLUTION: A container 100 comprises: an elongated body 101 having a sidewall 102 extending along a longitudinal axis and having a distal end 103 and a proximal end 104; an outlet 116 at the distal end 103. The container comprises a bung 110 arranged inside the elongated body 101, sealingly engaged with the sidewall and slidable along the longitudinal axis relative to the sidewall. The container comprise an interior volume 109 to receive an injectable medicament, the interior volume being confined by the sidewall, the outlet 116 and the bung 110. The container also comprises a measuring arrangement 120 arranged in or on the bung 110. The measuring arrangement 120 comprises a signal generator configured to emit a measurement signal into the interior volume 109, thereby capable of stimulating or of exciting a resonance of the container 100. The measuring arrangement 120 comprises a signal detector configured to detect a feedback signal indicative of a resonating interaction of the measurement signal with at least one of the sidewall, the outlet 116 and the interior volume 109.SELECTED DRAWING: Figure 3

Description

Technical Field

[0001] The present disclosure relates to measuring the internal volume of a container filled with a liquid substance, which is usually filled with an injectable drug. The present disclosure relates to a container for an injectable drug. This container enables and supports accurately measuring the size of the internal volume of the container occupied by the injectable drug. The present disclosure also relates to a method of determining the size of the internal volume of such a container.

Background Art

[0002] Drug delivery devices for setting and dispensing single or multiple doses of a liquid drug are well known in the art as such. Generally, such devices have substantially the same purpose as a normal syringe.

[0003] Drug delivery devices such as pen-type syringes must meet several requirements specific to the user. For example, in the case of patients with chronic diseases such as diabetes, the patient may be physically weak and may also have reduced vision. Therefore, an appropriate drug delivery device, especially for home drug therapy, must have a robust structure and must be easy to use. Furthermore, the operation of the device and its components, as well as general handling, must be understandable and easily comprehensible. Such an injection device must provide for the setting of variable-sized drug doses and subsequent dispensing. Furthermore, the dose setting as well as the dose dispensing procedure must be easy to operate and must be clear.

[0004] Generally, such a device includes a housing or a specific cartridge holder adapted to receive a cartridge at least partially filled with the drug scheduled for administration. The device further includes a drive mechanism, typically having a displaceable piston rod operably engaged with the stopper or piston of the cartridge. By the drive mechanism and its piston rod, the stopper or piston of the cartridge is displaceable in the distal or dosing direction and thus can discharge a predetermined amount of drug via a piercing assembly, such as in the form of a hypodermic needle, which is releasably connected to the distal end of the housing of the drug delivery device.

[0005] The drug scheduled for administration by the drug delivery device is provided and contained within a multi-dose cartridge. Such a cartridge typically includes a glass body that is sealed distally by a pierceable seal and further sealed proximally by a piston. In a reusable injection device, an empty cartridge is exchangeable with a filled one. In contrast, a disposable drug delivery device is discarded in its entirety when the drug within the cartridge has been administered or depleted.

SUMMARY OF THE INVENTION

PROBLEMS TO BE SOLVED BY THE INVENTION

[0006] While the cartridge is disposed inside the drug delivery device, it is desirable to determine the amount of drug remaining within the cartridge. A further objective is to determine the internal volume of the cartridge occupied by the liquid injection drug. The determination of the measured value of the internal volume must be fairly accurate, reliable and highly reproducible. It is desirable to provide a container for an injection drug that is easily equipped with volume measuring means that enable and assist electronic data processing.

MEANS FOR SOLVING THE PROBLEMS

[0007] This disclosure provides a container for an injection drug. The container includes an elongated body having a tubular sidewall extending along a longitudinal axis (z) and having a distal end and a proximal end. The distal end is opposite the proximal end It is in [the container]. The container further includes an outlet at the distal end of the elongated body. The container further includes a stopper or piston disposed inside the elongated body. The stopper is in sealing engagement with the sidewall and is slidable along the longitudinal axis relative to the sidewall. The container further includes an internal volume, sometimes also referred to as a filling volume. The internal volume or filling volume is configured to receive and contain an injectable medicament. The internal volume is bounded by the sidewall, the outlet, and the stopper.

[0008] The container further includes a measuring device disposed in or on the stopper. The measuring device includes a signal generator configured to emit a measuring signal into the internal volume or through the internal volume. The measuring signal can stimulate or excite the resonance of the container or its components. In particular, the measuring signal can stimulate or excite at least one acoustic resonance of such a container, or at least one acoustic resonance of the elongated body, the outlet, and the stopper of the container.

[0009] The measuring device further includes a signal detector configured to detect a feedback signal indicative of the resonant interaction between the measuring signal and at least one of the sidewall, the outlet, or the internal volume. The feedback signal can indicate the resonant interaction between the measuring signal and at least one of the container, the internal volume of the container, or the injectable medicament in the internal volume. When the container, and thus the internal volume, is occupied or at least partially filled by the injectable medicament, the feedback signal can further indicate the interaction between the measuring signal and the liquid medicament contained in the internal volume.

[0010] When the measuring device is in or on the stopper, a container with an integrated measuring device is provided. The stopper of the container is easily equipped with the measuring device. The signal generator and the signal detector of the measuring device are configured to perform measurements by emitting a measurement signal and detecting a feedback signal in return. A detectable feedback signal will be generated by the measurement signal and the interaction of the measurement signal with at least one of the side wall, the outlet, the internal volume, or the injectable drug. By detecting the feedback signal, it becomes possible to derive at least one physical or chemical parameter of the container. In particular, the feedback signal that can be obtained and detected by the signal detector can be processed to determine at least one of the size of the internal volume and the longitudinal position of the stopper relative to the side wall of the container body.

[0011] In another example, the signal detector is configured to detect a feedback signal coming from the signal generator during the emission of the measurement signal. The signal detector is connected or coupled to the signal generator to monitor the emission of the measurement signal performed by the signal generator. From the emission behavior, or from the emission of the signal generated, produced, and emitted by the signal generator, the signal detector can derive a feedback signal indicating a resonant interaction between the measurement signal and at least one of the side wall, the outlet, or the internal volume.

[0012] Integrating the signal generator and the signal detector in or on the stopper eliminates the need to separately attach and arrange the signal generator and the signal detector to the container. To provide a volume measurement of the internal or inner volume of the container, it may be sufficient to simply provide the container with the above-described specific stopper equipped with at least the signal generator and the signal detector.

[0013] At least one of the signal generator and the signal detector, or both the signal generator and the signal detector, are all installed inside the volume part of the stopper or inside the body of the stopper. The signal generator and / or the signal detector are completely sealed by the stopper. In another example, at least one of the signal generator and the signal detector is at least partially disposed inside the stopper. A part of at least one of the signal generator and the signal detector may be on the same plane as the outer surface of the stopper. In another example , at least a part of at least one of the signal generator and the signal detector may protrude from the outer surface of the stopper, for example, from the distal surface of the stopper. Since the signal generator is configured to emit a measurement signal into the internal volume part or via the internal volume part, the signal generator is installed near the distal surface of the stopper facing the outlet installed distally of the container. Also, the signal detector is installed on or near the distal surface of the stopper so as to have immediate access to the internal volume part.

[0014] In an example where at least one of the signal generator and the signal detector is completely sealed or embedded inside the stopper, the measurement signal or the feedback signal is configured to propagate through the stopper. When the signal generator is installed at a non-zero distance from both the distal end face and the proximal end face of the stopper inside the stopper, the measurement signal generated by the signal generator passes through the stopper and propagates into the internal volume part whose range is limited by the stopper. When the signal detector is completely embedded inside the stopper at a non-zero distance from both the distal end face and the proximal end face of the stopper, the feedback signal can also propagate from the internal volume part into the stopper so as to be detected by the signal detector.

[0015] By the signal generator and the signal detector being attached to the stopper or all installed inside the stopper, it is possible to retrofit a measuring device even to an existing container such as an injection cartridge and its elongated body. Here, the existing stopper, which is usually configured as a rubber stopper, is replaced with the above-described stopper, and this stopper is equipped with a measuring device.

[0016] Typically, the stopper includes an elastomeric material such as natural rubber or synthetic rubber. The stopper may include a cyclic olefin polymer (COP) and / or a cyclic olefin copolymer. The stopper may also include a polymer material based on EPDM ethylene propylene diene monomer rubber. The measuring device is encapsulated inside the stopper. The measuring device may include a hermetically sealed housing configured to accommodate at least a signal generator and a signal detector. The housing is embedded inside the body of the stopper.

[0017] Encapsulating at least one of the signal generator and the signal detector inside the housing of the measuring device enables a number of different ways to manufacture the stopper. For example, the housing with the signal generator and the signal detector installed therein is overmolded with the stopper-forming material.

[0018] In another example, the stopper may include at least two stopper components configured to be mechanically assembled together to form the stopper. Here, the measuring device is disposed between these stopper components to embed the measuring device inside the stopper.

[0019] By embedding the measuring device inside the stopper, the measuring device is essentially protected against environmental influences or hazards. Further, the measuring device is hidden inside by the stopper. Embedding the measuring device inside the stopper does not affect the geometry outside the stopper at all. When the measuring device is completely embedded inside the stopper and thus sealed by the stopper, the stopper is not visible from the outside. In this way, the measuring function of the container is effectively hidden. This can enable hidden supervision or monitoring of the filling level of the container.

[0020] According to another example, the container includes a processor connected to the signal detector. The processor is disposed inside the stopper. The processor may belong to the measuring device. Thus, the measuring device may include the processor. The processor is configured to process a signal obtainable from the signal detector when receiving at least one feedback signal. The signal detector is typically configured to generate an electrical signal in response to receiving a feedback signal. The conductive connection between the processor and the signal detector enables respective signal processing. Based on the signal obtainable from the signal detector, the processor is configured to determine at least one of the size of the internal volume or the longitudinal position of the stopper relative to the body of the container. to be configured to determine at least one of the longitudinal position of the stopper relative to the body of the container.

[0021] The processor may include an integrated circuit such as an application specific integrated circuit (ASIC). The processor is implemented as a microcontroller. The processor is at least electrically connected to the signal detector. The processor is also installed inside the stopper. Usually, the processor is installed on a printed circuit board (PCB). At least one of the signal generator and the signal detector is installed and incorporated on the same PCB. The entire measuring device is configured or implemented as an ASIC and provided on a single common PCB. In other examples, the processor is installed outside the measuring device. The processor is installed on the proximal surface of the stopper. The processor is also installed outside the stopper or at a non-zero predetermined distance from the stopper.

[0022] The processor is also installed outside the container. The connection between the processor and the signal detector may be of a wired type or a wireless type. When the processor is installed inside or on the stopper, a wired connection is provided between the processor and the signal detector. In the example where the processor is installed outside the stopper and / or outside the container, the processor is wirelessly connected to the signal detector.

[0023] In another example, the processor is configured to determine the size of the internal volume based on a feedback signal obtainable via a signal detector. For this purpose, the processor is configured to determine the magnitude or amplitude of the feedback signal. The processor is configured to determine the time or time delay at which the feedback signal is detected, compared to a reference signal. Alternatively, the processor is configured to determine the phase shift between the feedback signal and the reference signal. The processor is further configured to compare the feedback signal with a predetermined signal or with a previously detected feedback signal. In this way, the processor is configured to monitor and process a temporary change in the feedback signal or a series of feedback signals. A primary change in the feedback signal may indicate the size of the internal volume and / or the longitudinal position of the stopper.

[0024] In another example, the processor is connected to a signal generator. Generally, the processor is connected to both a signal generator and a signal detector. Here, the processor is configured to trigger the emission of a measurement signal. The processor is further configured to determine the size of the internal volume based on comparing at least one measurement signal with at least one feedback signal. The processor is further configured to perform a comparison of at least one measurement signal with several feedback signals. As an alternative or in addition, the processor is configured to compare at least one feedback signal with several measurement signals. Further, the processor is configured to compare a number of measurement signals with a number of feedback signals.

[0025] The signal generator is configured to emit a continuous or a series of measurement signals. Accordingly, the signal detector is configured to detect each continuous or series of the returned measurement signals. Here, the processor is configured to perform a mutual comparison between the feedback signals of a series of feedback signals. In this way, temporary fluctuations in the feedback signals are detected. Such temporary fluctuations may indicate the size of the internal volume portion and / or the longitudinal position of the stopper relative to the main body of the container.

[0026] Furthermore, since the processor is connected to both the signal generator and the signal detector, the processor can be configured to measure the time delay between the emission of the measurement signal by the signal generator and the detection of the feedback signal by the signal detector. By determining such a time delay, the size of the internal volume portion and / or the longitudinal position of the stopper is precisely determined. In addition, or alternatively, the processor is configured to compare the magnitude or amplitude of the feedback signal with a given reference amplitude. The amplitude or magnitude of the measurement signal may directly indicate the size of the internal volume portion and / or the longitudinal position of the stopper relative to the main body.

[0027] In another example, the measuring device includes a data storage device configured to store at least one of the initial size of the internal volume portion and at least one feedback signal. The data storage device is configured to store the initial size of the internal volume portion or at least one feedback signal during the calibration procedure of the container. When the container is filled with an injectable drug or thereafter, it is conceivable that the measuring device is triggered to perform a measurement, that is, to emit a measurement signal and detect the returned feedback signal.

[0028] Such an initial measurement can validate the calibration of the container. In such an initial measurement procedure, the internal volume derived by the processor and / or the feedback signal is stored as a reference volume or a reference signal in the data storage device. In the next measurement procedure, the volume derived or determined by the processor and / or by the feedback signal obtainable via the signal detector is compared with the reference volume and / or the reference signal previously stored in the data storage device. The processor is configured to perform a quantitative comparison between the feedback signal and the reference feedback signal previously stored in the data storage device. The size and / or the longitudinal position of the stopper of the internal volume part is directly derived from the size or magnitude of the feedback signal compared with the size or magnitude of the reference feedback signal.

[0029] The data storage device is usually connected to the processor. The processor is also connected to at least one of the signal generator and the signal detector. Connecting between the processor and the data storage device enables comparison of the actually detected feedback signal with the previously detected feedback signal. The data storage device may include a buffer for a series of feedback signals. The signal detector is configured to fill the buffer of the data storage device when a series or a succession of feedback signals are detected by the signal detector. The buffer of the data storage device and the series of feedback signals stored in the buffer may be subject to stepwise data processing. Thus, the data storage device effectively reduces the requirements on the processor in terms of computing power. The overall electrical energy consumption of the processor and the storage device is reduced by using the data storage device. The data storage device is usually incorporated into the integrated circuit of the measuring device. The data storage device is installed on the common PCB of the measuring device. The processor and the data storage device are installed and arranged on the common PCB.

[0030] In another example, the container includes a communication interface configured to exchange data with an external electronic device. This communication interface is installed inside the stopper. The communication interface may belong to the measuring device. Thus, the measuring device may include the communication interface. The communication interface member is installed inside or outside the housing of the measuring device. The communication interface may include a wireless communication interface. In another example, the communication interface is a wired communication interface. The communication interface is typically connected to a processor and / or a data storage device. The communication interface is also directly or indirectly connected to at least one of a signal generator and a signal detector. The communication interface is connected to both the signal generator and the signal detector. Typically, the communication interface is installed inside the stopper. The communication interface and the processor are connected via a wired connection.

[0031] In one example, the measuring device is installed or sealed inside the stopper, and the communication interface is installed on the outer surface of the stopper, for example, on the proximal surface of the stopper. The communication interface can also be incorporated into the measuring device. The communication interface is installed inside the housing of the measuring device. The communication interface is incorporated into the integrated circuit of the measuring device. The communication interface, the processor, and the storage device are arranged on a common PCB.

[0032] The communication interface is configured to communicate with an external electronic device. The communication interface is configured to communicate with an external electronic device according to a clearly defined communication standard or communication protocol, such as WIFI, Bluetooth, NFC, or other radio frequency-based communication standards. The communication interface is configured to exchange data, such as data acquired and generated by the processor, with an external electronic device. The external electronic device can be a portable electronic device such as a smartphone or a tablet computer.

[0033] Data exchange between the communication interface and the external electronic device may include an unprocessed feedback signal detected by the signal detector and transmitted to the external electronic device via the communication interface. In such an example, it is generally considered that the external electronic device includes a processor configured to process the feedback signal detected by the signal detector and transmitted to the external electronic device via the communication interface. In this way, the power consumption of the container, and thus the measuring device, is reduced. Further, the processor can be provided far outside the container. Accordingly, the manufacturing cost of the container and the manufacturing cost of the measuring device incorporated in the stopper are reduced.

[0034] According to another example, the container includes an antenna configured to draw electrical energy from the surrounding electromagnetic field. The measuring device may include the antenna. The antenna is disposed in or on the stopper of the container. Usually, the antenna is electrically connected to the processor. The antenna is further electrically connected directly to the communication interface. The antenna is incorporated in the communication interface or vice versa, i.e., the communication interface is incorporated in the antenna. It is conceivable that the communication interface communicates with the external electronic device via the antenna.

[0035] Accordingly, the antenna provides a dual function. The antenna enables data exchange with the external electronic device. Further, the antenna is configured to draw electrical energy from the surrounding electromagnetic field. Accordingly, the antenna can provide and supply the electrical energy obtainable from the surrounding electromagnetic field to the measuring device. The antenna may include an NFC antenna. The electrical energy required to drive or power the measuring device is provided exclusively from the antenna and drawn exclusively from the surrounding electromagnetic field. As an alternative or in addition, the measuring device is equipped with an electrical energy storage unit such as a battery. In another example, the measuring device, and thus the stopper, can be made connectable to an external source of electrical energy. For example, when combined inside an injection device, the stopper can make electrical contact with an electrical energy source.

[0036] In another example, the measuring device includes an electrical energy storage unit connected to the antenna. In this way, the antenna is configured to charge the electrical energy storage unit. In a situation where there is no ambient electromagnetic field, the electrical energy storage unit can provide sufficient power to drive or supply power to the measuring device. The electrical energy storage unit is usually connected to the measuring device. The measuring device is connected to a signal generator to generate and emit a measurement signal.

[0037] The electrical energy storage unit is also connected to a signal detector to enable the detection of feedback signals. The electrical energy storage unit is connected to a processor to enable the processing of detected feedback signals. The electrical energy storage unit is further connected to a data storage device. In this way, reading data from the storage device and writing data to the data storage device are enabled. The electrical energy storage unit is further connected to a communication interface to enable data exchange or data transmission with an external electronic device.

[0038] In another example, the signal generator is an acoustic signal generator. The acoustic signal generator is configured to generate and emit an acoustic measurement signal with a variable frequency. In particular, the acoustic signal generator is configured to generate and emit acoustic measurement signals at a first frequency, a second frequency, a third frequency, etc., and the first, second, and third frequencies are different from each other. The acoustic signal generator is configured to generate individual pulses of the acoustic measurement signal. By temporarily changing the frequency of the measurement signal or by providing a continuous series of measurement signal frequencies, the resonance interaction between the measurement signal and at least one of the side wall, the outlet, and the internal volume will undergo respective changes. The resonance behavior usually depends on the frequency of the measurement signal emitted into the internal volume.

[0039] In another example, the acoustic signal generator is configured to generate and emit a series or succession of acoustic measurement signals at different frequencies. Usually, the signal generator is configured to generate and emit a succession of measurement signals at increasing or decreasing frequencies. The signal generator is configured to generate a succession of measurement signals at frequencies that increase monotonically and / or steadily.

[0040] The acoustic signal generator can be made adjustable with respect to the frequency of the acoustic measurement signal. Successive pulses of the acoustic measurement signal can include different frequencies. Successive pulses of the acoustic measurement signal are frequency-shifted relative to each other. In particular, successive acoustic measurement signals can exhibit a constant frequency offset. Successive acoustic measurement signals, such as acoustic pulses, can include an increasing or decreasing frequency shift.

[0041] The acoustic signal generator is configured to emit successive acoustic measurement signals at variable frequencies. In other words, the frequency of the acoustic measurement signal may undergo regular or irregular changes. The frequency of the acoustic measurement signal can change continuously and / or monotonically. For example, the frequency of the acoustic measurement signal can increase steadily and slowly from a minimum frequency to a maximum frequency. When the acoustic measurement signal is at the maximum frequency, the acoustic signal generator is configured to abruptly change the frequency of the acoustic measurement signal to the minimum frequency; or vice versa. When the acoustic measurement signal reaches the maximum or minimum frequency, the frequency can return to the minimum or maximum frequency, respectively. Thereafter, the frequency increases continuously to the maximum frequency. For example, the acoustic signal generator can be operable to perform a frequency sweep. In the time domain, the frequency of the acoustic measurement signal can exhibit a sawtooth profile or a triangular profile.

[0042] The acoustic signal generator is configured to change the frequency of the acoustic measurement signal. Alternatively, the acoustic signal generator is driven by a processor and / or a communication interface, where at least one of the processor and the communication interface provides a control signal that defines the frequency of the acoustic measurement signal. At least one of the acoustic signal generator, the processor, and the communication interface is further configured to change the amplitude of the acoustic measurement signal.

[0043] The acoustic signal generator may include an electromechanical transducer. The electromechanical transducer may include a piezoelectric crystal or a piezoelectric ceramic component configured to convert an electrical signal into a mechanical excitation state, such as mechanical vibration. The acoustic signal generator may be operable in the audible spectrum range. The acoustic signal generator may be operable in the ultrasonic spectrum range. When driven in the ultrasonic range, the signal emitted by the acoustic signal generator is inaudible to humans and / or animals. There is no perceivable interface between the acoustic signal generator and the person using the container. When driven in the ultrasonic spectrum range, the acoustic signal generator is configured to generate and emit an acoustic measurement signal with a frequency above 20 kHz, above 100 kHz, above 1 MHz, or above 10 MHz.

[0044] When operated in the audible spectrum range, i.e., when the mechanical transducer is configured to generate and emit a measurement signal with a frequency less than 20 kHz or less than 10 kHz, less than 5 kHz, less than 1 kHz, less than 500 kHz, less than 200 kHz, less than 100 kHz, or less than 50 kHz, the mechanical resonance phenomenon of the container that can be easily and clearly detected may be stimulated or excited.

[0045] The acoustic signal generator may include a microelectromechanical (MEM) device. An embodiment of the acoustic signal generator of the MEM device is quite space-saving. Such a device can be easily implemented inside the stopper of the container. The device is further suitable for mass production at a reasonable cost.

[0046] Since the acoustic signal generator is configured to emit an acoustic measurement signal of variable frequency, this acoustic signal generator can be used to stimulate or excite the acoustic resonance of the container. The signal generator is configured to excite or stimulate the resonance frequency of the container or the higher harmonics of the resonance frequency. The resonance frequency or natural frequency of the container, and / or its higher harmonics, is determined by at least the total mass of the container. The resonance frequency and / or its higher harmonics are directly correlated with the amount of drug in the internal volume of the container. When the injectable drug is administered, that is, discharged or withdrawn from the outlet, the amount of drug present in the internal volume is reduced. This has a direct effect on the resonance frequency. By the acoustic signal generator, especially by generating and emitting an acoustic measurement signal of variable frequency, it is made effective to detect the modification of the resonance frequency of the container and / or its higher harmonics.

[0047] The relationship between the resonance frequency and the size of the internal volume is stored in a look-up table and determined before the container is marketed to the end consumer. Such a look-up table is stored in a data storage device. The relationship between the filling volume or the size of the internal volume and the resonance frequency is measured individually, for example, during the filling procedure of the container. The previously measured relationship or calculation formula between the resonance frequency or higher harmonics and the size of the internal volume is stored in the data storage device of the measuring device.

[0048] The excitation or stimulation of the container by an acoustic measurement signal whose frequency matches the resonance frequency of the container or its higher harmonics is precisely detected by a signal detector, and each feedback signal detected by the signal detector is processed by a processor. Based on the look-up table or based on calibration, the processor is configured to assign one feedback signal, for example, the frequency and / or amplitude of the feedback signal, to one size of the internal volume.

[0049] According to another example, the signal detector includes an electrical impedance measurement circuit connected to the acoustic signal generator. When implemented as an impedance measurement circuit, the acoustic signal generator is typically driven or operated in a frequency sweep mode. The frequency of the acoustic measurement signal is modified continuously or stepwise. The change in the frequency of the acoustic measurement signal follows a predetermined schedule. The impedance measurement circuit monitors either the voltage or the current present in the acoustic signal generator.

[0050] When the frequency of the acoustic measurement signal, and thus the mechanical vibration of the acoustic signal generator, coincides with the resonance frequency of the container or a higher harmonic of the reference frequency, the voltage across the acoustic signal generator or the current passing through the acoustic signal generator exhibits a positive or negative peak. Such a peak is detected by the electrical impedance measurement circuit and / or by a processor connected to the impedance measurement circuit. Since the sweep of the frequency of the acoustic measurement signal is typically driven by a clock signal, there is a clear assignment between the instantaneous frequency of the acoustic measurement signal and the clock signal. In this case, the impedance measurement circuit and / or the processor connected thereto is configured to determine at least one clock signal at which the output of the impedance measurement circuit exhibits a minimum or a maximum. At this time, the frequency corresponding to this particular clock signal is the resonance frequency or a higher harmonic of the container at that time.

[0051] In another example, the signal detector is incorporated into the signal generator. Alternatively, the signal detector is a component of the signal generator. By incorporating the signal detector into the signal generator, a separate signal detector or signal receiver becomes unnecessary. This enables the design of a considerably small and low-cost measuring device. A considerably small measuring device is particularly advantageous for placing or embedding the measuring device inside the stopper of the container.

[0052] In another example, the signal detector includes an acoustic sensor. The acoustic sensor includes a transducer configured to convert an acoustic signal into an electrical signal. The acoustic sensor may include a microphone. The acoustic sensor is configured to monitor and / or detect a feedback signal emerging from at least one of the sidewall, outlet, or internal volume of the container. The acoustic sensor is configured to determine and detect or measure at least one of the frequency and amplitude of the feedback signal. When the container is excited or stimulated at its resonance frequency, an acoustic feedback signal detectable by the acoustic sensor may exhibit a maximum amplitude at a specific frequency of the feedback signal. The frequency of the feedback signal may be exactly the resonance frequency.

[0053] According to another aspect, the present disclosure further relates to a method for determining the size of the internal volume of the container described above. The method includes generating a measurement signal and emitting it from a measuring device into or through the internal volume of the container. The measurement signal can stimulate or excite the resonance of the container. Thereafter, at least one feedback signal is typically detected by a signal detector. The detected feedback signal indicates the interaction between the measurement signal and at least one of the sidewall, outlet, or internal volume of the container. Then, in a final step, the size of the internal volume is determined based on the feedback signal. Typically, this method is implemented by a processor installed inside or provided outside the stopper. The processor is incorporated into the measuring device. In other examples, the processor is installed in an external electronic device. Here, the measuring device is equipped with a communication interface configured to transmit data to or exchange data with the external electronic device. In this case, the communication interface is connected to at least one of the signal generator and the signal detector. The communication interface may also be connected to both the signal generator and the signal detector.

[0054] Generally speaking, the method of determining the size of the internal volume portion of the container is implemented by the container as described above. Therefore, the functions, advantages, and modes of operation described above in relation to the container equally apply to the method of determining the size of the internal volume of the container; and vice versa.

[0055] As used herein, the terms "distal" or "distal end" are associated with the end of the injection device that faces the injection site of a human or animal. The terms "proximal" or "proximal end" are associated with the end of the injection device on the opposite side that is furthest from the injection site of a human or animal.

[0056] The term "drug" or "agent" as used herein means a pharmaceutical formulation containing at least one pharmaceutically active compound, wherein, in one embodiment, the pharmaceutically active compound has a molecular weight up to 1500 Da and / or is a peptide, protein, polysaccharide, vaccine, DNA, RNA, enzyme, antibody or fragment thereof, hormone, or oligonucleotide, or a mixture of the above-described pharmaceutically active compounds, wherein, in a further embodiment, the pharmaceutically active compound is useful for the treatment and / or prevention of diabetes or complications associated with diabetes, such as diabetic retinopathy, thromboembolic disorders, such as deep vein thrombosis or pulmonary embolism, acute coronary syndrome (ACS), angina, myocardial infarction, cancer, macular degeneration, inflammation, hay fever, atherosclerosis and / or rheumatoid arthritis, wherein, in a further embodiment, the pharmaceutically active compound contains at least one peptide for the treatment and / or prevention of diabetes or complications associated with diabetes, such as diabetic retinopathy, wherein, in a further embodiment, the pharmaceutically active compound contains at least one human insulin or human insulin analog or derivative, glucagon-like peptide (GLP-1) or its analog or derivative, or exendin-3 or exendin-4 or an analog or derivative of exendin-3 or exendin-4.

[0057] Insulin analogs include, for example, Gly(A21), Arg(B31), Arg(B32) human insulin; Lys(B3), Glu(B29) human insulin; Lys(B28), Pro(B29) human insulin; Asp(B28) human insulin; human insulin in which the proline at position B28 is 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.

[0058] Insulin derivatives include, for example, B29-N-myristoyl-des(B30) human insulin; 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-γ-glutamyl)-des(B30) human insulin; B29-N-(N-lithocholyl-γ-glutamyl)-des(B30) human insulin; B29-N-(ω-carboxyheptadecanoyl)-des(B30) human insulin and B29-N-(ω-carboxyheptadecanoyl) human insulin.

[0059] Exendin-4 means, for example, exendin-4(1-39), which is a peptide of the sequence H-His-Gly-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Leu-Ser-Lys-Gln-Met-Glu-Glu-Glu-Ala-Val-Arg-Leu-Phe-Ile-Glu-Trp-Leu-Lys-Asn-Gly-Gly-Pro-Ser-Ser-Gly-Ala-Pro-Pro-Pro-Ser-NH2.

[0060] Exendin-4 derivatives include, for example, the compounds in the following list: H-(Lys)4-desPro36,desPro37 exendin-4(1-39)-NH2, H-(Lys)5-desPro36,desPro37 exendin-4(1-39)-NH2, desPro36 exendin-4(1-39), desPro36[Asp28] exendin-4(1-39), desPro36[IsoAsp28] exendin-4(1-39), desPro36[Met(O)14,Asp28] exendin-4(1-39), desPro36[Met(O)14,IsoAsp28] exendin-4(1-39), desPro36[Trp(O2)25,Asp28] exendin-4(1-39) , desPro36[Trp(O2)25,IsoAsp28] exendin-4(1-39), desPro36[Met(O)14 Trp(O2)25,Asp28] exendin-4(1-39), desPro36[Met(O)14 Trp(O2)25,IsoAsp28] exendin-4(1-39); or desPro36[Asp28] exendin-4(1-39), desPro36[IsoAsp28] exendin-4(1-39), desPro36[Met(O)14,Asp28] exendin-4(1-39), desPro36[Met(O)14,IsoAsp28] exendin-4(1-39), desPro36[Trp(O2)25,Asp28] exendin-4(1-39), desPro36[Trp(O2)25,IsoAsp28] exendin-4(1-39), desPro36[Met(O)14 Trp(O2)25,Asp28]exendin-4(1-39), desPro36[Met(O)14 Trp(O2)25,IsoAsp28]exendin-4(1-39), (wherein the group - Lys6 - NH2 may be attached to the C - terminus of the exendin - 4 derivative);

[0061] or an exendin - 4 derivative of the following sequences: desPro36 exendin-4(1-39)-Lys6-NH2 (AVE0010), H-(Lys)6-desPro36[Asp28]exendin-4(1-39)-Lys6-NH2, desAsp28Pro36,Pro37,Pro38 exendin-4(1-39)-NH2, H-(Lys)6-desPro36,Pro38[Asp28]exendin-4(1-39)-NH2, H-Asn-(Glu)5desPro36,Pro37,Pro38[Asp28]exendin-4(1-39)-NH2, desPro36,Pro37,Pro38[Asp28]exendin-4(1-39)-(Lys)6-NH2, H-(Lys)6-desPro36,Pro37,Pro38[Asp28]exendin-4(1-39)-(Lys)6-NH2, H-Asn-(Glu)5-desPro36,Pro37,Pro38[Asp28]exendin-4(1-39)-(Lys)6-NH2, H-(Lys)6-desPro36[Trp(O2)25,Asp28]exendin-4(1-39)-Lys6-NH2, H-desAsp28Pro36,Pro37,Pro38[Trp(O2)25]exendin-4(1-39)-NH2, H-(Lys)6-desPro36,Pro37,Pro38[Trp(O2)25,Asp28]exendin-4(1-39)-NH2, H-Asn-(Glu)5-desPro36,Pro37,Pro38[Trp(O2)25,Asp28] Exendin-4(1-39)-NH2, desPro36,Pro37,Pro38[Trp(O2)25,Asp28] Exendin-4(1-39)-(Lys)6-NH2, H-(Lys)6-desPro36,Pro37,Pro38[Trp(O2)25,Asp28] Exendin-4(1-39)-(Lys)6-NH2, H-Asn-(Glu)5-desPro36,Pro37,Pro38[Trp(O2)25,Asp28] Exendin-4(1-39)-(Lys)6-NH2, H-(Lys)6-desPro36[Met(O)14,Asp28] Exendin-4(1-39)-Lys6-NH2, desMet(O)14 Asp28 Pro36,Pro37,Pro38 Exendin-4(1-39)-NH2, H-(Lys)6-desPro36,Pro37,Pro38[Met(O)14,Asp28] Exendin-4(1-39)-NH2, H-Asn-(Glu)5-desPro36,Pro37,Pro38[Met(O)14,Asp28] Exendin-4(1-39)-NH2, desPro36,Pro37,Pro38[Met(O)14,Asp28] Exendin-4(1-39)-(Lys)6-NH2, H-(Lys)6-desPro36,Pro37,Pro38[Met(O)14,Asp28] Exendin-4(1-39)-(Lys)6-NH2, H-Asn-(Glu)5 desPro36,Pro37,Pro38[Met(O)14,Asp28] Exendin-4(1-39)-(Lys)6-NH2, H-Lys6-desPro36[Met(O)14,Trp(O2)25,Asp28] Exendin-4(1-39)-Lys6-NH2, H-desAsp28Pro36,Pro37,Pro38[Met(O)14,Trp(O2)25] exendin-4(1-39)-NH2, H-(Lys)6-desPro36,Pro37,Pro38[Met(O)14,Asp28] exendin-4(1-39)-NH2, H-Asn-(Glu)5-desPro36,Pro37,Pro38[Met(O)14,Trp(O2)25,Asp28] exendin-4(1-39)-NH2, desPro36,Pro37,Pro38[Met(O)14,Trp(O2)25,Asp28] exendin-4(1-39)-(Lys)6-NH2, H-(Lys)6-desPro36,Pro37,Pro38[Met(O)14,Trp(O2)25,Asp28] exendin-4(S1-39)-(Lys)6-NH2, H-Asn-(Glu)5-desPro36,Pro37,Pro38[Met(O)14,Trp(O2)25,Asp28] exendin-4(1-39)-(Lys)6-NH2; or a pharmaceutically acceptable salt or solvate of any one of the aforementioned exendin-4 derivatives selected from.

[0062] The hormones are, for example, pituitary hormones or hypothalamic hormones or regulatory active peptides listed in Chapter 50 of the Rote Liste, 2008 edition, and their antagonists, for example, gonadotropins (folitropin, lutropin, chorionic gonadotropin, menotropin), somatropin (Somatropine), desmopressin, terlipressin, gonadorelin, triptorelin, leuprorelin, buserelin, nafarelin, goserelin.

[0063] The polysaccharide is, for example, glucosaminoglycan, hyaluronic acid, heparin, low molecular weight heparin or ultra-low molecular weight heparin or derivatives thereof, or a sulfated form such as a polysulfated form of the above-mentioned polysaccharide, and / or a pharmaceutically acceptable salt thereof. An example of a pharmaceutically acceptable salt of polysulfated low molecular weight heparin is enoxaparin sodium.

[0064] Antibodies are globular plasma proteins (about 150 kDa), also known as immunoglobulins, which share a basic structure. Since they have sugar chains attached to amino acid residues, they are glycoproteins. The basic functional unit of each antibody is an immunoglobulin (Ig) monomer (containing only Ig units), and secreted antibodies can also be dimers having two Ig units such as IgA, tetramers having four Ig units such as IgM of bony fish, or pentamers having five Ig units such as mammalian IgM.

[0065] The Ig monomer is a "Y"-shaped molecule consisting of four polypeptide chains; two identical heavy chains and two identical light chains joined by disulfide bonds between cysteine residues. Each heavy chain is about 440 amino acids long, and each light chain is about 220 amino acids long. The heavy and light chains each contain intra-chain disulfide bonds that stabilize their folded structures. Each chain is composed of structural domains called Ig domains. These domains contain 70 - 110 amino acids and are classified into different categories (e.g., variable or V, and constant or C) according to their size and function. They have a characteristic immunoglobulin fold structure in which two β-sheets are held together by interactions between conserved cysteines and other charged amino acids to create a "sandwich" shape.

[0066] There are five types of mammalian Ig heavy chains represented by α, δ, ε, γ, and μ. The isotype of the antibody is defined by the type of heavy chain present, and these chains are found in IgA, IgD, IgE, IgG, and IgM antibodies, respectively.

[0067] The different heavy chains vary in size and composition, with α and γ containing approximately 450 amino acids, δ containing approximately 500 amino acids, and μ and ε having approximately 550 amino acids. Each heavy chain has two regions, namely the constant region (C H ) and the variable region (V H ). In one species, the constant region is essentially identical for all antibodies of the same isotype, but different for antibodies of different isotypes. Heavy chains γ, α, and δ have a constant region composed of three tandem Ig domains and a hinge region for added flexibility, while heavy chains μ and ε have a constant region composed of four immunoglobulin domains. The variable region of the heavy chain varies among antibodies produced by different B cells, but is the same for all antibodies produced by a single B cell or B cell clone. The variable region of each heavy chain is approximately 110 amino acids in length and is composed of a single Ig domain.

[0068] In mammals, there are two types of immunoglobulin light chains, designated λ and κ. The light chains have two successive domains, namely one constant domain (CL) and one variable domain (VL). The approximate length of the light chain is 211 - 217 amino acids. Each antibody contains two light chains that are always identical, and for each antibody in a mammal, only one type of light chain, either κ or λ, is present.

[0069] The general structure of all antibodies is very similar, but the unique properties of a given antibody are determined by the variable (V) region, as detailed above. More specifically, three variable loops for each light chain (VL) and three for each heavy chain (HV) are involved in binding to the antigen, i.e., its antigen specificity. These loops are called complementarity-determining regions (CDRs). Since CDRs from both the VH domain and the VL domain contribute to the antigen-binding site, it is the combination of the heavy and light chains, not either alone, that determines the final antigen specificity.

[0070] "Antibody fragment" contains at least one antigen-binding fragment as defined above, and the fragment exhibits substantially the same function and specificity as the intact antibody from which the fragment is derived. Limited proteolytic digestion by papain cleaves the Ig prototype into three fragments. Two identical amino-terminal fragments, each containing one complete L chain and approximately half of the H chain, are the antigen-binding fragments (Fab). A third fragment containing the carboxyl terminus at the position of approximately half of both heavy chains, which are of equal size and have interchain disulfide bonds, is the crystallizable fragment (Fc). Fc contains carbohydrates, complement-binding sites, and FcR sites. Limited pepsin digestion yields a single F(ab')2 fragment containing both the Fab fragment and the hinge region containing the H-H interchain disulfide bond. F(ab')2 is bivalent with respect to antigen binding. The disulfide bond of F(ab')2 can be cleaved to obtain Fab'. Furthermore, the variable regions of the heavy and light chains can be fused to form a single-chain variable fragment (scFv). Pharmaceutically acceptable salts include, for example, acid addition salts and basic salts. Acid addition salts include, for example, HCl or HBr salts. Basic salts include, for example, cations selected from alkali or alkaline earth, such as Na+, or K+, or Ca2+, or ammonium ions N+(R1)(R2)(R3)(R4), (wherein R1 to R4 are independently of each other: hydrogen, optionally substituted C1-C6 alkyl group, optionally substituted C2-C6 alkenyl group, optionally substituted C6-C10 aryl group, or optionally substituted C6-C10 heteroaryl group). Further examples of pharmaceutically acceptable salts are described in "Remington’s Pharmaceutical Sciences", 17th edition, Alfonso R. Gennaro (ed.), Mark Publishing Company, Easton, Pa., U.S.A., 1985 and Encyclopedia of Pharmaceutical Technology.

[0071] ​

[0072] Pharmaceutically acceptable solvates are, for example, hydrates.

[0073] Furthermore, it will be apparent to those skilled in the art that various modifications and variations can be made to the present invention without departing from the spirit and scope of the invention. Additionally, it should be noted that any reference numerals used in the appended claims should not be construed as limiting the scope of the invention.

[0074] Hereinafter, a number of examples of containers and injection devices will be described in more detail with reference to the drawings.

Brief Description of the Drawings

[0075]

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5a

Figure 5b

Figure 6

Modes for Carrying Out the Invention

[0076] Figures 1 to 2 show an example of an injection device 1 configured as a pen-type syringe. The injection device 1 includes a housing 20. The housing 20 includes a cartridge holder 21 and a main body 22. The cartridge holder 21 is configured to accommodate a container 100, which may include at least a first injection drug-filled cartridge 50. The cartridge holder 21 and the main body 22 are permanently or releasably attached to each other. When using a permanent or non-detachable connection between the cartridge holder 21 and the main body 22, the injection device 1 is configured as a disposable injection device into which the container 100 is easily incorporated. Alternatively, the injection device 1 is configured as a reusable device. Here, the cartridge holder 21 is separated from the main body 22 so that the container 100 can be replaced or exchanged.

[0077] The cartridge holder 21 shown in Figure 2 includes a window 25 that allows visual inspection of the container 100 disposed therein. Near the distal end, the cartridge holder 21 includes a socket 31 having an external thread portion 32. The socket 31 is configured to support an injection needle 40. The injection needle 40 typically includes a double-ended hollow cannula having a proximal end and a distal end. The injection needle 40 typically includes a needle hub 41 having an internal thread portion for releasably connecting to a thread portion 132. The needle hub 41 includes a bottom portion and a side wall portion that form a cup-shaped receptacle configured to receive the threaded socket 31 of the cartridge holder 21. The side wall portion includes an internal thread portion that mates with the external thread portion 32 of the socket 31. The distal end face of the cartridge holder 21 includes a through hole 23, through which the proximal protruding portion of the needle 40 extends into the cartridge holder 21 when the injection needle 40 is attached to the cartridge holder 21 and when the container 100 is disposed within the cartridge holder 21, and thus can extend into the interior of the cartridge or container 100.

[0078] Container 100 is disposed inside the cartridge holder 21. The container is positioned and fixed inside the cartridge holder 21. Container 100 includes an elongated tubular body 101. The body 101 may include a vitreous body. The body 101 is made of glass. The body 101 can be made translucent or transparent to enable visual inspection of the contents of container 100. The elongated body 101 extends along the longitudinal direction (z). The body 101 includes a distal end 103 and a proximal end 104 disposed on the opposite side.

[0079] For the body 101, the distal end 103 is disposed near or at the distal end of the cartridge holder 21. The distal end 103 of the body 101 includes a narrowing shoulder 107 that extends into a diameter-reducing neck portion 105. The radially narrowing shoulder 107 is configured to axially abut or engage a shoulder section of a corresponding shape of the cartridge holder 21. The shoulder 107 is disposed in proximity to the distal end 103 of the cartridge or container 100.

[0080] At the distal end further away, the neck portion 105 extends into a radially expanding head portion 105a. The head portion 105a is provided with a sealing portion 106, for example in the form of a pierceable sealing disc. This sealing portion 106 may include a pierceable rubber septum that is fixed to the head portion 105a, and thus to the distal end 103 of the body 101, by a ferrule 108 or a crimped metal cap. The ferrule 108 may include a crimped aluminum cap. The sealing portion 106 can form or belong to an outlet 116 of the container 100 at the distal end 103 of the elongated body 101.

[0081] The injection device 100 is further equipped with a drive mechanism 14 that includes a plunger or piston rod 11. The drive mechanism 14 is further equipped with a trigger 18 that can trigger or control the dosing operation of the injection device 1. Optionally, the injection device 1 and the drive mechanism 14 include a dose dial 16 that can be individually set to the size of the dose to be administered, or the injection device 1 can be configured or prepared for subsequent dosing procedures.

[0082] Optionally, and as shown in FIG. 1, the body 22 of the housing 20 can include a dosage size display window 26. The size of the actually set dosage is visually displayed in the window 26, so that the user is informed of the amount of the drug scheduled for administration during subsequent dosing procedures.

[0083] As further shown in FIG. 1, the injection needle 40 includes an inner needle cap 27 configured to cover the distal end of the injection needle 40. The injection needle and / or the needle hub 41 is further covered by an outer needle cap 28. When not in use, the injection needle 40 must be removed from the distal end of the cartridge holder 21. At that time, the cartridge holder 21 can and must be covered by a protective cap 24. The protective cap 24 is configured to releasably engage at least one of the cartridge holder 21 and the body 22. The protective cap 24 must be removed from the housing 20 before the injection needle 40 is combined with the cartridge holder 21.

[0084] The above-described interaction between the container 100 and the pen-type injection device 1 shown in FIGS. 1-2 is merely exemplary. In the general operating principle of the container, it does not require interaction with the pen-type injection device 1. Generally, the container 100 is implemented or used as a manually operated syringe or as a container for an infusion device.

[0085] The container 100 shown in FIG. 3 includes a tubular elongated body 101 having a tubular side wall 102. At the distal end 103, the container 100 includes an outlet 116. The outlet 116 is sealed by a pierceable seal 106. Near the proximal end 104, on the opposite side of the distal end 103, the container 100 includes a stopper 110 or a piston. The stopper 110 is disposed inside the tubular side wall 101 of the container 100. The stopper 110 is in sealing engagement with the inner section of the side wall 102. The stopper 110 includes an outer tubular side wall 115 that frictionally engages the inside of the side wall 102 of the container 100.

[0086] The cross-section or diameter of the stopper 110 matches the respective cross-section or diameter of the body 101 and its side wall 102. The stopper 110 includes a body 111. The stopper 110 includes a distal surface 113 that faces towards the outlet 116 and thus towards the pierceable seal 106. On the opposite side of the distal surface 113, the stopper 110 includes a proximal surface 114. The proximal surface 114 functions as a thrust-receiving surface of the stopper 110. The proximal surface 114 can be axially or longitudinally abutted against the piston rod 11 of the drive mechanism 14 of the injection device 1, as shown in FIGS. 1 and 2.

[0087] In this way, the stopper 110 is biased or propelled in the distal direction 2 to discharge a predetermined amount of the injectable medicament 50 from the internal volume portion 109 of the container 100. The internal volume portion 109 is circumferentially or radially limited by the side wall 102 of the container 100. In the distal direction 2, the internal volume portion 109 is limited by the outlet 116. The internal volume portion 109 is limited in the distal direction 2 by the pierceable seal 106. In the proximal direction 3, the internal volume portion 109 is limited by the stopper 110. In particular, the internal volume portion 109 is limited by the distal surface 113 of the stopper 110.

[0088] The internal volume portion 109 defines the amount of the injectable medicament 50 accommodated inside the container 100. During use of the container 100 and when the injectable medicament 50 is being discharged from inside the container 100, the size of the internal volume portion 109 decreases as the stopper 110 is driven in the distal direction 2 towards the outlet 116. To measure or determine the size of the internal volume portion 109, the stopper 110 includes a measuring device 120. The measuring device 120 is disposed within or on the stopper 110. The measuring device 120 is entirely enclosed inside the body 111 of the stopper 110. The measuring device 120 is installed inside the stopper 110 at a predetermined non-zero distance from any of the distal surface 113, proximal surface 114, and outer side wall 115 of the stopper.

[0089] In one example, the measuring device 120 includes a housing 121. The measuring device 120 or at least one of its components is alternatively disposed inside the stopper 110 and outside the housing 121 such that the measuring device 120 or at least one of its components is flush with the outer surface of the main body 111 of the stopper 110. For example, the measuring device 120 can be flush with the distal surface 113 or the proximal surface 114. The measuring device 120 or its components can also protrude from at least one of the distal surface 113 and the proximal surface 114.

[0090] The measuring device 120 including its components is schematically shown in more detail in FIG. 4. The measuring device 120 includes a signal generator 122 configured to emit a measurement signal S1 into the internal volume 109 or via the internal volume 109. The measurement signal S1 can be an acoustic signal. The acoustic signal can include mechanical excitation or mechanical vibration.

[0091] The measuring device 120 further includes a signal detector 124 configured to detect a feedback signal F1. The feedback signal F1 indicates an interaction between the measurement signal and at least one of the side wall 102, the outlet 116, and the internal volume 109. The feedback signal F1 can be one of an acoustic signal, an electromagnetic signal, or an electrical signal. By emitting the measurement signal S1 into the internal volume 109, respective feedback signals F1 are generated that directly indicate an interaction between the measurement signal S1 and at least one of the side wall 102, the outlet 116, the pierceable seal 106, or the internal volume 109. Based only on the detected feedback signal F1 or based on a comparison of the feedback signal F1 and the measurement signal S1, a precise determination of the size of the internal volume 109 is obtained. Based only on the feedback signal F1 and / or based on each measurement signal S1, the longitudinal position of the stopper 110 relative to the main body 101 of the container 100 is determined or measured. Thereby, the instantaneous size of the internal volume 109 is derived.

[0092] The block diagram of FIG. 4 shows one example of the measuring device 120. The measuring device 120 may include a housing 121 that encloses and enables the measuring device 120 to be placed inside the main body 111 of the stopper 110. The measuring device 120 includes a processor 126. The processor 126 is a microprocessor in the form of, for example, a microcontroller or in the form of an application specific integrated circuit (ASIC). The measuring device 120 may include a PCB 129. In the example of FIG. 4, the signal generator 122 of the measuring device 120 includes an electromechanical transducer 136. The transducer 136 is configured to convert an electrical signal into mechanical vibrations.

[0093] The transducer 136, and thus the signal generator 122, is configured to generate and emit an acoustic measurement signal S1 that propagates into the internal volume 109 of the container 100 so as to generate an acoustic signal. The signal generator 122 is driven by the processor 126. The transducer 136 is connected to the processor 126 via a converter 140. The converter 140 may include a digital-to-analog converter (DAC). The measuring device 120 may further include a clock generator 132 and a data storage device 128. The converter 140, the clock generator 132, and the data storage device 128 are each connected to the processor 126. These may also be incorporated into the processor 126.

[0094] In one example, the signal detector 124 includes an electrical impedance measurement circuit 125. The electrical impedance measurement circuit 125 includes at least one diode 125a and a capacitor 125b arranged in parallel with the transducer 136. The diode 125a and the capacitor 125b are connected in series. A node 125c between the diode 125a and the capacitor 125b is connected to another converter 142. The other converter 142 is implemented as an analog-to-digital converter (ADC). The converter 142 is also connected to the processor 126. The electrical impedance measurement circuit 125 measures and monitors the voltage across the signal generator 122, and thus across the transducer 136. This results in an impedance measurement value of the transducer 136.

[0095] When the signal generator 122, particularly the transducer 136, is driven at a frequency that matches the instantaneous resonance frequency of the container 100, the Q of the signal generator 122 reaches its maximum value. The impedance measurement circuit 125, and thus the node 125c connected to the converter 142, is connected in parallel with the signal generator 122 and thus in parallel with the transducer 136. So, when the frequency of the signal generator 122 matches or equals the resonance frequency of the container 100, a maximum voltage or peak voltage will occur at the input of the converter 142.

[0096] Normally, the transducer 136 is driven at a variable frequency. The transducer 136 is driven in a frequency sweep mode by the processor 126 and the converter 140. Thus, the frequency at which the transducer 136 oscillates can undergo a distinct and continuous change, for example, as shown in the figure of Fig. 5a. As shown in the figure, the frequency ν changes over time t. The transducer 136 is driven at a monotonically increasing frequency or a monotonically decreasing frequency. The transducer 136 is repeatedly driven by such a variable frequency profile. For example, the transducer 136 is driven at a variable frequency that changes over time according to a sawtooth profile. Thus, the frequency of the transducer 136 can increase steadily and monotonically from a minimum frequency ν min to a maximum frequency ν max within a specific time interval δt. Once the maximum frequency ν max is reached, the frequency signal ν immediately returns to the minimum frequency ν min . In the next time interval δd, the frequency rises again to the maximum frequency ν max . As an alternative to the explanatory diagram of Fig. 5a, the frequency can change according to another frequency profile, where the frequency decreases steadily and monotonically from a maximum frequency ν max to a minimum frequency ν min and then suddenly returns to the maximum frequency.

[0097] The instantaneous frequency at each clock time is known to the processor 126.

[0098] νmin and ν max The frequency range between and is such that the resonance frequency of the container or the higher harmonics of the resonance frequency is ν min higher than but ν max lower than. In this way, at least one resonance frequency or its higher harmonics is ν min and ν max and is guaranteed to be between. While the frequency of the transducer 136 changes at a particular point in time, the container 100 is stimulated at the resonance frequency. If the instantaneous frequency of the transducer 136 coincides with the resonance frequency of the container 100 or the higher harmonics of the resonance frequency, as shown in FIG. 5b, a distinct peak is measured by the electrical impedance measurement circuit 125.

[0099] Here, at a specific frequency ν0, when the container 100 is acoustically stimulated by the transducer 136 at its instantaneous resonance frequency, a distinct and sharp peak develops. When the injectable drug 50 is discharged from the inside of the container 100, the total mass of the container 100 decreases. Accordingly, the resonance frequency will be detectably modified. For example, the resonance frequency of the container may increase in response to the decrease in the total mass of the container 100. This shift of the resonance frequency, for example, from ν0 to ν1, is detected by the electrical impedance measurement circuit.

[0100] From the appreciable change in the detectable resonance frequency of the container, the processor 126 can derive or calculate the size of the internal volume portion 109 and / or the longitudinal position of the stopper 110. The processor 126 is configured to determine and / or detect the instantaneous resonance frequency of the container 100. The processor 126 is further configured to determine or calculate the correction between the initial resonance frequency ν0 and the instantaneous resonance frequency ν1. Therefore, the difference in resonance frequency δν = ν1 - ν0 directly indicates the change in the volume of the internal volume portion 109.

[0101] When the container 100 is manufactured, assembled, or filled with the injectable agent 50, the resonance frequency of the container 100 is determined individually. The initial resonance frequency ν0 is stored in the data storage device 128. Later, and during the use of the container 100, and after a portion of the injectable agent 50 has been discharged from the container 100, an instantaneous resonance frequency ν1 is determined, and the difference from the initial resonance frequency ν0 is calculated. The difference in resonance frequency is a direct indication of a change in the size of the internal volume portion 109 and / or a direct indication of the longitudinal position of the stopper 110 relative to the body 101 of the container 100.

[0102] When the signal detector 124 is implemented as the electrical impedance measurement circuit 125, the signal obtained from the signal detector 124 is mapped to the signal emitted by the signal generator 122. Here, the processor 126 is connected to both the signal generator 122 and the signal detector 124. Further, the converters 140, 142 and the processor 126 are driven by the same clock signal. The processor 126 and the converters 140, 142 are synchronized based on the clock signal provided by the clock generator 132. In this way, the peak of the signal measured by the electrical impedance measurement circuit 125 is precisely mapped and assigned to each frequency according to the graph shown in FIG. 5a.

[0103] Further options and solutions are provided for detecting the resonance frequency of the container by the signal detector 124 incorporated in the signal generator 122. One solution for combined signal generation and signal detection includes a first oscillator and a second oscillator, where the second oscillator is driven or controlled by a reference. The first and second oscillators are connected by a mixer, and the output signal of the mixer is used as a DC signal, thereby indicating the resonance frequency of the system or entity driven by the second oscillator.

[0104] In another example, the signal detector 124 may include a direct digital gate frequency measuring device. Here, a pre-adjusted input signal is applied to one of the input parts of the digital AND gate. A second input to the gate is generated from a time base oscillator by using a configurable divider network. The time base oscillator provides a positive pulse of a required duration called the gate time (T gate ). While the pulse is in the high state, the input signal passes through the AND gate, and the number of its rising edges is counted by a frequency counter. Therefore, the number of cycles N of the input signal that enter within a known predetermined time period T gate is obtained. Therefore, the input signal frequency is calculated as F = N / T gate .

[0105] As an alternative to, or in addition to, the electrical impedance measurement circuit 125, the signal detector 124 may include an acoustic sensor 127. The acoustic sensor 127 may include a microphone. The acoustic sensor 127 is also connected to a converter 142, and thus to an analog-to-digital converter 142. The acoustic sensor 127 is configured to measure at least one of the frequency and amplitude of the feedback signal F1. When the signal generator 122, and thus the converter 136, is driven in a frequency sweep mode, the acoustic sensor 127 is configured to detect and sense the frequency at which the amplitude of each feedback signal F1 is maximized or minimized. In this way, the singularities or peaks of the acoustic response of the container are directly determined.

[0106] The measuring device 120 may further include a communication interface 130 configured to exchange data with the external electronic device 400 shown in FIG. 2. The external electronic device 400 generally includes a processor 402, a data storage device 404, and a communication interface 406. The communication interface 406 is configured to communicate with the communication interface 130 of the measuring device and to exchange data. Generally, the communication interface 130 and the communication interface 406 are configured for wireless data transmission. The communication interface 130 and / or the communication interface 406 are configured to communicate via RF electromagnetic signals. The communication interfaces 130, 406 are configured for wireless communication, for example, according to the Wi-Fi standard (IEEE802.11), RFID or NFC communication, or the Bluetooth communication protocol and standards.

[0107] The measuring device 120 further includes an antenna 134 to enable wireless data transmission between the measuring device 120 and the external electronic device 400. The antenna 134 is further configured to extract electromagnetic energy from an external electromagnetic field EM, for example, from a radio frequency electric field (RF). The measuring device 120 is generally considered to be driven entirely by the electromagnetic energy extracted from the external electromagnetic field EM. Alternatively, or in addition, the measuring device 120 may be considered to include an electrical energy storage unit 138 implemented, for example, as a rechargeable battery. The electrical energy storage unit 138 is connected to the antenna 134 and the processor 126. The electrical energy storage unit 138 is recharged by the electrical energy extracted from the external electromagnetic field EM via the antenna 134.

[0108] It is generally considered that the processor 126 is restricted from transferring the electrical signals obtainable from the converters 140, 142 to the external electronic device 400 via the communication interface 130. In this way, the computing power and power consumption of the measuring device 120 are reduced to a minimum. The processing of the signals of the converters 140, 142 is all performed by the processor 402 of the external electronic device 400. Accordingly, the software application implemented in the external electronic device 400 can provide a calculated value of the size of the internal volume portion 109 and is configured to determine the instantaneous filling level of the container 100.

[0109] In another example, the processor 126 is configured to determine or calculate the size of the internal volume portion 109 based on the signal provided to the converter 140 and returned from the converter 142. The pre-processed signal or unprocessed signal and / or processed data of the signal detector 124 derived from the detection feedback signal and / or obtained from the emitted measurement signal are also stored in the data storage device 128. Accordingly, the communication and data transfer between the measuring device 120 and the external electronic device 400 are limited to the size of the internal volume portion and / or the instantaneous longitudinal position of the plug 110 relative to the main body 101 of the container 100.

[0110] Furthermore, it is considered that the data storage device 128 is configured to store a number of size information regarding the internal volume portion or the longitudinal position of the plug 110. The data storage device 128 is configured to store the dosage history. The data storage device 128 is configured to store data derived from the measurement signal S1 and / or derived from the feedback signal F1 together with a time stamp. In this way, the dosage history of the container 100 is stored inside the plug 110.

[0111] The flowchart of FIG. 6 shows various method steps of a method for determining the size of the internal volume portion 109. In the first step 500, the container 100 is assembled. Here, the stopper 110 is inserted into the main body 101 of the container 100. Thereafter, the outlet 116 is sealed, for example, by disposing the pierceable seal portion 106 on the head portion 105a of the container 100. In the next step 502, the first measurement is performed. Here, the signal generator 122 is triggered so that at least one measurement signal S1 is emitted into or through the internal volume portion 109. At least one or a series of feedback signals F1 are detected by the signal detector 124. Thereafter, in the next step 504, the measured signal is calibrated. Thus, the result of the first measurement is assigned the actual size of the internal volume portion 109 that is determined or pre-determined during the assembly process.

[0112] In step 506, the calibration is stored in the data storage device 128. Later, also, for example, during the use of the container of the injection device, the measuring device 120 is triggered and respective measurements are performed, and at least the measurement signal S1 is emitted into or through the internal volume portion 109 in step 508. Accordingly, at least one or a series of feedback signals F1 are received by the signal detector 124. At least one of the measurement signal S1 and the feedback signal F1 is compared with the data stored in the data storage device 128. This comparison is performed in step 510. In the final step 512, the size of the internal volume portion 109 is derived or calculated based on this comparison.

[0113] Note that various modifications to the flowchart described above with respect to FIG. 6 are conceivable depending on the functions of various examples of the measuring device and the interaction of this function with, for example, the external electronic device 400. It should be noted that various modifications to the flowchart described above with respect to FIG. 6 are conceivable depending on the functions of various examples of the measuring device and the interaction of this function with, for example, the external electronic device 400.

Explanation of reference numerals

[0114] 1 Injection device 2 Distal direction 3 Proximal direction 11 Piston rod 14 Drive mechanism 16 Dosage dial 18 Trigger 20 Housing 21 Cartridge holder 22 Body 23 Through hole 24 Cap 25 Window 26 Window 27 Inner needle cap 28 Outer needle cap 31 Socket 32 Thread 40 Injection needle 41 Needle hub 50 Agent 100 Container 101 Body 102 Side wall 103 Distal end 104 Proximal end 105 Neck portion 105a Head portion 106 Pierceable sealing portion 107 Shoulder 108 Ferrule 109 Inner volume portion 110 Plug 111 Body 113 Distal surface 114 Proximal surface 115 Side wall 116 Outlet 120 Measuring device 121 Housing 122 Signal generator 124 Signal detector 125 Impedance measurement circuit 126 Processor 127 Acoustic sensor 128 Data storage device 129 Printed circuit board 130 Communication interface 132 Clock generator 134 Antenna 136 Converter 138 Electrical energy storage unit 140 Converter 142 Converter

Claims

1. An injection device (1), comprising: a drug container (100); a signal generator (122) configured to transmit one or more signals (S1) towards the drug container, the one or more signals (S1) being configured to excite one or more resonances for at least one of an elongated body of the drug container (100), an outlet (116) of the drug container (100), or a stopper (110) of the drug container (100); a signal detector (124) configured to measure one or more voltages or currents of the signal generator (122) while the signal generator (122) is transmitting the one or more signals (S1); a processor (126) configured to determine one or more characteristics of the drug container (100) based on the one or more measured voltages or currents; and the injection device (1).

2. The injection device (1) according to claim 1, wherein at least one of the signal generator (122), the signal detector (124), or the processor (126) is disposed within or in contact with the stopper (110) of the drug container (100).

3. The injection device (1) according to claim 1, wherein the signal generator (122), the signal detector (124), and the processor (126) are disposed within or in contact with the stopper (110) of the drug container (100).

4. The injection device (1) according to claim 1, wherein the one or more characteristics include at least one of a size of an internal volume portion of the drug container (100) or a position of the stopper (110) within the drug container (100).

5. The injection device (1) according to claim 4, wherein the processor (126) is configured to determine the one or more characteristics based on one or more positive or negative frequency-dependent peaks of the one or more measured voltages or currents.

6. The injection device (1) according to claim 5, wherein one or more frequencies of one or more positive or negative frequency-dependent peaks indicate one or more frequencies of one or more resonances of the drug container (100).

7. The injection device (1) according to claim 6, wherein a first frequency of one or more frequencies of one or more positive or negative frequency-dependent peaks indicates a fundamental resonance frequency of the drug container (100), and a second frequency of one or more frequencies of one or more positive or negative frequency-dependent peaks indicates a harmonic resonance frequency of the drug container (100).

8. The signal detector is configured to measure one or more voltages or currents of the signal generator (122) at each frequency of one or more signals (S1) while the signal generator transmits one or more signals (S1). The injection device (1) according to any one of claims 1 to 7.

9. The injection device (1) according to any one of claims 1 or 6 to 8, further comprising a circuit board (129) disposed within or in contact with the stopper (110) of the drug container (100), the circuit board including a processor (126), a signal generator (122), and a signal detector (124).

10. The injection device (1) according to any one of claims 1 to 9, wherein the signal detector (124) includes an impedance measurement circuit (125) including a diode (125a), a capacitor (125b), and an analog / digital converter (140, 142) electrically connected to a node (125c) between the diode (125a) and the capacitor (125b).

11. A drug container (100), A signal generator (122) configured to transmit one or more signals (S1) towards the drug container (100), the one or more signals (S1) being configured to excite one or more resonances for at least one of the elongated body of the drug container (100), the outlet (116) of the drug container (100), or the stopper (110) of the drug container (100). A signal detector (124) configured to measure one or more voltages or currents of a signal generator (122) while the signal generator (122) is transmitting one or more signals (S1), wherein the measured one or more voltages or currents indicate one or more frequencies of one or more resonances for at least one of the elongated body of the drug container (100), the outlet (116) of the drug container (100), or the stopper (110) of the drug container (100), and the signal detector (124) The drug container (100) comprising the same.

12. The drug container (100) according to claim 11, further comprising a processor (126) configured to determine one or more characteristics based on the measured one or more voltages or currents.

13. The drug container (100) according to claim 12, wherein at least one of the signal generator (122), the signal detector (124), or the processor (126) is disposed within or in contact with the stopper (110) of the drug container (100).

14. The drug container (100) according to claim 12, wherein the one or more characteristics include at least one of the size of the internal volume of the drug container (100) or the position of the stopper (110) within the drug container (100).

15. The drug container (100) according to any one of claims 12 to 14, wherein the processor (126) is configured to determine one or more characteristics based on one or more positive or negative frequency-dependent peaks of the measured one or more voltages or currents.

16. The drug container (100) according to claim 15, wherein the one or more frequencies of the one or more positive or negative frequency-dependent peaks indicate one or more frequencies of one or more resonances of the drug container (100).

17. The signal generator (122) transmits one or more signals (S1) towards the drug container (100) and excites one or more resonances in at least one of the elongated body of the drug container (100), the outlet (116) of the drug container (100), or the stopper (110) of the drug container (100), while the signal generator (122) is transmitting one or more signals (S1), the signal detector (124) measures one or more voltages or currents of the signal generator (122), and the processor (126) determines one or more characteristics of the drug container (100) based on the one or more measured voltages or currents A method comprising.

18. The method according to claim 17, wherein the one or more voltages or currents are measured at each frequency of the one or more signals (S1).

19. Determining the one or more characteristics includes determining one or more positive or negative frequency-dependent peaks of the one or more measured voltages or currents, the method according to claim 17 or 18.

20. Determining the one or more characteristics is determining one or more frequencies of the positive or negative frequency-dependent peaks, and determining one or more characteristics based on the one or more frequencies of the positive or negative frequency-dependent peaks The method according to claim 19, comprising.

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