Containers for injectable drugs

Abstract

A container for an injectable medicament is provided that can include an elongated body having a tubular sidewall extending along a longitudinal axis and having a distal end and a proximal end. The container can include an outlet at the distal end. The container can include a stopper disposed within the elongated body in sealing engagement with the sidewall and slidable relative to the sidewall along the longitudinal axis. The container can include an interior volume to receive the injectable medicament and bounded by the sidewall, the outlet, and the stopper. The container can include a measurement assembly disposed in or on the stopper. The measurement assembly can include a signal generator configured to emit an electromagnetic measurement signal into or through the interior volume and a signal receiver configured to detect a feedback signal indicative of an interaction of the measurement signal with at least one of the sidewall, the outlet, or the interior volume.

Description

[0001] The present disclosure relates to measuring the internal volume of a container filled with a liquid substance, typically filled with an injectable medicament. The present disclosure relates to a container for an injectable medicament. The container allows and supports an accurate measurement of the size of the internal volume of the container occupied by the injectable medicament. The present disclosure also relates to a method of determining the size of the internal volume of such a container.

[0002] Drug delivery devices for setting and dispensing a single or multiple doses of a liquid medicament are well-known in the art per se. Typically, such devices have a purpose which is essentially similar to that of an ordinary syringe.

[0003] Drug delivery devices, like pen-type injectors, have to meet a number of user-specific requirements. For example, in case the patient suffers from a chronic disease like diabetes, the patient can be physically infirm and can also have impaired vision. It is therefore desirable that a suitable drug delivery device, especially one intended for home medication, is robust in construction and easy to use. Furthermore, handling of the device and its components should be intelligible and easy to understand. Such an injection device should provide setting and subsequent dispensing of a dose of a medicament having variable size. Furthermore, the dose setting as well as the dose dispensing procedure must be easy to operate and must be unambiguous.

[0004] Typically, such devices comprise a housing or a specific cartridge holder which is adapted to receive a cartridge at least partially filled with a medicament to be dispensed. The device further comprises a drive mechanism usually having a displaceable piston rod to operably engage with a bung or piston of the cartridge. By means of the drive mechanism and its piston rod, the bung or piston of the cartridge is displaceable in a distal or dispensing direction and a predefined amount of medicament can thus be expelled via a piercing member, e.g. in the form of a needle, which is releasably coupled with a distal end section of the housing of the drug delivery device.

[0005] In a multiple dose cartridge, a medicament to be dispensed by the drug delivery device is provided and contained. Such a cartridge typically comprises a glass barrel which is sealed in the distal direction by means of a pierceable seal and further sealed in the proximal direction by a piston. For a reusable drug delivery device, an empty cartridge can be replaced by a filled cartridge. In contrast thereto, a drug delivery device of disposable type is completely discarded when the medicament in the cartridge has been dispensed or used up.

[0006] It is desirable to determine the amount of medicament remaining in a cartridge when the cartridge is arranged within a drug delivery device. It is also desirable to determine the internal volume of the cartridge occupied by a liquid injectable medicament. The determination of the internal volume measurement should be rather accurate, reliable and highly repeatable. It is desirable to provide a container for an injectable medicament which is easily equipped with a volume measurement device which enables and supports electronic data processing.

[0007] The present disclosure provides a container for an injectable medicament. The container comprises an elongated body having a tubular side wall extending along a longitudinal axis (z) and having a distal end and a proximal end. The distal end is positioned opposite the proximal end. The container further comprises an outlet at the distal end of the elongated body. The container further comprises a stopper or piston arranged within the elongated body. The stopper is sealingly engaged with the side wall and is slidable relative to the side wall along the longitudinal axis. The container further comprises an inner volume, which can also be denoted as a fill volume. The inner volume or fill volume is configured to receive and contain the injectable medicament. The inner volume is confined by the side wall, the outlet and the stopper.

[0008] The container further comprises a measurement assembly arranged in or on the stopper. The measurement assembly comprises a signal generator configured to emit a measurement signal into or through the inner volume. The measurement assembly further comprises a signal receiver configured to detect a feedback signal indicative of an interaction of the measurement signal with at least one of the side wall, the outlet or the inner volume. The feedback signal can also be indicative of an interaction of the measurement signal with a liquid medicament contained in the inner volume, if the container and thus the inner volume is occupied or at least partially filled with the injectable medicament.

[0009] With the measurement assembly in or on the stopper, a container is provided having an integrated measurement assembly. The stopper of the container can easily be equipped with the measurement assembly. The signal generator and the signal receiver of the measurement assembly are configured to perform a measurement by emitting a measurement signal and by detecting a feedback signal in return. The measurement signal and its interaction with at least one of the side wall, the outlet, the inner volume or the injectable medicament results in the generation of a detectable feedback signal. The detection of the feedback signal allows to derive at least one physical or chemical parameter of the container. In particular, the feedback signal, which can be obtained and detected by the signal receiver, can be processed to determine at least one of a size of the inner volume and a longitudinal position of the stopper relative to the side wall of the container body.

[0010] The integration of the signal generator and the signal receiver into or on the stopper makes it superfluous to attach and arrange the signal generator and the signal receiver to the container, respectively. In order to provide a volume measurement of the inner volume or content volume of the container, it can be sufficient to provide the container with a specific stopper as described above, which is at least equipped with the signal generator and the signal receiver.

[0011] At least one of the signal generator and the signal receiver or both the signal generator and the signal detector can be located entirely within the volume of the stopper or within the body of the stopper. The signal generator and / or the signal receiver can be entirely enclosed by the stopper. In other examples, at least one of the signal generator and the signal receiver can be at least partially arranged within the stopper. A portion of at least one of the signal generator and the signal receiver can be flush with an outer surface of the stopper. In other examples, at least a portion of at least one of the signal generator and the signal receiver can protrude from an outer surface of the stopper, for example, from a distal end face of the stopper. Since the signal generator is configured to emit a measurement signal into or through the interior volume, the signal generator can be located in the vicinity of a distal end face of the stopper, which points towards the distally located outlet of the container. Also, the signal receiver can be located at or in the vicinity of the distal end face of the stopper in order to immediately enter the interior volume.

[0012] In examples in which at least one of the signal generator and the signal receiver is entirely enclosed or embedded within the stopper, the measurement signal or the feedback signal can be configured to propagate through the stopper. If the signal generator is located within the stopper at a non-zero distance from both the distal end face and the proximal end face of the stopper, the measurement signal generated by the signal generator propagates through the stopper and into the interior volume confined by the stopper. If the signal receiver is entirely embedded within 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 interior volume into the stopper in order to be detected by the signal receiver.

[0013] By attaching the signal generator and the signal receiver to the stopper or entirely locating them within the stopper, even existing containers, such as cartridges for injectable medicaments and their elongated bodies, can be retrofitted with the measurement assembly. Here, the existing stopper, which is typically configured as a rubber bung, can be replaced by a stopper as described above, which is equipped with the measurement assembly.

[0014] Typically, the stopper comprises an elastomeric material, such as a natural or synthetic rubber. The stopper can comprise a cyclic olefin polymer (COP) and / or a cyclic olefin copolymer. The stopper can also comprise a polymer material based on EPDM ethylene propylene diene monomer rubber. The measurement assembly can be encapsulated within the stopper. The measurement assembly can comprise a sealed housing configured to at least house the signal generator and the signal receiver. The housing can be embedded within the body of the stopper. Encapsulating at least the signal generator and the signal receiver within the housing of the measurement assembly enables the stopper to be manufactured in a number of different ways. For example, the housing with the signal generator and the signal receiver located therein can be overmoulded by the material forming the stopper.

[0015] In other examples, the stopper may include at least two stopper components configured to be mechanically assembled together to form the stopper. Here, a measuring component may be arranged between these stopper components to embed the measuring component within the stopper.

[0016] By embedding the measuring component within a stopper, it is essentially protected from environmental influences or hazards. Furthermore, the measuring component can be concealed within the stopper. Embedding the measuring component within the stopper may not affect the external geometry of the stopper. If the measuring component is completely embedded within the stopper and thus surrounded by it, it is not visible from the outside. In this way, the measuring capability of the container can be effectively hidden. This allows for concealed monitoring or surveillance of the container's fill level.

[0017] According to another example, the container includes a processor connected to a signal receiver. The processor may be disposed within a stopper. The processor may belong to a measuring component. Therefore, the measuring component may include the processor. The processor is configured to process a signal available from the signal receiver upon receiving at least one feedback signal. The signal receiver is typically configured to generate an electrical signal in response to receiving a feedback signal. The conductive connection between the processor and the signal receiver enables the corresponding signal processing. Based on the signal available from the signal receiver, 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 container body.

[0018] The processor may include an integrated circuit, such as an application-specific integrated circuit (ASIC). The processor may be implemented as a microcontroller. The processor is electrically connected to at least the signal receiver. The processor may also be located within the plug. Typically, the processor is located on a printed circuit board (PCB). At least one of the signal generator and the signal receiver may be located and integrated on the same PCB. The entire measurement assembly may be configured or implemented as an ASIC and may be mounted on a single common PCB. In other examples, the processor may be located outside the measurement assembly. The processor may be located on the proximal surface of the plug. It may also be located outside the plug or at a predefined non-zero distance from the plug.

[0019] The processor can even be located outside the container. The connection between the processor and the signal receiver can be wired or wireless. When the processor is inside or above the plug, a wired connection is established between the processor and the signal receiver. In examples where the processor is outside the plug and / or outside the container, the processor can connect to the signal receiver wirelessly.

[0020] In another example, the processor is configured to determine the size of the internal volume based on a feedback signal obtainable from a signal receiver. To do this, the processor can be configured to determine the amplitude or oscillation of the feedback signal. The processor can be configured to determine the time or time delay at which the feedback signal was detected compared to a reference signal. Alternatively, the processor can be configured to determine the phase shift between the feedback signal and the reference signal. The processor can also be configured to compare the feedback signal with a predefined signal or with a previously detected feedback signal. In this way, the processor can be configured to monitor and process the temporal changes of the feedback signal or a series of feedback signals. Temporary changes in the feedback signal can indicate the size of the internal volume and / or the longitudinal position of the plug.

[0021] In another example, the processor is connected to a signal generator. Typically, the processor is connected to both the signal generator and the signal receiver. Here, the processor is configured to trigger the transmission of a measurement signal. The processor is also configured to determine the size of the internal volume based on a comparison of at least one measurement signal with at least one feedback signal. The processor may also be configured to perform a comparison of at least one measurement signal with several feedback signals. Alternatively or additionally, the processor may be configured to compare at least one feedback signal with several measurement signals. Furthermore, the processor may be configured to compare multiple measurement signals with multiple feedback signals.

[0022] A signal generator can be configured to emit a series or sequence of measurement signals. Correspondingly, a signal receiver can be configured to detect the corresponding series or sequence of measurement signals. Here, a processor can be configured to perform mutual comparisons of feedback signals in a sequence of feedback signals. In this way, time fluctuations in one or more feedback signals can be detected. Such time fluctuations can indicate the size of the internal volume and / or the longitudinal position of the stopper relative to the container body.

[0023] Furthermore, since the processor is connected to both the signal generator and the signal receiver, it can be configured to measure the time delay between the signal generator transmitting a measurement signal and the signal receiver detecting a feedback signal. From the determination of this time delay, the size of the internal volume and / or the longitudinal position of the plug can be accurately determined. Additionally, or alternatively, the processor can be configured to compare the amplitude or oscillation of the feedback signal with a given reference amplitude. The amplitude or oscillation of the measured signal can directly indicate the size of the internal volume and / or the longitudinal position of the plug relative to the body.

[0024] In another example, the measurement component includes a data storage device configured to store at least one of the initial size of the internal volume and at least one feedback signal. The data storage device can be configured to store either the initial size of the internal volume or at least one feedback signal during the container's calibration process. It is conceivable that the measurement component is triggered to perform a measurement, i.e., to emit a measurement signal and, in turn, detect the feedback signal, when or after the container is filled with the injectable agent.

[0025] This initial measurement enables the calibration of the container. During this initial measurement, the internal volume derived by the processor and / or feedback signal can be stored in the data memory as a reference volume or as a reference signal. For subsequent measurements, the volume derived or determined by the processor and / or the feedback signal obtainable from the signal receiver can be compared with the reference volume and / or with the reference signal previously stored in the data memory. The processor can be configured to perform a quantitative comparison between the feedback signal and the reference feedback signal previously stored in the data memory. From the magnitude or amplitude of the feedback signal compared to the magnitude or amplitude of the reference feedback signal, the size of the internal volume and / or the longitudinal position of the stopper can be directly determined.

[0026] Data memory is typically connected to a processor. It may also be connected to at least one of a signal generator and a signal receiver. The connection between the processor and the data memory allows for comparison of a currently detected feedback signal with a previously detected feedback signal. The data memory may include a buffer for a sequence of feedback signals. The signal receiver can be configured to fill the buffer of the data memory when the signal receiver detects a sequence or series of feedback signals. The buffer of the data memory and the sequence of feedback signals stored therein may undergo progressive data processing. Therefore, the data memory enables a reduction in the computational power requirements of the processor. Utilizing data memory can reduce the power consumption of the processor and the entire measurement component. Data memory is typically integrated into the integrated circuit of the measurement component. It may be located on a common PCB of the measurement component. The processor and data memory may be located and arranged on a common PCB.

[0027] In another example, the container includes a communication interface configured to exchange data with an external electronic device. The communication interface may be located within a plug. It may belong to a measurement component. Therefore, the measurement component may include the communication interface. The communication interface component is located inside or outside the housing of the measurement component. 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 data memory. The communication interface may also be directly or indirectly connected to at least one of a signal generator and a signal receiver. The communication interface may be connected to both the signal generator and the signal receiver. Typically, the communication interface is located within a plug. The communication interface and the processor are connected via a wired connection.

[0028] In one example, the measurement component can be positioned or packaged within a plug, while the communication interface is located on the outer surface of the plug, such as the proximal end face of the plug. Alternatively, the communication interface can be integrated into the measurement component. The communication interface can be located within the housing of the measurement component. Alternatively, the communication interface can be integrated into the integrated circuit of the measurement component. The communication interface, processor, and memory can be arranged on a common PCB.

[0029] The communication interface is configured to communicate with external electronic devices. The communication interface can be configured to communicate with external electronic devices according to well-defined communication standards or protocols (such as Wi-Fi, Bluetooth, NFC, or other radio frequency-based communication standards). The communication interface can be configured to exchange data with external electronic devices, such as data acquired and generated by a processor. The external electronic device can be a portable electronic device, such as a smartphone or tablet computer.

[0030] Data exchange between the communication interface and external electronics can include unprocessed feedback signals detected by a signal receiver and transmitted to the external electronics via the communication interface. In this example, it is generally conceivable that the external electronics include a processor configured to process the feedback signals detected by the signal receiver and transmitted to the external electronics via the communication interface. In this way, the power consumption of the container and therefore the power consumption of the measuring components can be reduced. Furthermore, the processor can be located outside and remote from the container. This reduces the manufacturing costs for both the container and the measuring components integrated into the plug.

[0031] According to another example, the container includes an antenna configured to extract electrical energy from the surrounding electromagnetic field. Measurement components may include the antenna. The antenna may be disposed within or on the container's plug. Typically, the antenna is electrically connected to a processor. The antenna may also be directly electrically connected to a communication interface. The antenna can be integrated into the communication interface, and vice versa; that is, the communication interface can be integrated into the antenna. It is conceivable that the communication interface communicates with external electronic devices via the antenna.

[0032] Therefore, the antenna can provide a dual function. It can enable data exchange with external electronic devices. Furthermore, the antenna is configured to extract electrical energy from the surrounding electromagnetic field. Thus, the antenna can provide and supply electrical energy obtainable from the surrounding electromagnetic field to the measuring component. The antenna may include an NFC antenna. The electrical energy required to drive or power the measuring component can be specifically provided by the antenna and can be specifically extracted from the surrounding electromagnetic field. Alternatively or additionally, the measuring component may be equipped with an energy storage device, such as a battery. In another example, the measuring component, and therefore the plug, may be connectable to an external power source. For example, when assembled within an injection device, the plug may be in electrical contact with the power source.

[0033] In another example, the measurement component includes a power storage device connected to an antenna. In this way, the antenna is configured to charge the power storage device. In the absence of an ambient electromagnetic field, the power storage device can provide sufficient electrical energy to drive or power the measurement component. The power storage device is typically connected to the measurement component. It is connected to a signal generator to generate and transmit measurement signals.

[0034] The energy storage device is also connected to a signal receiver to enable the detection of feedback signals. The energy storage device is connected to a processor to enable the processing of the detected feedback signals. The energy storage device can also be connected to a data storage device. In this way, it is possible to read data from the storage device and write data to the data storage device. The energy storage device is also connected to a communication interface to enable data exchange or data transfer with external electronic devices.

[0035] According to another example, the signal generator includes a light source configured to emit an optical measurement signal toward the outlet. Here, the signal generator can be configured as a light source. The signal generator may include a light-emitting diode (LED) configured to emit an optical signal, such as a beam or pulse of light at a predetermined frequency or within a predetermined spectral range or width. The optical measurement signal generated and emitted by the optical signal generator can be in the visible or invisible spectrum. The optical measurement signal may include frequencies within the infrared or ultraviolet spectral range. When the signal generator is configured to generate and emit an optical measurement signal in the invisible range, the user of the container cannot perceive the emission of the optical measurement signal. Therefore, when the optical signal generator emits an optical measurement signal, the capabilities and functions of the measurement components can be effectively concealed without distracting or confusing the user of the container.

[0036] An optical signal generator can be configured to emit a collimated beam or collimated light pulse into the internal volume of the container. A measurement signal, in the form of an optical measurement signal, propagates through at least a portion of the internal volume. The feedback signal is also an optical feedback signal. For example, the optical measurement signal may be reflected, e.g., at the sidewall of the container body and / or at the outlet. The optical feedback signal can be an optical measurement signal reflected by at least one of the outlet and the sidewall.

[0037] Signal receivers typically include photodetectors, such as charge-coupled photodetectors. Signal receivers may include photodiodes or charge-coupled devices (CCDs). Signal receivers can be configured to quantitatively determine the amplitude of the optical feedback signal. Depending on the transmittance of the internal volume and the injectable agent located therein, the decrease in the intensity of the optical feedback signal compared to the intensity of the optical measurement signal can directly indicate the optical path length through which both the optical measurement signal and the optical feedback signal propagate through the internal volume.

[0038] Compared to optical measurement signals, the intensity attenuation of optical feedback signals directly indicates the optical path length between a specific part of the signal generator, sidewall, or outlet and the signal receiver. When the stopper undergoes distally oriented sliding motion, the optical path length between the signal generator and the signal receiver continuously decreases, resulting in an increase in the intensity of the optical feedback signal. Therefore, changes in the intensity of the optical feedback signal directly indicate the longitudinal displacement of the stopper relative to the container sidewall.

[0039] In another example, the signal receiver includes a time-of-flight detector (TOF) or a TOF camera, configured to detect the optical measurement signal reflected from the exit as an optical feedback signal. The time-of-flight detector is configured to measure the time interval required for a light pulse to travel from the signal generator to the exit and back to the signal receiver. The measurement of the time of flight depends on the finite speed of light and the ability of the TOF to be measured directly by a clock or indirectly by, for example, comparing the phase of the emitted light beam or light pulse with the phase of the reflected light beam or light pulse.

[0040] In another example, a signal generator is configured to generate at least one or more light pulses at a first time point t1 and emit them into an internal volume, and a signal receiver is configured to detect at least one or more reflected light pulses. The signal receiver is typically configured to detect light pulses previously emitted by the signal generator and reflected by at least one of the sidewalls, the outlet, and the proximal surface of the pierceable seal. The signal receiver is configured to detect or determine a second time point t2 where the reflected light pulses are detected. The time interval between the first time point t1 and the second time point t2 indicates the time delay required for the emitted light to travel from the signal generator to the signal receiver. At least one of the processor and the signal receiver is configured to determine or measure this time delay, which indicates the optical path length between the signal generator and the signal receiver. For this purpose, the distance between the plug and the optical reflective structure (e.g., the proximal surface of the pierceable seal) can be precisely determined. Typically, both the signal generator and the signal receiver are connected to and driven or triggered by the processor.

[0041] Knowing that the speed of light is approximately 300,000 km / s allows for the precise determination of the optical path length between the signal generator, outlet, and receiver. The measurement or distance resolution of a TOF measurement assembly, including a TOF sensor, can be less than 1 cm, less than 5 mm, or less than 1 mm. Understanding the relative positions of the signal generator and receiver, as well as the internal volume and / or the refractive index of the injectable agent within, allows for the accurate determination of the geometric distance between the stopper and the outlet, thereby enabling the calculation of the internal volume and, consequently, the instantaneous fill level of the container.

[0042] In one operational example, when the optical signal generator and optical signal receiver are implemented as time-of-flight detectors, they are configured to generate and emit several optical pulses. As an alternative to measuring the time delay, the phase shift between the beam emitted by the optical signal generator and the reflected beam detected by the optical signal receiver can be compared, for example, by a processor. The time of flight can then be derived from the phase shift between the emitted and detected optical pulses, and thus the optical path length and geometric path length.

[0043] In a Time-of-Flight (TOF) implementation, a processor triggers an optical signal generator to emit at least one or a sequence of light pulses as an optical measurement signal. These pulses propagate into and through an internal volume. A time-of-flight sensor detects the optical feedback signal, provided by the reflection of the optical measurement signal, for example, at the inner or near-end face of the exit. Typically, a clock is used to measure the time delay between the emission of the optical measurement signal by the signal generator and the detection of the optical feedback signal by the signal receiver.

[0044] According to another example, the measuring component includes an optical interferometer configured to determine the distance between the outlet and the plug based on the optical phase shift between the optical feedback signal and a reference optical signal. The optical interferometer can be Mach-Zehnder or Michelson type. It may include a beam splitter and at least two reflectors, such as mirrors. The optical interferometer typically includes a reference path and a signal path. The beam emitted by the light source is split into a signal beam and a reference beam.

[0045] A reference beam is directed to a reflector. The distance between the reflector and the corresponding beam splitter is constant. A signal beam propagates from the beam splitter to the object. It is reflected by the object, and at least a portion of it returns to the beam splitter. At the beam splitter, the reference beam reflected from the reference reflector and the signal beam reflected from the object recombine and interfere. The coherence length of the light source and the beam emitted by the light source is at least half the distance of the total axial displacement path of the plug relative to the container body. The optical interferometer can be configured to have equal length signal and reference paths when the plug is approximately halfway between its near and far positions.

[0046] When the reflected reference beam and the reflected signal beam recombine, an interference pattern is generated at the optical signal receiver. Due to the longitudinal movement of the plug, the distance between the beam splitter and the object also changes, resulting in a quantitative modification of the interference pattern at the optical signal receiver. The optical signal receiver typically includes a charge-coupled device (CCD). The CCD comprises a linear array of charge-coupled detectors or pixels, and is therefore a one-dimensional or two-dimensional array. The pattern obtained at the optical signal receiver can be processed by a processor. Alternatively, the pattern detected at the optical signal receiver can be processed by external electronics.

[0047] For this purpose, the communication interface can be configured to transmit the pattern from the optical signal receiver to an external electronic device for further processing. The optical interferometer provides fairly accurate measurements of the stopper's position and displacement relative to the cartridge body.

[0048] In another example, the optical interferometer can be implemented at least partially using optical fiber. For example, the reference path can be provided by optical fiber. Here, the optical interferometer includes optical fiber forming a reference path for an optical reference signal. The free end of the optical fiber can include a reflective end. Furthermore, the optical fiber can be wound within a plug to reduce the space required for the measurement assembly. The optical interferometer can be configured to direct the signal beam to an exit. The exit can include a reflective surface, for example, in the form of a proximal surface of a pierceable membrane disposed on the exit.

[0049] Interferometry relies on the wave properties of light and the interferometry ability of waves. A signal receiver is typically connected to a signal generator. Typically, a processor is connected to both the signal generator and the signal receiver.

[0050] Typically, and for any of the examples described herein, the optical signal generator and the optical signal receiver can be integrated on a chip or printed circuit board, thereby allowing for further miniaturization of the measurement components.

[0051] When the measuring components are implemented optically, i.e., when the signal generator is an optical signal generator and the signal receiver is an optical signal receiver, the stopper may comprise a translucent material. Here, at least one of the optical signal generator and the optical signal receiver may be located within the stopper at a predetermined non-zero distance from the end face or circumference of the stopper. In other examples, at least one of the signal generator and the signal receiver may be located at the distal end face of the stopper. At least one of the optical signal generator and the optical signal receiver may be flush with the distal end face of the stopper. In other examples, both the signal generator and the signal receiver may be located at or flush with the distal end face of the stopper.

[0052] According to another example, at least one of the optical signal generator and the optical signal receiver is arranged in a recess on the distal face of the plug. For example, the optical signal generator is arranged in the recess. In this way, the propagation characteristics of the optical signal generated and emitted by the optical signal generator can be affected. Typically, the optical signal generator is arranged in the recess on the distal face of the plug, while the optical signal receiver is arranged at the distal face of the plug. Therefore, the optical signal generator and the optical signal receiver are arranged at a predefined longitudinal offset from each other. The optical signal generator and the optical signal receiver can also be offset in the radial or circumferential direction. By arranging the optical signal generator in the recess, the optical measurement signal emitted by the optical signal generator is prevented from directly impacting the optical signal receiver. In this respect, the recess forms a screen for the optical signal receiver.

[0053] In another example, the optical signal receiver is arranged in a recess on the distal face of the plug, and the optical signal generator is arranged on the distal face of the plug. In this way, the optical signal receiver is shielded at the distal face of the plug by the recessed assembly of the optical signal generator and one of the optical signal receivers. The advantage of this is that the optical signal receiver can only detect beams or light pulses reflected from the outlet.

[0054] When the stopper is positioned quite close to the container outlet, a recessed assembly of at least one of the optical signal generator and optical signal receiver in the distal face of the stopper is further advantageous. If the container is nearly empty and if the internal volume is close to its minimum size, the distance between the distal face of the stopper and the outlet will be close to its minimum. Through the recessed assembly of at least one of the optical signal generator and optical signal receiver, the optical path length between the optical signal generator, the outlet, and the optical signal receiver can be slightly increased compared to the geometric distance between the outlet and the distal face of the stopper. Even for small distances between the outlet and the stopper, this may be beneficial for achieving time-of-flight-based distance determination.

[0055] According to another aspect, this disclosure also relates to a method for determining the size of the internal volume of a container as described above. The method includes the steps of: generating a measurement signal from a measuring component and transmitting the measurement signal into or through the internal volume of the container. Subsequently, typically, at least one feedback signal is detected by a signal receiver. The detected feedback signal indicates the interaction of the measurement signal with at least one of the container's sidewall, outlet, or internal volume. Subsequently, and in a final step, the size of the internal volume is determined based on the feedback signal. Typically, the method is performed by a processor located inside or outside the stopper. The processor may be integrated into the measuring component. In other examples, the processor may be located in an external electronic device. Here, the measuring component may be equipped with a communication interface configured to transmit or exchange data with the external electronic device. The communication interface is then connected to at least one of a signal generator and a signal receiver. It may be connected to both the signal generator and the signal receiver.

[0056] Generally, the method for determining the internal volume of a container is carried out using the container described above. Accordingly, any features, benefits, and operating modes described above in conjunction with the container are equally applicable to the method for determining the internal volume of a container; and vice versa.

[0057] In this article, the term "distal" or "far end" refers to the end of the injection device facing the injection site in a human or animal. The term "proximal" or "proximal end" refers to the opposite end of the injection device, which is furthest from the injection site in a human or animal.

[0058] As used herein, the terms "drug" or "pharmaceutical preparation" mean a pharmaceutical formulation containing at least one pharmaceutically active compound.

[0059] In one embodiment, the pharmaceutically active compound has a molecular weight of up to 1500 Da, and / or is a peptide, protein, polysaccharide, vaccine, DNA, RNA, enzyme, antibody or antibody fragment, hormone or oligonucleotide, or a mixture of the above pharmaceutically active compounds.

[0060] In another embodiment, the pharmaceutically active compound can be used to treat and / or prevent diabetes or diabetes-related complications (such as diabetic retinopathy), thromboembolic diseases (such as deep vein or pulmonary thromboembolism), acute coronary syndrome (ACS), angina pectoris, myocardial infarction, cancer, macular degeneration, inflammation, hay fever, atherosclerosis and / or rheumatoid arthritis.

[0061] In another embodiment, the pharmaceutically active compound includes at least one peptide for treating and / or preventing diabetes or diabetes-related complications such as diabetic retinopathy.

[0062] In another embodiment, the pharmaceutically active compound includes at least one human insulin or human insulin analog or derivative, glucagon-like peptide-1 (GLP-1) or its analog or derivative, or exendin-3 or exendin-4 or an analog or derivative of exendin-3 or exendin-4.

[0063] 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 can be replaced by Pro; Ala(B26) human insulin; Des(B28-B30) human insulin; Des(B27) human insulin and Des(B30) human insulin.

[0064] 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; and B30-N-myristoyl-ThrB2 9LysB30 human insulin; B30-N-palmitoyl-ThrB29LysB30 human insulin; B29-N-(N-palmitoyl-Y-glutamyl)-des(B30) human insulin; B29-N-(N-lithochyl-Y-glutamyl)-des(B30) human insulin; B29-N-(ω-carboxyheptadecanoyl)-des(B30) human insulin and B29-N-(ω-carboxyheptadecanoyl) human insulin.

[0065] Venomous exopeptide-4, for example, refers to venomous exopeptide-4 (1-39), a peptide having the following 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.

[0066] Venomous lizard exopeptide-4 derivatives, for example, are selected from the following list of compounds:

[0067] H-(Lys)4-desPro36,desPro37 Venomous Lizard Exopeptide-4(1-39)-NH2、

[0068] H-(Lys)5-desPro36,desPro37 Venomous Lizard Exopeptide-4(1-39)-NH2、

[0069] des Pro36 Venomous Lizard Exopeptide-4(1-39)

[0070] des Pro36[Asp28] Venomous Lizard Exopeptide-4(1-39),

[0071] des Pro36[IsoAsp28] Venomous Lizard Exopeptide-4(1-39),

[0072] des Pro36[Met(O)14,Asp28]exotropic peptide-4(1-39),

[0073] des Pro36[Met(O)14,IsoAsp28]exotropic peptide-4(1-39),

[0074] des Pro36[Trp(O2)25,Asp28]exotropic peptide-4(1-39),

[0075] des Pro36[Trp(O2)25,IsoAsp28]exotropic peptide-4(1-39),

[0076] des Pro36[Met(O)14Trp(O2)25,Asp28]exotropic peptide-4(1-39),

[0077] des Pro36[Met(O)14Trp(O2)25,IsoAsp28] lizard exopeptide-4(1-39); or

[0078] des Pro36[Asp28] Venomous Lizard Exopeptide-4(1-39),

[0079] des Pro36[IsoAsp28] Venomous Lizard Exopeptide-4(1-39),

[0080] des Pro36[Met(O)14,Asp28]exotropic peptide-4(1-39),

[0081] des Pro36[Met(O)14,IsoAsp28]exotropic peptide-4(1-39),

[0082] des Pro36[Trp(O2)25,Asp28]exotropic peptide-4(1-39),

[0083] des Pro36[Trp(O2)25,IsoAsp28]exotropic peptide-4(1-39),

[0084] des Pro36[Met(O)14Trp(O2)25,Asp28]exotropic peptide-4(1-39),

[0085] des Pro36[Met(O)14Trp(O2)25,IsoAsp28] Lizard Exopeptide-4(1-39),

[0086] Among them, the group -Lys6-NH2 can bind to the C-terminus of the lizard exopeptide-4 derivative;

[0087] Or a lizard exopeptide-4 derivative having the following sequence:

[0088] des Pro36 Venomous Lizard Exopeptide-4(1-39)-Lys6-NH2(AVE0010),

[0089] H-(Lys)6-des Pro36[Asp28]exotropic peptide-4(1-39)-Lys6-NH2,

[0090] des Asp28 Pro36,Pro37,Pro38 Venomous Lizard Exopeptide-4(1-39)-NH2、

[0091] H-(Lys)6-des Pro36,Pro38[Asp28]exotropic peptide-4(1-39)-NH2、

[0092] H-Asn-(Glu)5des Pro36,Pro37,Pro38[Asp28]exotropic peptide-4(1-39)-NH2、

[0093] des Pro36,Pro37,Pro38[Asp28] Venomous Lizard Exopeptide-4(1-39)-(Lys)6-NH2、

[0094] H-(Lys)6-des Pro36,Pro37,Pro38[Asp28] Venomous Lizard Exopeptide-4(1-39)-(Lys)6-NH2、

[0095] H-Asn-(Glu)5-des Pro36,Pro37,Pro38[Asp28]exotropic peptide-4(1-39)-(Lys)6-NH2、

[0096] H-(Lys)6-des Pro36[Trp(O2)25,Asp28]exotropic peptide-4(1-39)-Lys6-NH2、

[0097] H-des Asp28 Pro36,Pro37,Pro38[Trp(O2)25]exotropic peptide-4(1-39)-NH2、

[0098] H-(Lys)6-des Pro36,Pro37,Pro38[Trp(O2)25,Asp28]exotropic peptide-4(1-39)-NH2、

[0099] H-Asn-(Glu)5-des Pro36,Pro37,Pro38[Trp(O2)25,Asp28]exotropic peptide-4(1-39)-NH2、

[0100] des Pro36,Pro37,Pro38[Trp(O2)25,Asp28]exotropic peptide-4(1-39)-(Lys)6-NH2、

[0101] H-(Lys)6-des Pro36,Pro37,Pro38[Trp(O2)25,Asp28]exotropic peptide-4(1-39)-(Lys)6-NH2、

[0102] H-Asn-(Glu)5-des Pro36,Pro37,Pro38[Trp(O2)25,Asp28]exotropic peptide-4(1-39)-(Lys)6-NH2、

[0103] H-(Lys)6-desPro36[Met(O)14,Asp28]exotropic peptide-4(1-39)-Lys6-NH2、

[0104] des Met(O)14Asp28 Pro36,Pro37,Pro38 Venomous Lizard Exopeptide-4(1-39)-NH2、

[0105] H-(Lys)6-desPro36,Pro37,Pro38[Met(O)14,Asp28]exotropic peptide-4(1-39)-NH2、

[0106] H-Asn-(Glu)5-des Pro36,Pro37,Pro38[Met(O)14,Asp28]exotropic peptide-4(1-39)-NH2、

[0107] des Pro36,Pro37,Pro38[Met(O)14,Asp28]exotropic peptide-4(1-39)-(Lys)6-NH2、

[0108] H-(Lys)6-des Pro36,Pro37,Pro38[Met(O)14,Asp28]exotropic peptide-4(1-39)-(Lys)6-NH2、

[0109] H-Asn-(Glu)5des Pro36,Pro37,Pro38[Met(O)14,Asp28]exotropic peptide-4(1-39)-(Lys)6-NH2、

[0110] H-Lys6-des Pro36[Met(O)14,Trp(O2)25,Asp28]exotropic peptide-4(1-39)-Lys6-NH2,

[0111] H-des Asp28 Pro36,Pro37,Pro38[Met(O)14,Trp(O2)25]exotropic peptide-4(1-39)-NH2、

[0112] H-(Lys)6-des Pro36,Pro37,Pro38[Met(O)14,Asp28]exotropic peptide-4(1-39)-NH2、

[0113] H-Asn-(Glu)5-des Pro36,Pro37,Pro38[Met(O)14,Trp(O2)25,Asp28]exotropic peptide-4(1-39)-NH2、

[0114] des Pro36,Pro37,Pro38[Met(O)14,Trp(O2)25,Asp28]exotropic peptide-4(1-39)-(Lys)6-NH2、

[0115] H-(Lys)6-des Pro36,Pro37,Pro38[Met(O)14,Trp(O2)25,Asp28]exotropic peptide-4(S1-39)-(Lys)6-NH2,

[0116] H-Asn-(Glu)5-des Pro36,Pro37,Pro38[Met(O)14,Trp(O2)25,Asp28]exotropic peptide-4(1-39)-(Lys)6-NH2;

[0117] Or a pharmaceutically acceptable salt or solvate of any of the above-mentioned lizard exopeptide-4 derivatives.

[0118] Hormones are, for example, pituitary or hypothalamic hormones or regulatory peptides and their antagonists listed in Chapter 50 of the Rote Liste, 2008 edition, such as gonadotropins (follicle-stimulating hormone, luteinizing hormone, human chorionic gonadotropin, gamete maturation hormone), somatropine (growth hormone), desmopressin, terlipressin, gonarelin, triptorelin, leuprorelin, buserrelin, nafarelin, and goserelin.

[0119] Polysaccharides are, for example, glycosaminoglycans, hyaluronic acid, heparin, low molecular weight heparin or ultra-low molecular weight heparin or derivatives thereof, or sulfated forms of the above polysaccharides (e.g., polysulfated forms), and / or pharmaceutically acceptable salts thereof. An example of a pharmaceutically acceptable salt of polysulfated low molecular weight heparin is enoxaparin sodium.

[0120] Antibodies are globular plasma proteins (approximately 150 kDa), also known as immunoglobulins sharing a basic structure. They are glycoproteins because they have sugar chains added to amino acid residues. The basic functional unit of each antibody is an immunoglobulin (Ig) monomer (containing only one Ig unit); secreted antibodies can also be dimers with two Ig units (such as IgA), tetramers with four Ig units (such as bony fish IgM), or pentamers with five Ig units (such as mammalian IgM).

[0121] Ig monomers are Y-shaped molecules composed of four polypeptide chains; two identical heavy chains and two identical light chains are linked by disulfide bonds between cysteine ​​residues. Each heavy chain is approximately 440 amino acids long; each light chain is approximately 220 amino acids long. Both heavy and light chains contain intrachain disulfide bonds that stabilize their folding. Each chain consists of domains called Ig domains. These domains contain approximately 70–110 amino acids and are categorized according to their size and function (e.g., variable regions or V regions and constant regions or C regions). These domains exhibit a characteristic immunoglobulin fold, where the two β-folds form a "sandwich" shape, held together by interactions between conserved cysteine ​​residues and other charged amino acids.

[0122] There are five types of mammalian Ig heavy chains, denoted by α, δ, ε, γ, and μ. The type of heavy chain present defines the isotype of the antibody; these chains are found in IgA, IgD, IgE, IgG, and IgM antibodies, respectively.

[0123] The different heavy chains vary in size and composition; α and γ contain approximately 450 amino acids, δ contains approximately 500 amino acids, and μ and ε contain approximately 550 amino acids. Each heavy chain has a constant region (C0). H ) and variable region (V H The heavy chain has two regions. Within a species, the constant region is substantially the same across all antibodies of the same isotype, but differs across antibodies of different isotypes. The heavy chains γ, α, and δ have a constant region consisting of three tandem Ig domains and a hinge region for increased flexibility; the heavy chains μ and ε have a constant region consisting of four immunoglobulin domains. The variable region of the heavy chain differs among antibodies produced by different B cells, but is the same for all antibodies produced by a single B cell or a B cell clone. The variable region of each heavy chain is approximately 110 amino acids long and consists of a single Ig domain.

[0124] In mammals, there are two types of immunoglobulin light chains, denoted by λ and κ. A light chain has two continuous domains: a constant domain (CL) and a variable domain (VL). The approximate length of a light chain is 211 to 217 amino acids. Each antibody contains two identical light chains; in mammals, each antibody possesses only one type of light chain, either κ or λ.

[0125] Although all antibodies share a very similar general structure, the unique properties of a given antibody are determined by variable (V) regions, as detailed above. More specifically, variable loops (three on each light chain (VL) and three on each heavy chain (VH)) are responsible for binding the antigen, i.e., for its antigen specificity. These loops are called complementarity-determining regions (CDRs). Because multiple CDRs from the VH and VL domains constitute the antigen-binding site, it is the combination of the heavy and light chains (rather than each individually) that determines the final antigen specificity.

[0126] An "antibody fragment" contains at least one antigen-binding fragment as defined above and exhibits essentially the same function and specificity as the intact antibody from which it is derived. Restrictive proteolysis with papain cleaves the Ig prototype into three fragments. Two identical N-terminal fragments are antigen-binding fragments (Fab), each containing a complete L-chain and approximately half an H-chain. The third fragment is a crystallizable fragment (Fc), similar in size but containing half of the carboxyl terminus of both heavy chains and their interchain disulfide bonds. Fc contains a carbohydrate, a complement binding site, and an FcR binding site. Restrictive pepsin digestion produces a single F(ab')2 fragment containing both the Fab segment and the hinge region, including the HH interchain disulfide bond. F(ab')2 is divalent for antigen binding. The disulfide bonds of F(ab')2 can be cleaved to obtain Fab'. Furthermore, the variable regions of the heavy and light chains can be fused together to form a single-chain variable fragment (scFv).

[0127] Pharmaceutically acceptable salts are, for example, acid addition salts and basic salts. Acid addition salts are, for example, HCl or HBr salts. Basic salts are, for example, salts having a cation selected from alkali metal or alkaline earth metal cations, such as Na+ or K+ or Ca2+, or ammonium ions N+(R1)(R2)(R3)(R4), wherein R1 to R4 represent, 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. Other examples of pharmaceutically acceptable salts are described in the following literature: Remington's Pharmaceutical Sciences, 17th edition, Alfonso R. Gennaro (ed.), Mark Publishing Company, Easton, Pa., USA, 1985, and Encyclopedia of Pharmaceutical Technology.

[0128] Pharmaceutically acceptable solvates are, for example, hydrates.

[0129] It will also be apparent to those skilled in the art that various modifications and variations can be made to the invention without departing from its spirit and scope. Furthermore, it should be noted that any reference numerals used in the appended claims should not be construed as limiting the scope of the invention.

[0130] In the following sections, several examples of containers and injection devices will be described in detail with reference to the accompanying drawings, wherein:

[0131] Figure 1 An example of an injection device is shown.

[0132] Figure 2 An injection device is shown, which is partially disassembled and equipped with a container filled with an injectable drug.

[0133] Figure 3 The example of a container illustrates a longitudinal section.

[0134] Figure 4 yes Figure 3 A block diagram of the measurement components.

[0135] Figure 5 This is another block diagram showing alternative measurement components, including an optical interferometer.

[0136] Figure 6 A flowchart illustrating the method for determining the internal volume of a container is shown.

[0137] Figure 7 Another example of a container illustrates a longitudinal section, and

[0138] Figure 8 This shows another example of a container.

[0139] exist Figures 1 to 2 The image shows an example of an injection device 1 configured as a pen syringe. The injection device 1 includes a housing 20. The housing 20 includes a cartridge holder 21 and a body 22. The cartridge holder 21 is configured to contain a container 100, which may include a cartridge pre-filled with at least a first injectable drug 50. The cartridge holder 21 and the body 22 may be permanently or releasably attached to each other. Through the permanent or non-releasable connection between the cartridge holder 21 and the body 22, the injection device 1 can be configured as a disposable injection device in which the container 100 is easily assembled. Alternatively, the injection device 1 can be configured as a reusable device. Here, the cartridge holder 21 can be detached from the body 22 to replace or replace the container 100.

[0140] like Figure 2The illustrated cartridge holder 21 includes a window 25 to allow visual inspection of the container 100 located therein. The cartridge holder 21 includes, near its distal end, a socket 31 having an externally threaded section 32. The socket 31 is configured to support an injection needle 40. The injection needle 40 typically includes a double-pointed hollow cannula having proximal and distal ends. The injection needle 40 typically includes a needle seat 41 having an internally threaded portion for releasable engagement with the threaded section 132. The needle seat 41 includes a bottom section and a sidewall section forming a cup-shaped receiver configured to receive the threaded socket 31 of the cartridge holder 21. The sidewall section includes an internally threaded section that mates with the externally threaded section 32 of the socket 31. The distal face of the cartridge holder 21 includes a through opening 23 through which the proximal protrusion of the needle 40 extends into the interior of the cartridge holder 21 and thus into the interior of the cartridge or container 100 when the injection needle 40 is attached to the cartridge holder 21 and when the container 100 is disposed in the cartridge holder 21.

[0141] Container 100 is disposed within cartridge holder 21. It is positioned and secured within cartridge holder 21. Container 100 includes an elongated, tubular body 101. Body 101 may include a vitreous body. Body 101 may be made of glass. Body 101 may be translucent or transparent to allow visual inspection of the contents of container 100. The elongated body 101 extends longitudinally (z). Body 101 includes a distal end 103 and a proximal end 104 positioned opposite to it.

[0142] The body 101 is disposed near or at the distal end of the cartridge holder 21 via the distal end 103. The distal end 103 of the body 101 includes a narrowed shoulder 107 extending into a neck 105 with a decreasing diameter. The radially narrowed shoulder 107 is configured to axially abut or engage with a corresponding shaped shoulder section of the cartridge holder 21. The shoulder 107 is located near the distal end 103 of the cartridge or container 100.

[0143] The neck 105 extends at a more distal end into a radially widened head 105a. A seal 206, for example in the form of a pierceable sealing disc, is provided at the head 105a. The seal 206 may include a pierceable rubber septum secured to the head 105a and thus to the distal end 103 of the body 101 by means of a collar 108 or a coiled metal cap. The collar 108 may include a coiled aluminum cap. The seal 206 may be formed at the distal end 103 of the elongated body 101 or belong to an outlet 109 of the container 100.

[0144] The injection device 100 may also be equipped with a drive mechanism 14 including a plunger or piston rod 11. The drive mechanism 14 may also be equipped with a trigger 18, which can trigger or control the dispensing action of the injection device 1. Optionally, the injection device 1 and the drive mechanism 14 include a dose selector 16, through which the dose to be dispensed can be set individually, or through which the injection device 1 can be deployed or prepared for a subsequent dispensing process.

[0145] Optional and as Figure 1 As shown, the main body 22 of the housing 20 may be provided with a window 26 for indicating the dosage. The actual set dosage can be visually displayed in the window 26, thereby informing the user of the amount of medication to be dispensed during the subsequent medication preparation process.

[0146] like Figure 1 As further shown, the injection needle 40 may be provided with an inner needle cap 27 configured to cover the distal end of the injection needle 40. The injection needle and / or needle hub 41 may also be covered by an outer needle cap 28. When not in use, the injection needle 40 should be detached from the distal end of the cartridge holder 21. The cartridge holder 21 can then be and should be covered by a protective cap 24. The protective cap 124 is configured to releasably engage with at least one of the cartridge holder 21 and the body 22. The protective cap 24 must be detached from the housing 20 before the injection needle 40 is assembled to the cartridge holder 21.

[0147] Container 100 and such Figures 1 to 2 The interactions described above with the pen-type injection device 1 shown are merely exemplary. The general operating principle of the container does not require interaction with the pen-type injection device 1. Typically, the container 100 can be implemented as, or can be used as, a container for a manually operated syringe or infusion device.

[0148] like Figure 3 The illustrated container 100 includes a tubular elongated body 101 with tubular sidewalls 102. The container 100 includes an outlet 116 at its distal end 103. The outlet 116 is sealed by a puncturable seal 206. The container 100 includes a stopper 210 or piston near its proximal end 104, opposite the distal end 103. The stopper 210 is disposed within the tubular sidewall 101 of the container 100. The stopper 210 is sealingly engaged with an inner section of the sidewall 102. The stopper 210 includes an outer tubular sidewall 212 that frictionally engages with the interior of the sidewall 102 of the container 100.

[0149] The cross-section or diameter of the plug 210 matches the corresponding cross-section or diameter of the body 101 and its sidewall 102. The plug 210 includes a body 211. The plug 210 includes a distal face 213 facing the outlet 116 and therefore the punctureable seal 206. The plug 210 includes a proximal face 214 opposite the distal face 213. The proximal face 214 serves as a thrust receiving surface for the plug 210. The proximal face 214 may be axially or longitudinally abutted against the piston rod 11 of the drive mechanism 14 of the injection device 1, such as... Figure 1 and Figure 2 As shown.

[0150] In this way, the plug 210 can be advanced or pushed in the distal direction 2 to discharge a predefined amount of injectable agent 50 from the internal volume 109 of the container 100. The internal volume 109 is limited in the circumferential or radial direction by the sidewall 102 of the container 100. The internal volume 109 is limited in the distal direction 2 by the outlet 116. The internal volume 109 may be limited in the distal direction 2 by a puncturable seal 206. The internal volume 109 is limited in the proximal direction 3 by the plug 210. In particular, the internal volume 109 is limited by the distal end face 213 of the plug 210.

[0151] The internal volume 109 defines the amount of injectable agent 50 contained within the container 100. During use of the container 100, and when the injectable agent 50 is expelled from the container 100, the size of the internal volume 109 decreases as the stopper 210 is driven distally toward the outlet 116. To measure or determine the size of the internal volume 109, the stopper 210 includes a measuring assembly 220. The measuring assembly 220 is disposed within or above the stopper 210. The measuring assembly 220 may be completely encapsulated within the body 211 of the stopper 210. The measuring assembly 220 may be located within the stopper 210 at a predefined non-zero distance from any of the distal end face 213, proximal end face 214, and outer side wall 212 of the stopper 210.

[0152] In one example, the measuring component 220 includes a housing 221. The measuring component 220, or at least one component thereof, may alternatively be arranged within the plug 210 and outside the housing 221, such that the measuring component 220, or at least one component thereof, is arranged flush with the outer surface of the body 211 of the plug 210. For example, the measuring component 220 may be flush with either the distal face 213 or the proximal face 214. The measuring component 220, or a component thereof, may also protrude from at least one of the distal face 213 and the proximal face 214.

[0153] exist Figure 4An example of a measurement assembly 220 and its components is shown schematically in more detail below. The measurement assembly 220 includes a signal generator 222 configured to emit an electromagnetic measurement signal S1 into or through the internal volume 109. The measurement signal S1 is an electromagnetic signal. The electromagnetic signal may include or represent an optical signal. It may include at least one of a light beam and a light pulse.

[0154] The measuring component 220 also includes a signal receiver 224 configured to detect an electromagnetic feedback signal F1. The electromagnetic feedback signal F1 indicates the interaction of the measuring signal with at least one of the sidewall 102, the outlet 116, and the internal volume 109. A corresponding feedback signal F1 is generated by transmitting the measuring signal S1 into the internal volume 109, which directly indicates the interaction of the measuring signal S1 with at least one of the sidewall 102, the outlet 116, the puncturable seal 206, or the internal volume 109. A precise determination of the size of the internal volume 109 can be provided based solely on the detected feedback signal F1 or based on a comparison of the feedback signal F1 with the measuring signal S1. The longitudinal position of the plug 210 relative to the body 101 of the container 100 can be determined or measured solely based on the feedback signal F1 and / or the corresponding measuring signal S1. For this purpose, the instantaneous size of the internal volume 109 can be derived.

[0155] Figure 4 The block diagram illustrates an example of a measurement component 220. The measurement component 220 may include a housing 221 that provides and implements the package of the measurement component 220 within the body 211 of a plug 210. The measurement component 220 includes a processor 226. The processor 226 is a microprocessor, for example, in the form of a microprocessor or in the form of an application-specific integrated circuit (ASIC). The measurement component 220 may include a PCB 229. Figure 4 In the example, the signal generator 222 of the measurement component 220 includes a light source 240, such as a light-emitting diode (LED).

[0156] When manufacturing, assembling, or filling container 100 with injectable agent 50, the measurable geometric properties of container 100 can be determined individually.

[0157] Measurement component 220 may also include a communication interface 230 configured to exchange data with external electronic device 400, such as Figure 2As shown. External electronic device 400 typically includes processor 402, data memory 404, and communication interface 406. Communication interface 406 is configured to communicate with and exchange data with communication interface 230 of measurement component 220. Typically, communication interface 230 and communication interface 406 are configured for wireless data transmission. Communication interface 230 and / or communication interface 406 may be configured to communicate via RF electromagnetic signals. Communication interfaces 230 and 406 may, for example, be configured for wireless communication according to Wi-Fi standards (IEEE 802.11), RFID or NFC communication protocols and standards, or Bluetooth communication protocols and standards.

[0158] Measurement component 220 may also include antenna 234 to enable wireless data transmission between measurement component 220 and external electronic device 400. Antenna 234 may also be configured to extract or harvest electromagnetic energy from an external electromagnetic field EM (e.g., from a radio frequency (RF) field). It is generally conceivable that measurement component 220 is driven entirely by electromagnetic energy extracted from the external electromagnetic field EM. Alternatively or additionally, it is conceivable that measurement component 220 includes energy storage device 238, for example, implemented as a rechargeable battery. Energy storage device 238 may be connected to antenna 234 and processor 226. Energy storage device 238 may be recharged by electrical energy extracted from the external electromagnetic field EM via antenna 234.

[0159] It is generally conceivable that processor 226 is limited to transmitting electrical signals obtainable from signal receiver 224 to external electronic device 400 via communication interface 230. In this way, the computing power and power consumption of measurement component 220 can be minimized. The processing of signals obtainable from signal receiver 224 can be performed entirely by processor 402 of external electronic device 400. Therefore, software applications implemented in external electronic device 400 can provide calculations of the size of internal volume 109 and can be configured to determine the instantaneous filling level of container 100.

[0160] In another example, processor 226 may be configured to determine or calculate the size of internal volume 109 based on signals received by signal receiver 224. Preprocessed or unprocessed signals from receiver 224 and / or processed data derived from detected feedback signals and / or transmitted measurement signals may also be stored in data memory 228. Data communication and transmission between measurement component 220 and external electronics 400 may therefore be limited to the size of internal volume and / or the instantaneous longitudinal position of plug 210 relative to the body 101 of container 100.

[0161] Furthermore, it is conceivable that the data storage 228 is configured to store a large amount of size information regarding the internal volume or the longitudinal position of the stopper 210. The data storage 228 can be configured to store dosing history. The data storage 228 can be configured to store data derived from the measurement signal S1 and / or from the feedback signal F1 along with a timestamp. In this way, the dosing history of the container 100 can be stored within the stopper 210.

[0162] according to Figure 3 and Figure 4 In this example, the signal generator 222 is configured to emit an optical measurement signal, and therefore an electromagnetic measurement signal S1. The electromagnetic measurement signal S1 is generated and emitted by the signal generator 222 in such a way that the optical measurement signal S1 propagates into the internal volume 109 of the container 100. The optical measurement signal S1 interacts with at least one of the sidewall 102, the outlet 116, or the internal volume 109, and thus with the injectable agent 50. The optical measurement signal S1 can be reflected, diffracted, and / or absorbed by at least one of the sidewall 102, the outlet 116, the internal volume 109, and the injectable agent 50 located therein. In response to this interaction, an electromagnetic feedback signal F1, detectable by the signal receiver 224, is generated or appears.

[0163] In one example, signal generator 222 includes a light source 240 to emit a light beam or light pulse into internal volume 109. Signal receiver 224 may include a photodiode or photodetector, for example in the form of a charge-coupled device, to detect the optical feedback signal F1. In one example, signal receiver includes an optical time-of-flight (TOF) detector 242. The optical feedback signal F1 may be a reflection of the optical measurement signal S1. Alternatively, it may be a portion of the optical measurement signal S1 scattered or scattered by at least one of the sidewall 102, outlet 116, internal volume 109, or injectable agent 50.

[0164] In one example, signal receiver 224 is a time-of-flight detector 242. For this purpose, both signal generator 222 (e.g., in the form of an ultrafast LED) and signal receiver 224 are connected to processor 226. Signal generator 222 can be pulsed by a faster current source 223 controlled and triggered by processor 226. Signal receiver 224 (e.g., in the form of an extremely fast or fast TOF sensor or photodiode) receives electromagnetic or optical feedback signals F1 reflected from the internal volume 109, from the outlet 116, or from the side wall 102 of the container body 101. Typically, signal generator 222 generates and emits several light pulses or a sequence of light pulses.

[0165] Signal receiver 224 detects the detected reflected light pulse that forms the optical feedback signal F1. From the phase shift and / or the time delay between the emission of the optical measurement signal S1 and the detection of the corresponding optical feedback signal F1, processor 226 can calculate or determine the operating time or distance between signal generator 222, the reflective structure of the container, and signal receiver 224. Typically, the inner surface 207 or proximal surface of the pierceable seal 206 may include a reflective surface. In this way, the optical measurement signal S1 propagating through the internal volume 109 is reflected at the proximal surface 207 and returned to signal receiver 224 as the optical feedback signal F1. Similarly, a corresponding calibration process can be performed here and during manufacturing, during assembly, or when filling container 100.

[0166] For example, signal generator 222 is configured to generate and emit at least one or more light pulses into internal volume 109 at a first time point t1, and signal receiver 224 is configured to detect at least one or more reflected light pulses. Signal receiver 224 is specifically configured to detect light pulses previously emitted by signal generator 222 and reflected by at least one of the sidewall 102, outlet 116, and proximal surface 207 of pierceable seal 206. Signal receiver 224 is configured to detect or determine a second time point t2 for detecting the reflected light pulses. The time interval between the first time point t1 and the second time point t2 indicates the time delay required for the emitted light to propagate from signal generator 224 to signal receiver 224. Typically, both signal generator 222 and signal receiver 224 are connected to and driven or triggered by processor 226. Optical signal generator 222 and / or optical signal receiver 224 may be completely enclosed or embedded within the body 211 of plug 210. Therefore, the material of the body 211 of the plug 210 can be substantially translucent for the wavelength of the electromagnetic measurement signal and the corresponding electromagnetic feedback signal. Alternatively, and through the non-translucent or opaque material of the plug 210, the optical signal generator 222 and the optical signal receiver 224 can be located at the distal end face 213 of the body 211 of the plug 210.

[0167] like Figure 3 As shown, at least one of the signal generator 222 and the signal receiver 224 can be located in the recess 215 of the distal end face 213 of the plug 210. Figure 3 As shown, a signal generator 222 (e.g., in the form of an LED) is located in the recess 215. An optical signal receiver 224 is flush with the distal end face 213 of the body 211 of the stopper 210. This ensures that even in the farthest position of the stopper 110, a minimum propagation distance is maintained for both the optical measurement signal S1 and the optical feedback signal F1, which is necessary for measuring the distance between the stopper 210 and the outlet 116.

[0168] The recessed assembly of the optical signal generator 222 also helps to prevent the electromagnetic or optical measurement signal S1 from directly illuminating the optical signal receiver 224. The recessed assembly of at least one of the signal generator 222 and the signal receiver 224 provides a shield for the optical signal receiver 224. In this way, it can be specified that only the optical feedback signal F1 reflected from at least one of the sidewall 102, the outlet 116, or the proximal surface 207 impacts the signal receiver 224.

[0169] In such Figure 5 In another example shown, the measurement component 320 includes an optical interferometer 321. The optical interferometer 321 includes an optical signal generator 322, which includes a light source 340, such as an LED configured to generate a beam or light pulse of sufficient coherence length. The optical interferometer 321 also includes a processor 326 and an optical signal receiver 324. The optical signal receiver may include a photodiode or an array of photodiodes or charge-coupled pixels.

[0170] like Figure 3 As shown, an optical interferometer 321 is embedded within a stopper 210. The optical interferometer 321 includes a beam splitter 327 and a reflector 228. A light beam generated by an optical signal generator 322 propagates to the beam splitter 327. There, the beam is split into a signal beam S2 and a reference beam RS. The reference beam RS is reflected toward the reflector 328. At the reflector 328, the reference beam RS is reflected toward the beam splitter 327. The signal beam S2, representing an optical measurement signal, propagates into the internal volume 109 of the container 100. There, it is reflected at a reflective structure, for example, at the inner surface 207 of the pierceable seal 206. In one example, the beam splitter 327, the optical signal receiver 224, and the reflector 328 are all implemented and arranged within the stopper 210.

[0171] The beam splitter 327 can be disposed in the distal end face 213 of the plug 210. It can also be disposed in the recess 215 of the distal end face 213, such as in combination with... Figure 3 The optical feedback signal F2 reflected from surface 207 is redirected to beam splitter 327. There, the reflected reference beam RS and optical feedback signal F2 are recombined and propagate together toward optical signal receiver 324. As a result, an interference pattern is formed on optical signal receiver 324. The structure of the interference pattern changes when the distance between beam splitter 327 and surface 207 changes due to the movement of plug 210 toward outlet 116. The change in the structure of the interference pattern directly indicates the displacement distance of plug 210 relative to body 101 of container 100.

[0172] The distance between beam splitter 327 and reflector 328 is constant. The reference beam RS can propagate through fiber optic 329, which also enables a longer optical path length between beam splitter 327 and reflector 328 within plug 210.

[0173] exist Figure 6 The flowchart illustrates various method steps for determining the size of the internal volume 109. In the initial step 500, the container 100 is assembled. Here, a plug 210 is inserted into the body 101 of the container 100. Afterward, the outlet 116 can be sealed, for example by arranging a puncture-resistant seal 206 on the head 105a of the container 100. In the subsequent step 502, an initial measurement is performed. Here, signal generators 222, 322 are triggered to emit at least one measurement signal S1, S2 into the internal volume 109 or to transmit said at least one measurement signal through the internal volume. Signal receivers 224, 324 detect at least one or a sequence of feedback signals F1, F2. Subsequently, in the subsequent step 504, the measured signals are calibrated. Thus, the result of the initial measurement is assigned the actual size of the internal volume 109 determined or predetermined during the assembly process.

[0174] In step 506, the calibration is stored in data memory 228. Later, and during use of the container, such as in an injection device, the measurement components 220, 320 may be triggered in step 508 to perform the corresponding measurement and to transmit at least one measurement signal S1, S2 into the internal volume 109 or to transmit the at least one measurement signal through the internal volume.

[0175] In subsequent step 510, signal receivers 224, 324 receive at least one or a series of feedback signals F1, F2. From one or more received signals, particularly from the time delay between the submitted electromagnetic measurement signal and the received reflected electromagnetic feedback signal, and knowing the refractive index of the medium through which the electromagnetic signal propagates, the optical path length between the signal generator and the signal receiver can be calculated based on the known velocity of electromagnetic radiation. From the time delay, the axial distance between the distal face 213 of the plug 210 and, for example, the proximal surface 207 of the puncture-resistant seal 206 can be calculated in step 512. Knowing the diameter and / or geometric cross-section of the container 100, the size of the internal volume 209 and the dosage of medication remaining within the container 100 can be accurately calculated.

[0176] It should be noted that, based on the functionality of the various examples of the measuring components and their interaction with, for example, external electronic device 400, one can conceive of the above-mentioned... Figure 6 The various modifications to the flowchart.

[0177] Figure 7 and Figure 8Two other examples of the drug container 100 are shown. There, the stopper 210 includes a fairly large recessed portion 215. The distal end face 213 of the stopper 210 contacts the liquid drug 50. The recessed portion 215 opens toward the internal volume 109. (See attached image.) Figure 7 As shown, the signal receiver 224 is located at the bottom of the recess 215. The axial length of the recess 215 is greater than 30% of the total axial length L of the plug 210. It can be greater than 50% of the total axial length L of the plug 210. In other examples, the axial length or axial depth of the recess 215 can be greater than 60%, greater than 75%, or even greater than or equal to 80% of the total axial length L of the plug 210.

[0178] and Figure 3 Compared to the example shown, this method can significantly extend the optical path length of the electromagnetic radiation emitted by the signal generator, reflected at the distal end 103, and detected by the signal receiver 224. This is particularly advantageous when the stopper 210 should be positioned very close to the distal end 103 of the container 100. The extended optical path length is beneficial for measuring the time-of-flight of the electromagnetic radiation emitted by the signal generator 222 and received by the signal receiver 224. The axial length of the recessed portion 215 provides a well-defined time offset for at least one of the electromagnetic signals S1 and F1.

[0179] In addition to this geometric change Figure 7 The plug 210 and about Figure 3 The described plug 210 is exactly the same or highly similar. In this regard, combining... Figure 3 All features and properties of the described plug 210 are for example Figure 7 and Figure 8 The plug 210 is also effective.

[0180] As Figure 7 As an alternative to the illustration, the recessed portion 215 may accommodate the signal generator 222, while the signal receiver 224 is located at the distal end face 213 of the plug 210. At least one of the signal generator 222 and the signal receiver 224 is located on the bottom of the recessed portion 215.

[0181] exist Figure 8In this example, the recessed portion 215 is divided into a first recessed section 215a and a second recessed section 215b. A signal receiver 224 is located in the first recessed section 215a. A signal generator 222 is located in the second recessed section 215b. The two recessed portions 215a and 215b are separated by a separator 216. The separator 216 may be formed by a partition wall that projectes axially in a distal direction from the bottom of the recessed portion 215. The first recessed section 215a and the second recessed section 215b are separated in a radial direction. They may be located at the same or different axial positions relative to the axial extension of the plug 210.

[0182] Similarly, here, the total axial length of the recessed portion 215 can be greater than 30% of 60% of the landmass, greater than 50%, greater than 75% of the total axial length L of the plug 210, or even greater than or equal to 80%. The axial length of the separator 216 can be less than the axial length of the recessed portion 215. In this regard, the free and distally extending end of the separator 216, facing away from the bottom of the recessed portion 215, can be recessed proximally compared to the distal end face 213 of the plug 210. In other examples, the total axial length of the separator 260 can be substantially equal to the axial length of the recessed portion 215 or any of its recessed segments 215a, 215b.

[0183] In any of the examples shown in the accompanying drawings and / or as described above, the recess 215 may be filled with liquid agent 50, or it may be filled with a transparent filler material 217. For example, the recess 215 may be filled with a transparent polymer. The filler material 217 may include at least one of COC, PA, PP, PE, POM, PS, ABS, COP, or mixtures thereof. Filling the recess 215 with the filler material 217 is beneficial for maintaining the mechanical stability of the stopper 210 and providing sufficient sealing functionality of the stopper 210 relative to the sidewall 212.

[0184] List of reference numerals

[0185] 1. Injection device

[0186] 2. Distal direction

[0187] 3. Proximal direction

[0188] 11 Piston rod

[0189] 14 Drive mechanism

[0190] 16 Dosage Selection Panel

[0191] 18 triggers

[0192] 20. Housing

[0193] 21. Cartridge Holder

[0194] 22 Main Body

[0195] 23 Through opening

[0196] 24 hats

[0197] 25 windows

[0198] 26 windows

[0199] 27 Inner needle cap

[0200] 28 Outer pin cap

[0201] 31 sockets

[0202] 32 thread

[0203] 40 injection needles

[0204] 41 Pin hub

[0205] 50 doses

[0206] 100 containers

[0207] 101 Main Body

[0208] 102 Sidewall

[0209] 103 Remote

[0210] 104 Proximal

[0211] 105 Neck

[0212] 105a head

[0213] 107 Shoulders

[0214] 108 rings

[0215] 109 Internal volume

[0216] 115 Sidewall

[0217] 116 Exports

[0218] 206 Punctureable seal

[0219] 207 surface

[0220] 209 Internal volume

[0221] 210 Plug

[0222] 211 Main Body

[0223] 212 Sidewall

[0224] 213 Distal face

[0225] 214 Proximal end face

[0226] 215 Depressed portion

[0227] 215a Depression Section

[0228] 215b Depression section

[0229] 216 Separator

[0230] 217 Filler Material

[0231] 220 Measurement Components

[0232] 221 Casing

[0233] 222 Signal Generator

[0234] 223 Current Source

[0235] 224 signal receiver

[0236] 226 processor

[0237] 228 Data Storage

[0238] 229 Printed Circuit Board

[0239] 230 Communication Interface

[0240] 234 antennas

[0241] 238 Energy storage device

[0242] 240 light source

[0243] 242 TOF detector

[0244] 320 Measurement Components

[0245] 321 Optical Interferometer

[0246] 322 signal generator

[0247] 324 signal receiver

[0248] 326 processor

[0249] 327 beam splitter

[0250] 328 reflector

[0251] 329 Fiber Optic

[0252] 340 light source

[0253] 400 External Electronic Devices

[0254] 402 processor

[0255] 404 Data Storage

[0256] 406 Communication Interface

Claims

1. A container (100) for an injectable medicament (50), the container comprising: an elongated body (101) having a tubular side wall (102) extending along a longitudinal axis (z) and having a distal end (103) and a proximal end (104), an outlet (116) at the distal end (103), a stopper (210) arranged within the elongated body (101), sealingly engaged with the side wall (102) and slidable relative to the side wall (102) along the longitudinal axis (z), an inner volume (109) receiving the injectable medicament (50) and being limited by the side wall (102), the outlet (116) and the stopper (210), a measurement assembly (220; 320) arranged in or on the stopper (210), the measurement assembly (320) comprising: an optical signal generator (222; 322) located in or on the stopper (210) and configured to emit an optical measurement signal (SI, S2) into or through the inner volume (109), and an optical signal receiver (224; 324) located in or on the stopper (210) and configured to detect an optical feedback signal (FI, F2) indicative of an interaction of the optical measurement signal (SI, S2) with at least one of the side wall (102), the outlet (116) or the inner volume (109).

2. The container according to claim 1, further comprising a processor (226; 326) connected to the optical signal receiver (224; 324).

3. The container according to claim 2, wherein the processor (226; 326) is configured to determine a size of the inner volume (109) based on the optical feedback signal (FI, F2) obtainable by the optical signal receiver (224, 324).

4. The container according to claim 2 or 3, wherein the processor (226; 326) is connected to the optical signal generator (222; 322), wherein the processor (226; 326) is configured to trigger an emission of the optical measurement signal (SI, S2), and wherein the processor (226; 326) is configured to determine the size of the inner volume (109) based on a comparison of at least one optical measurement signal (SI, S2) with at least one optical feedback signal (FI, F2).

5. The container according to claim 1 or 2, wherein the measurement assembly (220; 320) comprises a data memory (228) configured to store at least one of an initial size of the inner volume (109) and at least one optical feedback signal (FI, F2).

6. The container according to claim 1 or 2, further comprising a communication interface (230) configured to exchange data with an external electronic device (400).

7. The container according to claim 1 or 2, further comprising an antenna (234) configured to extract electrical energy from a surrounding electromagnetic field (EM).

8. The container according to claim 7, wherein the measurement assembly (220; 320) comprises an electrical energy storage (238) connected to the antenna (234).

9. The container according to claim 1 or 2, wherein the optical signal generator (222; 322) comprises a light source (240; 340) configured to emit an optical measurement signal (SI, S2) towards the outlet (116).

10. The container according to claim 9, wherein the optical signal receiver (224) comprises a time-of-flight detector (242) or a time-of-flight camera configured to detect the optical measurement signal (SI) reflected from the outlet (116) as the optical feedback signal (FI).

11. The container according to claim 10, wherein the optical signal generator (222) is configured to generate and emit at least one or several light pulses into the inner volume (109) at a first point in time, and wherein the optical signal receiver (224) is configured to detect at least one or several reflected light pulses at a second point in time, and wherein at least one of a processor (226) and the optical signal receiver (224) is configured to determine a time interval between the first point in time and the second point in time.

12. The container according to claim 9, wherein at least one of the optical signal generator (222) and the optical signal receiver (224) is arranged in a recessed portion (215) of a distal end face (213) of the plug (210).

13. The container according to claim 9, wherein the measurement assembly (320) comprises an optical interferometer (321) configured to determine a distance between the outlet (116) and the plug (210) based on an optical phase shift between the optical feedback signal (F2) and an optical reference signal (RS).

14. The container according to claim 13, wherein the optical interferometer (321) comprises an optical fiber (329) forming a reference path (332) for the optical reference signal (RS).

15. A method of determining a size of an inner volume (109) of a container according to any one of the preceding claims 1 to 14, the method comprising the steps of: generating an optical measurement signal (SI; S2) from the measurement assembly (120; 220; 320) and emitting the optical measurement signal into or through the inner volume (109) of the container (100), detecting at least one optical feedback signal (F1, F2) being indicative of an interaction of the optical measurement signal (S1, S2) with at least one of the sidewall (102), the outlet (116) or the inner volume (109) of the container (100), and determining a size of the inner volume (109) based on the optical feedback signal (F1, F2).

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