Optical configuration of a drug reservoir of a drug delivery device - Patents.com

Abstract

Implementations of the present disclosure are directed to a drug delivery device (102) including a reservoir (106), a stopper (109), and an optical emission and detection system. The reservoir includes a wall defining a proximal end and a distal end. The stopper includes an optically reflective element (109b). The stopper is configured to expel a portion of the medication contained within the reservoir by moving within the reservoir from the distal end to the proximal end, thereby indicating the amount of medication within the reservoir based on the position of the stopper. The optical emission system (134) is configured to provide an optical signal from the proximal end toward the stopper. The optical detection system (136) is configured to detect a reflected optical signal provided by reflection of the optical signal on the optically reflective element of the stopper and to provide an electrical signal in response to detecting the reflected optical signal.

Description

[Technical field]

[0001] The present disclosure relates to drug delivery devices, and more particularly to optical configurations of drug reservoirs and sealing of the drug reservoirs of drug delivery devices for sensing the amount of drug contained within the drug reservoirs. [Background technology]

[0002] Some diseases can be treated by regular injections of specific doses of medication. Such injections can be performed by using a drug delivery device, either used by a medical professional or by the patient himself. For example, a pre-filled disposable pen can be used as the drug delivery device. Alternatively, a reusable pen can be used, in which the medication is stored in a removable cartridge. In a reusable pen, the empty medication cartridge can be replaced with a new cartridge.

[0003] In some devices, the drug dose to be injected can be manually selected in the pen by turning a dose setting knob and observing the actual dose from a dose setting window or display on the drug pen. In other devices, such as auto-injectors, the entire volume of the cartridge (or pre-filled syringe) is injected into the body, so that no dose selection is necessary. It is desirable to measure information regarding the function and / or use of the drug delivery device to monitor the injection of the drug, for example, to prevent incorrect or improper handling of the drug delivery device, to know which doses have already been used (e.g., in the case of a multi-dose pen), or to know if all doses have been administered (e.g., in the case of an auto-injector). For example, one or more of the type of drug injected, the dose, and the timing of the injection can be detected in a reliable and accurate manner and the data shared with a remote device to optimize the treatment. Summary of the Invention [Means for solving the problem]

[0004] Implementations of the present disclosure include a drug delivery device configured to optically detect an amount of a drug fluid and share the detected data in a medical continuum. According to one aspect of the invention, the drug delivery device includes a reservoir, a stopper, a light emitting system, and a light detection system. The reservoir includes a wall defining a proximal end and a distal end. The stopper includes a light reflective element, and the stopper is configured to move within the reservoir in a direction from the distal end to the proximal end to expel a portion of the drug contained within the reservoir, such that the stopper position indicates the amount of drug within the reservoir. The light emitting system is configured to provide a light signal from the proximal end toward the stopper. The light detection system is configured to detect a reflected light signal provided by reflection of at least a portion of the light signal at the light reflective element of the stopper, the reflected light signal having traveled through a second portion of the wall of the reservoir traveling toward the proximal end, and the light detector is configured to provide an electrical signal in response to detecting the reflected light signal.

[0005] In some implementations, the optical signal is configured to travel through a first portion of the reservoir wall and the reflected optical signal is configured to travel through a second portion of the reservoir wall. In some implementations, the optical signal is configured to travel through a first portion of the reservoir wall and the reflected optical signal is configured to travel through a second portion of the reservoir wall, with at least one of the first portion of the wall and the second portion of the wall facing an inner surface of the stopper. In some implementations, at least one of the first portion of the wall and the second portion of the wall at the proximal end is substantially optically transparent. In some implementations, the light emitting system is configured to emit the optical signal toward a central portion of the stopper. In some implementations, at least one of the first portion of the wall and the second portion of the wall defines at least one of a flat horizontal shape and a flat inclined shape. In some implementations, at least one of the first portion of the wall and the second portion of the wall defines at least one of a convex shape and a concave shape. In some implementations, the light emitting system includes a light emitting diode and the light detecting system includes a light dependent resistor configured to emit an electrical signal based on a brightness of the reflected optical signal. In some implementations, the light emission system includes a laser diode, and the light detection system includes a laser receiver sensor configured to emit an electrical signal based on an angle or phase of the reflected light signal. In some implementations, the light detection system includes a concave lens. In some implementations, the light reflection element is located within a central portion of the stopper. In some implementations, the light reflection element includes one of a cylindrical lens and an aspheric lens. In some implementations, the drug delivery device includes a processor configured to process the electrical signal to determine an amount of the drug in the reservoir. In some implementations, the processor is configured to process the electrical signal to determine a characteristic of the drug in the reservoir. In some implementations, the drug reservoir is made of an optically transparent plastic material, preferably including one of a cyclic olefin copolymer (COC) and a cycloolefin polymer (COP).In some implementations, the light emission system and detection system can be positioned to emit and receive light perpendicular to the direction of movement of the stopper.

[0006] According to another aspect of the present invention, a drug delivery system includes a drug delivery device, a transmitter, and an external device. The drug delivery device includes a reservoir, a stopper, an illumination system, and an optical detection system. The reservoir includes a wall defining a proximal end and a distal end. The stopper includes an optical reflection element, and the stopper is configured to move within the reservoir in a direction from the distal end to the proximal end to expel a portion of the drug contained within the reservoir, such that the stopper position indicates the amount of drug within the reservoir. The illumination system is configured to provide an optical signal from the proximal end toward the stopper. The optical detection system is configured to detect a reflected optical signal provided by reflection of at least a portion of the optical signal at the optical reflection element of the stopper, the reflected optical signal having traveled through a second portion of the wall of the reservoir toward the proximal end, and the optical detector is configured to provide an electrical signal in response to detecting the reflected optical signal. The transmitter is configured to transmit data of the injection device. The external device includes a receiver configured to receive injection device data, and one or more processors configured to process the injection device data and generate result data.

[0007] It is understood that systems according to the present disclosure may include any combination of the aspects and features described herein, i.e., methods according to the present disclosure are not limited to the combinations of aspects and features specifically described herein, but include any and all combinations of the aspects and features provided.

[0008] The details of one or more embodiments of the disclosure are set forth in the accompanying drawings and the description below. Other features and advantages of the disclosure will become apparent from the description and drawings, and from the claims. [Brief description of the drawings]

[0009] [Figure 1A] FIG. 2 is an exploded view of an example device according to the present disclosure. [Figure 1B] FIG. 2 is an exploded view of an example device according to the present disclosure. [Figure 1C] FIG. 2 is an exploded view of an example device according to the present disclosure. [Figure 1D] FIG. 2 is an exploded view of an example device according to the present disclosure. [Figure 1E] FIG. 2 is an exploded view of an example device according to the present disclosure. [Figure 1F] FIG. 2 is an exploded view of an example device according to the present disclosure. [Figure 1G] FIG. 2 is an exploded view of an example device according to the present disclosure. [Figure 2A] 1 is a cross-sectional view of an example device according to the present disclosure. [Figure 2B] 1 is a cross-sectional view of an example device according to the present disclosure. [Figure 2C] 1 is a cross-sectional view of an example device according to the present disclosure. [Figure 2D] 1 is a cross-sectional view of an example device according to the present disclosure. [Figure 2E] 1 is a cross-sectional view of an example device according to the present disclosure. [Figure 2F] 1 is a cross-sectional view of an example device according to the present disclosure. [Figure 3A] FIG. 1 is a flow diagram illustrating an exemplary process that can be performed to detect and transmit level data of a drug delivery device. [Figure 3B] FIG. 1 is a flow diagram illustrating an exemplary process that can be performed to detect and transmit level data of a drug delivery device. [Figure 3C] FIG. 1 is a flow diagram illustrating an exemplary process that can be performed to detect and transmit level data of a drug delivery device. [Figure 4] FIG. 1 is a schematic diagram of an example computer system that can be used to execute implementations of the present disclosure. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0010] Like reference numbers in the various drawings indicate like elements.

[0011] Implementations of the present disclosure are generally directed to determining an amount of drug in a drug delivery device during operation of the drug delivery device using an optical system and transmitting the determined data. The optical system includes a stopper that includes a light reflective element and moves when the drug is dispensed, a light source that emits a light signal toward the stopper, and a light detector that detects reflections from the light reflective element of the stopper. The detected light signal can be processed to determine the position of the stopper before, during, and / or after ejection of the drug from the drug reservoir. The amount of drug in the drug delivery device can then be determined.

[0012] A drug delivery device configured to determine the amount of fluid (e.g., medication) in the drug delivery device before, during, or after operation of the drug delivery device can support medical treatment and facilitate sharing of medical data. For example, a medical practitioner can optimize treatment by avoiding the use of expired or improperly stored medication and avoiding shortages of medical supplies based on monitoring multiple parameters related to the medication. Medication data, such as the amount of medication contained within and delivered by the drug delivery device, can be shared (e.g., to replenish medical supplies) with one or more medical practitioners who can use this information, and with other entities in the healthcare continuum (e.g., a system that supports, guides, and tracks a patient's treatment over time through a comprehensive array of healthcare services across all levels and intensities of care).

[0013] 1A-1G show a system 100 that can be used to determine the amount of drug in an exemplary drug delivery device 102 and share the data with an external device 150 in some implementations. FIGS. 1A-1G include exploded views of an exemplary drug delivery device 102 that includes a different type of drug amount detection system 103 that can be used to determine the amount of drug in the drug delivery device 102 (e.g., using a light emission system, a light detection system, and a reflective stopper, described in more detail below). In some examples, the drug delivery device 102 can be a pen-type device (FIGS. 1A, 1B, and 1G) that includes a drug reservoir, such as a cartridge with an attachable needle, or a pre-filled syringe with a crimped needle (FIGS. 1C-1F). In one embodiment, the pen-type device can be a pre-filled disposable or reusable injection pen.

[0014] In one embodiment, the pen device can be used to deliver only one injection (administering the entire contents of the drug container). In another embodiment, the pen device can be used to deliver multiple injections (administering only a portion of the contents of the drug container). FIGS. 1A, 1B, and 1G show a variable dose pen device 102, and FIGS. 1C-1E show a syringe type device 102. Although each drug delivery device 102 in FIGS. 1A-1G is shown in combination with a particular type of drug amount detection system 103, it is understood that each type of drug amount detection system 103 can be implemented in any type of drug delivery device 102. In one embodiment, the drug delivery device 102 includes a housing 104 and a drug reservoir 106. In one embodiment, the drug reservoir 106 can include a cartridge or a pre-filled syringe. In one embodiment, the drug delivery device 102 can include a plunger 108. In one embodiment, the drug delivery device 102 can optionally include an injection button 110. In one embodiment, the drug delivery device 102 may optionally include a dose knob 112. In one embodiment, the drug delivery device 102 may optionally include a dose window 114.

[0015] In one embodiment, the housing 104 can include a wall 115 configured to define a drug container or can include a drug reservoir 106 including a wall 115 capable of housing a quantity of drug. The wall 115 can include an outer flange 115a, a core 115b, and an inner flange 115c. In one embodiment, the shape of the wall 115 can be configured as needed. In one embodiment, the material of construction of the wall 115 can be configured. The shape and / or material of construction of the wall 115 can be configured to enable one or more functions of the drug quantity detection system 103.

[0016] In one embodiment, the shape and / or composite material of the wall 115 may allow for the transmission, internal reflection, external reflection, and / or refraction of the light beam. For example, the end portion 117 of the wall 115 and / or the end portion 116 of the wall 115 may include a substantially flat horizontal portion (FIGS. 1A-1G) that allows for the transmission of the light beam, and / or a substantially flat inclined surface (FIGS. 1F and 1G) that allows for the reflection of the light beam. The portion of the wall 115 between the distal end 111 and the proximal ends 116, 117 may have a tubular (cylindrical) shape. At least a portion of the housing 104 and / or the drug reservoir 106 is made of a material that is optically transparent to light beams in the visible and infrared spectrum to enable the optical components (light emission system 134 and light detection system 136) to function when attached to the outer flange 115a of the wall 115.

[0017] In one embodiment, the composite material of the housing 104 and / or drug reservoir 106 can include glass and / or optically clear plastic materials, such as (preferably) either cyclic olefin copolymer (COC) or cycloolefin polymer (COP). The composite material can be configured to have high birefringence (e.g., optical refractive index greater than 1.5), high moisture resistance (e.g., moisture absorption less than 0.01), and good material strength (e.g., Charpy impact strength of about 13-15). For example, plastic materials such as COC materials include high purity, high moisture resistance, excellent birefringence, breakage resistance, and low density. Most COC grades can be sterilized by gamma radiation, high temperature steam, or ethylene oxide. COC also has a very low energy, non-reactive surface that can extend the shelf life and purity of pharmaceuticals such as insulin and other protein drugs contained in the drug reservoir 106 (e.g., reservoirs of vials, syringes, and cartridges).

[0018] The drug reservoir 106 (container) may include a wall 115 configured to contain a fluid drug. The drug may include a pharmaceutical formulation including at least one pharma- ceutical active compound. The drug may include an insulin analog, an insulin derivative, an analgesic, a hormonal agent, a beta agonist, a corticosteroid, or any combination of the drugs described above. The drug may be optionally transparent, thereby not affecting the functionality (e.g., optical transparency) of the drug amount detection system 103. The drug reservoir 106 may include a sealing component 148 and an aperture 149, which are described in detail with respect to Figures 2A-2F.

[0019] The plunger 108 can be configured to expel a portion of the drug contained within the drug reservoir 106. The plunger 108 can include a plunger rod 108a and a plunger head 108b configured to push a stopper 109. The stopper 109 can be configured to expel a portion of the drug contained within the drug reservoir 106 by moving within the tubular wall 115 of the drug reservoir 106 in a direction from the distal end 111 to the proximal ends 116, 117, such that the position of the stopper 109 indicates the amount of drug within the drug reservoir 106. The terms "proximal", "proximally", and "proximal end" refer to the end of the drug delivery device toward which the stopper moves during administration of the drug. The terms "distal", "distally", and "distal end" refer to the end of the drug delivery device opposite the "proximal end".

[0020] At least a portion of the stopper 109 can be configured to be optically reflective. For example, a portion of the surface 109a of the stopper 109 of the plunger 108 can include an optically reflective element, such as an optical coating 109b, deposited at a specific location (e.g., a central section) of the surface 109a (FIG. 1A). As another example, the entire surface of the stopper 109a can be configured to be optically reflective (FIGS. 1B, 1C, 1F, and 1G). As another example, the surface 109a of the stopper 109 can include an optically reflective element, such as a reflective lens 146 (FIGS. 1D and 1E). The portion of the surface of the stopper 109 that contacts the drug (e.g., at least 90%) can be configured to be flat to minimize the dead volume of the filling of the drug delivery device 102.

[0021] In one embodiment, the position of the stopper 109 can be related to the amount of drug in the drug delivery device 102. Any configuration of the stopper 109 described and illustrated can be similarly applied to any type of injection device 102, such as cartridges and pre-filled syringes. For example, the stopper 109 is illustrated in FIGS. 1A, 1B, 1C, 1F, and 1G as a simple block. The stopper 109 is illustrated in FIGS. 1D and 1E as having additional structure. Nevertheless, it is understood that each of the stoppers illustrated in FIGS. 1A, 1B, 1C, 1F, and 1G can also be used with the system illustrated in FIGS. 1D and 1E. Similarly, it is understood that each of the stoppers illustrated in FIGS. 1D and 1E can also be used with the system illustrated in FIGS. 1A, 1B, 1C, 1F, and 1G.

[0022] In some pen devices, particularly those configured to deliver multiple doses, a dose of the contained drug can be expelled from the drug delivery device 102 by turning the dose knob 112, where the selected dose is displayed via the dose window 114, for example in multiples of so-called international units (IU), where 1 IU is the bioequivalent of about 45.5 μg (1 / 22 mg) of pure crystalline drug. However, it is understood that the present disclosure also covers injection pens where the dose to be administered is fixed without the user having the freedom to select it (so-called "fixed dose" devices). An example of the selected dose displayed in the dose window 114 can be 30 IU, for example, as shown in FIG. 1A and FIG. 1B. In some implementations, the selected dose can be displayed in a different manner, for example by an electronic display.

[0023] In one embodiment, turning the dose knob 112 can generate a mechanical click sound to provide auditory feedback to the user. The numbers displayed in the dose window 114 can be printed on a sleeve housed in the housing 104 and mechanically interacting with the plunger 108 of the drug reservoir 106. With respect to a syringe, a dose of the contained drug can be expelled from the drug delivery device 102 by applying direct pressure to the plunger shown in Figures 1D and 1E. It is understood that the present disclosure also covers auto-injectors in which the entire contents of the drug container are automatically administered. In this case, in one embodiment, the optical system can function to monitor whether the stopper has actually traveled the expected distance (e.g., the entire distance) within the drug container.

[0024] In one embodiment, the housing 104 can be attached to the needle 122 using a handle 124. The needle 122 is protected by an inner needle cap 126 and an outer needle cap 128, which can be covered by a cap 130. The needle 122 can be inserted into a patient's skin portion, and then when the injection button 110 is pressed, the drug dose displayed in the viewing window 120 is expelled from the drug delivery device 102. When the needle 122 of the drug delivery device 102 remains in the skin portion for a certain period of time after the injection button 110 is pressed, a high percentage of the dose is actually injected into the patient's body. The expulsion of the drug dose can generate a mechanical click sound, which may be different from the sound emitted when using the dose knob 112. However, it is understood that the present disclosure is not limited to cartridges with an attachable needle assembly. In another embodiment, a pre-filled syringe with a crimped needle can also be used.

[0025] In one embodiment, the drug delivery device 102 can be used for multiple injection processes until the drug reservoir 106 is empty or until the expiration date of the drug delivery device 102 (e.g., 28 days after first use). However, it is understood that the present disclosure also covers systems in which the drug delivery device 102 is an auto-injector that delivers the entire dose in one injection process. When using a multiple dose injection device, it may be necessary to perform a so-called "dry shot" to remove air from the drug reservoir 106 and needle 122 before using the drug delivery device 102 for the first time, for example by selecting two units of drug and pressing the injection button 110 while holding the drug delivery device 102 with the needle 122 facing up.

[0026] In one embodiment, the drug amount detection system 103 may include an optical system configured to monitor changes in the amount of drug contained within the drug delivery device 102, thereby deriving the amount of drug delivered by the drug delivery device 102. The monitoring includes generating an optical signal and detecting a reflected signal to determine the position of the stopper 109 before and after each injection. In another example, the monitoring may also include generating an optical signal and detecting a reflected signal to determine the position of the stopper 109 before and after each second, third, fourth, etc. injection to determine the average ejected dose.

[0027] In one embodiment, the processor can be configured to compare the detected location information / data and calculate the amount of drug remaining in the drug reservoir 106. In some implementations, the processor can be configured to calculate the amount of drug expelled from the drug reservoir 106. The monitoring is performed throughout the life of the drug reservoir 106 and / or the drug delivery device 102, and preferably during operation of the drug delivery device 102. For example, the monitoring is performed each time drug is expelled by the drug delivery device 102.

[0028] In some implementations, the drug amount detection system 103 can be associated with an identifier. The identifier can be a random number r that can be encoded in a machine-readable medium, such as radio frequency identification (RFID) data, a two-dimensional (2D) bar code, and / or a QR code, included with the drug delivery device. The random number r can be associated with the drug amount detection system 103 and can be used to uniquely identify the drug amount detection system 103 and the corresponding drug delivery device level data stored in the repository.

[0029] In one embodiment, the drug amount detection system 103 can include a power source 132, a light emitting system 134, a light detection system 136, and a processor 138. In some implementations, the drug amount detection system 103 can include an antenna 140 and a sensor 142. In some implementations, the power source 132 is integrated into the light emitting system 134. The power source 132 can be an integrated battery or a supercapacitor. In some implementations, the power source 132 can include an energy harvester that harvests energy from an interrogation signal emitted by the external device 150 or mechanical energy generated by a user's interaction with the drug delivery device 102. The power source 132 can be configured to provide energy to the components of the drug amount detection system 103 continuously or under certain conditions (e.g., when the drug delivery device 102 is within a near field communication (NFC) field 152). In some implementations, the processor 138 is integrated into the light detection system 136.

[0030] In one embodiment, the light emitting system 134 can include a light source 134a, a light emitting element 134b, and a coupling element 134c. The light source 134a can include one or more light emitting diodes (LEDs) or laser diodes. In some implementations, the light source 134a can emit an invisible light signal (e.g., in the infrared spectrum). In some implementations, the wavelength of the light generated by the light source 134a depends on the drug to be expelled by the drug delivery device 102. For example, the light source 134a can be configured to emit a light signal at a specific wavelength that does not affect the pharmacological properties of the drug. The light source 134a can be mounted on the outer flange 115a of the wall 115, the inner flange 115c of the wall 115, or within the core 115b of the wall 115, or the light source 134a can be separated from the wall 115 of the drug reservoir 106 (e.g., mounted on the wall of the housing 104 of the drug delivery device 102 as shown in FIG. 1G).

[0031] In one embodiment, the light source 134a can be attached or inserted into a portion of the proximal end 117 of the wall 115 of the housing 104 or a portion of the proximal end 116 of the wall 115 of the drug reservoir 106 adjacent to the nosepiece 118. The light emitting element 134b can include an optical component, such as a lens (e.g., a convex lens or a plano-convex lens) or a mirror, configured to direct a light beam in a particular direction (e.g., the center of the surface of the stopper 109, as shown in Figures 1C, 1F, and 1G). The light emitting element 134b can be attached to the outer flange 115a of the wall 115, the inner flange 115c of the wall 115, or within the core 115b of the wall 115, or can be a portion of the wall 115 (e.g., the inner flange 115c, as shown in Figure 1G). The light emitting element 134b can be configured to direct light toward the stopper 109.

[0032] In one embodiment, the light emitting element 134b can be configured to maximize light refraction and minimize reflection. For example, the light emitting element 134b can include an anti-reflective coating. The light emitting element 134b can be a lens with a radius selected based on the position of the light source 134a to control the angle of incidence. In some implementations, the light source 134a and the light emitting element 134b are integrated into a single element, as shown in Figures 1A, 1B, 1D, and 1E. In some implementations, the light source 134a and the light emitting element 134b are separate components attached to different parts of the wall 115, as shown in Figures 1C, 1F, and 1G. The light source 134a and the light emitting element 134b can be optically connected to each other by a coupling element 134C, as shown in Figures 1C, 1F, and 1G.

[0033] In one embodiment, the coupling element 134c can be configured to transmit light between different optical components (e.g., between the light source 134a and the light emitting element 134b) and / or across the wall of the drug reservoir 106. The coupling element 134c can include active and / or passive optical elements, such as optical fibers or other light transmitting elements. In some implementations, the coupling element 134c can be configured to assist a light beam (e.g., having a particular wavelength) impinging on the outer flange 115a of the drug reservoir 106 to enter the inner space of the drug reservoir 106. For example, the light emitted by the light source 134a is directed horizontally toward a substantially flat inclined portion of the wall 115. The substantially flat inclined portion of the wall 115 acts as the coupling element 134c by reflecting the light beam toward the light emitting element 134b (e.g., the spherical element shown in FIG. 1F, or the substantially flat portion of the inner flange 115 shown in FIG. 1G).

[0034] The light detection system 136 may include a light detector 136a, a light collector 136b, and a coupling element 136c. The light detector 136a may include one or more photodiodes, phototransistors, photomultipliers, photoresistors, laser sensors, or any other device configured to convert an optical signal into an electrical signal. The light detector 136a may be mounted on the outer flange 115a, the inner flange 115c, or within the core 115b (e.g., beside the outer flange 115a) of the drug reservoir 106, or the light detector 136a may be spaced from the wall of the drug reservoir 106 (e.g., mounted on the wall of the housing 104 of the drug delivery device 102, as shown in FIG. 1G). The light collector 136b may include any optical element configured to receive a light beam from a particular direction (e.g., the center of the surface of the stopper 109), such as a lens (e.g., a convex lens or a plano-convex lens) or a mirror, as shown in FIG. 1C and FIG. 1F. The light concentrator 136b can be mounted on the outer flange 115a of the wall 115, on the inner flange 115c of the wall 115, or within the core 115b of the wall 115, or can be a portion of the wall, as shown in FIG. 1G.

[0035] In one embodiment, the light collector 136b can be configured to maximize the refraction of light and minimize the reflection. For example, the light collector 136b can include an anti-reflective coating. The light collector 136b can be a lens with a radius selected based on the position of the light detector 136a to control the refraction angle. In some implementations, the light detector 136a and the light collector 136b are integrated into a single element, as shown in Figures 1A, 1B, 1D, and 1E. In some implementations, the light detector 136a and the light collector 136b are separate components, as shown in Figures 1C, 1F, and 1G. The light detector 136a and the light collector 136b can be optically connected to each other by a coupling element 136C, as shown in Figures 1C and 1F. The coupling element 136c can be configured to transmit light between different optical components (eg, between the light detector 136a and the light collector 136b) and / or across the walls of the drug reservoir 106.

[0036] In one embodiment, the coupling element 136c can include active and / or passive optical elements, such as optical fibers or other light-transmitting elements. In some implementations, the coupling element 136c can be configured to help a light beam (e.g., having a particular wavelength) that strikes the inner wall of the drug reservoir 106 to exit the space outside the drug reservoir 106. For example, the light reflected by the stopper 109 is directed toward the light collector 136b (e.g., the hole-like element shown in FIG. 1F, or the substantially flat portion of the inner flange 115 shown in FIG. 1G). The light collector 136b directs the refracted light toward the substantially flat, inclined portion of the wall 115.

[0037] In one embodiment, the substantially flat inclined portion of the wall 115 can act as a coupling element 134c to reflect the light beam (e.g., at a right angle) and direct the light beam substantially horizontally toward the photodetector 136a (inserted into the core 115c as shown in FIG. 1F or spaced apart from the drug reservoir 106 as shown in FIG. 1G). The advantage of the internal reflection at the portion of the wall 115 shown in FIG. 1G corresponds to the drug reservoir 106 being free of optical components (e.g., the photodetector 136a and the light source 134a), such that neither the photodetector 136a nor the light source 134a need to be attached / embedded in the drug reservoir 106 (e.g., cartridge). For example, the light beam (generated outside the drug reservoir 106 by the light source 134a) can enter the wall 115 at a right angle (e.g., through the optically transparent outer flange 115 or a defined optical window).

[0038] In one embodiment, the light beam can be internally reflected by a portion of the wall 115 (acting as coupling element 134c) through the optically transparent inner flange 115c (acting as light emitting element 134b) towards the stopper 109. The light beam reflected by the stopper 109 can intersect the optically transparent inner flange 115c (acting as light collector 136b), undergo a second internal reflection on the opposite side of the wall 115 (acting as coupling element 136c), and then exit the wall 115, for example at a right angle. Any drug reservoir 106 (e.g., cartridge) configured (geometrically) to have an optical path (e.g., light emission, transmission, and detection) that can direct an external light beam towards the stopper 109 can be mounted on the drug reservoir 106 without any optical elements attached or inserted into the wall of the drug reservoir 106.

[0039] The light emitting system 134 and the light detecting system 136 can be included in (or attached to) either a cartridge insertable into a pen device (FIGS. 1A and 1B) or the drug reservoir 106 of a syringe (FIGS. 1C-1F). The light emitting system 134 and the light detecting system 136 can be attached to an outer wall of the drug reservoir 106 near the proximal end 116 (FIG. 1A), 117 (FIG. 1C). The light emitting system 134 and the light detecting system 136 can be fully or partially embedded in a wall portion of the drug reservoir 106 near the proximal end 116 or the proximal end 117 of the drug delivery device 102 (FIGS. 1D and 1E). In some implementations, when the light emitting system 134 and the light detecting system 136 are attached to the inner wall of the drug reservoir 106, the light emitting system 134 and the light detecting system 136 are covered by a protective layer to prevent contamination of the drug contained within the drug reservoir 106 (FIG. 1B).

[0040] In one embodiment, the light emitting system 134 can be present at a first portion of the proximal end 116 or 117. The light detecting system 136 can be present at a second portion relative to the proximal end 116 of the drug reservoir 106 or the wall portion 117 of the drug delivery device 102. The second portion can be selected relative to the first location to optimally detect the reflected light signal. For example, the light emitting system 134 and the light detecting system 136 can be positioned parallel and radially spaced apart from the longitudinal axis 107 of the drug delivery device 102 by a symmetric or asymmetric radial offset. In this example, the location of the proximal ends 116 and 117 faces the inner surface of the stopper 109. The light emitting system 134 and the light detecting system 136 can be positioned such that a light beam passes from the light emitting system 134 through the drug to the stopper 109 and reflects from the stopper 109 through the drug to the light detecting system 136. The light emission system 134 and the light detection system 136 can be positioned such that as the drug is expelled from the drug reservoir 106, the distance between the light emission system 134 and the light detection system 136 decreases.

[0041] The light emitting system 134 can be configured to emit an optical signal in a direction toward a center of a surface of the stopper 109 through the medication based on the first position. As shown in FIG. 1A, the surface of the stopper 109 can be flat and reflective and configured to reflect the optical signal toward the optical detection system 136. As shown in FIGS. 1D and 1E, the stopper 109 can include an insert configured to reflect the optical signal toward the optical detection system 136. For example, the insert 144 can include at least one of a mirror and a lens (e.g., a cylindrical or aspheric lens) that directs a laser beam toward the optical detection system 136.

[0042] In some implementations, the electrical signal generated by the optical detection system 136 is transmitted to the processor 138, e.g., via an analog-to-digital converter, which may be a stand-alone component or integrated into the processor. The processor 138 may be included in a wall of the housing 104 of the drug delivery device 102, as shown in FIG. 1B. The processor 138 may be a microprocessor including an arithmetic logic unit array. The microprocessor 138 may be provided on a semiconductor substrate and may be interconnected with the optical detection system 136, and may optionally be interconnected with the antenna 140 for performing operations on received data to generate output data, as described in detail with respect to FIG. 6. The processor 138 may be configured to determine an amount of drug in the drug delivery device based at least in part on the electrical signal, and transmit data including the amount of drug to the antenna 140 and the display 114. In some examples, the processor 138 includes a controller configured to shift the position of the stopper 109 based on a dose selected by a user of the drug delivery device 102.

[0043] In some implementations, the data generated by the processor 138 is transmitted to the antenna 140. The antenna 140 can be included in a wall of the housing 104 of the drug delivery device 102, as shown in FIG. 1B. The antenna 140 can be a near field communication (NFC) antenna. The antenna 140 can be configured to obtain energy for the power source 132. The antenna 140 can be configured to transmit signals to the microprocessor 138 and the external processor. The signals transmitted by the antenna 140 can include the amount of drug in the drug reservoir 106, one or more additional characteristics of the drug measured by the sensor 142 (e.g., temperature), and an identifier of the drug amount detection system 103 in use of the drug delivery device (102). The antenna 140 can be configured to transmit data at data rates of, for example, 106 kb / s, 212 kb / s, or 424 kb / s using techniques such as Manchester bit coding and OOK load modulation at 846 kHz.

[0044] In some implementations, the drug delivery device 102 is within an NFC field 152 that can be generated by an interrogator 154. The interrogator 154 can be separate from the external device 150 (FIG. 1B) or can be an integrated module within the external device 150. The interrogator 154 can include a signal generator 156 (e.g., an RF module), a transmitter 158, a receiver 160, and a processor 162. In implementations where the interrogator 154 is separate from the external device 150, the interrogator 154 can be configured to transmit data received from the drug delivery device 102 to the external device 150. The external device 150 is configured to process and display data associated with the drug delivery device 102 (e.g., drug amount).

[0045] 2A-2F show an example of a drug reservoir 106 for a drug delivery device, such as a cartridge having multiple types of sealing systems 200, 212, 222, 232, and 242. The drug reservoir 106 includes a cavity 204, a distal end 206, and a proximal end 208. The distal end 206 can be sealed by a plunger head 108b. The proximal end 208 includes an aperture 149 that can be sealed by the sealing systems 200, 212, 222, 232. The sealing systems 200, 212, 222, 232 can be included or attached to the proximal end 208 as a closure. The drug reservoir 106 is configured to allow a proximal end 208 to be securely attached to the injection needle 122 (see FIGS. 1A-1F) (e.g., by a push-in mechanism, a screw-in mechanism, or a combination of the two mechanisms) to prevent unintentional removal during operation of the drug delivery device 102. The proximal end 208 typically includes a screw thread 203 to provide a secure connection for connecting the injection needle.

[0046] The sealing system 200, 212, 222, 232 is configured to maintain a fluid-tight seal between the cavity 204 and the injection needle 122. The fluid-tight seal created by the sealing system 200, 212, 222, 232 allows substantially all (e.g., greater than 99%) of the drug expelled by the drug delivery device 106 to be expelled through the injection needle 122. The fluid-tight seal created by the sealing system 200, 212, 222, 232 increases the accuracy of the stopper position-based drug quantity detection system described with respect to Figures 1A-1F by eliminating unaccounted drug leakage. The sealing system 200, 212, 222, 232 can prevent contamination of the drug contained in the cavity 204. The sealing system 200, 212, 222, 232 can include a one-way valve that allows flow from the cavity 204 toward the injection needle 122 and prevents flow from the injection needle 122 toward the cavity 204. The sealing system 200, 212, 222, 232 can be aligned to the central longitudinal axis of the drug delivery device 106. As opposed to conventional cartridges that are closed and sealed at the proximal end by a crimp cap (including a rubber seal and a metal crimp element), the sealing system 200, 212, 222, 232 has the advantage of reducing part count, manufacturing complexity, and manufacturing costs. The sealing system 200, 212, 222, 232 is easier to manufacture than a crimp cap.

[0047] The sealing system 200, 212, 222, 232 can include one or more components, such as septa 202, 216, 224, 234 (FIGS. 2A-2F), septum or sealing disk 214 (FIG. 2B), and septum carriers 226, 236 (FIGS. 2C and 2D). One or more components of the sealing system 200, 212, 222, 232 are fabricated from a material selected from the group of pharmaceutical grade plastics, silicon oxide coated plastics, thermoplastic elastomers, rubber elastomers, and combinations thereof. At least one component of the sealing system 200, 212, 222, 232, such as the septa 202, 214, 224, 234 (FIGS. 2A-2F) and / or the sealing disk 214 (FIG. 2B), is fabricated from a thermoplastic elastomer or rubber elastomer to form a liquid-tight seal. The septum carriers 226 , 236 ( FIGS. 2C and 2D ) can be manufactured from a material or combination of materials that enables and optimizes attachment of the septum carriers 226 , 236 to the proximal end 208 .

[0048] The sealing system 200 shown in FIG. 2A includes a septum 202 that is insert molded or 2k molded to seal the proximal end 208 of the drug reservoir 106 (e.g., cartridge). The septum 202 can be manufactured from a material that allows for piercing by the piercing member of the injection needle 122. The material of the septum 202 can be different from the material used for the outer wall. For example, the material is specifically softer to allow the needle to pierce the septum 202 and cross the aperture 149 to reach the drug stored in the cavity 204. The material is also elastic in the sense that once the injection needle is separated, the piercing hole closes to form a liquid-tight seal. The septum 202 has extensions 202a, 202b that provide a connection between the septum and the cartridge material and help fix the septum in a particular position. In some implementations, the material of the sealing system 200 is melted together with the drug reservoir 106. The septum 202 can have a transverse diameter that is larger than the diameter of the piercing member of the injection needle 122 and larger than the aperture 149 .

[0049] The sealing system 212 shown in FIG. 2B includes a septum 216 and a sealing disk 214 configured to seal the aperture 149. The septum 216 and / or the sealing disk 214 are configured to form a liquid-tight seal. The septum 216 and / or the sealing disk 214 can have a thinner cross-sectional thickness to facilitate piercing by the piercing member of the injection needle 122. The septum 216 can be fitted against the aperture 149 near the distal end of the proximal end 208, between the side walls of the proximal closure 208. The fit can be a form fit, a positive fit, a force closure, a closed linkage, or any combination thereof. The proximal end 208 can have a retention feature (e.g., a notch) to secure the sealing disk 214 in place. The incision can be an annular rib or can include multiple protrusions, e.g., two, three, four protrusions, as a retention feature. The septum 216 can be attached to the proximal end 208 before filling the cavity 204 with the drug. The septum 216 or sealing disk 214 can be molded to the proximal end 208 by a multiple component injection molding process. In some implementations, the sealing disk 214 can be manufactured from a material that allows for piercing by the piercing member of the injection needle 122, such that the material of the septum 214 is different from the material used for the outer wall. In some implementations, the sealing disk 214 can have a narrow section in the center to improve pierceability. The diameter of the narrow section does not exceed the diameter of the bore to ensure that there is a liquid-tight seal.

[0050] 2C includes a septum 224 attached to the proximal end 208 using a septum carrier 226. The septum carrier 226 includes an opening configured to match the geometric characteristics of the septum 224, allowing for attachment of the septum 224 to the septum carrier 226. The septum 224 is fluid-tightly attached to the septum carrier 226 using, for example, an adhesive (permanent glue), crimping or heat staking, or 2k injection molding.

[0051] The septum carrier 226 may have a bore in the center to facilitate piercing of the septum 224. The septum carrier 226 may include any attachment means that allows the septum 224 to be fixedly attached to the proximal end 208 such that the septum 224 is maintained in a fluid-tight seal with the cavity 204. For example, the septum carrier 226 may include a ring-shaped connector 238 having a hook-shaped formation at its end to prevent the carrier from being pushed out of its position when pressure is applied to the stopper 109 inside the cartridge. Additionally, the hook-shaped end provides an annular contact area against the inner surface of the proximal end 208 to ensure a fluid-tight seal. Additionally, the hook-shaped end is chamfered to facilitate insertion of the carrier during assembly. The configuration of the sealing system 222 allows for a secure, fluid-tight attachment to the outer surface of the proximal end 208. Similar to the embodiment previously described with respect to FIG. 2B, the proximal end 208 has an aperture 149 that is sealed by a sealing system 222 .

[0052] The sealing system 232 shown in FIG. 2D is similar to the sealing system 222 described with respect to FIG. 2C. The sealing system 232 includes a septum 234 and a septum carrier 236 configured to form a single component. The septum 234 and the septum carrier 236 are attached to the proximal end 208 such that the septum 234 covers the aperture 149 of the proximal end 208. The septum carrier 236 can include any attachment means that allows the septum 234 to be fixedly attached to the proximal closure 208 such that the septum 234 is maintained in a fluid-tight seal with the cavity 204. In some implementations, the attachment means includes an annular ring having a hook-shaped end as described with respect to FIG. 2C.

[0053] The sealing system 242 shown in FIGS. 2E and 2F includes a septum 216 configured to seal the aperture 149 and a septum pocket 240. The septum 216 can be made of rubber or customized foam, which is compressed prior to or during assembly. The compression can be supported by low temperature or by the customized composite material of the septum 216, which is configured to form a liquid-tight seal. The septum 216 can be fitted between the inner walls of the septum pocket 240. The fit can be a form fit, a positive fit, a force closure, a closed linkage, or any combination thereof. In some implementations, the septum pocket 240 can include an opening to allow for the insertion of the septum 216. The opening of the septum pocket 240 can be closed by a closure feature 244 after the septum 216 is fitted into the septum pocket. The septum 216 can have a thinner cross-sectional thickness to facilitate piercing by the piercing member of the injection needle 122. The diameter of the narrowed section does not exceed the diameter of the bore to ensure that there is a fluid-tight seal.

[0054] The sealing systems 200, 212, 222, 232, 242 described with respect to FIGS. 2A-2E may be included in any type of drug reservoir 106.

[0055] The drug reservoir 106 can include interfaces 205a, 205b, 205c, 205d. In some implementations, the interfaces 205a, 205b can be included in or attached to the wall of the drug reservoir 106, such that the wall thickness of the drug reservoir 106 can vary in the longitudinal direction, as shown in FIGS. 2A-2F. In some implementations, the interfaces 205a, 205b can be proximal to the distal end 111, as shown in FIGS. 2A-2C, 2E, and 2F. In some implementations, the interfaces 205c, 205d can be included in or attached to the wall of the drug reservoir 106 by the proximal end 116, as shown in FIGS. 2A, 2B, 2D, 2E, and 2F.

[0056] The interfaces 205a, 205b, 205c, 205d can be configured to ensure accurate positioning of the drug reservoir 106 (cartridge) relative to the drug quantity detection system 103 (e.g., optics). For example, the interfaces 205a, 205b, 205c, 205d can include a circumferential groove around the outer periphery of the wall of the drug reservoir 106, or a blind hole with a tapered opening. The interfaces 205a, 205b, 205c, 205d can be configured to provide an anti-rotation lock. For example, the interfaces 205a, 205b, 205c, 205d can include a series of tabs or features spaced around the outer periphery of the wall of the drug reservoir 106 and corresponding grooves or features on the inner diameter of the housing 104. The interfaces 205a, 205b, 205c, 205d can be used to identify a particular cartridge type and / or medication to prevent mismatches (coding or proprietary) between the medication and the drug delivery device 102. For example, the interfaces 205a, 205b, 205c, 205d can include circumferential webs or other drug-specific design solutions.

[0057] 3A-3C are flow charts illustrating example processes 300, 320, and 340 that can be performed to determine drug quantity data using an optical system during operation of a drug delivery device. The processes 300, 320, and 340 can be performed by the devices and systems described with respect to FIGS. 1-2.

[0058] The process 300 illustrated by Figure 3A begins by receiving a trigger signal (302). The trigger signal may include a priming operation for a drug delivery device having an ultrasound probe inserted into a rigid stopper. The priming operation may be initiated by a user of the drug delivery device or by a user of an external device in communication with the drug delivery device.

[0059] An example of a priming action performed with a drug delivery device may include selecting a particular number of drug units (e.g., 1 or 2) and pressing an injection button while holding the drug delivery device with the needle pointing up. Another example of a priming action performed with a drug delivery device may include pressing a priming button on a drug delivery device configured as an electrical switch.

[0060] In some implementations, the trigger signal can include an interrogation signal generated by the external device. The interrogation signal can be generated automatically by the external device based on one or more conditions. These conditions can include a transmission frequency, a transmission time, and / or a time interval (304). For example, a drug treatment can be scheduled to occur within a particular time interval during which the external device can generate an interrogation signal at a given frequency. The signal can be generated by the external device in response to a user input to the external device. For example, a user can interact with the external device to initiate a drug dispensing service. The trigger signal can include at least one of a mechanical signal, an auditory signal, and an electrical signal. The trigger signal can include a command to generate an ultrasound signal.

[0061] In response to receiving the trigger signal, a light emitting system can be activated to illuminate an optical target. For example, one or more LEDs or laser diodes can direct a light signal toward a section of a surface of the stopper of the drug delivery device described with respect to FIGS. 1A-1C. A light detection system including a photodiode or a light dependent resistor can detect at least a portion of the light signal reflected by the stopper surface (308). One or more features of the reflected light signal can indicate the amount of drug contained in the drug reservoir and the state of the drug. For example, the luminescence of the reflected signal can vary depending on the length of the light propagation path and the angle of reflection, which are indicative of the amount of drug contained in the drug reservoir. The luminescence of the reflected signal can vary depending on the refractive index of the drug, which can change over time due to temperature or contaminants, which are indicative of the state of the drug.

[0062] An electrical signal may be generated by the optical sensor in response to receiving the reflected optical signal. The electrical signal may be used by the processor to generate data for the drug delivery device (310). The drug delivery device data may include the electrical signal, a unique identifier for the drug delivery device, characteristics of the drug (e.g., rate of descent of sediments in the drug, concentration of the drug, optical absorption coefficient, and / or temperature), sensor measurements (e.g., drug temperature), internal clock measurements (e.g., timestamp of receipt of the ultrasound signal), drug identifier, alignment with the drug volume, location, and / or state specific data for the drug delivery device.

[0063] The drug temperature can be determined for the drug including additives or sediment based on the optical signal detected by the optical detection system and the known descent rate of the sediment. The amount of drug in the drug delivery device can be determined based on one or more characteristics of the optical signal detected by the optical detection system. For example, the position of the stopper can be determined based on the phase of the reflected optical signal using a particular detection method. The detection method can include interferometric distance detection and / or phase modulation methods combined with known geometric characteristics (e.g., cross-sectional area) of the drug delivery device and drug reservoir. In some implementations, the amount of drug in the drug delivery device can be determined based on a differential measurement associated with an initial position of the plunger (before dispensing the drug) and a final position of the plunger (after dispensing the drug).

[0064] The correct drug insertion into the drug delivery device can be determined based on the optical signal detected by the optical detection system and a comparison of the determined optical absorption coefficient with the known optical absorption coefficient of the drug. The consistency between the drug volume and the available drug volume can be determined based on the optical signal detected by the optical detection system and the optical absorption coefficient of the drug relative to air. The consistency between the drug volume and the available drug volume can be used to confirm that the drug reservoir is not empty or partially empty. The drug temperature can be determined for drugs containing additives or sediment based on the optical signal detected by the optical detection system and the known rate of descent of the sediment.

[0065] The antenna of the drug delivery device can be configured to transmit data to an external device to analyze one or more parameters related to administration of the medication and the operating conditions of the drug delivery device (312). The drug delivery device data can be transmitted using radio frequency (RF) communication, Bluetooth communication, millimeter wave communication, or any other type of short-range communication. The drug delivery device data can be processed by a processor of the external device to generate result data. In response to obtaining the result data, the result data can be stored for future reference and displayed via a graphical user interface of the external device. In some implementations, in response to successfully transmitting the data, the drug delivery device can initiate a sleep mode to conserve energy of the power source (314). In some implementations, the drug delivery device is configured to periodically resume the process based on a preset time interval (316).

[0066] The process 320 shown in FIG. 3B begins by identifying whether the drug delivery device is within a communication (NFC) field (322). For example, the drug delivery device can be configured to periodically check its proximity to the NFC field. The drug delivery device can include one or more components configured to check the proximity of the drug delivery device to the NFC field. In some implementations, a user (e.g., a medical practitioner or a patient) can swipe the drug delivery device over an external device to generate a signal indicating that the drug delivery device has entered within a communication field (e.g., an NFC field or a Bluetooth field). The medical practitioner can store and use the drug delivery device while in a medical facility configured to be within an NFC field.

[0067] In response to determining that the drug delivery device is within the NFC region, the drug delivery device determines whether a radio frequency signal is being applied (324). In some implementations, the radio frequency signal is generated automatically in response to use of the drug delivery device. For example, the radio frequency signal is generated automatically after a quantity of a medication contained within the drug delivery device is injected using the drug delivery device.

[0068] In response to determining that the radio frequency signal is being applied, the drug delivery device can be powered up (326). For example, in preparation for creating data associated with the drug delivery device, one or more electronic components of the drug delivery device can be energized (as described with respect to FIGS. 1A-1C) using a power source integrated within the drug delivery device or by obtaining energy from an external device. For example, if the power source runs out of energy, it can be recharged by obtaining energy from an external device while the drug delivery device is in the NFC range.

[0069] In response to one or more components of the drug delivery device being activated, a light source, such as one or more LEDs or laser diodes, can direct a light signal toward a stopper of the drug delivery device (328), as described with respect to FIGS. 1A-1C. In some implementations, the light source can be configured to generate the light signal continuously during dose administration. In some implementations, the light source can be configured to generate the light signal periodically every few seconds, for example, every 1 second, 3 seconds, 10 seconds, or 20 seconds. Generating the light signal intermittently can be implemented to extend battery life.

[0070] An optical detection system, such as a photodiode or a light-dependent resistor, can detect at least a portion of the optical signal reflected by the stopper and generate data related to the detected portion of the optical signal (330). The optical detection system is powered in sync with the light source, such that each reflected optical signal can be detected by the optical detection system. The detection method can be based on interferometric distance detection and / or phase modulation methods, which estimate the position of the stopper with an accuracy of approximately 10 nm. Phase modulation is an optical technique for measuring distance using a laser beam as a light source. The laser beam has a sinusoidally modulated optical power. The laser beam is directed towards a target (e.g., the lens of the stopper). The reflected light (e.g., by the lens of the stopper) is detected and recorded. The phase of the optical power modulation of the reflected light is compared to the phase of the optical power modulation of the light source. The resulting phase shift is the product of 2π and the time of flight and the modulation frequency. The choice of modulation frequency affects the spatial resolution of the estimated distance, such that a higher modulation frequency can provide a higher spatial resolution.

[0071] The data may include the amount of drug contained within the drug delivery device, characteristics of the drug (e.g., drug concentration, optical absorption coefficient, and / or temperature), correct drug insertion into the drug delivery device, matching of drug volume with available drug volume, drug temperature, and / or other data. The amount of drug in the drug delivery device can be determined based on the optical signal detected by the optical detection system and known geometric characteristics (e.g., cross-sectional area) of the drug delivery device and drug reservoir.

[0072] The correct drug insertion into the drug delivery device can be determined based on the optical signal detected by the optical detection system and a comparison of the determined optical absorption coefficient with the known optical absorption coefficient of the drug. The consistency between the drug volume and the available drug volume can be determined based on the optical signal detected by the optical detection system and the optical absorption coefficient of the drug relative to air. The consistency between the drug volume and the available drug volume can be used to confirm that the drug reservoir is not empty or partially empty. The drug temperature can be determined for drugs containing additives or sediment based on the optical signal detected by the optical detection system and the known rate of descent of the sediment.

[0073] The drug delivery device can be configured to transmit the data to a database, such as a central database 412 described with reference to FIG. 4B. In response to a successful transmission of the data, the drug delivery device can initiate a sleep mode to conserve energy of the power source (334). In some implementations, a user (e.g., a medical professional or a patient) can swipe the drug delivery device over an external device to generate a signal to initiate the sleep mode. In some implementations, the drug delivery device is configured to periodically resume the process based on a preset time interval (336).

[0074] The process 340 illustrated by FIG. 3C begins by initiating a reminder function on the external device (342). The reminder function can be an application that generates an audio, tactile, and / or visual alert on the external device. The reminder function may allow the user to select the type of reminder and alert based on the treatment schedule. The treatment includes delivering a drug dose using a drug delivery device.

[0075] In response to the reminder alert, the user may confirm initiation of treatment or postpone treatment for a specific time interval (344). If the user confirms initiation of treatment, a user input to the external device may select a dose of the drug to be injected or may confirm a preselected dose (346). In response to confirming the dose, the user may be instructed to manually select a dose on the drug delivery device. For example, the user may select a dose on the drug delivery device by turning a dose dial and / or by pressing a dose release button. After dose selection, the user may generate a user input on the drug delivery device confirming the setting of the dose (350).

[0076] In response to a user input or in response to setting a dose, communication can be established between the drug delivery device and the external device (352). Establishing communication between the drug delivery device and the external device can include powering up the drug delivery device. For example, at least some of the electronic components of the drug delivery device, including a light source (e.g., an LED or laser diode) and a light detection system (e.g., a photodiode or a light-dependent resistor), are energized.

[0077] A first measurement can be initiated by energizing electronic components of the drug delivery device (354). The first measurement can include generating and directing an optical signal toward a portion of a stopper of the drug delivery device (e.g., a lens of the stopper) with a light emission system, detecting a reflected signal with a light detection system, and determining a first position of the stopper. The first position of the stopper can be determined using interferometric distance detection and / or phase modulation methods. The determined data including the first position of the stopper, and optionally one or more environmental sensor data (e.g., temperature, humidity, and light intensity) can be stored in a short-term memory (356).

[0078] After the set dose of the drug is expelled, a signal is generated indicating completion of the treatment (358). For example, the signal can be generated in response to a user activating a power off switch. The power off may include a time delay for initiating a second measurement (360). The second measurement can include generating and directing a light signal by a light source toward a portion of a stopper of the drug delivery device (e.g., a lens of the stopper), detecting a reflected signal by a light detection system, and determining a second position of the stopper. A processor of the drug delivery device can receive the second position value of the stopper and the first position value of the stopper to determine a displacement of the stopper (362). Drug delivery device data including the displacement of the stopper and one or more environmental sensor data (e.g., temperature, humidity, and light intensity) is transmitted from the drug delivery device to an external device by an antenna of the drug delivery device (364). In response to successful transmission of the drug delivery device data, the drug delivery device can initiate a sleep mode to conserve energy of the power source. In some implementations, the drug delivery device is configured to periodically resume 366 the process 320 based on a preset time interval.

[0079] 4, a schematic diagram of an exemplary computing system 400 is provided. The system 400 can be used for the operations described in connection with the implementations described herein. For example, the system 400 can be included in any or all of the server components discussed herein. The system 400 includes a processor 410, a memory 420, a storage device 430, and an input / output device 440. Each of the components 410, 420, 430, and 440 are interconnected using a system bus 450. The processor 410 can process instructions for execution within the system 400. In one implementation, the processor 410 is a single-threaded processor. In another implementation, the processor 410 is a multi-threaded processor. The processor 410 can process instructions stored in the memory 420 or the storage device 430 to display graphical information for a user interface of the input / output device 440.

[0080] The memory 420 stores information within the system 400. In one implementation, the memory 420 is a computer readable medium. In one implementation, the memory 420 is a volatile memory unit. In another implementation, the memory 420 is a non-volatile memory unit. The storage device 430 can provide mass storage for the system 400. In one implementation, the storage device 430 is a computer readable medium. In various different implementations, the storage device 430 can be a floppy disk device, a hard disk device, an optical disk device, or a tape device. The input / output device 440 performs input / output operations for the system 400. In one implementation, the input / output device 440 includes a keyboard and / or a pointing device. In another implementation, the input / output device 440 includes a display unit for displaying a graphical user interface, which allows a user to access data related to the drug delivery device that is retrieved, stored, and queried as described with respect to FIGS. 1-4.

[0081] The described functions can be implemented in digital electronic circuitry, or in computer hardware, firmware, software, or in combinations of these. The apparatus can be implemented in a computer program product tangibly embodied in an information carrier, for example a machine-readable storage device, for execution by a programmable processor; the method steps can be performed by the programmable processor executing a program of instructions for performing the functions of the described implementation, operating on input data and generating output. The described functions can advantageously be implemented in one or more computer programs, which are executable on a programmable system including at least one programmable processor connected to transmit and receive data and instructions to and from a data storage system, at least one input device, and at least one output device. A computer program is a set of instructions that can be used directly or indirectly in a computer to perform a particular activity or cause a particular result. Computer programs can be written in any form of programming language, including compiled or interpreted languages, and computer programs can be implemented in any form, including as a stand-alone program or as a module, component, subroutine, or other unit suitable for use in a computing environment.

[0082] Processors suitable for executing a program of instructions include, by way of example, both general purpose and special purpose microprocessors, and the sole processor or one of multiple processors of any type of computer. In general, a processor will receive instructions and data from a read-only memory or a random access memory or both. The essential elements of a computer are a processor for executing instructions and one or more memories for storing instructions and data. In general, a computer also includes, or is operatively coupled to communicate with, one or more mass storage devices for storing data files; such devices include magnetic disks, such as internal hard disks and removable disks; magneto-optical disks; and optical disks. Storage devices suitable for tangibly embodying computer program instructions and data include semiconductor memory devices, such as, for example, EPROM, EEPROM, and flash memory devices; magnetic disks, such as, for example, internal hard disks or removable disks; magneto-optical disks; and all forms of non-volatile memory, including, by way of example, CD-ROM and DVD-ROM disks. The processor and memory may be supplemented by or incorporated in an ASIC (Application Specific Integrated Circuit).

[0083] To interact with a user, the functionality can be implemented in a computer that has a display device, such as a CRT (cathode ray tube) monitor or LCD (liquid crystal display) monitor for displaying information to the user, a keyboard by which the user can provide input to the computer, and a pointing device, such as a mouse or trackball.

[0084] The functionality may be implemented in computer systems including back-end components such as data servers, or computer systems including middleware components such as application servers or Internet servers, or computer systems including front-end components such as client computers having a graphical user interface or Internet browser, or any combination thereof. The components of the system may be connected by any form or medium of digital data communication, such as a communications network. Examples of communications networks include, for example, LANs, WANs, and the computers and networks forming the Internet.

[0085] A computer system may include clients and servers. Clients and servers are generally remote from each other and typically interact through a network, such as the networks mentioned above. The relationship of client and server arises by virtue of computer programs running on the respective computers and having a client-server relationship to each other.

[0086] Additionally, the logic flows depicted in the figures do not require the particular order or sequence depicted to achieve desired results. Additionally, other steps could be provided or steps could be deleted from the described flows, and other components could be added to or removed from the described systems. Accordingly, other implementations are within the scope of the following claims.

[0087] The term "drug" or "medicament" is used herein to describe one or more pharmacologic active compounds. As described below, a drug or medicament may include at least one small molecule or a macromolecule or a combination thereof in various types of formulations for the treatment of one or more diseases. Exemplary pharmacologic active compounds may include small molecules; polypeptides, peptides, and proteins (e.g., hormones, growth factors, antibodies, antibody fragments, and enzymes); carbohydrates and polysaccharides; and nucleic acids, double-stranded or single-stranded DNA (including naked and cDNA), RNA, antisense nucleic acids such as antisense DNA and RNA, small interfering RNA (siRNA), ribozymes, genes, and oligonucleotides. Nucleic acids may be incorporated into vectors, plasmids, or molecular delivery systems such as liposomes. Mixtures of one or more of these drugs are also contemplated.

[0088] The term "drug delivery device" is intended to encompass any type of device or system configured to administer a volume of a drug to a human or animal body. The volume can typically range from about 0.5 ml to about 10 ml. Without limitation, drug delivery devices may include syringes, needle-safe systems, pen injectors, autoinjectors, large volume devices (LVDs), pumps, perfusion systems, or other devices configured for subcutaneous, intramuscular, or intravascular delivery of drugs. Such devices often include a needle, which may include a small gauge needle (e.g., greater than about 24 gauge, including 27, 29, or 31 gauge).

[0089] In combination with a particular drug, the devices described herein can also be customized to operate within required parameters, such as within a certain time period (e.g., about 3 to about 20 seconds for a syringe, about 5 to about 60 minutes for an LVD), with low or minimal levels of discomfort, or within certain conditions related to human factors, shelf life, expiration date, biocompatibility, environmental considerations, etc. Such variations may occur due to a variety of factors, such as, for example, drugs with viscosities ranging from about 3 cP to about 50 cP.

[0090] The drug or agent can be contained in a primary package or "drug container" adapted for use in a drug delivery device. The drug container can be, for example, a cartridge, syringe, reservoir, or other vessel configured to provide a chamber suitable for storage (e.g., short-term or long-term storage) of one or more pharma- ceutically active compounds. For example, in some cases, the chamber can be designed to store the drug for at least one day (e.g., from one day to at least 30 days). In some cases, the chamber can be designed to store the drug for about one month to about two years. Storage can be at room temperature (e.g., about 20° C.) or at refrigerated temperatures (e.g., from about −4° C. to about 4° C.). In some cases, the drug container can be or include a dual-chamber cartridge configured to separately store two or more components of a drug formulation (e.g., a drug and a diluent, or two different types of drugs), one in each chamber. In such cases, the two chambers of the dual-chamber cartridge can be configured to allow mixing between two or more components of a drug or agent prior to and / or during administration to the human or animal body. For example, the two chambers can be configured to be in fluid communication with each other (e.g., via a conduit between the two chambers) and to allow mixing of the two components by a user, if desired, prior to administration. Alternatively or additionally, the two chambers can be configured to allow mixing upon administration of the components to the human or animal body.

[0091] The drug delivery devices and drugs according to the present invention can be used for the treatment and / or prevention of many different types of disorders. Exemplary disorders include, for example, diabetes or complications associated with diabetes, such as diabetic retinopathy, thromboembolic disorders, such as deep vein thromboembolism or pulmonary thromboembolism. Further exemplary disorders are acute coronary syndrome (ACS), angina, myocardial infarction, cancer, macular degeneration, inflammation, hay fever, atherosclerosis and / or rheumatoid arthritis.

[0092] Exemplary drugs for the treatment and / or prevention of diabetes or complications associated with diabetes include insulin, e.g., human insulin, or a human insulin analog or derivative, glucagon-like peptide (GLP-1), a GLP-1 analog or GLP-1 receptor agonist, or an analog or derivative thereof, a dipeptidyl peptidase-4 (DPP4) inhibitor, or a pharma- ceutically acceptable salt or solvate thereof, or any mixture thereof. As used herein, the term "derivative" refers to any substance that is sufficiently structurally similar to the original substance so as to have substantially the same functionality or activity (e.g., therapeutic effect).

[0093] Exemplary insulin analogs are Gly(A21), Arg(B31), Arg(B32) human insulin (insulin glargine); 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 Lys at position B29 may be replaced by Pro; Ala(B26) human insulin; Des(B28-B30) human insulin; Des(B27) human insulin and Des(B30) human insulin.

[0094] Exemplary insulin derivatives include, for example, B29-N-myristoyl-des(B30) human insulin; B29-N-palmitoyl-des(B30) human insulin; B29-N-myristoyl human insulin; B29-N-palmitoyl human insulin; B28-N-myristoyl-LysB28ProB29 human insulin; B28-N-palmitoyl-LysB28ProB29 human insulin; B30-N-myristoyl-ThrB29Lys B30 human insulin; B30-N-palmitoyl-ThrB29LysB30 human insulin; B29-N-(N-palmitoyl-gamma-glutamyl)-des(B30) human insulin; B29-N-(N-lithocholyl-gamma-glutamyl)-des(B30) human insulin; B29-N-(ω-carboxyheptadecanoyl)-des(B30) human insulin and B29-N-(ω-carboxyheptadecanoyl) human insulin. Exemplary GLP-1, GLP-1 analogs and GLP-1 receptor agonists include, for example: lixisenatide / AVE0010 / ZP10 / Lyxumia, exenatide / exendin-4 / Byetta / Bydureon / ITCA650 / AC-2993 (a 39 amino acid peptide produced by the salivary glands of the flathead monster), liraglutide / Victoza, semaglutide, taspoglutide, synclear / albiglutide, dulaglutide, rExendin-4, CJC-1134-PC, PB-1023, TTP-054, Langrena These include: cefotide / HM-11260C, CM-3, GLP-1 Erigen, ORMD-0901, NN-9924, NN-9926, NN-9927, nodexene, Viadol-GLP-1, CVX-096, ZYOG-1, ZYD-1, GSK-2374697, DA-3091, MAR-701, MAR709, ZP-2929, ZP-3022, TT-401, BHM-034, MOD-6030, CAM-2036, DA-15864, ARI-2651, ARI-2255, exenatide-XTEN and glucagon-Xten.

[0095] An exemplary oligonucleotide is, for example: the cholesterol-lowering antisense therapeutic mipomersen / quinamro for the treatment of familial hypercholesterolemia.

[0096] Exemplary DPP4 inhibitors are vidagliptin, sitagliptin, denagliptin, saxagliptin, berberine.

[0097] Exemplary hormones include pituitary or hypothalamic hormones or regulatory active peptides and their antagonists, such as gonadotropins (follitropin, lutropin, chorion gonadotropin, menotropin), somatropine (somatropin), desmopressin, terlipressin, gonadorelin, triptorelin, leuprorelin, buserelin, nafarelin, and goserelin.

[0098] Exemplary polysaccharides include glycosaminoglycans, hyaluronic acid, heparin, low molecular weight heparin or very low molecular weight heparin or derivatives thereof, or sulfated polysaccharides, such as the above-mentioned polysaccharides in polysulfated form, and / or their pharmaceutically acceptable salts.An example of a pharmaceutically acceptable salt of polysulfated low molecular weight heparin is enoxaparin sodium.An example of a hyaluronic acid derivative is Hylan G-F20 / Synvisc, sodium hyaluronate.

[0099] The term "antibody" as used herein refers to an immunoglobulin molecule or an antigen-binding portion thereof. Examples of antigen-binding portions of an immunoglobulin molecule include F(ab) and F(ab')2 fragments that retain the ability to bind to an antigen. The antibody can be a polyclonal antibody, a monoclonal antibody, a recombinant antibody, a chimeric antibody, a deimmunized or humanized antibody, a fully human antibody, a non-human (e.g., murine) antibody, or a single chain antibody. In some embodiments, the antibody has effector function and is capable of fixing complement. In some embodiments, the antibody has reduced or no binding ability to Fc receptors. For example, the antibody can be an isotype or subtype, an antibody fragment, or a mutant that does not support binding to Fc receptors, e.g., has a mutation or deletion of the Fc receptor binding region.

[0100] The term "fragment" or "antibody fragment" refers to a polypeptide (e.g., antibody heavy and / or light chain polypeptide) derived from an antibody polypeptide molecule that does not include the full-length antibody polypeptide but includes at least a portion of the full-length antibody polypeptide that is still capable of binding to an antigen. An antibody fragment can include truncated portions of a full-length antibody polypeptide, but the term is not limited to such truncated fragments. Antibody fragments useful in the present disclosure include, for example, Fab fragments, F(ab')2 fragments, scFv (single-chain Fv) fragments, linear antibodies, monospecific or multispecific antibody fragments, such as bispecific, trispecific, and multispecific antibodies (e.g., diabodies, triabodies, tetrabodies), minibodies, chelating recombinant antibodies, tribodies or bibodies, intrabodies, nanobodies, small modular immunopharmaceuticals (SMIPs), binding domain immunoglobulin fusion proteins, camelized antibodies, and VHH-containing antibodies. Additional examples of antigen-binding antibody fragments are known in the art.

[0101] The term "complementarity determining region" or "CDR" refers to short polypeptide sequences in the variable regions of both heavy and light chain polypeptides that are primarily responsible for mediating specific antigen recognition. The term "framework region" refers to amino acid sequences in the variable regions of both heavy and light chain polypeptides that are not CDR sequences and are primarily responsible for maintaining the proper arrangement of the CDR sequences to allow antigen binding. Although the framework region itself typically does not directly participate in antigen binding, as is known in the art, certain residues in the framework region of a particular antibody may be directly involved in antigen binding or may affect the ability of one or more amino acids in the CDR to interact with the antigen.

[0102] Exemplary antibodies are anti-PCSK-9 mAbs (e.g., alirocumab), anti-IL-6 mAbs (e.g., sarilumab), and anti-IL-4 mAbs (e.g., dupilumab).

[0103] The compounds described herein can be used in pharmaceutical preparations that include (a) the compounds or their pharmaceutically acceptable salts, and (b) pharmaceutically acceptable carriers.The compounds can also be used in pharmaceutical preparations that include one or more other active pharmaceutical ingredients, or in pharmaceutical preparations in which the compounds or their pharmaceutically acceptable salts are the only active ingredient.Thus, the pharmaceutical preparations of the present disclosure encompass any preparation made by mixing the compounds described herein with a pharmaceutically acceptable carrier.

[0104] Pharmaceutically acceptable salts of any of the drugs described herein are contemplated for use in the drug delivery device. Pharmaceutically acceptable salts are, for example, acid addition salts and base salts. Acid addition salts are, for example, HCl or HBr salts. Base salts are, for example, salts with a cation selected from an alkali or alkaline earth metal, for example, Na+, or K+, or Ca2+, or an ammonium ion N+(R1)(R2)(R3)(R4), where R1 to R4 are each independently: hydrogen, an optionally substituted C1-C6-alkyl group, an optionally substituted C2-C6-alkenyl group, an optionally substituted C6-C10-aryl group, or an optionally substituted C6-C10-heteroaryl group. Further examples of pharma-ceutically acceptable salts are known to those skilled in the art.

[0105] Pharmaceutically acceptable solvates are, for example, hydrates or alkanolates, such as methanolates or ethanolates.

[0106] A number of implementations of the present disclosure have been described. However, it will be understood that various modifications may be made without departing from the spirit and scope of the disclosure. Accordingly, other implementations are within the scope of the following claims. [Explanation of symbols]

[0107] 100 Drug Systems 102 Drug delivery devices 103 Drug Amount Detection System 104 Drug container housing 106 Drug Reservoir 107 Longitudinal Axis 108 Plunger 108a Plunger rod 108b Plunger head 109 Stopper 109a Stopper surface 110 Injection button 111 Distal end 112 Dosage knob 114 Dosage Window 115 Wall 116 Proximal end of wall section 117 Proximal end of wall section 118 Nosepiece 120 Display window 122 needles 124 Handle 126 Inner needle cap 128 Outer needle cap 130 Cap 132 Power supply 134 Lighting System 136 Optical Detection System 138 processors 140 Antenna 142 Sensors 144 Insert 146 Lens 148 Sealing Components 149 Aperture 150 External Devices 152 Short-distance communication field 154 Interrogator 156 Signal Generator 160 Receiver 200 Sealing System 202 Septum 204 Cavity 206 Distal end 208 Proximal end 212 Sealing System 214 Sealing disk 216 Septum 222 Sealing System 224 Septum 226 Septum Carrier 232 Sealing System 234 Septum 236 Septum Carrier 238 Connector 300 processes 400 Computing Systems 410 Processor 420 Memory 430 Storage Devices 440 Input / Output Devices 450 System Bus

Claims

1. A drug delivery device (102) comprising: a reservoir (106) including a wall defining a proximal end (116, 117) and a distal end (111); a stopper (109) including a light reflective element (109b, 146) configured to move within the reservoir (106) in a direction from the distal end (111) to the proximal end (116, 117) to expel a portion of the medicament contained within the reservoir (106), such that the position of the stopper (109) indicates the amount of medicament within the reservoir (106); an illumination system (134) configured to provide a light signal through a first portion of a wall of the reservoir (106) from a proximal end (116, 117) of the reservoir (106) in a distal direction toward a light reflecting element (109b, 146) of the stopper (109); an optical detection system (136) configured to detect a reflected optical signal provided by reflection of at least a portion of the optical signal from the optical emission system (134) at the optical reflecting element (109) of the stopper (109), the reflected optical signal traveling from the optical reflecting element (109b, 146) of the stopper (109) towards the proximal end (116, 117) of the reservoir (106), passing through a second portion of the wall of the reservoir (106), and passing through an optical collector (136b) including a shape configured to direct the reflected optical signal towards an optical detector (136a) configured to provide an electrical signal in response to detecting the reflected optical signal; a first portion of the wall defining a convex or concave shape and a second portion of the wall defining the other of the convex or concave shape; and The drug delivery device comprising:

2. The drug delivery device (102) of claim 1, wherein at least one of the first portion of the wall and the second portion of the wall faces an inner surface of the stopper (109).

3. The drug delivery device (102) of claim 1 or 2, wherein at least one of the first wall portion and the second wall portion of the proximal end (116, 117) is substantially optically transparent.

4. The drug delivery device (102) of any one of claims 1 to 3, wherein the light emitting system (134) is configured to emit a light signal towards a central portion of the stopper (109).

5. The drug delivery device (102) of any one of claims 1 to 4, wherein the first portion of the wall defines a convex shape and the second portion of the wall defines a concave shape.

6. The drug delivery device (102) of any one of claims 1 to 4, wherein the first portion of the wall defines a concave shape and the second portion of the wall defines a convex shape.

7. The drug delivery device (102) according to any one of claims 1 to 6, wherein the concave and convex shapes are located on the inner flange (115c) or the outer flange (115a) of the wall.

8. The drug delivery device (102) of claim 7, wherein the concave and convex shapes are located on an inner flange (115c) of the wall.

9. The drug delivery device (102) of claim 7, wherein the concave and convex shapes are located on an outer flange (115a) of the wall.

10. The drug delivery device (102) of any one of claims 1 to 9, wherein the light emitting system (134) comprises a light emitting diode and the light detecting system (136) comprises a light dependent resistor configured to emit an electrical signal based on the brightness of the reflected light signal.

11. The drug delivery device (102) of any one of claims 1 to 9, wherein the light emission system (134) includes a laser diode and the light detection system (136) includes a laser receiver sensor configured to emit an electrical signal based on the angle or phase of the reflected light signal.

12. The drug delivery device (102) of any one of claims 1 to 10, wherein the optical detection system (136) comprises a concave lens and the optical reflecting element (146) comprises one of a cylindrical lens and an aspheric lens.

13. The drug delivery device (102) according to any one of claims 1 to 11, wherein the light reflecting element (146) is located within a central portion of the stopper (109).

14. The drug delivery device (102) of any one of claims 1 to 13, comprising a processor (138) configured to process the electrical signal to determine the amount of drug in the reservoir (106) and to determine characteristics of the drug in the reservoir (106).

15. The drug delivery device (102) of any one of claims 1 to 14, wherein the drug reservoir (106) is made from an optically transparent plastic material.

16. 16. The drug delivery device (102) of claim 15, wherein the optically transparent plastic material comprises one of a cyclic olefin copolymer (COC) or a cycloolefin polymer (COP).

17. The drug delivery device (102) of any one of claims 1 to 14, wherein the light emitting system (134) and the light detecting system (136) can be positioned to emit and receive light, respectively, perpendicular to the direction of movement of the stopper (109).

18. The drug reservoir (106) contains a drug according to any one of claims 1 to 17. A delivery system (102).

19. A drug delivery system (100) comprising: A drug delivery device (102) according to any one of claims 1 to 18; and an external device (104), the external device comprising: a receiver (158) configured to receive data from the injection device; and One or more processors (160) configured to process the injection device data and generate result data. The drug delivery system comprising:

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