Droplet delivery device with high dose reliability mode

Abstract

The droplet delivery device includes a high dose confidence mode that monitors a user's inhalation of the composition and activates and deactivates aerosol generation by monitoring the user's inhalation to assist the user in completing a full dose of the composition when the user does not inhale the full dose when using the device.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS

[0001]

[0001] This application claims the benefit of priority to U.S. Provisional Application No. 63 / 437,909, entitled "Droplet Delivery Device with High Dose Confidence Mode," filed January 9, 2023, and incorporated herein by reference in its entirety. [Technical Field]

[0002]

[0002] The present disclosure relates to droplet delivery devices, and more particularly to droplet delivery devices for the delivery of inhaled fluids to the mouth, throat, nose, and / or lungs. The present invention is particularly concerned with the delivery of therapeutic compositions, although in some embodiments, non-therapeutic compositions that can be aerosolized may also be used. [Background technology]

[0003]

[0003] This application incorporates by reference in its entirety the contents of WO2020 / 264501 (describing "ring mode" ejection), PCT / US2022 / 034552 (describing "push mode" ejection), U.S. Patent No. 10,449,314 (describing dose verification), and U.S. Patent Application Publication No. 20190134330 (describing user feedback and instruction manual).

[0004]

[0004] There is a need for a droplet delivery device, such as the device described in Applicant's referenced patent publication, to measure dosage throughout the patient administration / inhalation process to provide a high dose reliability mode of administering the correct dosage to the patient. Specifically, the present invention can determine if the patient has not initially administered the full dose, and the device will calculate the remaining dosage and provide a voice command, visual notification, or similar communication to the patient to inhale again to complete the medication. Summary of the Invention

[0005]

[0006] Droplet delivery devices of the invention, for example for inhaling drugs, pharmaceuticals, biologics, vaccines, and other therapeutic substances, use differential pressure sensors to measure a user's inhalation profile over the course of a dose. In some embodiments, a Sensirion SDP3x™ sensor (available from Sensirion AG, Laubisruetistrasse 50, 8712 Staefa, Switzerland, with US headquarters / affiliate Sensirion Connected Solutions Inc., 11 East Adams Suite 220, Chicago, IL 60603), with a pressure update rate of 0.5 milliseconds and an accuracy of 0.1 Pa, is included in the droplet delivery device to measure a user's inhalation profile in near real time.

[0006]

[0007] In one embodiment, a user initiates their dose by inhaling through the mouthpiece of the droplet delivery device. Upon inhalation, the device begins to activate an ejector member, such as a piezoelectric element / transducer combined with a mesh or plate having openings for generating an aerosol, i.e., a piezoelectric transducer in a "push mode" ejection device and a piezoelectric element in a "ring mode" ejection device (disclosed herein by reference). If the patient stops inhaling through the mouthpiece before completing their metered dose, the device will stop generating aerosol. The device will then wait to deliver the remaining dose until the patient inhales through the mouthpiece.

[0007]

[0008] For example, if a user's dosage requires 1.5 seconds of inhalation and the user stops inhaling midway at 0.75 seconds, the user still needs to take the remaining half of their dosage. The droplet device of the present invention senses that the remaining amount of medication has not yet been administered, stops generating aerosol, and then prompts the user that the user has not yet administered the entire dosage and instructs the user to inhale again through the mouthpiece. When the user begins to spray a second time, the device will begin generating aerosol and continue until the remaining half of the dosage is inhaled. It will be understood that the remaining dosage and the aerosol generation time for the remaining dosage can be any difference between the total dosage and the amount inhaled by the user during the first administration event (e.g., based on time). [Brief explanation of the drawings]

[0008] [Figure 1]

[0009] FIG. 1 illustrates a relationship block diagram of droplet device components and a microcontroller unit (MCU) in one embodiment of the present invention. DETAILED DESCRIPTION OF THE INVENTION

[0009]

[0010] Referring to Figure 1, the MCU 100 reads all switches and sensors and controls all main functions, including piezoelectric waveform generation, dose and user interface (UI) display, voice prompts, chip ID reading, and user compliance archiving. The main MCU 100 activates and holds digital power on when initiated by the power MCU 175. The on / off switch 120 may close when the mouth cap is opened, initiating power delivery and readiness for the device to provide aerosol generation. A battery test 135 may also be operably connected to the MCU 100.

[0010]

[0011] The total inhalation time is determined by the drug application. The droplet device of the present invention is metered to a specific drug dispense rate, and depending on that parameter, the total inhalation time can be determined. A predetermined dose time is then specified in the microcontroller software to provide a high dose reliability mode. The cartridge ID resistor 110 can provide different resistances to identify different liquid supply cartridges, so that the corresponding dosage, including the dispense rate and inhalation time, can be determined for the corresponding drug application.

[0011]

[0012] In some embodiments, drug effectiveness may be calculated through some combination of instantaneous flow rate from the user and the amount of time inhaled. For example, if the user inhales at a sufficient flow rate for the entire dosing time, the drug effectiveness will be 100%. If the user inhales at less than a sufficient flow rate for the entire dosing time, the drug effectiveness will be less than 100%. If the user inhales at a sufficient flow rate for half the dosing time, the drug effectiveness will be 50%. In this case, the device may allow successive administration to deliver the remainder of the user's dosage.

[0012]

[0013] The timing of the start / stop method is a timer programmed in the microcontroller based on pressure changes measured from pressure sensor 105. The droplet delivery device begins activating the piezoelectric element / transducer using piezoelectric driver IC 155 and starts a timer via clock IC 150 when the system recognizes a drop in pressure from the user's inhalation at the mouthpiece and senses it via pressure sensor 105. The device then stops the timer via clock IC 150 and stops activating the piezoelectric element / transducer after the sensed pressure sensor value from sensor 105 falls below an acceptable value. The delay from when the user begins inhaling to when the device activates nebulization can be 0.5 milliseconds or less due to the measurement time in Sensirion™ pressure sensor 105. The delay from when the dosing timer starts to when the piezoelectric is activated is much smaller, on the scale of microseconds.

[0013]

[0014] The pressure sensor 105 can be calibrated, for example, by using a standard 3 L syringe for spirometry as described at https: / / www.a-msystems.com / p-60-fixed-volume-calibration-syringe.aspx (incorporated herein by reference). The start / stop conditions can be triggered by any of the following (which can be useful to ensure drug delivery to specific parts of the lungs):

[0015] (1) Instantaneous pressure threshold—either the user stops inhaling completely or the user is not inhaling with sufficient flow rate; and

[0016] (2) A threshold value for air volume or some other calculated value can be used for the start / stop condition.

[0014]

[0017] In some embodiments, a communication or notification may be provided to the user that there are still remaining doses needed to reach the full dosage. The user may be prompted to inhale again into the device to finish administering the dose, such as by an audio speaker or visual notification in communication with the sound chip 115. Voice switch up 125 and voice switch down 130 inputs allow the user to adjust the volume of audio from the speaker. Visual notifications to communicate user actions and device readiness are provided to the user by an LED indicator 160, such as a tri-color LED, and power status is represented by a battery LED indicator 165. An LCD driver 170 may display a dose counter or similar indicator of the administered and / or remaining dosage to the user.

[0015]

[0018] The piezoelectric element / transducer will then be activated for the remaining amount of medication time (i.e., deliver the amount remaining to reach the full dose based on the calculated time remaining to reach the full dose) upon detecting another pressure drop from the pressure sensor as the user inhales to complete the dose. The microcontroller will deactivate the piezoelectric element after the user has completed inhaling for the remaining duration to reach the full dose.

[0016]

[0019] The trickle charge real-time clock circuit 150 is important for Internet of Things (IoT) applications (with paired mobile / desktop applications, such as via Bluetooth module 140) because it will allow each medication dose to be accurately tracked in real time. This circuit can use a very small amount of power to keep the clock running on the device even while the device is completely powered off.

[0017]

[0020] There are at least two alternatives that can be used to drive the piezoelectric element / transducer. The first alternative is for the piezoelectric element / transducer to be driven by a waveform generated by a boost converter, an H-bridge circuit. The second alternative is an autotransformer and MOSFET circuit 180. Both of these function similarly in that the frequency generated by the microcontroller pulse width modulation or a separate integrated circuit determines the frequency of the waveform applied to the piezoelectric element / transducer. These alternatives differ in the way the high voltage (>30V) is generated. Starting the ejection, or activating the piezoelectric element / transducer, is initiated by the microcontroller in software by either sending a PWM to the MOSFET or an I2C signal to the frequency generator chip. Stopping the ejection, or deactivating the piezoelectric element / transducer, is initiated by either stopping the PWM to the MOSFET or sending another I2C signal to the frequency generator chip.

[0018]

[0021] A Bluetooth module 140 may be provided in embodiments to enable communication with a smart device, such as a smartphone, for tracking dosage administration and / or other data associated with the user and the device via a Bluetooth-enabled application running on the smart device. Data received by the application may be communicated to a network (e.g., via an Internet connection) to process such data, including providing resulting messages and information about the user's treatment, compliance, dosage, and device use to a healthcare provider or patient / personal monitoring service. An accelerometer 145 may also be operably connected to the MCU 100 to provide orientation and tilt information about the device, which may require changes in dosage calculations or may trigger notifications to the user to adjust how the device is positioned to optimize delivery of a medication application.

[0019]

[0022] While piezotronics, including particular types and brands of electronics, have been described in embodiments of the present invention, it will be understood that other elements may be utilized as transducers to provide vibrational functionality to the ejector for aerosol generation. Similarly, while particular data communication protocols (e.g., I2C, SPI, etc.) have been described or illustrated in certain embodiments of the present invention, it will be understood by those skilled in the art that various other data communication protocols may be applied with equal effect.

[0020]

[0023] Although various embodiments of the present invention have been described, it will be apparent that various modifications and changes to those embodiments may be made and additional embodiments may be implemented without departing from the broader scope of the invention as set forth by this disclosure. This specification is to be considered in an illustrative, and not a restrictive, sense.

Claims

1. A droplet delivery device comprising a housing, a reservoir, a piezoelectric transducer, and a pressure sensor (105), the device further comprising a microcontroller (100) configured to determine an inhalation profile based on pressure values ​​measured by the pressure sensor (105), compare the inhalation profile with a stored total dosage inhalation profile, calculate a remaining dosage, and re-activate the piezoelectric transducer only to deliver the remaining dosage.

2. The device described in claim 1, wherein the suction profile is determined from the differential pressure measured by the pressure sensor (105).

3. The device described in claim 1, wherein the inhalation profile is integrated over time to determine the inhalation volume.

4. The device described in claim 1, further comprising a cartridge identifier (110) that encodes total dosage inhalation parameters.

5. The device described in claim 1, wherein cessation of inhalation is detected using a pressure threshold.

6. The device described in claim 1, further comprising an audible or visual notification system (115, 160) to prompt completion of the dosage.

7. The device described in claim 1, wherein the transducer is reactivated only to deliver the remaining dosage.

8. The device described in claim 1, wherein aerosol generation is controlled using a pressure or volume threshold.

9. The device described in claim 1, wherein the effectiveness of the drug is calculated from the inhalation flow rate and inhalation time.

10. The device described in claim 1, wherein the microcontroller (100) controls waveform generation for the piezoelectric transducer.

11. The device described in claim 1, wherein the pressure sensor (105) is calibrated using a fixed volume syringe.

12. The device described in claim 4, wherein the cartridge identifier (110) encodes an administration rate and an inhalation time.

13. The device of claim 1, further comprising a visual indicator (160) that indicates the remaining dosage.

14. The device described in claim 1, wherein the microcontroller (100) adjusts timing and power based on inhalation detected by the pressure sensor (105).

15. The device of claim 1, further comprising a wireless communication module (140).

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