Vaccine dispensing apparatus and methods

Abstract

The dispensing device (100) is used by a user to remove a chamber (110), fill the chamber with an aerosolized vaccine or other medicament (104), and dispose of the used chamber (120). A display (103) provides instructions to encourage the user to inhale promptly from the dispensed and filled chamber. The device allows for the rapid dispensing of vaccines to a large number of people. The aerosol dispensing device detects that the chamber is in the correct position and delivers a pre-set aerosol dose. Once the dose is delivered, visual and / or audible indicators notify the user that the chamber is full and they can inhale. The single-dose aerosol chamber (110) is optimized for efficient aerosol dispensing.

Description

Technical Field

[0001] The present invention relates to administering aerosols to humans, whether therapeutic or non-therapeutic. The invention has particular application in administering aerosols, such as vaccines, where the exact volume is not important but a basic volume that can be reliably administered is sufficient. Background Art

[0002] It is well known to deliver aerosol doses into a chamber housing, such as described in document US 10,589,040. It has an inhaler opening, an internal barrier and a one-way inhalation valve. Document US 4953545 describes a disposable chamber housing for an inhaler.

[0003] The present invention aims to provide a method for administering aerosol doses, such as vaccines, to large numbers of people in a rapid, efficient and cost-effective manner. Summary of the Invention

[0004] We describe an aerosol dispensing device comprising: a controller; a dispenser having a support for a single-dose aerosol housing, the housing having a nebulizer delivery port and an inhalation port; and a nebulizer having an aerosol generator and an outlet conduit adapted to deliver an aerosol dose into the housing via the nebulizer delivery port. Preferably, the dispenser is configured to automatically engage the nebulizer outlet conduit with the nebulizer delivery port and disengage it after a dose has been delivered.

[0005] Preferably, the dispenser includes an automated housing manipulator for automatically engaging the housing with the nebulizer. Preferably, the nebulizer is configured to deliver doses at a preset flow rate according to a preset time. Preferably, the device also includes a housing dispenser for dispensing the housing to a user approaching the nebulizer.

[0006] Preferably, the device further comprises a user interface having a display screen and / or a speaker, and the controller is configured to generate instructions for use of the device and for inhaling from the housing. Preferably, the controller is configured to instruct the user to inhale from the housing within a set time period. Preferably, the controller is configured to provide an instruction to consume the aerosol within 10 seconds. Preferably, the controller is configured to generate, via the interface, an advisory communication regarding a desired number of inhalations and breaths. Preferably, the controller is configured to generate an advisory communication recommending a maximum of two breaths. Preferably, the controller is configured to generate an advisory communication advising the user to perform a short inhalation.

[0007] Preferably, the apparatus further comprises a reservoir for used chamber shells.Preferably, the apparatus is arranged to be used in a series of stages comprising: (a) a stage of dispensing chamber shells, (b) a stage of filling chamber shells, and (c) a stage of disposing of used chamber shells.

[0008] Preferably, the nebulizer is configured to deliver a dose between 0.05 mL and 0.25 mL. Preferably, the nebulizer is configured to deliver at a flow rate exceeding 0.01 mL / min. Preferably, the nebulizer is configured to deliver at a flow rate in the range of 0.5 mL / min to 2.5 mL / min. Preferably, the nebulizer is configured to deliver the aerosol into the cavity housing in less than 15 seconds.

[0009] Preferably, the dispenser comprises an automated housing manipulator for engaging the housing with the nebulizer in an automated manner, and the manipulator comprises a housing support movable from a housing receiving position to an aerosol generator engaging position.

[0010] Preferably, the receiver includes a sensor for detecting a cavity housing present in the receiver, and the controller is configured to trigger a fill cycle upon detection of the cavity housing in the receiver, and preferably the receiver is annular.

[0011] Preferably, the sensor is configured to detect the concentricity of the cavity housing in the receiver. Preferably, the receiver is located on an arm that can be rotated from a front position of the receiving cavity housing facing the user to a rear position for filling. Preferably, the arm supports a cover for the dispensing stage at the end opposite the receiver so that the cover is presented to the user during filling to provide an interlock. Preferably, the cover is curved to present a convex surface towards the front of the dispensing station.

[0012] Optionally, the nebulizer comprises a support member which supports the aerosol generator during movement of the aerosol generator from the non-operating position to the operative position for filling.Preferably, the non-operating position is above the cavity housing in use.

[0013] Preferably, the support is movable on a vertical track to move the aerosol generator between the positions. Preferably, the nebulizer includes a housing sensor for detecting the presence of a housing engaged with the outlet conduit, and the controller is configured to initiate aerosolization only upon detection of the housing. Optionally, the nebulizer includes a pusher for pushing against the housing during disengagement of the outlet conduit to prevent movement of the housing or a cover of the housing.

[0014] Preferably, the nebulizer comprises a vibrating mesh plate, a vibration driver for causing the plate to vibrate, and a reservoir for delivering a therapeutic fluid to a top surface of the plate, such that vibration of the plate causes aerosol to enter the outlet conduit.

[0015] Optionally, the apertures of the orifice plate are sized to provide aerosol droplets, at least 80% of which are less than 6 μm in size, and further optionally, the orifice plate has apertures ranging in size from 0.5 μm to 10 μm, preferably from 0.5 μm to 6.0 μm. Preferably, the orifice plate has more than 100 aerosol-forming apertures per square millimeter. Preferably, the orifice plate has an upper storage layer with a liquid supply channel and a lower layer with aerosol-forming apertures. Preferably, the diameter of the liquid supply channel of the storage layer is in the range of 20 μm to 400 μm.

[0016] Preferably, the nebulizer is configured to automatically detect dose exhaustion on the orifice plate and stop the operation of the nebulizer when there is no liquid on the orifice plate, and provide an alert at the interface accordingly. Optionally, the controller is configured to perform the following steps: measuring the orifice plate drive current at each of a plurality of measurement points in a scan, each measurement point having a drive frequency; determining a minimum value of the drive current in the scan; determining a maximum rate of change value for the drive current during the scan; and using the minimum value in combination with the maximum rate of change value to perform an algorithm to calculate an indicator value for dose exhaustion. Optionally, the controller is configured to provide the indicator using a ratio of a maximum slope value to a minimum parameter value, and preferably, the controller is configured to multiply the ratio or a value derived from the ratio by a constant value to provide the indicator. Preferably, the controller is configured to perform the scan in a frequency range of 128kHz to 165kHz, and optionally the controller initiates the scan in response to a trigger to possible dose exhaustion.

[0017] Preferably, the nebulizer is configured to supply only a single dose to the aerosol generator for each dispensing operation to fill the cavity housing.

[0018] We also describe a method of using the device of any example described herein to provide an aerosol for treating multiple patients, the method comprising automatically delivering an aerosol dose to each of a series of single-dose housings and automatically providing instructions to the user for inhalation via an interface.

[0019] Preferably, the controller provides an indication for inhalation within a recommended time period. Preferably, the method includes automatically engaging an outlet conduit of the nebulizer with a nebulizer delivery port of the chamber housing, and separating the conduit from the chamber housing after delivery of a dose. In some examples, the nebulizer delivers an aerosolized vaccine into the chamber housing.

[0020] Preferably, the dispenser comprises an automated chamber housing manipulator and the manipulator performs the movement of each chamber housing and the engagement of the chamber housing with the outlet conduit of the aerosol generator in an automated manner.Preferably, the nebulizer provides doses at a preset flow rate and for a preset time.

[0021] Optionally, the method further comprises a chamber housing dispenser to dispense chamber housings to a user proximate to the nebulizer.

[0022] Preferably, the device further comprises a user interface having a display screen and / or a speaker, and the controller generates user instructions for using the device and for inhaling from the housing via the interface. Preferably, the controller provides information to counsel and / or remind the user, including a desired number of inhalations and breaths, for example, an advisory communication suggesting a maximum of two breaths. Preferably, the controller generates the advisory communication to advise the user to perform a short inhalation.

[0023] Optionally, the method further comprises a receptacle for receiving the used chamber shell. Preferably, the device delivers a dose between 0.05 mL and 0.25 mL. Preferably, the nebulizer performs delivery in less than 15 seconds. Preferably, the nebulizer aerosolizes at a flow rate in the range of 0.5 mL / min to 2.5 mL / min, more preferably 0.75 mL / min to 1.5 mL / min.

[0024] Preferably, the dispenser includes an automated housing manipulator for engaging the housing with the nebulizer in an automated manner, and the manipulator includes a housing support that moves from a housing receiving position to an aerosol generator engaging position.

[0025] Preferably, the receiver includes a sensor for detecting the presence of a cavity shell in the receiver, and the controller triggers the filling cycle upon detection of the cavity shell in the receiver. Preferably, the sensor detects the concentricity of the cavity shell in the receiver. Optionally, the receiver is located on an arm that is rotatable from a forward position for receiving the cavity shell to a rearward position for filling. Preferably, the arm supports a dispensing stage cover at an end opposite the receiver, the cover being presented to the user during filling to serve as an interlock, while the cavity shell receiver is presented to the user for placement of the cavity shell.

[0026] Preferably, the atomizer is moved from a non-operating position to an operating position for filling, and the non-operating position is above the chamber housing in use. Preferably, the viscosity of the atomized liquid is in the range of 1 to 15 cP, and the surface tension of the atomized liquid is in the range of 0.5 mN / m to 72 mN / m.

[0027] Preferably, the nebulizer includes a housing sensor for detecting the presence of the housing engaged with the outlet conduit, and the controller initiates aerosolization only when the housing is detected. Optionally, the nebulizer includes a pusher that pushes against the housing during disengagement of the outlet conduit to prevent the housing or a cover of the housing from moving.

[0028] Preferably, the nebulizer includes a vibrating mesh plate, a vibration driver for causing the mesh plate to vibrate, and a reservoir for delivering a therapeutic fluid to a top surface of the mesh plate, such that vibration of the mesh plate causes aerosol to enter the outlet conduit, and the mesh plate provides aerosol droplets, at least 80% of the aerosol droplets having a size of less than 6 μm.

[0029] Preferably, the nebulizer automatically detects when the dose on the orifice plate is depleted and stops operation of the aerosol generator when there is no liquid on the orifice plate, and accordingly provides an alert on the interface. Preferably, the controller performs the following steps: measuring the orifice plate drive current at each of a plurality of measurement points in a scan, each measurement point having a drive frequency; determining a minimum value of the drive current in the scan; determining a maximum rate of change value of the drive current during the scan; and performing an algorithm using the minimum value in combination with the maximum rate of change value to calculate an indicator value for dose depletion. Preferably, the controller provides the indicator using a ratio of a maximum slope value to a minimum parameter value.

[0030] Preferably, the time from dispensing from the cavity housing to inhalation is less than 60 seconds. Preferably, the time for delivering the aerosol to the cavity housing is less than 15 seconds. Preferably, after completing the delivery of the aerosol, the controller provides a user suggestion that the time for inhalation should be less than 10 seconds.

[0031] Preferably, the nebulizer provides only a single dose to the aerosol generator for each housing filling operation.

[0032] We also describe a single-dose aerosol housing for dispensing a single dose of aerosol from a nebulizer, the housing comprising: a container; a nebulizer delivery port configured to engage a nebulizer outlet conduit; and an inhalation port for a user to inhale the contents of the container, the container being configured to receive the aerosol via the nebulizer delivery port and mix the aerosol with gas in the container for delivery via the inhalation port.

[0033] The top wall may be in the form of a removable cover.

[0034] Preferably, the container comprises a base, a top wall, and a side wall extending between the base and the top. Preferably, the atomizer delivery port is located in the top wall. Preferably, the inhalation port is located in the top wall. Preferably, the inhalation port is located in a raised portion of the top wall.

[0035] Preferably, the inhalation port is elongated, preferably with its major axis in the circumferential direction.Preferably, the nebulizer delivery port is off-center relative to the axis of the container, adjacent to the side wall.

[0036] Preferably, the nebulizer delivery port is located in the top wall and adjacent to the side wall. Preferably, the inhalation port is adjacent to the side wall on the side opposite the nebulizer delivery port. Preferably, the container is made of an insulating material, which may optionally be a polymer and / or a wood-derived material.

[0037] Preferably, the container volume is in the range of 100 mL to 600 mL, and for many applications preferably the housing volume is in the range of 150 mL to 400 mL.

[0038] Preferably, the side walls are tapered so that the container narrows downwardly towards the base. Preferably, the area of ​​the atomizer delivery port is 30 mm 2 Up to 700mm 2 For some applications, such as delivery to the lungs in an efficient manner, the area of ​​the nebulizer delivery port is preferably within the range of 30 mm. 2 Up to 120mm 2 within the range.

[0039] Optionally, the container includes an observation window for viewing the contents. Optionally, the container includes a hydrophobic material on the inner surface. Optionally, there are one or more holes in the base of the container. Optionally, there is an antimicrobial coating on the outer surface of the cavity shell. Optionally, the cavity shell includes a valve to prevent the aerosol from escaping from the container after dispensing. Optionally, the container includes multiple vents to limit pressure buildup during dispensing. Optionally, the inhalation port includes a nasal interface. Optionally, the inhalation port includes a mask. Optionally, the inhalation port includes a mouthpiece. Optionally, the cavity shell includes a baffle for selective rain-out of the aerosol, thereby performing droplet size filtering. Optionally, the baffle is tubular and extends inward from the nebulizer delivery port.

[0040] We also describe any example single-dose aerosol housing for delivering an aerosol to a user in a manner such that the aerosol is delivered into a container through a nebulizer delivery port and the user inhales the aerosol through an inhalation port.

[0041] Optionally, the time period between delivery of the aerosol through the nebulizer connection port and inhalation is less than 60 seconds. Optionally, the time period for aerosol delivery through the nebulizer delivery port is less than 15 seconds. Optionally, the time period for aerosol inhalation through the inhalation port is less than 10 seconds. Optionally, the volume of the dose is in the range of 0.5 mL to 0.25 mL.

[0042] In some examples, the aerosol is a vaccine, such as a Covid-19 vaccine.

[0043] Supplementary Statement

[0044] We describe an aerosol housing for single-dose dispensing of an aerosol dose, the housing being disposable and comprising a container, an aerosol inlet configured to engage with a nebulizer outlet conduit, and an inhalation port for a user to inhale the contents of the container.

[0045] Preferably, the aerosol inlet is located in the top wall of the cavity housing. Preferably, the inhalation port is located in the top wall of the cavity housing. Preferably, the inhalation port is located in the raised portion of the cavity housing. Preferably, the inhalation port is elongated, preferably having a major axis in the circumferential direction. Preferably, the aerosol inlet is adjacent to the wall of the cavity housing. Preferably, the aerosol inlet is located in the top wall of the cavity housing and adjacent to the side wall of the cavity housing. Preferably, the inhalation port is adjacent to the side wall of the cavity housing on the side opposite to the aerosol inlet.

[0046] Preferably, the container is made of an insulating material, such as a polymer or paper-based material. Preferably, the cavity shell includes an observation window for viewing the contents. Preferably, the cavity shell includes a hydrophobic material on the inner surface. Preferably, the cavity shell is similar in overall structure to a drinking cup.

[0047] In some examples, there are one or more holes in the base of the cavity housing. In some examples, there is an antimicrobial coating on the outer surface of the cavity housing.

[0048] We also describe an aerosol dispensing device comprising: a dispensing station having a support for a housing; and a nebulizer adapted to deliver an aerosol dose into the housing via an aerosol inlet. In some examples, the nebulizer is positioned on an automated support for automated engagement of the nebulizer outlet conduit with the housing aerosol inlet and separation after delivery of a dose. In some examples, an automated housing manipulator is provided for automated engagement of the housing with the nebulizer.

[0049] In some examples, the nebulizer is configured to provide a dose at a preset flow rate according to a preset time. In some examples, the device further comprises a chamber shell dispenser for dispensing chamber shells to a user proximate to the nebulizer.

[0050] In some examples, the device further comprises a user interface having a display screen and a speaker, and a controller generates user instructions for use of the device and for inhalation from the cavity housing. In some examples, the user interface is configured to instruct the user to inhale from the cavity housing within a set time period. Preferably, the device further comprises a storage container for storing used cavity housings.

[0051] In some examples, the device is arranged to be used in a series of stages including: (a) a stage of dispensing the chamber shell, (b) a stage of filling the chamber shell, and (c) a stage of disposing of the used chamber shell. In some examples, the device is configured to deliver a dose between 0.05 mL and 0.25 mL. In some examples, the nebulizer is configured to deliver in less than 15 seconds.

[0052] In some examples, the device has a user interface that is configured to suggest a maximum number of breaths and / or inhalations, for example, it may prescribe a maximum of 2 breaths and / or may also suggest shorter inhalations.

[0053] We also describe a method of treating multiple patients using the device of any example, the method comprising automatically delivering doses into a series of chambers and providing a user with instructions to remove a chamber and inhale from the chamber within a recommended time period. In some examples, a nebulizer delivers aerosolized vaccine into the chambers. BRIEF DESCRIPTION OF THE DRAWINGS

[0054] The present invention will be more clearly understood from the following description of some embodiments thereof, which are given by way of example only with reference to the accompanying drawings, in which:

[0055] Figure 1 Schematically illustrates a vaccine station and method of use thereof for dispensing vaccines to persons in a rapid manner with minimal requirements for trained staff;

[0056] Figure 2 Is shown by Figure 1 A perspective view of a vaccine station delivering aerosol from a nebulizer into a disposable cavity housing;

[0057] Figure 3 is a cross-sectional view showing a chamber housing and an atomizer coupled to the chamber housing;

[0058] Figure 4 It is a side view of the chamber housing and atomizer;

[0059] Figure 5(a) to Figure 5(g) A series of annotated images are included to illustrate the benefits of the mutual positioning of the aerosol filling opening and the inhalation port of the chamber housing;

[0060] Figures 6 to 9 is a view of another dispensing device, which is smaller for mounting on a table or the like, wherein Figure 6 is a perspective view showing the front of the equipment in interlock operation, Figure 7 is a perspective view showing the front portion when the cavity case is presented for a user to take, and Figure 8 and Figure 9are perspective and bottom views showing the rear of the device with the rear cover removed;

[0061] Figure 10 is a perspective view of an interlocking automated cavity shell manipulator of a dispensing apparatus, and Figure 11 It is an exploded view;

[0062] Figure 12 An exploded view of an automated atomizer working in conjunction with a chamber shell manipulator;

[0063] Figure 13 and Figure 14 is a side view showing the automated nebulizer in use; and

[0064] Figure 15 is a set of images showing different configurations of filled cavity shells used for testing purposes. DETAILED DESCRIPTION

[0065] A dispensing device or dispensing "station" 100 is used by a user to take a single-dose device (or "aerosol chamber") 110, fill the chamber with an aerosolized medicament (such as a vaccine), and dispose (120) of the used chamber 110. A display 103 provides instructions to encourage the user to inhale promptly from the dispensed and filled chamber. The dispensing station can very quickly dispense vaccines or other aerosolized medicaments to a large number of people. The aerosol dispensing device 100 detects whether the chamber is in the correct position and delivers a pre-set aerosol dose. Once the dose is delivered, visual and / or audible indicators notify the user that the chamber has been filled and they can inhale.

[0066] In more detail, refer to Figure 1 The device 100 comprises a housing 101, which is provided with a first stage 1 for dispensing a disposable, single-use / single-dose device, namely an aerosol chamber 110. The second stage comprises an indicator display 103 linked to a processor and memory, and a vaccine dispenser 104 for delivering a dose of aerosolized vaccine into the chamber 110. The third stage comprises a disposal container 120 for safely disposing of used chambers 110. As shown by arrow 10, the typical timeline for these three stages is only about 60 seconds.

[0067] The device 1 has a main controller with a digital data processor for controlling the overall operation of the device, including generating user instructions at the interface 103, and also high-level control instructions for the atomizer / dispenser 104. The atomizer 104 has a dedicated controller that controls low-level operations of the atomizer 104, such as controlling the piezoelectric actuator at a desired frequency (typically 128 kHz) and voltage and duration.

[0068] The dispensing stage includes a platform on which the chamber housing 110 rests during filling.

[0069] Aerosol generator

[0070] Reference Figures 2 to 4 The chamber 110 is filled in the dispenser 104 by an atomizer 200, which may be of the type described in our application WO2012046220, the contents of which are incorporated herein by reference. This atomizer comprises a vibrating orifice plate mounted to a gasket on which there is a piezoelectric actuator vibrating at a frequency of approximately 128 kHz. This atomizer may be of the type sold under the name Solo™ by the company Aerogen™. Figure 4 Most clearly shown, the aerosol is delivered through the outlet conduit and nebulizer delivery port 114 .

[0071] The liquid to be aerosolized is received at the first upper surface of the vibrating mesh plate, and the piezoelectric actuator is activated. Aerosolized liquid is produced at the lower surface of the orifice plate by ejecting droplets of liquid upon activation. The size of the holes in the orifice plate is designed to aerosolize the liquid so that the majority of the droplets are less than 6 μm in size. The geometry of the orifice plate is dome-shaped. Electrical energy is supplied to the piezoelectric actuator via conductive needles. A supporting washer extends through the center hole of the orifice plate to support the orifice plate and the piezoelectric actuator, and the supporting washer engages the upper and lower elastomeric seals to provide uniform support, thereby helping to achieve stable operation of the aerosol generator, reduce the risk of fatigue, and produce a predictable orifice plate vibration response to the applied electrical drive.

[0072] Dose depletion detection

[0073] During each dispensing operation, the pump delivers liquid to the nebulizer's reservoir, with only enough liquid for one dose. The reliability of the nebulizer 200 is aided by a controller having an automatic dose-end detector, thereby preventing the nebulizer from running dry. In one example, this is achieved by the operating method described in our published PCT document No. WO2017 / 055166, the contents of which are incorporated herein by reference. The method comprises the following steps performed by the controller's aerosol generator:

[0074] measuring an aperture plate drive current at each of a plurality of measurement points in a scan, each measurement point having a drive frequency;

[0075] determining a minimum value of the driving current in the scan;

[0076] determining a maximum rate of change of the drive current during a scan; and

[0077] An algorithm is executed using the minimum value in combination with the maximum rate of change value to calculate an indicator value for dose depletion.

[0078] In one example, the controller provides the indicator using a ratio of a maximum slope value to a minimum parameter value. Preferably, in one example, the controller multiplies the ratio, or a value derived from the ratio, by a constant value to provide the indicator. In one embodiment, the controller performs a scan over a frequency range of 128 kHz to 165 kHz. Preferably, the controller initiates the scan in response to a trigger indicating possible dose depletion.

[0079] In one example, the trigger is a short scan with a small number of measurement points, and it detects a change in the drive current above a threshold. In one embodiment, the drive current threshold change is higher than 5mA, and preferably about 8mA. In one example, such a minimum value of the drive current is determined to indicate dose exhaustion, and the minimum value of the drive current is about 30% smaller than the minimum value of the drive current for scanning the wet state of the orifice plate. For example, this may result in a trigger from a short scan to possible dose exhaustion, and it may be the only triggering event. In a preferred example, the steps of the method include the controller automatically stopping the operation of the actuator when dose exhaustion is detected.

[0080] Storage layer plate

[0081] In a different example, a nebulizer orifice plate having an upper reservoir with a liquid supply channel and a lower layer with aerosol-forming holes is manufactured using the photo-definition manufacturing process described in our published PCT document No. WO2013 / 186031, the contents of which are incorporated herein by reference. For example, there can be more than 2,500 aerosol-forming holes per square millimeter.

[0082] The diameter of the liquid supply channel is selected so that a predetermined number of droplet size formation holes are exposed. This determines the number of active orifices, thereby limiting the amount of liquid aerosolized per unit time. The size and number of orifices in the two layers are selected to achieve the desired range of droplet size and flow rate distribution.

[0083] Below is a table showing examples of different configurations for an orifice plate (AP) with a diameter of 5 mm:

[0084] Liquid supply channel diameter (mm) 0.10 0.08 0.06 0.04 Number of cavities 815 1085 1464 2179 For each channel, the number of holes 12 7 4 1 For each AP, the number of holes 9780 7595 5856 2179

[0085] This "reservoir layer" arrangement of the covered liquid supply channel makes it possible to more stably achieve smaller and more controllable particle / droplet sizes in the range of 2 μm to 4 μm. It can also more stably achieve higher flow rates, for example, in the range of 0.5 ml / min to 2.5 ml / min, more typically in the range of 0.75 ml / min to 1.5 ml / min.

[0086] As described in document WO 2016 / 198667, the storage layer is particularly suitable for the aerosolization of liquids with certain surface tension and viscosity, and the content of this application is incorporated herein by reference. In particular, the liquid to be aerosolized preferably has a viscosity in the range of 1 to 15 cP and a surface tension in the range of 0.5 mN / m to 72 mN / m, and preferably an output rate of at least 0.01 ml / min. As described above, the flow rate is more particularly preferably in the range of, for example, 0.5 ml / min to 2.5 ml / min, more preferably in the range of 0.75 ml / min to 1.5 ml / min. The orifice plate can have 60,000 aerosol-forming holes in the region, and these holes are preferably provided by the liquid supply cavity in the storage layer.

[0087] Single-dose aerosol chamber shell

[0088] The aerosol chamber housing 110 is a single-use / dosage device for delivering a single-dose aerosol. Under normal circumstances, the user does not need to examine it carefully, and the overall appearance of the aerosol chamber housing is like a disposable beverage cup. This helps its use because it is intuitive for the user to consume the aerosol in a manner similar to drinking a beverage in terms of how to manipulate the aerosol chamber housing. The chamber housing 110 has a container consisting of a generally tubular sidewall 111 and a cover 112, the sidewalls of which are narrowed by tapering inward toward the base 117. The cover 112 includes a center wall 113, and a circular opening 114 in the center wall substantially matches the outer diameter of the outlet of the atomizer 200. This is the atomizer connection port or delivery port, also referred to herein as the aerosol inlet. There is an inhalation port 115 in a raised edge 116 near the side diametrically opposite to the atomizer delivery port 114.

[0089] Nebulizer delivery port for single-dose aerosol chamber housing

[0090] In this case, the nebulizer delivery port has a diameter of 24 mm, which matches the outlet conduit of the aerosol generator, which has an inner diameter of 22 mm according to ISO 5356. This gives a diameter of approximately 450 mm. 2 Generally speaking, the diameter of the nebulizer delivery port is preferably in the range of about 6 mm to 30 mm, with a diameter of 30 mm being preferred. 2 Up to 700mm 2However, if efficient aerosol delivery to the lungs is important (which is not necessarily important for vaccines), we have found that a smaller nebulizer port is advantageous, preferably with an area at the lower end of the above range, preferably 30 mm. 2 Up to 120mm 2 The nebulizer delivery port has two functions, namely (a) delivering the aerosol to the delivery device and (b) acting as a vent during inhalation. If the area of ​​the nebulizer delivery port is at the lower limit of the above range, the air flowing into the cavity shell during inhalation will be reduced, thereby being more efficiently transmitted downward into the bronchi and bronchioles through the mouth or nose. For such a nebulizer delivery port, the nebulizer can have a conduit whose diameter is narrowed from the standard 22mm to a relevant size. In addition, for this use, it is preferred that there are no other openings besides the inhalation port and the nebulizer delivery port, and therefore the only ventilation opening during inhalation is the nebulizer delivery port.

[0091] Additional Features of Single-Dose Cavity Housings

[0092] The aerosol outlet delivery / inhalation port 115 is located in a raised edge 116, similar to the drinking hole of a beverage cup. The volume of the cavity shell 110 is preferably in the range of 100mL to 600mL, more preferably in the range of 150mL to 400mL. This volume is sufficient for a single dose of disposable inhalation via the inhalation port 115. The material of the cavity shell is paper-based or plastic (preferably recyclable). The material preferably has good thermal insulation properties to reduce the rain-out effect on the inner surface. The container 111 has a curved wall that tapers to narrow downwards toward the flat base.

[0093] Advantageously, the atomizer delivery port 114 and the inhalation port 115 are each offset from the center, adjacent to the walls of the container 111 on opposite sides of the container, and preferably substantially coplanar. This results in efficient aerosol flow into the container 111 during the second phase, and subsequently out during inhalation, as described in more detail below. Advantageously, the inhalation port 115 has a substantially circumferentially extending curved elongated shape, as this makes it easier for the user to inhale in a manner similar to drinking from a disposable cup.

[0094] The nebulizer 200 of the dispensing stage 104 is calibrated to have a certain flow rate so as to deliver the desired dose within a specific time that its outlet is engaged with the nebulizer delivery port 114. A single dose of liquid is delivered to the nebulizer's reservoir and aerosolized until exhaustion is sensed. The nebulizer controller can be stopped and started based on the presence of the chamber housing 110 that is engaged with the nebulizer 200 outlet. In either example, the user perceives the workstation 100 as operating like a beverage dispenser, selecting or automatically delivering a "cup," filling and removing a filled "cup," aspirating the contents of the "cup," and disposing of the empty "cup."

[0095] There is no need to close the atomizer delivery port with a valve, as the chamber is typically held upright and the contents are drawn in within a minute. The analogy with a hot drinks machine helps as users naturally tend to hold the chamber upright, just as they would a cup.

[0096] In one example, the cavity housing is fully or partially transparent, for example with a window similar to an envelope, to allow observation of the aerosol to ensure the presence of the aerosol and that the aerosol has been fully inhaled.

[0097] In one embodiment, the valve of the chamber housing inlet is provided.Although there is not the valve for the chamber housing inlet in the present example, there can be a valve in other examples.If this is the case, the valve may be very simple, only the flap of the capping material, and the flap is elastically hinged to close the opening after the atomizer is disengaged.This arrangement utilizes the live spring characteristic of the capping material, to deflect and close the opening before inhalation, and slightly opens to assist circulation during inhalation.If the flap is hinged on a side closer to the edge, so during inhalation, flowing will be directed towards the center of the container, or if the flap is hinged on a side further away from the wall, so during inhalation, flowing will likely be directed towards the wall.The hinged position can be selected according to the dynamics of the preferred ventilation assistance flow during inhalation.

[0098] Characteristics and properties of allocation methods

[0099] It will be appreciated that the present invention can dispense aerosols, such as vaccines, to very large numbers of people in a short period of time. The fact that the dosage is not very precise is not a problem, as only a minimum volume is required for applications such as vaccination.

[0100] The size of the cavity shell is optimized according to the required dose and minimizes the time between the start of "filling" of the aerosol and the patient's inhalation to reduce the loss of aerosol due to precipitation and collision of the "raining out effect".

[0101] In other examples, the cavity shell is constructed from a single piece of material that is folded to provide the cover. Drinking cups of this construction are known, and indeed, the present invention is advantageous in that it can utilize the advantages of advancements in drink cups in terms of ease of safe recycling and insulation, as well as advancements in stacking and transport, to minimize the footprint associated with the use of the drink cup.

[0102] Preferably, the droplet size is small, preferably at least 80% of the droplets are less than 6 μm. This can be achieved using a vibrating orifice plate, which is characterized by manufacturing the aerosol-forming orifice using a light-defined process, such as described in document WO 2013 / 186031 (EP 2859137B). In this case, there is a storage layer with cavities, each of which is above a certain number of aerosol-forming holes. The diameter of the cavity can be in the range of 20 μm to 400 μm, while the diameter of the aerosol-forming hole can be in the range of 0.5 μm to 10 μm, preferably in the range of 0.5 μm to 6.0 μm. Such an arrangement helps to achieve a small droplet size, thereby helping to optimize delivery into the lungs and minimize the rain-out effect on the inner surface of the cavity shell.

[0103] However, depending on the nature of the formulation being administered, it may be desirable to deliver larger droplets so as to enter the user's upper respiratory tract or possibly the nasal cavity.Such larger droplets may have a size distribution in the range of 6μm to 10μm, or larger than 10μm.

[0104] like Figure 1 As shown, there is a simple three-step procedure to vaccinate a person. The first step can be replaced by the user's instruction to the workstation, which causes the automatic placement and filling of the cavity shell without user intervention.

[0105] Reference Figure 5(a) to Figure 5(g) It is obvious that there are great benefits in having the nebulizer delivery port and the suction port adjacent to both sides of the chamber shell, because it benefits from the Coanda effect ( effect). In these images, lighter shades indicate greater concentrations of aerosol.

[0106] FIG5( a ) shows that positioning the orifice near the wall can promote the Coanda effect, with arrows 200 indicating the general flow pattern, i.e., downward and upward toward outlet 115. Positioning the mouth opening near the wall promotes the Coanda effect and encourages air to flow deeper into the cup. FIG5( b ) shows the flow as indicated by arrows 250, with velocities as high as 1.2 m / s in the local volume near the sidewall. FIG5( c ) shows the early stages of filling as aerosol 300 enters through delivery port 114, with pressures as high as approximately 0.2 Pa. FIG5( d ) shows the downward progression of aerosol 350, FIG5( e ) shows further downward flow 400, FIG5( f ) shows further downward flow 500, filling a larger volume downward toward the bottom of the housing, and FIG5( g ) shows flow 600 reaching the bottom of housing 111.

[0107] like Figure 5(b) to Figure 5(g) As shown, a low pressure imbalance is created near the wall, which tends to drag the aerosol flow toward the wall. These images show the progress of filling the aerosol. This benefit is achieved by having the filling opening adjacent to the container 111 wall. It is also advantageous that the inhalation port 115 is adjacent to the opposite side of the chamber housing.

[0108] It will be appreciated that the present invention achieves low-speed aerosol dispensing, minimizes aerosol collisions within the container, and maximizes the aerosol's residence time within the container. By using a photo-defined aperture plate ("PDAP") with a storage layer in the nebulizer, a lower volume median diameter (VMD) can be consistently maintained at a higher plume density and higher flow rate, minimizing potential settling time within the container. This means delivering more aerosol in a shorter period of time and maximizing the aerosol's residence time at a lower VMD. The shape and size of the inhalation port are elongated in the circumferential direction and resemble the drinking port of a disposable beverage cup, making it more convenient for the user to inhale.

[0109] There may be a hydrophobic coating on at least some of the interior surfaces of the cavity housing to reduce adhesion of the aerosol to the walls and closure of the container, to reduce impingement on surfaces and to increase the aerosol available to the receptor.

[0110] It is envisioned that the chamber housing can only have a single port, for nebulizer delivery and suction, thereby minimizing the risk of cross contamination. However, preferably there are two ports, because this will contribute to the outflow during suction and can optimize size. Transparent material or window can be arranged in the chamber housing, to allow visibility. The dispensing mechanism preferably has a proximity sensor to detect the existence of the chamber housing, to allow automation and fixed dose delivery. The electronic drive control of the nebulizer can realize the desired aerosol flow rate preferably for the chamber housing of many applications, and this chamber housing has the volume of about 300mL+ / -50mL. The nebulizer is preferably configured to deliver in less than 15 seconds, and the inhalation time is preferably less than 10 seconds after the dosage is completed aerosolization.

[0111] The method and apparatus can be used in large-scale vaccination programs where small unit volumes of vaccine need to be delivered at an economical price. It is particularly suitable for use with small volume doses of approximately 0.1 mL (between 0.05 mL and 0.25 mL) because aerosol losses between filling and dispensing will be reduced.

[0112] Paper could be used as the primary material for the cavity housing, but the clear plastic cup has the advantage of providing visual confirmation that the aerosol dose has been taken. The present invention utilizes extremely low cost and available manufacturing resources to manufacture very high volume components, such as cavity housings.

[0113] In testing, the following inhalation doses were achieved in adult subjects (a mix of 12 adults, 7 males and 5 females, 3 doses each, a maximum 5-second delay from dose exhaustion to inhalation, 0.1 mL dose, and a maximum 2-second inhalation time). The overall mean inhalation dose was 34.39% ± 1.50% (36 doses total).

[0114]

[0115]

[0116] Smaller droplet sizes are preferred for aerosols. Smaller droplets offer advantages in terms of: Inhaled dose

[0117] Sensitivity to delayed inhalation

[0118]

[0119]

[0120] In some cases, where convenient for formulation purposes, a range of dose volumes may be used, with smaller dose volumes providing the largest inhaled dose.

[0121] Dose volume (mL) Delay (seconds) Inhaled dose (%) AVG STDEV 0.1 1 26.86 1.31 0.1 5 21.45 1.16 0.1 10 20.10 0.44 0.2 1 17.39 0.53 0.2 5 14.40 0.36 0.2 10 11.69 0.44 0.05 1 32.46 1.74 0.05 5 26.48 1.34 0.05 10 21.64 0.89

[0122] In some examples, the user can take multiple smaller doses with breaths in between (e.g., 0.05 mL, breath, 0.05 mL, breath, giving a total of 0.1 mL dose (39.08% maximum) in 2 breaths. In other examples, for increasing doses, a 0.2 mL dose (41.32% maximum) is given in 4 breaths. Advantageously, the controller can be programmed to provide relevant user instructions, of course, regarding the delivery point. Further examples are provided in the table below.

[0123]

[0124] The present invention is also applicable to pediatric patients. For example, evaluating a tidal volume of 155 mL, we noted a maximum of 10.91%, however, the percentage inhaled can be increased using other dosing strategies outlined herein (eg, droplet size, mouthpiece design, etc.).

[0125] It is conceivable that a one-way valve is provided in the container base (opposite to the mouthpiece) to allow air to flow into the chamber housing for better cleaning. One or more holes may be provided in the base to allow air to enter for better cleaning. The controller may be configured to provide a suggestion of the maximum number of breaths / inhalations via indicator screen 103, for example, the controller may specify a maximum of 2 breaths. The controller may also suggest a short inhalation. The atomizer may have a driver configured to output an abnormally high flow rate, such as by high voltage (faster flow rate) or pulse control (softer plume, lower density aerosol).

[0126] The inner surface of the cavity shell can have a hydrophobic coating or texture to repel suspended aerosol droplets. An antimicrobial coating can be provided on the outside of the cavity shell to prevent cross contamination during manipulation. The cavity shell or device can have the feature of reducing the aerosol being discharged after atomization. For example, a filter or cover can be attached to the aerosol generator port so that it can be closed after the cavity shell is taken out (reason: reducing emissions that may become safety or regulatory issues). For example, it can be installed as a flap that is pushed open by an actuator and a spring during filling and enters a closed position when removed from the aerosol outlet. There may be additional openings in the cavity shell to ensure that the pressure in the cavity shell does not increase to more than the desired level during filling. The mouthpiece 115 performs this function, but one or more small additional vents can also play an assisting role. The existence of this vent is for the purpose of delivering the expected pressure. The mouthpiece can be oval, circular, or elongated to help improve the efficiency of aerosol delivery. The cap can have a protruding, recessed, or flat mouthpiece for delivering aerosol.

[0127] Atomizer can be any type, is suitable for being less than one minute time period, dosage is carried out aerosolization.Preferred atomizer is the type with vibrating net, such as Aerogen Solo™ atomizer, and particularly because this atomizer can provide very fine aerosol, the size of aerosol is consistent and in the scope of 1 μ m to 6 μ m.Yet, according to the surface tension and the viscosity of the liquid that is atomized, aerosol generator also can be the venturi of surface acoustic wave, pressurized metered dose inhaler, actuated dry powder inhaler, compressed air drive or the electro-hydraulic atomization type alternatively.

[0128] The dispensing device can be linked to a remote nebulizer via a conduit, or the dispensing device can have a nebulizer locally, but the nebulizer is connected to an aerosol outlet via a conduit. Alternatively, the dispensing device can be part of a group of devices to which a central controller provides advanced control, e.g., each device being in a compartment.

[0129] The material of the cavity shell is preferably thermally insulating to prevent condensation, and is also preferably inexpensive and recyclable. An example of such a material suitable for high-speed laser processing is polystyrene. The cavity shell can have an outlet suitable for inhalation through the nose. This may include soft and molded materials that conform to or surround the characteristics of an adult, child, or infant nose, as vaccines may also be targeted to the nasal cavity, nasal passages, and lungs to elicit an immune response and / or deliver therapeutic agents such as steroids (budesonide), interferon (antiviral), or flumist (vaccine).

[0130] The mask can be attached to the chamber housing, as it allows for both nasal and pulmonary delivery, particularly for children. The chamber housing can have multiple ports for inhalation, such as two orifices for nasal inhalation. For the reasons mentioned above, the aerosol port is preferably located near the edge to encourage flow down the container wall. However, it is contemplated that the aerosol port could be located closer to the center to facilitate automation.

[0131] The dispensing device may be adapted to deliver a variety of formulations including, but not limited to, vaccines, antivirals, antibodies, bronchodilators, mucosal rhythm regulators, psychotomimetic drugs, or restorative inhalants.

[0132] Tabletop dispensing equipment

[0133] The dispensing device may take the form of a smaller configuration, such as for placement on a desk or table. Figures 6 to 14An example of such an apparatus 500 is shown. Apparatus 500 comprises a housing 501 with a handle 520 and a top light 510 that can be controlled to illuminate in desired colors to indicate various stages, such as red to indicate the duration of a dispense and green to indicate a filled shell is ready for removal. Immediately below light 510 is a display screen 511, and below that is a dispensing station with an automated shell manipulator 512 with interlocking functionality. The general operation of apparatus 500 is similar to apparatus 1, but it is smaller and, in some cases, more convenient.

[0134] The housing manipulator 512 includes a housing receiving annular receiver 530 having a housing 531 and a limit switch ring 532 for detecting the presence of a housing in the receiver and whether the housing is concentric. The receiver 530 is located at one end of a robotic arm 533 that is rotated 180° in multiple cycles by a motor drive 535. The other end of the arm 533 supports a curved cover 540 having a radius of curvature equal to the radius of the arm 533. Figure 6 In the ready-to-use configuration shown, the outer surface of the cover 540 can be seen. This acts as an interlock to prevent the user from touching the cavity shell while it is being filled. The manipulator 512 is controlled by a digital controller (not shown) which also controls the Figures 12 to 13 Shown in figure 600 of automation atomizer.Atomizer is supplied with by container 570 and pump 571, and they are linked to each other by tubing, and pump is the peristaltic pump that links with atomizer 600 by tubing.Automation atomizer 600 comprises the crossbeam 601 with end carriage 620 and 621, and these carriages are driven on guide rail 625 by lead screw drive mechanism and vertically slide.Crossbeam 601 is supporting the aerosol generator of name Solo that is sold by AerogenTM.The cylindrical outlet conduit of vibratory orifice plate downstream engages with support ring 611, and support ring accommodates the sensor ring 612 that has proximity sensor 615, and has the pusher 602 that is positioned on spring strut 603 below proximity sensor.Sensor 615 is a limit switch, and it detects the chamber shell that has near pusher 602, and this is understood as being enough to be actuated aerosolization by aerosol generator 610 by controller.

[0135] After the desired period of aerosolization has been achieved, the vibration of the orifice plate is stopped and the crossbar 601 is lifted, while the pusher 602 is kept in contact with the spring support 603 along its length to ensure that the cover of the chamber housing is not lifted or displaced in any way. The robot arm 533 is then rotated 180 degrees so that the filled chamber housing 110 is Figure 10 Shown is presented, for the user to take out. This is carried out synchronously with the indication display on the controller and screen 511.

[0136] Alternative functions and features

[0137] It is contemplated that in other examples, it is not necessary for the user to place the cavity shell in the manipulator, as the cavity shell can be automatically extracted from the nested stack held internally.

[0138] Dispensing device 500 is particularly suitable for use in remote areas without a developed technological infrastructure.

[0139] The dispensing apparatus may include a vacuum system to clear the environment of excess aerosol during the dispensing phase, such as aerosol that may escape when the chamber housing is separated from the nebulizer outlet. Such a system may include a disposable filter to reduce emissions for safety purposes.

[0140] As described above, in a preferred embodiment, the nebulizer has a dose end detection, and it may have an interface to notify the user and / or supervisor of dose end or dose reduction on the orifice plate. The dose end detector may include features of a liquid detection sensor or a vibration driver to detect dose end based on the vibration characteristics of the orifice plate, as described in document WO2015 / 010809 (EP3024590B) or document WO2017 / 055166 (EP3356056B).

[0141] The controller is preferably programmed to keep the record of the preparation (for example, vaccine) batch number being distributed. These records can be linked together with the unique identification of each cavity shell by the mode of optically reading bar code or other codes. In addition, the controller can be programmed to have different operating modes, and a kind of pattern is applicable to each in the multiple preparation being distributed. The controlled parameter comprises any or all of the dosage strategies, volume information, the actuation time of the orifice plate that works. Power supply can be provided by solar cell, particularly uses in the place that can't obtain main power supply.

[0142] The device is particularly suitable for dispensing any therapeutic agent that can be dispensed in a dose volume of approximately or less than 0.5 mL. It preferably has a status light and / or a sound emitter to notify the next user when approaching the vaccination station. It may have a proximity sensor to detect the presence of an individual to determine when to start vaccination. The device can be configured to be distributed for pediatric use, in which case the cavity shell can have a relatively small volume, such as 250 mL. There may be an insert as part of the patient interface, and during inhalation, air is preferentially inhaled from the lower end of the cavity shell. A tube runs from the inhalation port down to the bottom, i.e., a "straw". The patient interface can be incorporated into a separate part of the cavity shell except for the cover. For example, an aerosol is introduced through the cover, but inhalation is introduced via one or more ports in other parts of the cavity shell.

[0143] It is understood that inhaled vaccines provide respiratory mucosal vaccination, that is, direct delivery of the vaccine to the respiratory tract through intranasal delivery or aerosol inhalation, which is particularly beneficial for diseases that use the respiratory tract as the initial site of infection (e.g., SARS-CoV-2). If SARS-CoV-2 infection in the respiratory tract is not controlled early, it may cause high viral burden and dysregulation, potentially fatal inflammatory responses and immunopathological responses, including acute respiratory distress syndrome.

[0144] Studies have shown that vaccination via the respiratory mucosal route is good at inducing antibodies and lung tissue-resident memory T cells (TRM cells) in the respiratory mucosa, as well as macrophage-mediated trained immunity, and these immunogenic responses are enhanced compared to vaccination via other routes.

[0145] Because respiratory mucosal immunity is critical for early clearance of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), inducing trained immunity in alveolar macrophages and other innate cells through respiratory mucosal vaccination could be an effective strategy.

[0146] Respiratory mucosal vaccination has the additional advantage of not requiring a needle and requiring a much smaller dose, potentially up to 80% less than the parenteral route, allowing significantly more people to be immunized with the same initial vaccine volume.

[0147] Advantages of chamber housing and equipment

[0148] Vibrating orifice plate is used for atomization, which 2 There are more than 2000 holes and the ability to aerosolize a range of viscosities and surface tensions. The viscosity of the aerosolized liquid is preferably in the range of 1 to 15 cP, the surface tension of the aerosolized liquid is in the range of 0.5 mN / m and 72 mN / m, and the output rate is preferably at least 0.01 mL / min. Potential formulations to be delivered include but are not limited to liposomes, exosomes, viruses, RNA, DNA, phages, cells, non-viral vectors, antibodies, small molecular weight active substances, etc. These formulations may or may not be loaded with cargo, such as genetic material (e.g., DNA / RNA) or active therapeutic / prophylactic drugs.

[0149] The diameter of the orifice plate is preferably greater than 5 mm, for example 8 mm. It is preferred to have a large number of orifice plates and areas so that a target amount of aerosol is produced per unit time, without increasing the drive voltage as a means of increasing the output rate (and therefore increasing the temperature), and the time for a full dose of aerosol is minimized.

[0150] In some examples, two or more aerosol generators may be provided to the chamber housing simultaneously. This has the advantage of reducing the aerosolization time of the dose volume. Preferably, the orifice plate has holes with a diameter between 1 and 6 microns. Holes within this range can minimize the heat and shear forces experienced by the preparation. Preferably, the aerosol generator is deactivated when the dose is exhausted. This has the advantage of minimizing heat accumulation on the aerosol generator assembly, as this may adversely affect the aerosolized preparation.

[0151] The housing can be configured to be appropriately attached to a patient interface to facilitate aiming of the aerosolized formulation toward the lungs (mouthpiece) or both the nose and lungs (mask or nasal interface). The device and / or housing can be configured to be suitable for use with infant and pediatric patients. Children and infants are typically administered aerosols via a mask, however, older children may be able to breathe in conjunction with a mouthpiece.

[0152] Table: Typical respiratory parameters for children and infants

[0153] Respiratory parameters child baby Tidal volume 155 ml 50ml I:E Ratio 1:2 1:3 BPM 25 30

[0154] Table: Summary of doses inhaled via the mouthpiece in the closure - single breath for a 330 ml cavity housing and 155 ml tidal volume (child's breathing)

[0155]

[0156] The location where the aerosol is inhaled is important for smaller patients. The combination of collaborative breathing and the ability to clear the aerosol chamber with fewer breaths is crucial. Here, we describe some configurations that significantly increase the inhaled dose when using a 330 mL chamber and minimize the need to change dispensing stations.

[0157] Alternative cavity housing embodiments may be used, such as the following:

[0158] Configuration 1: Fill the aerosol from the cap. Inhale the aerosol close to the base of the housing.

[0159] Configuration 2: Aerosol is filled from the cap and the aerosol is inhaled from the middle of the cavity shell.

[0160] Configuration 3: Aerosol filling from the cap. Aerosol is inhaled from the center of the cavity shell, which is oriented horizontally.

[0161] Configuration 4: Aerosol filling from the cap. Aerosol is inhaled from the base of the chamber housing, which is oriented horizontally.

[0162] Table: Inhalation dose for a pediatric respiratory set using a 330 ml chamber housing - multiple breaths.

[0163] Cavity shell configuration Delay after atomization average% STDEV 1 1 second 27.17 1.13 1 5 seconds 24.40 0.79 1 10 seconds 22.26 0.38 1 30 seconds 15.97 1.70 2 1 second 33.21 0.75 2 5 seconds 27.80 0.79 2 10 seconds 24.15 1.00 2 30 seconds 17.99 0.44 3 1 second 21.76 2.08 3 5 seconds 16.73 1.15 3 10 seconds 15.60 0.58 3 30 seconds 13.58 0.38 4 1 second 24.78 0.79 4 5 seconds 17.61 0.79 4 10 seconds 13.08 0.95 4 30 seconds 10.19 0.75

[0164] Table: Inhalation dose for Infant Breathing set-up, 330ml chamber housing - multiple breaths.

[0165]

[0166]

[0167] Given that children and infants inhale smaller volumes, it would seem sensible to reduce the housing volume to clear the smaller volume more quickly. The test results below demonstrate that this is not the case. Here, we evaluated inhaled doses for four configurations / options and two housing volumes (330 mL and 234 mL). This demonstrated that the 330 mL housing volume was the optimal housing volume for all patient types, minimizing aerosol loss within the housing after nebulization and before inhalation.

[0168] Table: Inhalation dose for pediatric breathing set using 234 ml chamber housing - multiple breaths.

[0169]

[0170]

[0171] Table: Inhaled dose for the Infant Breathing Set with a 234 mL chamber housing - multiple breaths.

[0172] Cavity Shell Options Delay after atomization average% STDEV 1 1 second 26.42 0.38 1 5 seconds 24.78 1.78 1 10 seconds 22.77 0.58 1 30 seconds 15.09 1.36 2 1 second 23.90 1.33 2 5 seconds 20.75 0.38 2 10 seconds 19.37 0.44 2 30 seconds 15.47 0.65 3 1 second 15.60 2.31 3 5 seconds 12.45 0.65 3 10 seconds 9.94 1.21 3 30 seconds 5.66 0.38 4 1 second 14.97 0.58 4 5 seconds 13.08 1.15 4 10 seconds 10.31 1.53 4 30 seconds 8.18 0.44

[0173] The purpose of the above-mentioned configurations 3 and 4 is to allow the chamber housing to be filled with aerosol, but the orientation of the configuration is not directly in front of the patient's eyes. This impact on the visual field may interfere with the patient's ability to follow instructions and divert attention from the inhalation operation. However, these configurations are not believed to provide benefits in performing an inhaled dose. Therefore, a vertical, upright orientation of the chamber housing is preferred.

[0174] Another method of clearing a vertical chamber shell of aerosol involves the use of a tube that is inserted into the inner cavity of the chamber shell. After the aerosol generator is removed, the tube is inserted into the orifice where the aerosol is introduced. The tube itself can be used as a mouthpiece that is connected to a mask or a nasal interface for inhalation through the nose. The purpose of this is to place the vacuum point of the chamber shell (during inhalation) at the position where the maximum aerosol is entrained in the inhaled flow. This method is suitable for patients who require mask inhalation (adults, children and infants). Figure 15 Of the four configurations shown (A, B, C, D), two configurations were evaluated:

[0175] Configuration A: The end point of the tubing is approximately 1 cm from the base of the cavity housing.

[0176] Configuration B: The tubing terminates approximately midway between the base of the housing and the top wall of the housing. Table: Tubing in a 330ml housing (Adult - Single Breath, Pediatric / Infant - Multiple Breaths)

[0177]

[0178]

[0179] Table: Tubing in 234ml chamber housing, Child and Infant Breathing Set - Multiple Breaths

[0180] Parameters / Cavity Shell Size Pipe fitting location Delay after atomization average% STDEV Children (234ml) 1cm from the base 1 second 15.47 0.38 Children (234ml) 1cm from the base 5 seconds 15.72 0.22 Children (234ml) 1cm from the base 10 seconds 13.96 1.36 Children (234ml) 1cm from the base 30 seconds 4.40 0.58 Children (234ml) Halfway inside the housing 1 second 21.01 0.79 Children (234ml) Halfway inside the housing 5 seconds 20.88 0.22 Children (234ml) Halfway inside the housing 10 seconds 16.73 1.15 Children (234ml) Halfway inside the housing 30 seconds 9.06 1.31 Baby (234ml) 1cm from the base 1 second 13.21 0.65 Baby (234ml) 1cm from the base 5 seconds 13.21 0.38 Baby (234ml) 1cm from the base 10 seconds 11.19 0.22 Baby (234ml) 1cm from the base 30 seconds 4.78 0.079 Baby (234ml) Halfway inside the housing 1 second 17.36 0.38 Baby (234ml) Halfway inside the housing 5 seconds 17.36 0.38 Baby (234ml) Halfway inside the housing 10 seconds 15.35 0.79 Baby (234ml) Halfway inside the housing 30 seconds 8.43 0.95

[0181] It will be appreciated that the use of a vibrating mesh plate aerosol generator helps prevent shearing or similar damage to the cells of microbial agents such as vaccines. Such features are described in our published PCT document WO2016 / 198667, the contents of which are incorporated herein by reference.

[0182] The present invention is not limited to the embodiments described, but may vary in structure and detail. Distributing nebulizers are preferably of the vibrating orifice plate type, while jet nebulizers are less suitable because the drive gas may clear the cavity shell. Generally speaking, the nebulizer is preferably of the type having a vibrating mesh aerosol generator, or a surface acoustic wave or Fourier angle aerosol generator.

[0183] In various preferred embodiments, the aerosol dispenser detects that the housing is in the correct position and delivers a pre-set aerosol dose. Once the dose is delivered, visual and / or audible indicators notify the user that the housing has been filled and they can inhale. This is a very beneficial part of the operation of the user interface 103.

[0184] The top wall with aerosol inlet can be tilted, and / or the nebulizer outlet conduit can be tilted, so that according to the filling effect of expectation, towards or away from the sidewall, conveying.In addition, additional openings can also be arranged in the top wall, such as the gap near the edge, to assist in the flow during suction.

[0185] The distribution station can provide any suitable support for the filled cavity shell. In one example, the distribution station is a simple platform for placing the cavity shell on it, while in another example, the distribution station includes a receiving ring on a rotating arm. However, in other examples, the distribution station may include a gripping mechanism to actively / form-fit the cavity shell by, for example, opposing claws. In the case of gripping the cavity shell in some way, in some examples, the cavity shell can be rotated and oriented to optimize delivery. In addition, the distribution device can also be used to distribute aerosols other than vaccines, such as monoclonal antibodies or other therapeutics. In addition, the cavity shell can have a baffle near the aerosol inlet to provide selective rainout, thereby filtering the droplet size. In this way, the cavity shell can be adapted to a specific type of aerosol to optimize efficiency. For example, the baffle can take the form of a tube extending inwardly from the aerosol inlet.

[0186] Those skilled in the art will understand that any feature described with respect to one embodiment may be used to perform an equivalent function in a device or housing of a different embodiment.

Claims

1. An aerosol dispensing device (100), comprising: a nebulizer (104, 200, 600) having an aerosol generator and an outlet conduit, and controller, The device comprises a single-dose aerosol housing (110) having a housing nebulizer delivery port (114) and an inhalation port (115), The device comprises a filling stage comprising the nebulizer and a support for the single-dose aerosol chamber housing (110), and The nebulizer (104, 200, 600) is adapted to deliver an aerosol dose into the housing via the housing nebulizer delivery port (114), the filling stage being configured to automatically engage the nebulizer outlet conduit with the housing nebulizer delivery port (114) and disengage after delivery of a dose, The nebulizer is configured to deliver at a flow rate exceeding 0.01 mL / min, and The nebulizer includes a housing sensor (615) for detecting the presence of the housing engaged with the outlet conduit, and the controller is configured to initiate aerosolization only when the housing is detected.

2. The device according to claim 1, wherein The nebulizer includes an automated housing manipulator (512) for engaging the housing with the nebulizer in an automated manner.

3. The device according to claim 1 or 2, wherein: The nebulizer is configured to deliver a dose at a preset flow rate according to a preset time.

4. The device according to claim 1 or 2, further comprising a chamber housing dispenser (102) for distributing chamber housings to a user in proximity to the atomizer.

5. The device according to claim 1 or 2, further comprising a user interface (103, 511) having a display screen and / or a speaker, and the controller is configured to generate user instructions for using the device and for inhaling from the cavity housing.

6. The device according to claim 5, wherein The controller is configured to instruct the user to inhale from the cavity housing within a set period of time.

7. The apparatus according to claim 5, wherein The controller is configured to provide an indication that the aerosol is consumed within 10 seconds.

8. The apparatus according to claim 5, wherein The controller is configured to generate, via the user interface, an advisory communication regarding a desired number of inhalations and breaths.

9. The apparatus according to claim 8, wherein The controller is configured to generate an advisory communication advising taking a maximum of two breaths.

10. The apparatus according to claim 8, wherein The controller is configured to generate an advisory communication advising the user to take a short inhalation.

11. The apparatus according to claim 1 or 2, further comprising a receiver (120) for used chamber shells.

12. The apparatus according to claim 1 or 2, wherein: The device is arranged in a series of stages comprising the filling stage, a stage for distributing the chamber shells, and a stage for disposing of the used chamber shells.

13. The apparatus according to claim 1 or 2, wherein: The nebulizer is configured to deliver doses between 0.05 mL and 0.25 mL.

14. The apparatus according to claim 1 or 2, wherein: The nebulizer was configured to deliver at a flow rate in the range of 0.5 mL / min to 2.5 mL / min.

15. The apparatus according to claim 1 or 2, wherein: The nebulizer is configured to deliver the aerosol into the housing in less than 15 seconds.

16. The apparatus according to claim 2, wherein The manipulator includes a housing receiver (530) movable from a housing receiving position to an aerosol generator (610) engaging position.

17. The apparatus according to claim 16, wherein The receiver includes a sensor (532) for detecting the presence of a cavity housing in the receiver, and the controller is configured to trigger a fill cycle upon detecting the cavity housing in the receiver.

18. The apparatus according to claim 17, wherein The receiver (530) is ring-shaped.

19. The apparatus according to claim 17, wherein The sensor (532) is configured to detect the concentricity of the cavity housing in the receiver.

20. The apparatus of claim 17, wherein: The receiver is located on an arm (533) which can be rotated from a front position receiving the cavity housing and facing the user to a rear position for filling.

21. The apparatus according to claim 20, wherein The arm supports a dispensing stage cover (540) at an end opposite the receptacle so that the cover is presented to the user during filling to provide an interlock.

22. The apparatus according to claim 21, wherein The cover (540) is curved to present a convex surface towards the front of the dispensing station.

23. The apparatus according to claim 1 or 2, wherein: The nebulizer comprises a further support (601) which supports the aerosol generator (610) during movement of the aerosol generator from an inoperative position to an operative position for filling.

24. The apparatus according to claim 23, wherein The non-operating position is above the cavity housing in use.

25. The apparatus of claim 23, wherein: A further support is movable on a vertical track (625) to move the aerosol generator (610) between the inoperative position and the operative position.

26. The apparatus according to claim 1 or 2, wherein: The atomizer includes a pusher (602) that pushes against the chamber housing during disengagement of the outlet conduit to prevent the chamber housing or a cover of the chamber housing from moving.

27. The apparatus according to claim 1 or 2, wherein: The nebulizer includes a vibrating mesh plate, a vibration driver for causing the plate to vibrate, and a reservoir for delivering a therapeutic fluid to a top surface of the plate such that vibration of the plate causes an aerosol to enter the outlet conduit.

28. The apparatus of claim 27, wherein The aperture size of the aperture plate is designed to provide aerosol droplets, at least 80% of which are less than 6 μm in size.

29. The apparatus of claim 27, wherein The pore size of the orifice plate is in the range of 0.5 μm to 10 μm.

30. The apparatus of claim 27, wherein: The pore size of the orifice plate is in the range of 0.5 μm to 6.0 μm.

31. The apparatus of claim 27, wherein: The apertured plate has more than 100 aerosol-forming apertures per square millimeter.

32. The apparatus of claim 27, wherein: The orifice plate has an upper storage layer with a liquid supply channel and a lower layer with aerosol-forming orifices.

33. The apparatus of claim 32, wherein: The diameter of the liquid supply channel of the storage layer is in the range of 20 μm to 400 μm.

34. The apparatus of claim 27, wherein: The nebulizer is configured to automatically detect exhaustion of the dose on the orifice plate and to stop operation of the nebulizer if there is no liquid on the orifice plate and to provide an alert at the interface accordingly.

35. The apparatus of claim 34, wherein The controller is configured to perform the following steps: measuring an aperture plate drive current at each of a plurality of measurement points in a scan, each measurement point having a drive frequency; determining a minimum value of the drive current in the scan; Determining the maximum rate of change of the drive current during the scan period; and executing an algorithm using the minimum value in combination with the maximum rate of change value to calculate an indicator value for dose depletion.

36. The apparatus of claim 35, wherein The controller is configured to provide the indicator using a ratio of a maximum slope value and a minimum parameter value.

37. The apparatus of claim 36, wherein: The controller is configured to multiply the ratio or a value derived from the ratio by a constant value to provide the indicator.

38. The apparatus of claim 36, wherein: The controller is configured to perform the scan within a frequency range of 128 kHz to 165 kHz.

39. The apparatus of claim 38, wherein The controller initiates the scan in response to triggering a possible dose depletion.

40. The apparatus according to claim 1 or 2, wherein The nebulizer is configured to provide only a single dose to the aerosol generator for each dispensing operation that fills the cavity housing.

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