Integrated dose counter

Abstract

The display device has a mechanical dose counter adapted to count the number of doses dispensed from or remaining in the container, and an electronics module coupled to the mechanical dose counter and adapted to record when a dose is dispensed from the container. Methods of using and assembling the display device are provided.

Description

[Technical Field]

[0001] The present invention relates generally to dose counters, and more particularly to integrated dose counters having a mechanical dose counter and an electronic module, as well as to methods of dispensing aerosol medications and the like and methods of assembling the integrated dose counters.

[0002] REFERENCE TO RELATED APPLICATIONS This application claims the benefit of U.S. Provisional Patent Application No. 62 / 946,259, filed December 10, 2019, entitled "Integrated Dose Counter," and U.S. Provisional Patent Application No. 62 / 956,846, filed January 3, 2020, entitled "Integrated Dose Counter," the disclosures of which are incorporated by reference in their entireties. [Background technology]

[0003] Metered dose inhalers (MDIs) are non-reusable devices and are therefore disposed of after the preloaded number of doses have been dispensed or the medication's specified shelf life has expired. Mechanical dose counter mechanisms may be integrated into the MDI and may be required by the FDA. Two common types of mechanical dose counters exist: (1) the displacement of the MDI canister relative to the actuator, or (2) the force applied to the MDI as a means of detecting and therefore counting the actuation or expulsion of a dose. Mechanical dose counters typically only provide information regarding the number of doses dispensed or remaining in the container, and usually not information regarding how or when the doses were removed. Summary of the Invention

[0004] In one aspect, one embodiment of the display device is characterized by having a mechanical dose counter adapted to count the number of doses dispensed from or remaining in the container, and an electronic module coupled to the mechanical dose counter adapted to record when a dose is dispensed from the container.

[0005] In another aspect, one embodiment of a method of assembling a medication dispensing device features the steps of coupling a mechanical dose counter adapted to count the number of doses dispensed from or remaining in the container to an electronic module adapted to record when a dose is dispensed from the container; coupling at least one of the mechanical dose counter or the electronic module to the container or an actuator housing; and coupling the container to the actuator housing.

[0006] In another aspect, a method of counting doses dispensed from a medication dispensing device includes pressing one of a mechanical dose counter or an electronic module coupled to the mechanical dose counter, wherein at least one of the mechanical dose counter and the electronic module is coupled to a container or an actuator housing that holds the container, the method further including dispensing a dose of medication from the container; counting with the mechanical dose counter the doses of medication dispensed from the container and displaying with the mechanical dose counter the number of doses dispensed from or remaining in the container; and recording with the electronic module when a dose of medication is dispensed from the container. [Brief explanation of the drawings]

[0007] [Figure 1] 1A and 1B are perspective and side views of a metered dose inhaler with a mechanical dose counter coupled to the canister. [Figure 2] FIG. 1 is a side view of a mechanical dose counter and electronic module mounted on a metered dose inhaler. [Figure 3] FIG. 1 is a diagram of an electronic module. [Figure 4] FIG. 1 is a side view of a metered dose inhaler with the mechanical dose counter and electronic module activated. [Figure 5] FIG. 2 is an exploded view of one embodiment of a force sensitive resistor assembly. [Figure 6] FIG. 1 is a side view of one embodiment of a mechanical dose counter and electronic module mounted on a metered dose inhaler. [Figure 7] FIG. 1 is a side view of one embodiment of a mechanical dose counter and electronic module mounted on a metered dose inhaler. [Figure 8] FIG. 1 is a side view of one embodiment of a mechanical dose counter and electronic module mounted on a metered dose inhaler. [Figure 9] FIG. 1 is a side view of one embodiment of an electronic module mounted on a metered dose inhaler. [Figure 10] FIG. 1 is a side view of one embodiment of an electronic module mounted on a metered dose inhaler. [Figure 11] FIG. 1 is a cross-sectional view of one embodiment of a mechanical dose counter coupled to an electronic module. [Figure 12] FIG. 1 is a cross-sectional view of one embodiment of a mechanical dose counter coupled to an electronic module. [Figure 13] FIG. 1 is a cross-sectional view of a metered dose inhaler fitted with a mechanical dose indicator. [Figure 14] FIG. 1 is a cross-sectional view of a metered dose inhaler fitted with a mechanical dose indicator. [Figure 15] FIG. 1 is a cross-sectional view of one embodiment of a mechanical dose counter in operation. [Figure 16] FIG. 1 is a cross-sectional view of one embodiment of a mechanical dose counter in operation. [Figure 17] FIG. 1 is a cross-sectional view of one embodiment of a mechanical dose counter in operation. [Figure 18] FIG. 1 is a cross-sectional view of one embodiment of a mechanical dose counter in operation. [Figure 19] FIG. 1 is a cross-sectional view of one embodiment of a mechanical dose counter. [Figure 20]FIG. 1 is a cross-sectional view of one embodiment of a mechanical dose counter. [Figure 21] 4 is a flow diagram illustrating the operation of one embodiment of an electronic module. [Figure 22] 4 is a flow diagram illustrating the operation of one embodiment of an electronic module. [Figure 23] 4 is a flow diagram illustrating the operation of one embodiment of an electronic module. [Figure 24] 1 is a schematic diagram of one embodiment of a system. [Figure 25] FIG. 1 illustrates one embodiment of an electronic module. [Figure 26] FIG. 1 is an exploded view of one embodiment of an electronic module. [Figure 27] 10 is a flow diagram showing a TX event for waiting for a BLE connection. [Figure 28] FIG. 1 illustrates a force sensitive resistor sensor assembly. [Figure 29] FIG. 1 is a cross-sectional view of a mechanical dose counter attached to the bottom of a container. [Figure 30] 1 is a schematic diagram showing a computer structure. [Figure 31] 1 is a schematic diagram of a communication system. [Figure 32] FIG. 1 is an exploded view of a mechanical dose counter. [Figure 33] FIG. 1 is a cross-sectional view of one embodiment of a wake-up switch. [Figure 34] FIG. 1 is a partial cross-sectional view of one embodiment of a mechanical dose counter and electronic module mounted on a metered dose inhaler. [Figure 35] FIG. 1 is a side perspective view of one embodiment of a mechanical dose counter and electronic module. [Figure 36] FIG. 36 is a bottom view of the mechanical dose counter and electronic module shown in FIG. 35. [Figure 37] FIG. 10 is a partial cross-sectional view of another embodiment of a mechanical dose counter and electronic module mounted on a metered dose inhaler. [Figure 38] FIG. 10 is a side perspective view of another embodiment of a mechanical dose counter and electronic module. [Figure 39] FIG. 39 is a bottom perspective view of the mechanical dose counter and electronic module shown in FIG. 38. [Figure 40] FIG. 10 is a partial cross-sectional view of another embodiment of a mechanical dose counter and electronic module mounted on a metered dose inhaler. [Figure 41A] FIG. 10 is a cross-sectional side view of another embodiment of a mechanical dose counter and electronic module mounted on a medication container. [Figure 41B] FIG. 1 is a partial cross-sectional view of a mechanical dose counter and electronic module mounted on a medication container of a metered dose inhaler assembly. [Figure 42A] FIG. 1 is a top perspective view of one embodiment of a pressurized metered dose inhaler. [Figure 42B] FIG. 1 is a partial cross-sectional side view of one embodiment of a pressurized metered dose inhaler. [Figure 43] FIG. 1 is a schematic side view of a pressurized metered dose inhaler showing communication between a valved holding chamber and a local computing device. [Figure 44] 1 is a diagram illustrating communication between various smart devices. [Figure 45] 1 is a diagram illustrating communication between various smart devices. [Figure 46] 1 is a schematic diagram illustrating an electronic module architecture. [Figure 47-47A] 1 is a flow diagram illustrating the operation of one embodiment of the system. [Figure 47B] 1 is a flow diagram illustrating the operation of one embodiment of the system. [Figure 48] 10 is a flow diagram illustrating the accelerometer and wake / shake detection logic. [Figure 49] 1 is a flow diagram illustrating the microcontroller logic. [Figure 50] 1 is a flow diagram illustrating Bluetooth and connection wait packet logic. [Figure 51] 10 is a flow diagram illustrating the IR detection and ADC block logic. [Figure 52]1 is a diagram illustrating the finite state machine logic for the system. DETAILED DESCRIPTION OF THE INVENTION

[0008] Detailed Description of the Drawings and Presently Preferred Embodiments

[0009] Overall description of the implementation:

[0010] In one aspect, an embodiment of the display device allows for mechanical and electronic dose counting, thereby enabling additional information to be captured and communicated externally to a drug administration device or system, including, but not limited to, a metered dose inhaler (MDI) 2 shown in Figures 1, 2, and 4. For example, such information may aid in determining whether a patient has adhered closely to their prescribed treatment (in which case adherence may be said to be "sustained"), whether the medication was taken and at the correct time, and whether compliance occurred, i.e., whether the medication was taken properly.

[0011] The Electronic Dose Counting and Tracking Module (EM) 4 is extremely low cost and can be easily integrated into existing MDIs that are already manufactured on extremely low cost platforms. Second, the electronics are developed in an extremely small form factor that has the advantage of being easy to integrate into existing MDIs, and such electronics offer great flexibility in how they are integrated, yet with minimal impact on overall MDI functionality and usability. Along with the low cost and size requirements, the selection of electronics and components (or parts; note that, as used herein, "components" and "parts" are interchangeable) accurately and reliably detects, stores, and communicates each actuation of the dose counter while having extremely low energy consumption requirements.

[0012] In one embodiment, the EM4 is permanently attached to an existing mechanical dose counter, such as a mechanical top-mounted actuation indicator (TMAI) 6, thereby forming an electronic TMAI (eTMAI) assembly. The resulting eTMAI can then be permanently bonded to the canister portion of a pressurized metered dose inhaler (pMDI) by the pMDI manufacturer, for example, using an adhesive label wrap 600, 1600, 1602. The EM4 provides additional connectivity, improved functionality, and strict compliance tracking to the existing TMAI 6 while retaining mechanical dose counting functionality.

[0013] Description of the Preferred Embodiment - Electromechanical Dose Counter and Tracker:

[0014] One mechanical dose counter, for example, is the TMAI6 manufactured by Trudell Medical International, which is a force-sensing dose counter. Various embodiments of dose counters are disclosed in U.S. Patent Nos. 6,082,358, 6,926,002, and 8,074,594, the disclosures of which are incorporated by reference herein in their entireties. (No license, express or implied, is intended to be granted to any of these patents by virtue of incorporation by reference.)

[0015] Referring to the figures, and in particular to Figures 1, 2, 4, 13-20, 34, 37, 40, 42A and 42B, an aerosol dispenser is shown having a housing 200, or actuator boot, and a container 12 disposed within the housing. The housing has a longitudinally extending cavity 202 shaped to receive the container. The top portion of the housing is generally open so that the container can be inserted into the housing through an opening 204, with the lower end 14 of the container projecting from the housing and operably exposed to a user.

[0016] As used herein, the terms "longitudinal" and "axial" are meant to refer to the direction of reciprocating movement of the container relative to the housing and the indicating cap member relative to the base or base member. The terms "top," "bottom," "upper," and "lower" are intended to refer to directions when viewing the illustrated inhalation device, with the understanding that the container is inverted so that its top surface is positioned adjacent the bottom of the housing, or vice versa. It should further be understood that a user can use the container and dispenser in any number of positions, including, but not limited to, the preferred upright positions shown in Figures 1, 2, 4, 13, and 14.

[0017] As shown in Figures 13 and 14, a cylindrical support block 212 having a well 214 is formed in the bottom portion 206 of the housing. An orifice 210 passes through the support block and communicates with the bottom portion of the well. In one embodiment, a mouthpiece 208 adapted for insertion into a patient's mouth forms an exhaust port 216 in communication with the orifice and the well. The mouthpiece 208 extends laterally from the housing to facilitate insertion of the mouthpiece into the patient's mouth.

[0018] The vessel 12 is cylindrical and has a hub 16 mounted on its top surface 17. A valve stem 18 extends longitudinally from the hub. The valve stem extends coaxially from the vessel and is biased outwardly from the vessel by a spring (not shown) mounted within the vessel's valve stem. The vessel 12 is mounted within the housing by a force fit of the valve stem 18 within a well 214 in the support block.

[0019] In a preferred embodiment, the container 12 is filled with pressurized aerosol and the medicated pressurized aerosol is dispensed from the container in specific metered doses by depressing or moving the valve stem 18 from an extended closed position to a depressed open position. One metered dose is dispensed from the container with each reciprocating longitudinal movement of the valve stem.

[0020] In operation, opening of the valve stem is accomplished by reciprocating the container 12 within the housing 200 along the longitudinal axis defined by the valve stem, which is accomplished by depressing the lower end 14 of the container relative to the housing to move the valve stem 18 to the open position as it is supported in the well by a support block. When the valve stem is moved to the open position, the container dispenses a metered dose of aerosol medication through the well 214 and orifice 210. The aerosol and medication are then delivered to the patient through an exhaust port in the mouthpiece by either self-generated or assisted airflow.

[0021] In other delivery systems, a housing and holder for the container are attached to a component having a chamber with an output end. Examples of this type of delivery system are shown, for example, in U.S. Pat. No. 5,012,803, issued May 7, 1991, and U.S. Pat. No. 4,460,412, issued September 11, 1984, both of which are incorporated by reference herein. (No license, express or implied, is intended to be granted in any of these patents by reference.) In these types of delivery systems, the component having the chamber may be configured to accept a mouthpiece of the housing or may be integrally connected to a holder that supports the container. In either embodiment, a metered dose of medication in the aerosol is first dispensed from the container into the chamber, and then inhaled by the patient.

[0022] In a preferred embodiment, the container 12 is adapted to dispense a predetermined number of metered doses of medication. For example, conventional inhaler containers typically hold on the order of 100-200 metered doses. However, it should be understood that the range of available doses can potentially vary from as little as 1 dose to as many as 500 doses, further depending, for example, on the volume of the container and / or the size of the valve that meters the doses. In operation, it may be important for a patient to know how many metered doses remain in the container so that the patient is not unaware that the container is empty when they need medication.

[0023] Referring now to the figures generally, a mechanical dose indicator 6 is shown. The indicator 6 displays the number of metered doses dispensed from or remaining in a container. As shown in the embodiments of Figures 1, 2, 4, and 13-20, respectively, the indicator 6 includes a cap member 20, 220 mounted to a base member 40. The base member 40 is configured to be attached to the bottom of a container 12. In a first embodiment, shown in Figures 15-18, 29, and 32, the base member has a convex or curved bottom portion 50, i.e., floor, that is shaped to be received within and mate with the lower end 14 of the container, which has a concave or inwardly curved profile (see Figure 29, the disclosure of which is incorporated herein in its entirety). The base member 40 is preferably bonded to the bottom of the container with an adhesive, double-sided tape, or similar bonding agent. Alternatively, a label 600, 1600 or other wrap component may be wrapped around the base member and the container, which in one embodiment have the same perimeter. As shown in the embodiment of Figures 15-20 and 32, a circumferential skirt member 94 extends upwardly from the base portion to form a cavity 96.

[0024] Alternatively, as shown in Figures 13 and 14, the base member 90 has a bottom portion, a downwardly extending circumferential skirt 152, and an upwardly extending circumferential skirt. The depending skirt 152 forms a recess or cavity shaped to receive the lower end of the container 12. The base member is attached to the container either by bonding one or more of the bottom portion or skirt to the container, or by press-fitting the container into the cavity to create an interference fit between the container and the depending skirt. The upwardly extending skirt and bottom portion form an upper cavity that overlaps the lower cavity.

[0025] Although the disclosed containers and displays, and particularly the cap and base members, are shown as preferably having circular cross sections, those skilled in the art will appreciate that the containers and displays, including any adapters, may be made in other shapes, including, but not limited to, rectangular or triangular cross sections.

[0026] As best seen in FIG. 1 , the cap member 20 has a top portion 52 with an observation window 34 formed therein. Preferably, the cap member 20 is circular, with the observation window formed in the top portion adjacent the outer periphery of the cap member to overlie indicia formed on the top of the indicator member supported below the cap member. The observation window can be configured in a variety of shapes. For example, the observation window may be tapered or, as shown in FIG. 1 , an arcuate window bounded by coaxial inner and outer curved boundaries and radial side boundaries. The top of the cap member preferably has a plurality of raised portions or recesses that form a grippable pattern for a user's thumb or fingers. This allows the user to firmly press down on the cap member without slipping. Those skilled in the art will recognize that other patterns or grippable surfaces, such as a knurled pattern, can be applied to the cap member to facilitate use of the indicator.

[0027] 13-20 and 32, the cap member 20, 220 has a circumferential skirt 92, 292 that extends or depends downwardly from the top portion 52, 252. The skirt preferably has a smaller diameter than the upwardly extending skirt of the base member, such that the cap member skirt fits or nests within the upwardly extending skirt of the base member. Alternatively, the cap member may include a skirt that has a larger diameter than the skirt of the base member, such that the base member skirt fits or nests within the cap member skirt. The cap member 20, 220 is movably attached to the base member 40 by a snap fit.

[0028] In particular, as shown in FIG. 19, the cap member has a plurality of engaging members extending from the outer peripheral surface of the skirt that are captured in pockets formed along the inner peripheral surface of the base member skirt to create a snap-lock fit. Specifically, the upper surfaces of the engaging members engage engaging surfaces 45 that define the tops of the pockets. In this manner, the cap member can move relative to the base member along an axial or longitudinal path. Alternatively, the rim of the base member may be slightly curved inward, such that the engaging members engage the inwardly curved rim portion to prevent separation of the cap member from the base member.

[0029] Axial movement of the cap member 20, 220 relative to the base member 40 is limited or constrained by engagement of the engagement member with the top of the base member pocket (or base member rim) at the fully extended position, and by engagement of the bottom rim 21, 221 of the cap member skirt with the upper surface of the bottom portion at the bottom of the stroke as shown in Figures 15-18. Those skilled in the art will appreciate that, alternatively, the engagement member may be formed on the base member skirt to engage a pocket or opening or rim (or similar protrusion) formed in the cap member skirt.

[0030] As shown in FIGS. 15-19 and 32, a spring 100 is disposed between the cap member and the base member. The spring is preferably disposed within the downwardly extending hub portion 30, 230 of the cap member and the upwardly extending hub portion 44 of the base member. Alternatively, the spring is disposed between the cap member and the base member, the spring being sized so that the coil is disposed adjacent the inner circumferential surface of the cap member skirt. The spring 100 serves as a return mechanism, biasing the cap member 60, 260 upward within the base member so that the engaging member 28, 228 of the cap member engages the upper portion of the pocket in the base member. While a compression spring is shown, it should be understood that a Belleville washer, cantilever spring, torsion spring, leaf spring, and / or tension spring may also serve to bias the cap member upward into engagement with the base member. The spring may be constructed of metal or plastic.

[0031] As shown in FIG. 20 , the return mechanism acting between the cap member and the base member includes a plurality of resilient arm members 400 extending downward from the cap member. As the cap member is moved toward the base member, one or more of the arm members engage an inclined biasing surface 402 formed along the outer portion of the hub portion 44. The inclined biasing surface biases one or more of the resilient arm members outward as the cap member approaches the base member. The resilient arm members act as cantilever springs that bias the cap member away from the base member when the cap member is released by the user. As would be understood by one skilled in the art, the resilient arm members may be formed on the base member to engage the inclined surface formed on the cap member. As would be further understood by one skilled in the art, the springs and resilient arm members may be used together, as shown in FIG. 20 , or separately.

[0032] 1, 15-20, and 32, an indicator member 260 is rotatably mounted within the cap member 20, 220 about an axis substantially parallel to the axial movement of the cap member relative to the base member. The indicator member is generally open centrally and has a top portion 276 with an upper surface 262 that rotatably slides along the underside of the top of the cap member. Alternatively, the indicator member may be mounted on the exterior of the cap member with an observation window formed in the indicator member for viewing indicia applied to the top of the cap member.

[0033] The indicator member 260 has a circumferential skirt 274 extending or depending downwardly from the top portion. Referring to FIGS. 5 and 8, a plurality of projections or engagement tab members extend from the inner periphery of the cap member skirt and engage a rim 264 formed at the bottom of the indicator member skirt. Alternatively, the indicator member may have an engagement member or rim that fits into a groove or similar opening in the cap member. In this manner, the indicator member is secured to the cap member to prevent axial movement of the indicator member and cap member, but may rotate relative to the cap member. The indicator member is attached by snap-fitting the indicator member into the cap member. As will be appreciated by those skilled in the art, the indicator member may alternatively be rotatably attached to a cap member hub portion (with a portion of the key member removed) or a similar axle secured to the cap member.

[0034] The indicator member 260 has a plurality of inwardly directed teeth 266 formed along the inner periphery of the skirt, which teeth are preferably formed around only a portion of the periphery.

[0035] The indicator member 60 has a plurality of recesses 68 formed around the outer periphery of the skirt 74. The cap member has a pair of upwardly extending resilient indexing members 22, each having an end portion that fits into one of the recesses to releasably engage the indicator member and prevent rotation between the end portion and the indicator member. The angular distance between the recesses 68 is substantially the same as the angular distance between the plurality of indicator member teeth 66. In this manner, the indexing member selectively engages the next recess with each incremental advance of the indicator member defined by the distance between adjacent teeth.

[0036] Alternatively, the recess and indexing member may be inverted, i.e., the recess is formed around the inner periphery of the cap member skirt and the indexing member extends or depends downwardly from the indicator member within a cavity formed in the indicator member skirt.

[0037] As shown in FIG. 1 , dosage indicia 72 in the form of numeric or color coding are provided on the top surface of the indicator member, and the dosage indicia are visible to the user through an observation window 34 located on the top of the cap member. Those skilled in the art will appreciate that other indicia indicating the number of doses remaining in or dispensed from the container include, but are not limited to, various alphanumeric characters, words, terms, or phrases (e.g., "full" and "empty"), scales, grids, arrows, raised portions, indentations, color and segmentation, shading, and similar markings, or any combination thereof. For example, a segmented color grid 172 displayed in the indicator window (e.g., as shown in FIG. 1 ) changes from green to indicate a full container, to yellow to indicate a medium capacity container, and finally to red to indicate an empty container. It should also be understood that the indicia may be integrally formed with the counter member or applied to the counter member by paint, dye, etching, pad printing, hot foil stamping, or adhesive label. If numeric indicators are used, the numbers may be arranged to progress from 0 (or some starting number) to a predetermined number of doses available so that display of that number to the user indicates that the container is empty, or alternatively, they may be arranged to progress from a starting predetermined number to 0 (or some ending number), again indicating to the user that the container is empty.

[0038] In a preferred embodiment, the indicator member is made of acrylonitrile butadiene styrene ("ABS"), a material that is amenable to certain alternative processes for printing or applying indicia, including pad printing and hot foil stamping. The cap member and base member are preferably made of a hard plastic material, such as Acetel.

[0039] 15-20 and 32, the drive assembly is shown to include a drive assembly 80 disposed between the cap and base. The drive assembly includes a ratchet wheel 82 coaxially mounted to a drive member attached to an axle 84. The ratchet wheel, drive member, and axle may be made separately and the ratchet wheel and drive member may then be attached to the axle, or all three components may be integrally molded as a unitary piece. The drive assembly is preferably made of a hard plastic material, such as Acetel.

[0040] The ratchet wheel 82 has a plurality (preferably ten) of teeth 88 formed around its circumference. Each of the teeth has an engagement surface 89 and a tapered surface 87. The drive member 86 has a single tooth 81 extending radially from the axle 84. The drive assembly is attached to the cap member by engaging opposite ends of the axle 84 with downwardly extending hub portions 36, 236, so that the axle, ratchet wheel, and drive member are adapted for axial movement of the cap member relative to the base member and rotation about an axis substantially perpendicular to the axis of rotation of the indicator member. Alternatively, the drive assembly may be attached to the base member in a similar manner.

[0041] The drive mechanism further includes a pawl member 48, shown as a flexible rod or finger, which extends upward from the bottom portion of the base member and selectively engages one of the teeth of the ratchet wheel. Alternatively, the pawl member may be movably secured to the cap member and extend through the base member to engage the top of the container, such that axial movement of the cap member toward the container moves the pawl toward the ratchet wheel and engages one of the teeth of the ratchet wheel as described above. A non-return member 238, also shown as a flexible rod or finger, extends downward from the top portion of the cap member and selectively engages another one of the teeth 88 of the ratchet wheel. It should be understood that the pawl member may alternatively extend from the cap member (and the non-return member may extend from the base member) when the drive assembly is attached to the base member, as described above.

[0042] In operation, as shown in Figures 15-18 and 32, a user presses the cap member 220 from a fully extended position (see Figure 15) downwards towards the base member until the cap member bottoms out within the base member at the bottom of its stroke (Figure 16) and the base member applies an axial load to the container until a metered dose is dispensed from the container. In a preferred embodiment, the biasing force of spring 100 or another return mechanism, such as a resilient arm member acting as a spring, is less than the biasing force of a spring in the metering valve of the container, so that the cap member first bottoms out within the base member and then the container is moved downwardly within the housing until a metered dose is dispensed.

[0043] 15-17, as the cap member 220 is depressed toward the base member 40, the pawl 48 selectively engages the engagement surface 89 of one of the ratchet wheel teeth to rotate the ratchet wheel. The tapered surface 87 of one of the teeth formed on the ratchet wheel simultaneously urges the non-return member 238 outward until the non-return member selectively engages the next tooth near the bottom of its stroke. The user then releases the cap member, whereupon the spring 100 or similar return mechanism urges the cap member 220 away from the base member 40 until the engagement member engages the base portion at the top of its stroke, as shown in FIG. 18. When the user releases the cap member, the container is urged upward within the housing along the longitudinal axis, thereby moving the valve stem into a closed position within the container. At the same time, as the cap member is released and moves away from the base member, the pawl 48 is urged outward by the tapered surface 87 of one of the ratchet wheel teeth, as the non-return member 238 prevents its backward rotation, maintaining unidirectional rotation of the ratchet wheel. At the top of the stroke (shown in FIG. 18 ), the pawl 48 is again positioned for selective engagement with one of the ratchet wheel teeth. Thus, the ratchet wheel 82 and its associated drive member 86 advance a small amount with each actuation of the container and the resulting release of medication. The small amount is determined by and depends on the number of teeth formed along the circumference of the ratchet wheel. With ten teeth as shown in the preferred embodiment, the ratchet wheel rotates one full revolution for ten actuations of the indicator member and container, or one-tenth of a revolution for each actuation. As will be appreciated by those skilled in the art, the ratchet wheel may have a varying number of teeth formed along its circumference such that around ten axial movements or actuations of the container are required to produce one complete rotation of the ratchet wheel.As can be appreciated, the various movements of the ratchet and indexing portions of the drive and non-return mechanism result in various clicking sounds during each actuation of the dose counter.

[0044] As noted, the mechanical dose counter or TMAI 6, and particularly the base member 40, in one embodiment, is attached to the top of the MDI or to the bottom 14 of the container 12, and together form one half of the MDI's user interface. The TMAI 6 is attached to the MDI canister by a polymer label, which is wrapped around both devices as shown in FIG. 1.

[0045] In one embodiment, the integrated dose indicator includes an electronics module 4 that can be combined with a mechanical dose counter, e.g., a TMAI 6, and attached to the bottom of the TMAI via a fastening system, such that the TMAI and electronics module form an assembly. Various fastening systems or attachment devices can include modifications to the bottom of the TMAI that form an extension, e.g., a circumferential skirt, that accommodates and houses the EM. Other attachment methods can include adhesives that permanently or releasably attach the EM to the TMAI. The final eTMAI assembly is then attached to the MDI, e.g., with a polymeric label wrap 600, 1600, 1602, as shown in Figures 6, 7, 41A, 41B, 42A, and 42B. To ensure that the EM is suitable for label wrapping, a conventional method of connecting a TMAI and an MDI, the maximum diameter of the integrated TMAI and EM needs to be equal to or less than the diameter of the TMAI alone. Additionally, it may be desirable for the EM to be as short (longitudinal) as possible, thus adding as little height as possible to the final integrated assembly. By minimizing the increase in overall assembly height and the distance between the top of the TMAI and the bottom working surface of the housing 200, the addition of the EM does not adversely affect the usability of existing MDIs. As noted above, the EM preferably remains within the maximum diameter dictated by the diameter of the existing MDI canister and TMAI. Thus, the height, which is preferably minimized, combined with the maximum diameter defines the usable volume and cylindrical shape that fits within that volume, and the EM must be configured within this volume, for example, as shown in FIG. 2.

[0046] Referring to Figures 3, 5 and 28, the electronic module may include one or more of the following elements: 1. Force sensor 602 that detects the force applied to the system by the user exerting a force on top of the TMAI. 2. Coin cell lithium-ion battery 604 3. Printed Circuit Board Assembly (PCBA) 606 4. Bluetooth® Low Energy Module / Transceiver 608 (e.g., Nordic Chip) 5. LED610 6. On / Off Switch 612 7. Infrared LED and Phototransistor (IR LED & PT) 8. Microcontroller (in BTLE SoC) 9. Accelerometer

[0047] Electronic Module (EM) Description:

[0048] The EM registers the time and date when the MDI (and mechanical dose counter) is activated and stores this information. Wireless means may be incorporated into the EM so that the activation data stored in the device can be transmitted to another device, such as a smartphone, where the data can be analyzed, processed, and presented in a meaningful way to the patient or healthcare provider via a software application (app), as shown in Figures 30 and 31 , for example. The EM may be attached to the bottom of the TMAI, which may require minor modifications to the TMAI, but otherwise leaves the TMAI counter mechanism unaltered. In this way, the EM can be incorporated into existing MDI and TMAI systems or allows for the retrofitting of such systems, so that it has been found that TMAI mechanical dose counters do not need to be significantly modified to add EM functionality. Furthermore, manufacturing can be simplified by adding the EM module as an assembly step without extensive modifications to existing TMAI assembly processes.

[0049] During actuation, the user applies an actuation force to the top of the TMAI and the bottom of the MDI, causing displacement of both the TMAI and MDI mechanisms, which is required for both devices to operate, i.e., for the TMAI to measure out a medication dose and the MDI to release it, as shown in Figure 3.

[0050] The EM receives applied force directed at it through the bottom of the TMAI and the MDI, particularly the top of the container. In one embodiment, the force sensor may be configured as a force-sensitive resistor (FSR)-type sensor 602, which changes electrical resistance in response to pressure applied to the sensor. Various suitable types of FSR sensors are provided, and a preferred embodiment uses a pressure-sensitive conductive sheet (Velostat) as shown in FIG. 28. The FSR is a preferred sensor configuration due to its low power consumption requirements. Due to packaging (size) and cost constraints, low power consumption is a consideration. Velostat-based FSRs, when properly configured within a target design, are extremely inexpensive, which is an advantage compared to other, more costly FSR-type sensors. In this application, the Velostat material is incorporated into the design between two conductive layers to form a sandwich. This sandwich provides an effective configuration for the FSR, as shown in FIG. 28. Alternative FSRs can be used, including those configured as shown in Figure 5 and including an active area 302, a plastic spacer 304, and a conductive film 306. It should be understood that other force sensors suitable for integration into the EM can be used, including, but not limited to, resistive, capacitive, piezoelectric, load cell, and / or microelectromechanical systems (EMES) force sensors, and / or combinations thereof. Referring to Figure 45, in one embodiment, an eTMAI includes an EM and a TMAI architecture with various inputs and outputs, including BOL (beginning of operational life), FTA (force to actuate the TMAI), and FTF (force to fire the pMDI) inputs.

[0051] Battery:

[0052] In one embodiment, the battery 604 in the EM can be a standard coin-cell lithium-ion (Li-ion) battery. Coin-cell Li-ion batteries are readily available in a wide variety of configurations suitable for this application, thus providing a low-cost battery option for portable electronics. Second, coin-cell Li-ion batteries have an energy storage capacity suitable for this application. Third, coin-cell Li-ion batteries have a circular shape suitable for integration requirements. For example, coin-cell Li-ion batteries can be configured in a cylindrical format with diameters that match the TMAI and EM. In this way, the largest possible coin-cell Li-ion battery can be selected within the maximum diameter constraints imposed by the TMAI / MDI, thereby achieving maximum storage capacity with the lowest possible height. The outer diameter of a TMAI / MDI canister is typically 22 mm to 24 mm. One particular battery suitable for this application is the CR2012 (20 mm diameter, 1.2 mm height, 50 mAh capacity). At 20 mm in diameter, the battery fits within the 22 mm diameter constraint of the TMAI / MDI canister, leaving enough room for the plastic walls to accommodate this assembly in its final form. This allows for label wrapping of the entire TMAI-EM assembly, a method currently used by manufacturers to couple existing TMAIs to MDI canisters.

[0053] In an alternative embodiment shown in Figures 41A, 41B, 42A, and 42B, batteries 1600, 1602 are constructed using imprinted flexible battery technology to produce ultra-thin, flexible printed batteries. Batteries 1600, 1602 can be constructed as imprinted flexible 360° full-wrap batteries. The battery can be wrapped around canister 12 as label 1600 attaches eMTAI 4, 6 to the container, or battery wrap 1602 can be wrapped around only eMTAI components 4, 6 and then covered by label 600 that couples the dose counter to the container.

[0054] Bluetooth Low Energy Transceiver:

[0055] Cost and size are similarly important in selecting an embodiment of the wireless transceiver 608 to enable communication with a smartphone or tablet. As with the selection of a sensor for detecting actuation, low power consumption is a consideration in selecting the transceiver, along with overall size or footprint, to minimize the overall size of the package. One suitable embodiment uses the nRF24L01P 2.4 GHz Bluetooth Low Energy (BLE) transceiver 700, selected for low power consumption and minimal packaging dimensions for integration into the overall PCBA. While a BLE transceiver with only transmit capabilities may be suitable for certain applications, it should be understood that a transceiver with both transmit and receive capabilities may also be suitable for other applications, such as when smartphone-initiated communications enable certain functions of the EM.

[0056] LED:

[0057] A light-emitting diode 610 is configured to provide the user with some feedback regarding the operation of the EM. In one embodiment, the operation of the EM may not be observable in terms of metered-dose inhaler integration, but feedback is considered beneficial for many purposes. In one embodiment, the LED is located behind a label overwrap 600 used to connect the TMAI / EM subassembly to the MDI canister. The label may comprise a polymer label with suitable strength and durability characteristics to maintain optimal device connectivity during use, but also translucency, allowing the user to see the light from the LED through the label. Thus, no further customization of the integrated device is required, yet a convenient and low-cost means of conveying information to the user is provided. Communicable information may include confirmation that activation has been recorded, confirmation of operation, confirmation of communication or connection via smartphone, and troubleshooting diagnostic information in case of problems. Other information regarding the operation of the EM, including information that the EM is being detected, stored, and communicated, is also contemplated. For example, the EM can help a user locate their inhaler if they misplace it or in the dark via an LED.

[0058] Referring to FIG. 40, the EM or eTMAI can include various feedback devices and systems that can be programmed to illuminate in response to various inputs, including, for example, indicator lights 802 (e.g., red and / or green LEDs). In an alternative embodiment, the outer casing can be made of a glow-in-the-dark material to help the user find the inhaler in low-light conditions. Alternatively, the device can include an ambient light sensor so that, in low or no light, the eTMAI periodically pulses an LED to indicate its location, allowing the user to locate the device in a dark room. For example, the system can pulse every 3-5 seconds, or the frequency can be user-programmable according to preference.

[0059] On / Off Switch:

[0060] A switch 612 is provided that allows the module to be turned off to conserve power. Other power control systems may be suitable, for example using an accelerometer to put the device into sleep mode or to wake the device up by remote actuation, for example.

[0061] Referring to FIG. 33 , one embodiment of a wake-up device allows for initial use only during a priming stage, and can wake the device from deep sleep mode using a tactile switch 612. Subsequent counting is performed using the same switch 612. In one suitable embodiment, the tactile switch 612 is a TL3780 Ultra Miniature. The switch is configured in a normally open (“NO”) configuration. A PCBA 606 is attached to the underside of the TMAI. A cantilever arm 700 is molded as part of the eTMAI carrier component, contoured to a cylindrical shape. The arm functions as a lever or lever, pivoting about a prong 704 defined at the primary joint to the base. A force is applied to an engagement pad 702 on the cantilever, which is spaced from the prong 704 by the rim of the cap 20, and the opposite end of the arm 706 engages a switch positioned on the surface of the PCBA facing the base. The switch 612 is sized and shaped to fit into an enlarged notch 708 in the base near the orientation paddle. The engagement pad 702 on the cantilever arm extends upward into the TMAI's interior space 710 and engages the rim of the cap. Any overtravel of the cap 20 is absorbed by the bending compliance of the cantilever arm 700. Closing the switch during the first priming shot brings the processor out of deep sleep. Subsequent TMAI actuations are counted by this same switch.

[0062] Working principle explanation:

[0063] The EM can be integrated with existing mechanical TMAI designs and their manufacturing processes. In one embodiment, the EM can be added as a simple assembly step with easy mounting means. What makes this feasible is that the EM detects actuation events with a force sensor. Similarly, the mechanical TMAI is essentially a mechanical force sensor. When a predetermined force is applied, the mechanical TMAI advances and registers that an actuation of the MDI has occurred. Similarly, the EM detects actuation when a predetermined force is applied, only in this case the EM uses electronic means for detection. Using the same method, the two devices can be "stacked" or placed serially, thereby simplifying integration.

[0064] In operation, a force generated by a user's finger is applied to the top of the TMAI, which is then directed through the TMAI, through the EM, and into the MDI canister or container. In this stack, i.e., serial arrangement, the direct transmission of force into each component ensures stable mechanical contact between the EM and both the TMAI and the MDI canister. This allows for accurate and consistent force transmission, and therefore reliable detection of force events by the EM.

[0065] One component to consider in this configuration is the label wrap 600 that connects the TMAI-EM assembly to the canister. While the stack of TMAI-EM and MDI canisters exerts negligible compression, the assembly should be such that the label wrap does not introduce variability into the force event detection capabilities of the EM. The FSR used in this embodiment is selected not only for cost and integration benefits, but also because it exerts negligible compression. Label materials generally exhibit high compliance, so even when a label is applied, the label does not significantly interfere with the force event detection capabilities of the force sensor.

[0066] Additionally, the coupling system between the EM and the TMAI should be configured to ensure proper force transmission and indication. Force must be transmitted directly from the user's finger through the TMAI, through the EM, and then to the canister. In a preferred embodiment, the bottom of the TMAI is modified to include a cup adapter into which the EM can be pressed. A snap-fit ​​action may be used to capture the EM, although other methods may be used, including adhesives, tape, etc., as discussed above. An extension on the bottom of the TMAI can provide an extended surface area onto which a label can be attached, ensuring seamless integration with the MDI canister and minimizing gaps that may result in creases that are visible to the user. However, in one embodiment, the extension does not contact the top of the MDI canister, thereby preventing direct force transmission from the TMAI to the canister; instead, the force is directed through the EM, avoiding any bypass of the EM and thereby preventing the EM from detecting the force event. In one embodiment, the skirt extends downward from the top of the TMAI, but upon final assembly with the EM, a gap remains between the TMAI skirt and the MDI canister, allowing forces to be directed from the TMAI through the EM and into the MDI canister rather than through the skirt extension, as shown in Figure 6.

[0067] In an alternative embodiment, the arrangement may be reversed, and a separate adapter component may be used to house the EM, as shown in FIG. 7. In this embodiment, the stack is such that the adapter directly contacts the top of the MDI canister, and the EM fits inside it. The TMAI then seats directly on top of the EM. In this embodiment, a gap is required between the adapter and the TMAI, similar to the gap described above with respect to the embodiment of FIG. 6. In this case, various coupling systems may be used to couple the EM to the TMAI, such as with a snap fit, adhesive, etc., as shown in FIG. 7.

[0068] In operation, with reference to Figures 47-52, the EM electronically registers each actuation once a predetermined force is applied to the force sensor. A microprocessor monitors the force response of the force sensor and determines when the actuation occurs. Once an actuation is registered, it is stored in memory. When connected to a smartphone, an information packet is sent that, at a minimum, represents the registered actuation and its corresponding time and date. The EM may further include a decrementing counter that is continuously updated to subtract actuations to calculate the exact "dosage" or "count" remaining. This information may also be sent to the connected device. With reference to Figures 21-23, 27, and 47-52, the operation of the device and system is shown.

[0069] Other variations:

[0070] Alternative locations for EM:

[0071] The EM can operate in a variety of configurations as a dose counter or tracker, whether integrated with the TMAI or not. In one embodiment shown in FIG. 8, the EM 4 can be configured to be integrated with the top of the TMAI rather than the bottom. In this configuration, the user's finger contacts the top of the EM rather than the TMAI, and thus actuation forces are directed through the EM to the top of the TMAI. There are other mechanical considerations that must be considered with this embodiment, including that the EM must define the user interface and therefore be suitable for contact with the user's finger. Additionally, any mechanical counting display provided on the top of the TMAI must be visible and therefore not obscured or obstructed by the addition of the EM, for example, by providing an observation window in the side wall of the TMAI so that the indicators and indicia can be viewed through the observation window.

[0072] In another embodiment, the EM may be a standalone dose counter or tracker by itself, excluding any mechanical devices. The low cost and slim integration of the EM, making it suitable for integration with a mechanical dose counter, are also advantageous in a standalone form. In this embodiment, the EM may or may not include a display element that directly communicates the number of remaining actuations to the user, as does a mechanical dose counter. If configured without a display element, the EM can instead communicate dose or count status and tracking information via a smartphone. Integration of the EM into the top of the MDI canister, similar to the previously described embodiment, requires that the EM form a user interface suitable for the user's finger. Attachment of the EM to the MDI canister can be achieved in a variety of ways, including adhesive or by adding an adapter component that receives the EM and facilitates attachment to the MDI canister, such as a friction-fit collar as shown in FIG. 9 or other attachment means.

[0073] In another embodiment, the EM may be attached to or integrated into the actuator portion or bottom of the actuator housing of the MDI. As a low-cost, force-based counter / tracker, the EM may be well-suited for addition in this configuration because it requires minimal modification to existing and well-established MDI platforms. As with the previous embodiment in which the EM is attached to the MDI canister, the EM in this configuration may also include a display to communicate remaining doses or tracking information, but similarly, no display or screen may be incorporated and instead the screen of a smartphone or connected device may be utilized. Attachment to the bottom of the MDI actuator can be accomplished in many standard ways, including snap-fit, pressure-fit, adhesive, etc. As with the other embodiments, the bottom of the EM becomes part of the user interface where the user applies the actuation force.

[0074] Alternative embodiment - Alternative counting detection method - Infrared sensor displacement sensor:

[0075] Similar to the force sensor described in the preferred embodiment above, whatever actuation detection method is used, the method allows for low power consumption, low cost, and extremely small overall packaging. Another method that meets these requirements uses an infrared LED 620 and a sensor 622 that detects displacement of internal TMAI components. While the TMAI is a force-based counter, it still requires displacement to operate and achieves highly accurate and consistent displacement to operate. In one embodiment, the infrared LED and sensor are mounted on the EM, which has approximately the same overall geometry as the EM described above with the force sensor. However, in this embodiment, instead of a force-based methodology to detect actuation events, the EM uses displacement of the TMAI mechanism, i.e., includes a displacement sensor. In this embodiment, the EM is similarly positioned between the bottom of the TMAI and the top of the MDI canister. The infrared LED and sensor are configured to be directed upward and into the TMAI mechanism, where the infrared LED 620 can illuminate a feature within the TMAI mechanism. The LED light shines vertically upward onto the TMAI, and a sensor 622 senses or reads the reflected light as shown in FIG. 11 , the operation of which is disclosed in FIG. 51 . A displacement sensor may also be provided between the base and cap of the TMAI. It should be understood that other types of displacement sensors besides infrared LEDs with sensors may be suitable, such as various proximity switches. Advantageously, the bottom of the TMAI may already have a number of holes or openings 624 to enable manufacturing and molding. These holes or openings 624, or additional holes, allow the LEDs with sensors to access the internal mechanism and detect the movement of one or more components of the mechanism. Detection may be accomplished by sensing the movement of existing features within the TMAI mechanism, such as any of the elements (caps, gears, supports, guide features, etc.). Alternatively, existing features within the TMAI may be modified to increase the capability and accuracy of displacement detection by the infrared sensor, with minimal modification to the existing TMAI mechanism.This may include optimizing the location and shape of features, as well as color or texture. Additionally, features may be added without affecting the TMAI mechanism, such as flat-topped posts that optimize displacement detection for external sensors and bring mechanical features within closer range of the sensors. Other factors may also be identified for optimization with minimal impact on the basic TMAI mechanism. This may include minimizing ambient light intrusion, which may interfere with the infrared sensor's ability to pick up actuation events. An infrared sensor approach may offer some advantages over force detection, since force detection, as mentioned above, eliminates any integration with the MDI canister. All necessary interfaces to enable accurate operation may be included in the TMAI and EM. In operation, the EM is programmed with a displacement that, once exceeded, will cause the TMAI to register an actuation. For example, in one embodiment, the TMAI has a total travel of approximately 3.5 mm from its normal rest position to bottoming out at its fully depressed position. The actuation point typically occurs about halfway through the stroke.

[0076] Alternative embodiment - Alternative counting detection method - Infrared sensor displacement switch:

[0077] The eTMAI and / or EM are configured to provide various count detection methods and features, including: (1) the aerosol "whoosh" emitted from the canister picked up by a microphone in the eTMAI and recording the actuation count; (2) the air flow in the airflow transmission channel picked up by a flow sensor and recording the actuation count; (3) the pressure drop in the airflow transmission channel picked up by a pressure sensor and recording the actuation count; (4) a temperature sensor in the eTMAI measures the temperature of the canister, which is very cold during actuation, thereby indicating that the device has been used, and thus recording or confirming the actuation count; (5) a microphone in the eTMAI picks up the clicking sound that is the signature of an actuating rotating gear of a mechanical dose counter, such as a TMI dose counter; and / or combinations of the various devices and systems disclosed herein, which can confirm the count and thereby improve the overall accuracy of the system by increasing the accuracy of the data captured and / or reported.

[0078] Alternative embodiment - Alternative counting detection method - Infrared sensor displacement switch:

[0079] An alternative displacement sensor includes many of the same features as the displacement sensor described above, including an infrared LED and sensor; however, rather than measuring displacement to determine whether an activation event has occurred when a predetermined displacement is reached, this alternative embodiment may be used to generate infrared LED light that must be completely blocked by a feature from the TMAI. In this configuration, which also serves as a displacement sensor as shown in FIG. 12, the infrared sensor and detector are arranged in a facing configuration. The LED shines directly at the sensor. Activation is determined when a blocking feature 624 from the moving part of the TMAI is detected by the sensor and interrupts the light beam, which is determined by the CPU to be activated, or when a predetermined displacement measurement condition is met. In this embodiment, which is concerned with reaching a displacement threshold rather than measuring displacement, the system does not need to detect a specific displacement. In this way, the displacement sensor functions as a switch-like configuration (or absolute displacement), and the difference between the deactivated and activated states in terms of detected IR energy is significant, making it more tolerant to interference sources, including external optical emissions. A blocking feature 624 is incorporated into the TMAI, configured to block the light beam from the LED at a predetermined displacement corresponding to the activation point of the TMAI. Because the activation point of the TMAI occurs midway through its travel, provisions must be made for overtravel of the added beam blocking feature.

[0080] Other sensor variations:

[0081] Once the actuation is detected and stored by the EM, and referring to Figures 47-51, the EM can wirelessly transmit the time and date of the actuation and the total number of button presses that occurred to the user's mobile device application.

[0082] Apart from the force and displacement sensors mentioned above, other basic types of sensors or combinations thereof are also suitable, each measuring one or more of the following measurands to detect actuation, such as a button press (downward push). For example, movement can be detected by an IMU sensor, which detects the user pushing a button as well as vibrations caused by a spring-like mechanical part that decrements a mechanical counter. A button push produces a clicking sound, and this noise can be detected by a MEMS microphone. Additionally, mechanical actuation, such as the distance of a button push, can be detected by an IR emitter (LED) and a detector (phototransistor), which behaves like an IR proximity sensor or a displacement sensor as described above.

[0083] In various embodiments, the eTMAI or EM has various detection functions and features, namely: (1) breath detection: sound, flow, or pressure sensors ensure the user is breathing in correctly during medication administration; (2) inhaler identification: identifies the type of medication being used and includes a module that is pre-assembled by the pharmaceutical company, programmed according to the medication type, attached to the canister and mated with the pMDI actuator, and the EM communicates with the pMDI actuator, or vice versa; (3) shaking detection: an accelerometer 900 shaking detection sensor, monitors shaking events and / or the effectiveness of shaking to properly mix the medication before use; (4) canister temperature actuation detection: the temperature of the canister is increased upon actuation due to the rapid expansion of the propellant; This indicates that the device has been used / triggered; (5) Acoustic Activation Detection: A microphone mounted on or near the canister listens to sounds from inside the canister, and the canister amplifies the sound like a speaker box; (6) Chemical Sensor Activation Detection: A chemical / biomarker odor sensor detects the type of agent activated and / or the propellant released; (7) Humidity or Moisture Sensor Activation Detection: A humidity sensor to detect the amount of humidity at the time of agent release confirms activation; (8) Movement or Handling Detection and Tracking: Information, interpretation of accelerometer data, technology used; and (9) Location: In one embodiment, it may be configured to provide the geographic or physical location of the device coupled to the application.

[0084] Detailed embodiments for detecting inhalation detection:

[0085] Current TMAIs sit on top of the MDI canister and are generally detached from the MDI's air inlet, which is formed by the gap between the exterior wall of the pMDI canister and the interior wall of the pMDI actuator body. In one embodiment, with reference to FIGS. 35-39, multiple air inlets 330 or channels, shown as two, are formed in the sidewall of the EM housing. One or more outlets 332 are also formed in the bottom of the EM. A flow passage 336 is formed between the inlets 330 and the outlets 332. One or more sensors 334 can be provided on the bottom of the EM circuit board and within the flow passage. In this manner, the eTMAI's EM is configured to confirm breath detection. A top-mounted dose counter EM is attached to the top of the medication canister 12. An extension configured as a skirt 320 can be coupled to the EM, thereby extending multiple airflow path communication channels 338 into the interior of the MDI boot. The airflow path communication channel 338 is configured to allow air inhaled by the patient during inspiration to flow through the inlet 330 and flow passage 336, and through the outlet 332 and into the channel 338. When the eTMAI is coupled to the canister, the air inlet channel must be able to move relative to the pMDI actuator so that this movement is unimpeded and effective actuation of the pMDI can occur. Therefore, the air inlet channel walls can be made of a two-shot soft silicone rubber material to conform to the MDI shape by mating with the soft plastic in a precise manner that allows movement during actuation while minimizing gaps. Importantly, a relatively leak-tight and movable seal can be formed to allow a sufficient and consistent flow of air to be inhaled through the air inlet channel 338 so that a sufficient inspiratory flow signature is present for the sensors to register the flow. In one embodiment, flow, pressure, and microphone sensors can be located within the EM of the eTMAI.In use, air is drawn in either through ports 330 in the TMAI body, through existing gaps in the design that allow sufficient airflow, or through dedicated ports 330. The ports are designed in such a way that a sufficient amount of airflow is directed over the sensor 334.

[0086] Referring to Figures 35-38, the skirt that fits around the dose counter fits within the MDI boot, has a shape that allows for up-and-down sliding movement, and forms the same airflow path communication channel described above, allowing airflow to communicate with the eTMAI sensor. The skirt and flow channel can direct air past one or more sensors. For example, the sensor may include a microphone that picks up changes in sound as the flow increases or decreases. Alternatively, a pressure sensor may respond to the vacuum created during inspiration, providing an output located near the flow. In both cases, an algorithm may be used to modify the sound or pressure output from the sensor to the airflow. Flow, sound, and / or pressure sensors may be located within the EM or at some point within the flow channel or skirt. In the latter embodiment, this allows the sensor to be positioned near where the flow source may be, thereby increasing the sensitivity and robustness of the reading. The EM can communicate with the sensor via a connector wire or wireless communication.

[0087] The canister has a first end with a valve stem coupled to the boot, and an electronics module is coupled to an opposite second end of the canister. A skirt is disposed in the space between the exterior surface of the canister and the interior surface of the actuator boot. The skirt extends along the side of the canister. A channel 338 extends longitudinally and defines an outlet port 340 at the bottom of the skirt.

[0088] Referring to FIG. 37 , in one embodiment, the eTMAI has two units or modules 352, 354, where module 354 is both reusable and replaceable, and module 352 is consumable or disposable. Separating the modules into two parts reduces manufacturing costs and makes it easier for users to access the smartphone app, since they do not need to customize and program their device every time they purchase a new boot. Programming and customization only need to be performed once for module 354. However, module 352 can automatically connect to module 354 upon installation and wake up from deep sleep mode. Module 354 may be bonded to the exterior of the actuator boot, for example, with an adhesive, and may include a large rechargeable battery, while the small, non-reusable unit 352 may include a coin-cell battery in a top-mounted mechanical counter. The mechanical counter and the electronic unit 352 attached to the canister are not reusable. The two units communicate over very low power, with the main unit 354 then transmitting the signal further to a smartphone application or other communication system.

[0089] A microcontroller equipped with one or more motion, sound, and / or distance sensors may be used to complete the task of detecting a user button press. The sensor input data is processed by the microcontroller to detect whether an actuation, such as a user button press, has occurred and is then transmitted to the mobile app via wireless communication. The microcontroller does not necessarily need embedded wireless communication capabilities to transmit data to the mobile device. Instead, the microcontroller may have an external wireless transceiver IC.

[0090] Some example selection parameters for microcontroller selection are listed below, where the microcontroller selection applies to both microcontrollers with and without embedded wireless communication capabilities.

[0091] Small form factor. For example, it is smaller than VFQFN-20 for microcontrollers without a BLE transceiver, and smaller than VFQFN-48 for microcontrollers with an internal wireless transceiver.

[0092] Can operate at a supply voltage of 1.8V to 3.6V.

[0093] Internal RC oscillator (both fast and slow clocks). SoCs with embedded wireless transceivers may include an external crystal.

[0094] Equipped with SPI communication capability, required for microcontrollers without embedded wireless transceivers and for the need to communicate with external transceivers such as the nRF24L01+. SPI (or I 2 C / TWI) may also be required if sensors, e.g., IMUs, are used.

[0095] Equipped with ADC block. Needed for MEMS microphone and IR detector (phototransistor). · It has an internal reference voltage for the ADC. The sensor is SPI (or 2 This is not necessary when using C / TWI.

[0096] Low power consumption. For example, less than 10µA in sleep mode.

[0097] Have enough RAM and flash to handle click detection (should that be required).

[0098] The microcontroller may further include Bluetooth To reduce the overall cost of the click detection module, one embodiment includes a separate transceiver for BLE communication.

[0099] The sensor parameters utilized for click detection include:

[0100] Small form factor. For example, smaller than VFQFN-20 and less than 1mm high.

[0101] It can operate at a supply voltage of 1.8V to 3.6V.

[0102] SPI or I when using digital communication for data output 2 C communication is used.

[0103] Low power consumption. For example, less than 10µA in low power mode (averaged over 1 hour of operation).

[0104] Another sensor may be an Inertial Measurement Unit 900 (IMU) = gyro, accelerometer, etc. A push button TMAI device generates vibrations when the button is depressed, both from the movement of the button being depressed and from the clicking mechanism that decrements a mechanical counter. This movement can be captured by the IMU sensor 900, e.g., an accelerometer.

[0105] Vibrations resulting from actuation, e.g., a button press, are captured by the IMU sensor 900, which then triggers an interrupt event and sends a wake-up signal to the microcontroller 902. The microcontroller 902 wakes up from sleep mode and IMU2. Begin recording IMU sensor data for 10 seconds. Once data collection is complete, the recorded data is processed using a DSP algorithm (e.g., FFT or Goertzel algorithm) along with the previously recorded button press profile data to determine if the button was pressed.

[0106] The IMU sensor can operate in a low-power mode until motion is detected, and then outputs an event trigger signal for the microcontroller to wake up (the trigger event occurs when one or more axis readings exceed a programmed threshold). This reduces overall power consumption for both the IMU and the microcontroller, as the microcontroller does not need to continuously poll to check if motion has been detected.

[0107] One suitable IMU embodiment is the KXTJ3-1057 accelerometer. The IMU sensor has vibration detection capability and consumes relatively low power (i.e., 0.9 and 10 μA) during both sleep and sensor reading modes. In one embodiment, the vibration caused by a button press is due to a clicking sound that comes from a spring-like mechanical component within the mechanical dose counter.

[0108] In another embodiment, the push button device consists of a mechanical counter that decrements the counter value each time the user presses the button. When the counter decrements, a click is generated that is captured by a microphone. The click resulting from actuation is picked up by the microphone and an audio signal is read by the microcontroller ADC. The microcontroller converts the audio data into T ACD Once data collection is complete, the recorded audio data is processed using a DSP algorithm (e.g., FFT or Goertz algorithm) along with the previously recorded button press profile data to determine if a button was pressed. After processing is complete, the microcontrollersleep and then repeats the previous steps. In one embodiment, a digital MEMS microphone with an internal amplifier (with a PDM signal output) can be used.

[0109] In another embodiment, small holes are provided under the mechanical dose counter through which the cap depression action can be observed. That is, as the cap is depressed, a spring-like mechanical component approaches the hole. A proximity or displacement sensor can detect the distance of the mechanical component through the hole, which then detects whether the cap and mechanical dose counter have been activated. The cap depression is detected by a microcontroller using a combination of IR detectors and emitters. The microcontroller then ADC IR The microcontroller reads the IR detector (phototransistor) data for T seconds. Once data collection is complete, the recorded IR intensity (distance) data is processed to determine if a button was pressed or not. After processing is complete, the microcontroller sleep and repeats the previous steps.

[0110] Various microcontrollers operate only in a Bluetooth advertising mode or establish a connection between a mobile device and the microcontroller itself.

[0111] As shown in Figure 26, the EM includes a battery, PCB, and components. The overall module diameter is 20 mm, and the maximum height between the battery and the largest circuit component (centered with the IC) is 2.55 mm. The height of the module near the edge of the PCB between the battery and the PCB is 1.6 mm, which indicates that the module can fit within the required internal volume, assuming the concave curvature of the inhaler metal capsule exists.

[0112] To enable rapid and accurate processing of sensor data generated within the EM, the data may be wirelessly transmitted to a smartphone, local computing device, and / or remote computing device for interpreting and acting on the raw sensor data.

[0113] In one embodiment, the EM includes circuitry that transmits raw sensor data in real time to a local device, such as a smartphone. The smartphone can display graphics or instructions to the user and execute processing software to interpret and act on the raw data. The smartphone may include software that filters and processes the raw sensor data and outputs relevant status information contained in the raw sensor data to the smartphone's display. The smartphone or other local computing device may alternatively use its local resources to contact a remote database or server to retrieve processing instructions or forward raw sensor data for remote processing and interpretation, and receive processed and interpreted sensor data back from the remote server for display to the user or caregiver accompanying the MDI user.

[0114] In addition to simply providing data, statistics, or instructions to a display on a smartphone or other local computer located near an MDI equipped with an EM, proactive operations associated with the MDI can be actively managed and controlled. For example, if a smartphone or other local computer located near the MDI determines that sensor data indicates that the end of treatment has been reached, the smartphone or other local computing device can communicate directly with the EM to provide a signal, such as an audio or visual signal. In yet another embodiment, real-time data collected by the EM and streamed to a remote server via the smartphone can trigger the remote server to seek out and notify a physician or supervising caregiver regarding a problem with a particular medication administration session or a pattern that has developed over time based on past sessions for a particular user. Based on data from one or more sensors in the EM, the remote server can generate and send an alert to the user's physician or other caregiver via text, email, or other electronic communication medium.

[0115] The electronic circuitry, local computing device, and / or remote server within the EM described above may include some or all of the capabilities of computer 500, which is in communication with network 526 and / or in direct communication with other computers. As shown in FIG. 30, computer 500 may include processor 502, storage device 516, display or other output device 510, input device 512, and network interface device 520, all connected to one another via bus 508. A battery 503 is coupled to the computer to power it. The computer may communicate with the network. Processor 502 represents a central processing unit of any type of architecture, such as Complex Instruction Set Computing (CISC), Reduced Instruction Set Computing (RISC), Very Long Instruction Word (VLIW), or hybrid architecture, although any suitable processor may be used. Processor 502 executes instructions and includes the portion of computer 500 that controls the overall operation of the computer. 31, the processor 502 typically includes a control unit that organizes data and program storage areas in memory and transfers data and other information between various portions of the computer 500. The processor 502 receives input data from an input device 512 and a network 526, which reads and stores instructions (e.g., processor executable code) 524 and data in main memory 504, e.g., random access memory (RAM), static memory 506, e.g., read-only memory (ROM), and memory device 516. The processor 502 can provide data to a user by way of an output device 510.

[0116] Although computer 500 is shown as including only a single processor 502 and a single bus 508, the disclosed embodiments apply equally to computers that may have multiple processors and multiple buses, some or all of which perform different functions in different ways.

[0117] Storage 516 represents one or more mechanisms for storing data. For example, storage 516 may include computer-readable media 522, such as read-only memory (ROM), RAM, non-volatile storage media, optical storage media, flash memory devices, and / or other machine-readable media. In other embodiments, any suitable type of storage may be used. While only one storage device 516 is shown, multiple storage devices and multiple types of storage devices may be present. Furthermore, while computer 500 is depicted as having storage device 516, computer 500 may be distributed across other computers, such as on a server.

[0118] The storage device 516 may include a computer-readable medium 522 containing instructions 524 executable on the processor 502 to perform the functions described above in connection with the controller (not shown) and processing of sensor data, to display sensor data or instructions based on the sensor data, to control aspects of the smart nebulizer to modify its operation, or to contact third parties or other remotely located resources to provide update information to or retrieve data from such remotely located resources. In another embodiment, some or all of the functions are implemented by hardware instead of a processor-based system. In one embodiment, the controller is a web browser, but in other embodiments, the controller may be a database system, a file system, an email system, a media manager, an image manager, or any other functionality capable of accessing data items. The storage device 516 may also include additional software and data (not shown) that are not necessary to understanding the present invention.

[0119] Output device 510 is the portion of computer 500 that displays output to a user. Output device 510 may be a liquid crystal display (LCD), which is well known in the computer hardware art. In other embodiments, output device 510 may be replaced by a gas or plasma-based flat panel display or a traditional cathode ray tube (CRT) display. In still other embodiments, any suitable display device may be used. Although only one output device 510 is shown, in other embodiments, any number of output devices, of different or the same type, may be present. In one embodiment, output device 510 displays a user interface. Input device 512 may be a keyboard, a mouse or other pointing device, a trackball, a touchpad, a touchscreen, a keypad, a microphone, a voice recognition device, or any other suitable mechanism for a user to input data into computer 500 and operate the user interface described above. Although only one input device 512 is shown, in other embodiments, any number and type of input devices may be present.

[0120] The network interface device 520 provides connectivity from the computer 500 to a network 526 via any suitable communication protocol. The network interface device 520 sends and receives data items to and from the network 526 via a wireless or wired transceiver 514. The transceiver 514 may be cellular frequency, radio frequency (RF), infrared (IR), or any of a number of known wireless or wired transmission systems capable of communicating with the network 526 or other smart devices 102 having some or all of the features of the example computer of FIG. 2. The bus 508 may represent one or more buses, such as USB, PCI, ISA (Industry Standard Architecture), X-Bus, EISA (Extended Industry Standard Architecture), or any other suitable bus and / or bridge (also called a bus controller).

[0121] Computer 500 may be implemented using any suitable hardware and / or software, such as a personal computer or other electronic computing device. Computer 500 may be a portable computer, laptop, tablet, or notebook computer, a smartphone, a PDA, a pocket computer, an appliance, a telephone, or a mainframe computer are examples of other possible forms of computer 500. Network 526 may be any suitable network, and network 526 may support any suitable protocol suitable for communication to computer 500. In one embodiment, network 526 may support wireless communication. In another embodiment, network 526 may support hardwired communication, such as telephone lines or cables. In another embodiment, network 526 may support the Ethernet IEEE (Institute of Electrical and Electronics Engineers) 802.3x specification. In another embodiment, network 526 may be the Internet, and such a network may support IP (Internet Protocol). In another embodiment, network 526 may be a LAN or WAN. In another embodiment, network 526 may be a hotspot service provider network. In another embodiment, network 526 may be an intranet. In another embodiment, network 526 may be a General Packet Radio Service (GPRS) network. In another embodiment, network 526 may be any suitable cellular data network or cell-based wireless network technology. In another embodiment, network 526 may be an IEEE 802.11 wireless network. In yet another embodiment, network 526 may be any suitable network or combination of networks.Although one network 526 is shown, in other embodiments, any number of networks (of the same type or of different types) may be present.

[0122] It should be understood that the various techniques described herein can be implemented in connection with hardware or software, or a combination of both, where applicable. Thus, the methods and apparatus of the present invention disclosed herein, or certain aspects or portions thereof, may be in the form of program code (i.e., instructions) embodied in a tangible medium, such as a floppy disk, CD-ROM, hard drive, or any other machine-readable storage medium, such that when the program code is loaded into and executed by a machine, such as a computer, the machine becomes an apparatus for implementing the invention disclosed herein. In the case of program code execution on a programmable computer, the computing device generally includes a processor, a processor-readable storage medium (including volatile and nonvolatile memory and / or storage elements), at least one input device, and at least one output device. One or more programs may embody or use the processes described in connection with the invention disclosed herein, for example, through the use of an API, reusable controller, etc. Such programs may be implemented in a high-level procedural or object-oriented programming language to communicate with a computer system. However, the programs may also be implemented in assembly or machine language, if desired. In either case, the language may be a compiled or interpreted language, and the language may be combined with hardware implementations. While example embodiments may refer to use of the inventive aspects disclosed herein in connection with one or more stand-alone computer systems, the invention is not so limited and may instead be embodied in connection with any computing environment, such as a networked or distributed computing environment. Furthermore, the inventive aspects disclosed herein may be embodied within or among multiple processing chips or devices, and storage may similarly be spread across multiple devices. Such devices may include, for example, personal computers, network servers, and handheld devices.

[0123] Referring to Figures 43 to 45, eTMAI4, 6 are designed to be able to communicate with other nearby devices if necessary, and may include one or more connection protocols, such as (1) proximity (0 to 10 m): NFC, RFID, (2) wireless personal area network (10 to 100 m): BLE, ZigBee, ISA100, (3) wireless local area network (100 to 1000 m): 802.11 IEEE, (4) wireless neighborhood area network (approximately 5 to 10 km): Wi-SUN, and / or (5) wireless wide area network (up to 100 km): cellular (LTE CAT M1, 4G, 5G, LPWAN, SigFox, LoRa).

[0124] In one embodiment shown in FIG. 43, a smart valved holding chamber 950 (SVHC) can communicate with the eTMAI 4, 6. To best confirm that the medication released by the eTMAI has been inhaled, the SVHC 950, when used inline with the eTMAI, can detect inhalation detection and completion of inhalation, ensuring compliance that medication inhalation / delivery has occurred and the patient has inhaled. Compliance data captured by the eTMAI and SVHC is transmitted to the SVHC's smartphone application, where it is analyzed and displayed on the screen. Inhalation confirmation is a combination of inhalation detection and completion of inhalation. The VHC / SVHC helps ensure the correct amount of medication is properly delivered to the lungs, not the back of the throat. The SVHC can also recognize actuation detection, inhalation detection, and completion of inhalation, and provide an event timestamp. This combination thereby provides high value (assurance and reliability) to the user and compliance tracking. At the same time, the eTMAI can recognize the medication used and the number of doses remaining in the canister. Referring to FIG. 44, the eTMAI is connected to a smartphone application and other associated medical devices, which may include a smart vibrating positive expiratory pressure device 960, a smart nebulizer device 970, a smart valved holding chamber 950, and / or a smart peak flow device 980. The eTMAI can thus couple itself to a range of other nearby smart devices. In an exemplary connected environment, a virtual assistant may be connected to provide reminders to the user to take specific medications, or a Philips Hue programmable light may provide a visual output, e.g., a specific color at a specific time, as a reminder that an MDI medication has been taken. Alternatively, a smartwatch may provide reminders regarding the time and type of medication to be taken.

[0125] Alternative feedback embodiments:

[0126] In another embodiment, a tactile feedback module may be located inside the eTMAI, which generates vibrations that notify the user by emitting buzzing sounds at different frequencies, and which may be programmed by the user during application setup.

[0127] In other embodiments, various speakers may provide auditory or audible feedback including, for example, musical tones and / or spoken voices notifying the user of activity events such as (a) a buzzer or beep accompanied by a green LED flashing once, or vice versa, for good technique; (b) a buzzer or beep accompanied by two red LEDs flashing twice, or vice versa, for poor technique; or (c) a buzzer accompanied by a sound or melody (programmable via the app) that reminds the user to take their medication at a preset time.

[0128] In other embodiments, the scent-releasing system may provide olfactory or scent feedback, including a device that emits scent A when drug A is used and scent B when drug B is used. The scent emitter may be a scratch-off olfactory label applied by the drug manufacturer. Scent-releasing systems may be particularly useful for deaf or blind individuals in identifying medications being dispensed via an MDI.

[0129] In another embodiment, the device may include a Braille indicator 804, for example including an on / off protruding feature, or may display a letter in Braille representing a Drug A canister and another letter representing a Drug B canister by hand.

[0130] In another embodiment, the system may include a detection device that can be activated, for example, by pressing an icon on an application, to locate a nearby inhaler, or the system may incorporate hardware that responds to auditory input, for example, a whistle or clap, and the device, for example equipped with a microphone, will provide an auditory output or signal, for example a whistle or a reply or response sound (so that the location of the inhaler is known).

[0131] While the present invention has been described with reference to preferred embodiments, those skilled in the art will recognize that changes can be made in form and detail without departing from the spirit and scope of the invention. Accordingly, it is intended that the foregoing detailed description be considered illustrative rather than limiting of the invention, and that the appended claims, including all equivalents thereof, define the scope of the invention.

Claims

1. 1. A display device for indicating actuation of a metered dose inhaler having a medication container, comprising: a mechanical dose counter having a cap movable relative to a base along a longitudinal axis between a first position and a second position when a predetermined force is applied to the cap, the mechanical dose counter being adapted to register axial movement of the cap relative to the base and corresponding actuation of the medication container in response to application of the predetermined force, the base having a bottom configured to be coupled to the medication container; a display device comprising: an electronic module directly coupled to the bottom of the base of the mechanical dose counter such that the electronic module is positioned above the medication container, the electronic module adapted to record an actuation force of relative movement of the cap and the base between the first position and the second position.

2. The display device of claim 1 , wherein at least one of the base and the electronic module is adapted to be coupled to the medication container.

3. The display device of claim 1 , further comprising a wrap surrounding at least a peripheral portion of the base and the electronic module, the wrap coupling the base to the electronic module.

4. 10. The display device of claim 1, wherein the electronic module has a cross-sectional area perpendicular to the longitudinal axis that is less than or equal to a cross-sectional area of ​​the mechanical dose counter perpendicular to the longitudinal axis.

5. The display device of claim 1 , wherein the electronic module comprises a force sensor.

6. The display device of claim 1 , wherein the electronic module comprises an inertial measurement unit sensor.

7. The display device of claim 6 , wherein the inertial measurement unit sensor comprises an accelerometer.

8. 10. The display device of claim 1, wherein the electronic module comprises a microphone.

9. 9. The display device of claim 8, wherein the microphone is adapted to pick up the sound of operation of the mechanical dose counter in response to the movement of the component between the first position and the second position.

10. 2. The display device of claim 1, wherein said electronic module comprises a displacement sensor responsive to said movement of said component between said first position and said second position.

11. The display device according to claim 10 , wherein the displacement sensor comprises an infrared displacement sensor.

12. The display device of claim 3 , wherein the wrap comprises an LED.

13. The display device of claim 12 , wherein the wrap is translucent and covers the LED.

14. The display device of claim 3 , wherein the wrap has an adhesive that bonds the base and the electronic module together.

Images