Patent Publication Number: US-2023141645-A1

Title: Intraoral aerosol delivery device

Description:
FIELD OF THE INVENTION 
     The present invention relates to mist-delivery devices and refillable and/or replaceable containers for use therein, and to methods for using such devices. In particular the present invention relates to devices for intraoral use for delivering an aerosol to a user&#39;s oropharynx. 
     BACKGROUND 
     EXisting oral inhalers suffer from the problem that any mist produced must traverse the tongue and other parts of the oral cavity, causing part of any dosed substance to fail to reach the oropharynx. Therefore a need exists for an intraoral inhaler capable of delivering a precise dosage of a substance to a user&#39;s oropharynx, preferably configured to place a mist-generating location and/or mist-exiting location of the inhaler far enough into the oral cavity to overcome the aforementioned shortcoming. There is also a need for such an inhalation device to be compact and comfortable to use. 
     SUMMARY 
     According to embodiments disclosed herein, an electrically-powered inhalation device for delivery of an aerosol to the oropharynx of a user comprises: (a) respective proximal and distal portions, the proximal portion including an inlet for a liquid, the distal portion including (i) an aerosol outlet defining a mist-exiting location and (ii) a piezo assembly including an ultrasonically vibrable mesh membrane, for producing, upon electrical activation, a mist comprising droplets of the liquid, the mesh membrane defining a mist-generating location; and (b) an intermediate portion disposed distally from the proximal portion and proximally from the distal portion, wherein the inhalation device is shaped such that when the user&#39;s lips and/or teeth are transversely engaged with the intermediate portion, the mist-generating location resides within the user&#39;s oral cavity and the mist-exiting location is in direct fluid communication with the user&#39;s oropharynx. 
     According to embodiments, an electrically-powered inhalation device for delivery of an aerosol to the oropharynx of a user comprises: (a) respective proximal and distal portions, the proximal portion including an inlet for a liquid, the distal portion including (i) an aerosol outlet defining a mist-exiting location and (ii) a piezo assembly including an ultrasonically vibrable mesh membrane, for producing, upon electrical activation, a mist comprising droplets of the liquid, the mesh membrane defining a mist-generating location; and (b) an intermediate portion disposed distally from the proximal portion and proximally from the distal portion, wherein the distal portion is dimensioned to vertically span the user&#39;s oral cavity from tongue to hard-palate when the user&#39;s lips and/or teeth are transversely engaged with the intermediate portion, so as to place the mist-exiting location in fluid communication with the user&#39;s oropharynx. 
     In some embodiments, the liquid-inlet can be configured to receive liquid from a container, the liquid-inlet and the container having respective mating arrangements for mating with each other. In some embodiments, the mating can be reversible. 
     In some embodiments, the container can be detachably attachable to the proximal portion. In some embodiments, the inhalation device can additionally comprise the container. In some embodiments, the proximal portion can comprise a compartment for storing the liquid. 
     In some embodiments, the inhalation device can additionally comprise a portable power source. In some embodiments, the inhalation device can additionally comprise an inhalation sensor for monitoring a flow in an inhalation flow-path. In some embodiments, the inhalation sensor can be effective to detect an air pressure in the inhalation-flow path. In some embodiments, the inhalation sensor can be effective to detect a difference between an air pressure in the inhalation flow-path and an ambient air pressure outside the inhalation device. In some embodiments, the inhalation device can comprise control circuitry configured to initiate and/or cease activation of the mesh membrane in response to a result of the monitoring of the flow in the inhalation-path. 
     In some embodiments, the inhalation device can additionally comprise an exhalation sensor for monitoring a flow in an exhalation-flow path. In some embodiments, the exhalation sensor can be configured to detect a concentration of a chemical compound in the exhalation-flow path. In some embodiments, the chemical compound can be a component of the liquid. In some embodiments, the inhalation device can comprise control circuitry configured to cease or delay activation of the mesh membrane in response to a result of the monitoring of the flow in the exhalation flow path. 
     In some embodiments, the mesh membrane can be effective to eject at least 5 times, or at least 10 times, or at least 20 times, or at least 50 times more liquid in the mist during user inhalation than during user exhalation. 
     In some embodiments, the inhalation device can comprise an inhalation flow-path and an exhalation flow-path, each of the flow-paths including a respective one-way fluid valve. 
     In some embodiments, at least a portion of the distal portion can comprise a coating for generating a taste and/or odor sensation. In some embodiments, at least a portion of the intermediate portion can comprise a coating for generating a taste and/or odor sensation. 
     In some embodiments, the inhalation device comprises control circuitry programable to cause the mesh membrane to eject, in the mist, a liquid quantity that is either predetermined or received in an input from a user. 
     In some embodiments, at least a portion of the container can be above a plane longitudinally bisecting the intermediate portion when the device is rotated such that the plane is horizontal. In some embodiments, all of the container can be above a plane longitudinally bisecting the intermediate portion when the device is rotated such that the plane is horizontal. 
     In some embodiments, the distal portion can comprise a liquid-retaining compartment in fluid communication with the liquid inlet via a conduit, and the liquid-retaining compartment can be shaped to receive a quantity of the liquid via the conduit by force of gravity when the inhalation device is in a first orientation, and to retain at least a part of the quantity against the force of gravity when the inhalation device is in a second orientation. In some embodiments, the retaining can be by a wall of the liquid-retaining compartment, and wall can be effective to partially block an egress of the retained at least a part of the quantity. 
     In some embodiments, the second orientation can be such that substantially all of the mesh membrane is in liquid communication with the retained at least a part of the quantity. In some embodiments, the second orientation can be such that a surface liquid level in the liquid-retaining compartment is higher than a surface liquid level in the container. 
     In some embodiments, a maximum retainable fluid capacity of the liquid-retaining compartment is at least 0.5 cc and not more than 4 cc, or at least 1 cc and not more 3 cc, or at least 1.5 cc and not more 2.5 cc. 
     In some embodiments, a ratio of (i) a combined fluid capacity of the container and the conduit to (ii) a maximum retainable fluid capacity of the liquid-retaining compartment, can be at least 1 and not more than 4, or at least 1.5 and not more than 3, or at least 1.75 and not more than 2.5. 
     In some embodiments, the inhalation device can additionally comprise a capillary pathway for conveying a portion of the liquid by capillary action from the liquid-inlet to the mesh membrane or to within 1 mm of the mesh membrane. 
     In some embodiments, the mist-generating location can be at least 20% deep or at least 30% deep or at least 40% deep or at least 50% deep or at least 60% deep or at least 70% deep or at least 80% deep into an oral-cavity volume beneath the user&#39;s hard palate. 
     In some embodiments, the inhalation device can additionally comprise a display device configured to display information about at least one of: (i) a currently-remaining quantity of the liquid or of a component thereof, (ii) an already-misted quantity of the liquid or of a component thereof, and/or (iii) the identity of a component of the liquid. 
     In some embodiments in which the inhalation device includes an exhalation sensor, the inhalation device can additionally comprising a display device configured to display information about at least one of: (i) a currently-remaining quantity of the liquid or of a component thereof, (ii) an already-misted quantity of the liquid or of a component thereof, (iii) the identity of a component of the liquid, and (iv) the detected concentration of the chemical compound in the exhalation-flow path. 
     According to embodiments disclosed herein, an electrically-powered inhalation device for delivery of an aerosol to the oropharynx of a user comprises: (a) respective proximal and distal portions, the distal portion including (i) a volume for storing a liquid, (ii) an aerosol outlet defining a mist-exiting location and (iii) a piezo assembly including an ultrasonically vibrable mesh membrane, for producing, upon electrical activation, a mist comprising droplets of the liquid, the mesh membrane defining a mist-generating location; and (b) an intermediate portion disposed distally from the proximal portion and proximally from the distal portion, wherein the inhalation device is shaped such that when the user&#39;s lips and/or teeth are transversely engaged with the intermediate portion, the mist-generating location resides within the user&#39;s oral cavity and the mist-exiting location is in direct fluid communication with the user&#39;s oropharynx. 
     According to embodiments, an electrically-powered inhalation device for delivery of an aerosol to the oropharynx of a user comprises: (a) respective proximal and distal portions, the distal portion including (i) a volume for storing a liquid, (ii) an aerosol outlet defining a mist-exiting location and (iii) a piezo assembly including an ultrasonically vibrable mesh membrane, for producing, upon electrical activation, a mist comprising droplets of the liquid, the mesh membrane defining a mist-generating location; and (b) an intermediate portion disposed distally from the proximal portion and proximally from the distal portion, wherein the distal portion is dimensioned to vertically span the user&#39;s oral cavity from tongue to hard-palate when the user&#39;s lips and/or teeth are transversely engaged with the intermediate portion, so as to place the mist-exiting location in fluid communication with the user&#39;s oropharynx. 
     In some embodiments, the inhalation device can additionally comprise a portable power source. In some embodiments, the inhalation device can additionally comprise an inhalation sensor for monitoring a flow in an inhalation flow-path. In some embodiments, the inhalation sensor can be effective to detect an air pressure in the inhalation-flow path. In some embodiments, the inhalation sensor can be effective to detect a difference between an air pressure in the inhalation flow-path and an ambient air pressure outside the inhalation device. In some embodiments, the inhalation device can comprise control circuitry configured to initiate and/or cease activation of the mesh membrane in response to a result of the monitoring of the flow in the inhalation-path. 
     In some embodiments, the inhalation device can additionally comprise an exhalation sensor for monitoring a flow in an exhalation-flow path. In some embodiments, the exhalation sensor can be configured to detect a concentration of a chemical compound in the exhalation-flow path. In some embodiments, the chemical compound can be a component of the liquid. In some embodiments, the inhalation device can comprise control circuitry configured to cease or delay activation of the mesh membrane in response to a result of the monitoring of the flow in the exhalation flow path. 
     In some embodiments, the mesh membrane can be effective to eject at least 5 times, or at least 10 times, or at least 20 times, or at least 50 times more liquid in the mist during user inhalation than during user exhalation. In some embodiments, the inhalation device can comprise an inhalation flow-path and an exhalation flow-path, each of the flow-paths including a respective one-way fluid valve. 
     In some embodiments, at least a portion of the distal portion can comprise a coating for generating a taste and/or odor sensation. In some embodiments, at least a portion of the intermediate portion can comprise a coating for generating a taste and/or odor sensation. 
     In some embodiments, the inhalation device comprises control circuitry programable to cause the mesh membrane to eject, in the mist, a liquid quantity that is either predetermined or received in an input from a user. 
     In some embodiments, a maximum retainable fluid capacity of the liquid-retaining compartment is at least 0.5 cc and not more than 4 cc, or at least 1 cc and not more 3 cc, or at least 1.5 cc and not more 2.5 cc. 
     In some embodiments, a ratio of (i) a combined fluid capacity of the container and the conduit to (ii) a maximum retainable fluid capacity of the liquid-retaining compartment, can be at least 1 and not more than 4, or at least 1.5 and not more than 3, or at least 1.75 and not more than 2.5. 
     In some embodiments, the inhalation device can additionally comprise a capillary pathway for conveying a portion of the liquid by capillary action from the liquid-inlet to the mesh membrane or to within 1 mm of the mesh membrane. 
     In some embodiments, the inhalation device can additionally comprise a capillary pathway for conveying a portion of the liquid by capillary action from within the liquid-storing volume to the mesh membrane 
     In some embodiments, the mist-generating location can be at least 20% deep or at least 30% deep or at least 40% deep or at least 50% deep or at least 60% deep or at least 70% deep or at least 80% deep into an oral-cavity volume beneath the user&#39;s hard palate. 
     In some embodiments, the inhalation device can additionally comprise a display device configured to display information about at least one of: (i) a currently-remaining quantity of the liquid or of a component thereof, (ii) an already-misted quantity of the liquid or of a component thereof, and/or (iii) the identity of a component of the liquid. 
     In some embodiments in which the inhalation device includes an exhalation sensor, the inhalation device can additionally comprising a display device configured to display information about at least one of: (i) a currently-remaining quantity of the liquid or of a component thereof, (ii) an already-misted quantity of the liquid or of a component thereof, (iii) the identity of a component of the liquid, and (iv) the detected concentration of the chemical compound in the exhalation-flow path. 
    
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
         FIG.  1 A  is a schematic elevation drawing of an inhalation device, according to embodiments of the present invention. 
         FIG.  1 B  shows the inhalation device of  FIG.  1 A  together with optional wick and removable liquid container, according to embodiments of the present invention. 
         FIG.  1 C  shows the inhalation device of  FIG.  1 B , with optional removal liquid container mated thereto, according to embodiments of the present invention. 
         FIG.  2 A  shows the inhalation device of  FIG.  1 C , in situ, in an activated state producing a mist in a user&#39;s oral cavity, according to embodiments of the present invention. 
         FIG.  2 B  schematically illustrates percentages of deepness into the volume beneath the hard palate. 
         FIG.  3    is a schematic elevation drawing of an inhalation device having a compact design, according to embodiments of the present invention. 
         FIG.  4    shows the inhalation device of  FIG.  3   , in situ, in an activated state producing a mist in a user&#39;s oral cavity, according to embodiments of the present invention. 
         FIG.  5    shows an inhalation device having inhalation and exhalation conveyances, in situ, in an activated state producing a mist in a user&#39;s oral cavity, according to embodiments of the present invention. 
         FIGS.  6 A- 6 C  show schematic views of an inhalation device according to embodiments of the present invention. 
         FIGS.  7 A- 7 B  show schematic views of an inhalation device according to embodiments of the present invention. 
         FIG.  8    shows an inhalation device according to embodiments of the present invention. 
         FIGS.  9 A-D  are schematic cross-sectional illustrations of the inhalation device of  FIG.  8    and a liquid, according to embodiments of the present invention. 
         FIGS.  10 A and  10 B  are cross-sectional views of inhalation devices according to embodiments of the present invention, showing liquid conduits having, respectively, circular and oval cross-sections. 
         FIG.  10 C  is a partial cutaway view of the proximal end of an inhalation device according to embodiments of the present invention, showing inhalation and exhalation sensors. 
         FIGS.  11 A and  11 B  are schematic cross-sectional illustrations of an inhalation device having a distal liquid-storage volume, according to embodiments of the present invention, at two respective orientations. 
         FIGS.  12 A and  12 B  are, respectively, schematic top- and side-view illustrations of an inhalation device having a display screen affixed to an intermediate portion of the inhalation device, according to embodiments of the present invention. 
         FIGS.  13 A and  13 B  are, respectively, schematic top- and side-view illustrations of an inhalation device having a display screen affixed to a proximal portion of the inhalation device, according to embodiments of the present invention. 
     
    
    
     DETAILED DESCRIPTION OF THE ILLUSTRATED EMBODIMENTS 
     The invention is herein described, by way of example only, with reference to the accompanying drawings. With specific reference now to the drawings in detail, it is stressed that the particulars shown are by way of example and for purposes of illustrative discussion of the preferred embodiments of the present invention only, and are presented in the cause of providing what is believed to be the most useful and readily understood description of the principles and conceptual aspects of the invention. In this regard, no attempt is made to show structural details of the invention in more detail than is necessary for a fundamental understanding of the invention, the description taken with the drawings making apparent to those skilled in the art how the several forms of the invention may be embodied in practice. Throughout the drawings, like-referenced characters are generally used to designate like elements. 
     Following is a list of reference numbers used in the figures for physiological features:
           10 —oral cavity     15 —lips     20 —teeth     25 —tongue     30 —hard palate     40 —nasal cavity     50 —oropharynx     60 —velo-pharyngeal port     70 —pharyngeal cavity       

     Note: Throughout this disclosure, subscripted reference numbers (e.g., 10 1  or 10 A ) may be used to designate multiple separate appearances of elements of a single species, whether in a drawing or not; for example 10 1  is a single appearance (out of a plurality of appearances) of element  10 . The same elements can alternatively be referred to without subscript (e.g.,  10  and not 10 1 ) when not referring to a specific one of the multiple separate appearances, i.e., to the species in general. 
     For convenience, in the context of the description herein, various terms are presented here. To the extent that definitions are provided, explicitly or implicitly, here or elsewhere in this application, such definitions are understood to be consistent with the usage of the defined terms by those of skill in the pertinent art(s). Furthermore, such definitions are to be construed in the broadest possible sense consistent with such usage. Physiological terms as used herein are to be understood according to their generally accepted meanings. 
     The terms ‘aerosol’ and ‘mist’ as used herein are synonymous and are used to describe a suspension of liquid droplets in air. The terms ‘inhalation device’ and ‘inhaler’ as used herein are synonymous and are used to describe a device that delivers an aerosol to a user&#39;s oral cavity. 
     An inhalation device is disclosed herein for delivering an aerosol of a liquid well inside the user&#39;s oral cavity such that the device largely prevents the user&#39;s tongue from interfering with the delivery of the aerosol to the user&#39;s oropharynx. The exemplary devices disclosed herein use a piezo assembly that includes an ultrasonically vibrable mesh membrane to generate the aerosol, and so the piezo assembly has an aerosol outlet that in intended use will release the aerosol where desired. 
     Referring now to the figures and in particular to  FIGS.  1 A,  1 B and  1 C , an inhalation device  100  according to embodiments is illustrated schematically. As seen in  FIG.  1 A , an inhalation device  100  has a distal portion  175  which includes the distal end of the inhalation device  100 . The term ‘distal end’ is used herein to mean the end of the inhaler  100  at which an aerosol exits the inhaler  100 . During normal intended use, the distal end is farthest from a user&#39;s hand, and/or is the first part of the device that enters a user&#39;s oral cavity. The term ‘distal’ may also used herein to indicate a direction towards the distal end. ‘Proximal’ as used herein refers to the end or direction which is opposite to the distal end or direction. The device  100  also includes a proximal portion  165 . It should be noted that in some contexts the terms proximal portion and distal portion may be understood more broadly than the specific respective portions demarcated in  FIG.  1 A , and can refer to any portion that includes the respective end of the device. 
       FIGS.  1 A-C  show side elevation views, such that according to embodiments, the ‘top’ of the device  100  in each of the figures is the intended ‘top’ of the device  100  in actual use. Thus, in embodiments, an upper surface  178  of the distal portion  175  is intended to be ‘on top’ during use, and the lower surface  176  is intended to be ‘on the bottom’ during use. Nonetheless, in some embodiments, the inhalation device  100  is usable in other positions, e.g., with top and bottom reversed. The shape of the device  100  throughout the figures is shown as asymmetrical, i.e., the top of the device has a different contour than the bottom of the device. This can be beneficial for conforming to a user&#39;s oral cavity. Nonetheless, in some embodiments, the shape is symmetrical and does not have different contours on the top and the bottom of the device  100 . In addition, the ‘thickness’ (dimension from top to bottom) of the distal portion  175  is shown as substantially thicker than the thickness of some of, most of, or all of the proximal portion  165 . In embodiments, the distal portion  175  can have a thickness (e.g., maximum thickness, minimum thickness or average thickness) at least 30% or at least 50% or at least 100% greater than a corresponding thickness (respectively, maximum thickness, minimum thickness or average thickness) of the proximal portion  165 . The relative thickness of the distal portion  175  can be useful in encouraging the user to place the distal portion  175  on top of the tongue so as to allow a mist generated by the device to directly reach the oropharynx. 
     The distal portion  175  includes a piezo assembly  180  that includes an ultrasonically vibrable mesh membrane  185 . The mesh membrane  185  is the location at which an aerosol is generated/produced. In some embodiments (not shown) the distal portion can include an aerosol outlet displaced distally from the mesh membrane  185 , where the aerosol exits the device  100  via such an aerosol outlet. This can be useful, for example for bringing the aerosol closer to the user&#39;s oropharynx or for directing the generated mist in a specific direction. Thus, in some embodiments the ‘mist-generating’ location and the ‘mist-exiting’ location are the same location (for example, in  FIGS.  1 A- 1 C ) and in some embodiments these two locations are displaced from each other. 
     In embodiments, the proximal portion  165  can include a liquid inlet  160 , through which a liquid  120  can be introduced into the device  100  for producing the mist. The liquid inlet is preferably mateable with a source of the liquid  120 . In the example shown in  FIG.  1 B , the source of liquid is a replaceable/removable (i.e., attachable/detachable) container  110 . The term ‘mateable’ is used herein to indicate that a mating arrangement exists, e.g., corresponding threading, snap-closures or appropriately sized inlet-outlet diameters. According to the example, the container  110  has a liquid storage volume  115  and an outlet  117 . The outlet  117  is mateable with the liquid-inlet  160  of the device  100 .  FIG.  1 B  also shows a capillary pathway  140  for distally transporting liquid  120  in the direction of the mesh membrane  185 . The capillary pathway  140  is typically disposed, and optionally held, so that a distal portion thereof is in contact with the mesh membrane  185 , or displaced no more than 2 mm or no more than 1 mm from the mesh membrane  185 . A proximal portion of the capillary pathway  140  is generally disposed within the liquid-storage volume  115  of the container  110  so as to establish a pathway for water transport from the liquid-storage volume  115  to the mesh membrane  85 . In some embodiments, the container  110  is formed and/or provided as a component of the inhalation device  100 . 
     A ‘capillary pathway’  140  as the term is used herein is a material suitable for transport of a liquid) along a pathway by capillary action. Such a material often includes fibers, such as plant-based fibers e.g., cellulose, polymer-based fibers e.g., polyester, glass fibers e.g., in a woven fabric or bundled or unbundled glass fibers, or carbon fibers. In some non-limiting examples, the fibers can be very small, i.e., having diameters in the range of several or tens of microns. In other examples, the fibers can be larger. While the term “pathway” may appear to imply that a pathway for liquid transport to a mesh membrane may be a direct path, that is not necessarily the case. The transport of a liquid through the capillary pathway may include progression in random directions or omnidirectional progression. In some embodiments, the capillary pathway  140  can include fibers arranged so as to form direct pathways from various parts of the liquid-storage volume  115  but this is not necessary for the capillary transport to be effective. In some embodiments, the capillary pathway can comprise a hydrophilic material that is effective to facilitate transport of an aqueous liquid. 
     As shown in  FIG.  1 A , an inhalation device  100  according to embodiments can include comfort element(s)  123  for ease of placement of teeth and/or lips. The two bumps shown in  FIG.  1 C  are just one non-limiting example of such comfort elements; other non-limiting examples include depressions and single bumps. Such elements are not present in all designs within the scope of the present invention, but can be useful in some cases for optimal positioning of the device  100 , and especially positioning of the distal portion  175 , within the oral cavity. As shown in  FIG.  1 A . an inhalation device  100  according to embodiments can include a power and electronics module  125 , which can include, for example, a power source (e.g., a battery or connection for mains electricity), wireless communication arrangements, and/or control circuitry. The control circuitry can include electronic hardware such as a printed circuit board, and firmware or software for operation of the device. 
     Referring now to  FIG.  2 A , the in-situ placement of an inhalation device  100  according to embodiments (and according to the example of  FIGS.  1 A-C ) is shown with respect to a user&#39;s oral cavity  10  and mouth parts such as upper and lower teeth  20   u ,  20   u , upper and lower lips  15   u ,  15   u , tongue  25  and hard palate  30 . The inhalation device  150  is preferably dimensioned such that the distal portion  175  spans the oral cavity  10  from the tongue  25  to the hard palate  30 . Teeth  20  and/or lips  15  can close on the device  100  at teeth-engaging portions or lip-engaging portions that are distally displaced from the proximal portion  165 , and thus help to maintain the position of the device  100  as illustrated. The comfort elements  123  illustrated one non-limiting example of a teeth-engaging portion. Mist  141 , as shown schematically in  FIG.  2 A , is produced at the mesh membrane  185 ; as mentioned hereinabove, the mist-generating location and mist-exiting location (i.e., the aerosol exit from inhaler  100 ) are the same location in this exemplary design. In other words, not only is the aerosol outlet located in the distal portion  175  of the inhalation device  100 , in this design the mesh membrane  185  is also located in the distal portion  175 . Thus when positioned as illustrated with the top surface of  178  of the distal portion  175  in contact with the hard palate  30 , and the bottom surface of  176  of the distal portion  175  in contact with the tongue  20 , both the mesh membrane and the aerosol exit are placed in fluid communication with the user&#39;s oropharynx  50 . A proximal air inlet (not shown in  FIG.  2 A ) can be added for ensuring that proper inhalation can still occur when lips  15  are closed around the device  100 . 
     In embodiments, the distal portion  175  of the inhalation device  150  can comprise a coating for generating a taste and/or odor sensation for the user. The coating can be applied, for example, on the tongue-contacting portion of the distal portion. 
     In another design example, which is not illustrated, the inhaler  100  of  FIGS.  1 - 2    can be formed to be shorter, so that the container  110  is part of the proximal portion and the teeth-engaging and/or lip-engaging location is on a surface of the container  110 . 
     In embodiments, the distal portion  175  of the inhalation device  150  includes the mist-generating location, i.e., the mesh membrane  185 , and the device  150  is formed so that the mist-generating location is beneath the hard palate  30 . In some embodiments, the volume of the oral cavity beneath the hard palate can be demarcated according to ‘hard-palate-deepness’ as illustrated schematically in  FIG.  2 B . For example, the mist-generating location can be in the deeper half of the volume beneath the hard palate  30 —or in the deepest 40% in the example of  FIG.  2 B , or in the deepest 20% (not shown). In other words, the mist-generating location (and the mist-exiting location) can be at least 50% deep into the volume beneath the hard palate  30  or at least 60% deep or at least 70% deep or at least 80% deep. In other embodiments, the mist-generating location might not be quite as deep—for example, the mist-generating location can be at least 20% deep or at least 30% deep or at least 40% deep into the volume beneath the hard palate. Greater ‘deepness’ can be advantageous so as to shorten the path of fluid communication between the mist-exiting location and the oropharynx. 
     We now refer to  FIGS.  3  and  4   . 
       FIG.  3    illustrates a more compact design for an inhalation device  100  according to embodiments of the present invention, and  FIG.  4    shows the in-situ placement of the device  100 . Like the inhaler  100  of  FIGS.  1 A- 2   , the inhaler  100  of  FIGS.  3  and  4    has a distal portion  175  (comprising the piezo assembly  180  and the aerosol outlet which happens to be co-located with mesh membrane  185 ) and a proximal portion  165 , power and electronics module  125 , and optional comfort elements  123 . Liquid  120  for producing therefrom a mist is stored in compartment  131  (which is optionally detachable/attachable). Compartment  131  has a opening for filling and refilling; the compartment  131  has an openable closing element  132 . The inhalation device  100  of  FIG.  3    includes an airflow channel  121  having a proximal air inlet  122  for ensuring that proper inhalation can still occur when lips  15  are closed around the device  100 . As can be seen in  FIG.  4   , the air inlet  122  is positioned so as to remain outside the lips  15  when the device  100  is positioned for operation in situ. Referring again to  FIG.  3   , an ‘inhalation sensor’, i.e., flowmeter or airflow sensor  126   IN  is provided for activating the piezo assembly  180  upon detection of inhalation. In embodiments, a piezo assembly  180  can be activated to produce a mist (in the presence of liquid) manually, e.g., by control circuitry in response to a user pressing a button or moving a switch, and/or automatically by control circuitry (e.g., in power and electronics module  125 ) monitoring the inhalation sensor  126   IN  for indication of an inhalation airflow. In some embodiments, the inhalation sensor  126   IN  is configured to detect an air pressure. In some embodiments, the inhalation sensor  126   IN  is configured to detect a difference between an air pressure in the inhalation flow-path and an ambient air pressure outside the inhalation device 
     Referring now to  FIG.  5   , an inhalation device  100  is shown in-situ from a different angle than that of  FIGS.  2 A-B  and  4 . Two airflow channels  121 ,  129  are provided for conveyance of an inhalation airflow (indicated by arrow  150   IN ) and an exhalation airflow (indicated by arrow  150   EX ), respectively. As also shown in  FIG.  3   , the inhalation airflow-channel  121  of  FIG.  5    includes an air-inlet  122  positioned beyond user&#39;s lips  15  outside of a potentially closed mouth. Similarly, the exhalation airflow-channel  129  includes an exhaust outlet  127  positioned beyond the user&#39;s lips  15 . In embodiments, each of the airflow channels  121   IN ,  121   EX  can be equipped with respective one-way fluid valves  128   IN ,  128   EX  which by their presence define the directionality of airflow within each respective airflow-channel. An inhalation sensor  126   IN , e.g., a flowmeter or air-pressure sensor, can be provided for monitoring and detecting the presence of an inhalation breath, so that control circuitry can activate or deactivate or otherwise modify the mist-generation of the mesh membrane  180 . In embodiments, the mesh membrane can be effective to eject at least 5 times, or at least 10 times, or at least 20 times, or at least 50 times more liquid  120  in the mist  141  during user inhalation than during user exhalation. It will be apparent to those skilled in the art that it does not matter which of the airflow channels  121  is used for inhalation and which is used for exhalation, and the labeling in the figures is merely for convenience. 
     We now refer to  FIGS.  6 A to  6 C , which show various schematic views of an inhalation device  100  according to embodiments, including embodiments already described hereinabove. Respective distal and proximal directions are illustrated by arrow  1200 . 
     As seen in the elevation view of  FIG.  6 A , the inhalation device  100  includes a distal portion  230 , a proximal portion  210  and an intermediate portion  220  that is displaced proximally from the distal portion  230  and distally from proximal portion  210 . The proportions of the respective portions  210 ,  220 ,  230  are entirely for illustration purposes only, and any of the respective portions  210 ,  220 ,  230  can be larger or smaller. In some examples, they can also be contiguous, i.e., without gaps between the various portions. When the inhalation device  100  is in use according to preferred use modes, the intermediate portion  220  is contacted, i.e., transversely engaged, by a user&#39;s lips  15  and or teeth  20 , and the distal portion  230 , which includes the mist-generating mesh  185 , is disposed within the user&#39;s oral cavity  10 . 
       FIG.  6 B , where the outer envelope of the inhalation device  100  is made ‘transparent’, schematically illustrates typical internal components of the inhalation device of  FIG.  6 A : capillary pathway  140  leading from liquid inlet  160  (where a container or compartment, not shown, would hold a quantity of a liquid) to the mesh  185 , and electrical wire(s)  146  leading from control circuitry and power supply  125  to the mesh  185 . 
     As shown in  FIG.  6 C , the inhalation device  100  can include air-inlet holes  122  which are proximal of the intermediate portion  220  such that the air-inlet holes  122  are outside the mouth. A taste-producing surface section  224  can be provided in the distal portion  230  and/or the intermediate portion  220 . The taste-producing surface section  224  is preferably on the ‘bottom’ of the inhalation device  100  during use so as to bring the taste-producing surface section  224  into contact with the user&#39;s tongue  25 . 
     Referring now to  FIGS.  7 A and  7 B , another inhalation device  100  according to embodiments is illustrated. The inhalation device of  FIGS.  7 A-B  can operate effectively without a capillary pathway for transport of liquid from the container  110  to the mesh  185  because of a gravity-aided design. A plane  1150  is shown longitudinally bisecting the intermediate portion  220  (and/or the distal portion  230 ). When the horizontally-bisecting plane  1150  is held horizontal, e.g., parallel to a floor (not shown), the container  110  is held higher than the plane  1150  and therefore higher than the mesh  185 , so that liquid can be made by gravity to flow to the mesh  185 . While  FIG.  7 B  shows the entire container  110  as being higher than the plane, in some designs it can be that a portion of the container higher than the plane. 
       FIG.  8    illustrates another inhalation device  100  according to embodiments, wherein the container  110  does not extend across the entire proximal portion  210  of the inhalation device  100 . Features of the inhalation device  100  of  FIG.  8    according to embodiments, are illustrated in the cross-sectional views of  FIGS.  9 A-D , which correspond to section B-B in  FIG.  8   . In  FIG.  9 A , a quantity of liquid  120  is disposed in a container  110  which is engaged with liquid-inlet  160 . The distal portion  230  includes a liquid-retaining compartment  105  in fluid communication with the proximal liquid inlet  160  vis a liquid conduit  108 , illustrated in  FIGS.  9 A-D  as a connecting tube or pipe. The liquid-retaining compartment  105  is partially bounded on one side by a liquid-retaining wall  104 . When the inhalation device  100  is turned upside-down as shown in  FIG.  9 B , the liquid  120  flows down with gravity (indicated by arrow  1300 ) to fill the liquid-retaining compartment  105 , as well as at least a portion of the liquid conduit  108 . While  FIG.  9 B  shows the entire liquid conduit  108  full of liquid, and a portion of the liquid remaining in the container  110 , in other examples there can be more or less liquid  120  provided, and/or the relative capacities of the retaining compartment  105 , the liquid conduit  108  and/or the container  110  can be larger or smaller than illustrated in  FIG.  9 B  such that the liquid  120  fills the liquid-retaining compartment  105  but only some or none of the liquid conduit  108 , such that the container  110  is emptied in such examples. 
       FIG.  9 C  illustrates the function of the liquid-retaining wall  104  that partially bounds the liquid-retaining compartment  105 . After the reversing of the inhalation device as shown in  FIG.  9 B , the inhalation can be brought to a horizontal position for use as shown in  FIG.  9 C , which causes the liquid in the connected reservoirs of the liquid-retaining compartment  105  and the container  110  to tend to ‘seek its own level’. However, the liquid-retaining wall  104  prevents a portion of the liquid  120  delivered to the liquid-retaining compartment  105  (during the reversing of the inhalation device  100 ) from leaving the liquid-retaining compartment  105  after the inhalation device  100  is turned horizontal, or, as illustrated in  FIG.  9 D , ‘below horizontal’. The liquid  120  in the liquid-retaining compartment  105  can thus be ‘cut off’ from the remainder of the liquid in the container  110  and conduit  108 . The height of the liquid-retaining wall  104  is preferably sufficient to ensure that for a range of angles 0 (horizontal, e.g., as in  FIG.  9 C ) to θ (e.g., as in  FIG.  9 D ), the mesh  185  is kept in contact with liquid  120  retained in the liquid-retaining compartment  105 . Setting the value of θ is a design choice which reflects a desired range of angles at which the inhalation device  100  can work effectively. The height of the liquid-retaining wall  104  should be sufficient to retain liquid  120  in the compartment  105  through the range of angles 0 to θ even though the surface level of the liquid  120  in the compartment  105  is higher than in the container  110 , as illustrated in the example of  FIG.  9 D . During normal operation, whenever enough liquid  120  is nebulized out of the inhalation device to cause a portion or substantial portion, e.g., over 1 mm, of the mesh  185  to no longer be in contact with liquid  120 , the user can simply upend the inhalation device (as in  FIG.  9 B ) to ‘refill’ the liquid-retaining compartment  105  from the remaining liquid  120  in the container  110  and conduit  108 . and then restore the comfortable use position of  FIG.  9 C  or  FIG.  9 D . 
     In embodiments, a maximum retainable fluid capacity of the liquid-retaining compartment  105  (i.e., the quantity of the liquid  120  retained by the liquid-retaining wall  104 ) is at least 0.5 cc and not more than 4 cc. In some embodiments, the maximum retainable fluid capacity of the liquid-retaining compartment  105  is at least 1 cc and not more 3 cc. In some embodiments, the maximum retainable fluid capacity of the liquid-retaining compartment  105  is at least 1.5 cc and not more 2.5 cc. A ratio of (i) a combined fluid capacity of the container  110  and the conduit  108  to (ii) the maximum retainable fluid capacity of the liquid-retaining compartment  105 , is at least 1 and not more than 4. In some embodiments, this ratio is at least 1.5 and not more than 3. In some embodiments, this ratio is at least 1.75 and not more than 2.5. 
     Reference is made to  FIGS.  10 A,  10 B and  10 C , both of which show cross-sectional views corresponding to section A-A in  FIG.  8    such that the liquid conduit  108  and respective airflow channels  121   IN ,  121   EX  can be seen. The liquid conduit  108  of  FIG.  10 A  has a circular cross-section. The liquid conduit  108  of  FIG.  10 B  has an oval cross-section, which, inter alia, can be effective to reduce turbulent flow within the liquid conduit  108 . 
       FIG.  10 C  shows respective inhalation and exhalations sensors  126   IN ,  126   EX . When present each of the sensors  126  is in communication with a respective flow path  121 . In some embodiments, only one of the sensors  126  is present. 
     The inhalation sensor  126   IN  is provided for monitoring a flow in an inhalation flow-path, e.g., inhalation flow path  121   IN . In an example, the inhalation sensor  126   IN  can be effective to detect an air pressure in the inhalation-flow path  121   IN . In another example, the inhalation sensor can be effective to detect a difference between an air pressure in the inhalation flow-path  121   IN  and an ambient air pressure outside the inhalation device  100 . In some embodiments, the control circuitry  135  is configured to initiate and/or cease activation of the mesh membrane  185  in response to a result of the monitoring of the flow in the inhalation-path  121   IN . 
     The exhalation sensor  126   EX  is for monitoring a flow in an exhalation-flow path, e.g., exhalation flow path  121   EX . In an example, the exhalation sensor  126   EX  is configured to detect a concentration of a chemical compound in the exhalation-flow path  121   EX . In some embodiments, the chemical compound is a component of the liquid  120  which is misted by the inhalation device. In some embodiments, the chemical compound is a chemical compound of interest to a user. For example, a user may wish to know the concentration of an intoxicating chemical compound in an exhalation, such as, for example, and not exhaustively, alcohol or tetrahydrocannabinol. In another example, the chemical compound can be an indicator of a disease or of a current health condition of the user. In some embodiments, the control circuitry  135  is configured to cease or delay activation of the mesh membrane  185  in response to a result of the monitoring of the flow in the exhalation flow path  121   EX . 
     Referring now to  FIGS.  11 A and  11 B : an inhalation device  100  comprises a distal liquid-storage compartment  105  fillable through filling port  103 . In the design of  FIGS.  11 A and  11 B , the inhalation device  100  does not include a proximal source of liquid  120 , nor does it include a liquid conduit  108 . Instead, the liquid in the distal liquid-storage compartment  105  is in contact with the mesh membrane. The distal liquid-storage compartment  105  is designed such that for a range of angles 0 (horizontal, e.g., as in  FIG.  11 A ) to θ (e.g., as in  FIG.  11 B ), the mesh  185  is kept in contact with liquid  120  retained in the liquid-storage compartment  105 . Setting the value of θ is a design choice which reflects a desired range of angles at which the inhalation device  100  can work effectively. 
     It can be desirable to add a display screen (or, equivalently, any display device) to an inhalation device for visually communicating information to a user. The information to be communicated can include, for example, and not exhaustively: the quantity or percentage of liquid remaining; the quantity or percentage of a compound in the liquid that is remaining; the amount or percentage of liquid (or of the compound in the liquid) that has already been consumed by the delivery of the mist, with or without including prior any fills of the liquid; the identity of the compound; a power meter showing remaining battery life; a concentration of a compound detected in an exhalation airflow; whether a concentration of a substance in the exhalation airflow exceeds a preset limit for intoxication; and a health indicator such as the presence of a virus, bacteria, or any other health indicator that can be detected in an exhalation. 
     A display screen can be mounted to or installed on any convenient section of any of the inhalation devices  100  disclosed herein.  FIGS.  12 A and  12 B  (top and ide views, respectively of an inhalation device  100  according to embodiments) show a display screen  155  mounted to the intermediate portion  220  of the inhalation device  100 .  FIGS.  13 A and  13 B  (top and ide views, respectively of an inhalation device  100  according to embodiments) show a display screen  155  mounted to the proximal portion  210  of the inhalation device  100 . 
     In any of the embodiments disclosed herein, the liquid  120  can include a medicament. In some embodiments, the quantity of liquid  120  used to generate the mist  141  can be a based on a predetermined dosage. This can be accomplished by the control circuitry in accordance with previous programming or in response to a user input. 
     In any of the embodiments disclosed herein, a capillary pathway  140  may be used to transport liquid to the mesh membrane. 
     In any of the embodiments disclosed herein, the inhalation device  150  can be used ‘hands-free’, i.e., when the inhalation device  150  is disposed so that the user&#39;s teeth are engaged with a front-teeth-engaging portion distally displaced from the proximal portion  165 , and/or the user&#39;s lips are engaged with a lip-engaging portion distally displaced from the proximal portion  165 , the device  150  can be held in place by the user&#39;s lips  15  and or teeth  20  during activation/operation and mist-generation without having to use a hand to keep it in place. 
     The present invention has been described using detailed descriptions of embodiments thereof that are provided by way of example and are not intended to limit the scope of the invention. The described embodiments comprise different features, not all of which are required in all embodiments of the invention. Some embodiments of the present invention utilize only some of the features or possible combinations of the features. Variations of embodiments of the present invention that are described and embodiments of the present invention comprising different combinations of features noted in the described embodiments will occur to persons skilled in the art to which the invention pertains. 
     It will be clear to the skilled artisan that any of the features described in connection with any of the figures can be combined with each other with the scope of the present invention even if not explicitly combined in this disclosure. For example, a design for which an airflow sensor was not explicitly shown may include an airflow sensor to trigger activation/initiation (or deactivation/cessation) of the piezo assembly and generation of mist by the mesh membrane, or a design for which a capillary pathway was not explicitly shown may include a capillary path for transport of liquid to the mesh membrane. As another non-limiting example, any of the designs illustrated can incorporate a liquid-retaining compartment effective to be filled using gravity and to retain liquid using a liquid-retaining wall, such that the mesh remains in contact with liquid, after the inhalation device is turned horizontal or ‘below horizontal’, i.e., with the container at least partly higher than the liquid-retaining compartment. 
     In the description and claims of the present disclosure, each of the verbs, “comprise”, “include” and “have”, and conjugates thereof, are used to indicate that the object or objects of the verb are not necessarily a complete listing of members, components, elements or parts of the subject or subjects of the verb. As used herein, the singular form “a”, “an” and “the” include plural references unless the context clearly dictates otherwise. For example, the term “a marking” or “at least one marking” may include a plurality of markings.