Nebulisation system without facial deposit

Abstract

The invention relates to an inhalation system (100) comprising a mesh nebulizer (103), and a face mask having a mask body (102) and a substantially vertical intake tube (104) connected to the mesh nebulizer.

Description

FACIAL DEPOSIT-FREE NEBULIZATION SYSTEM FIELD OF THE INVENTION

[0001] The present invention relates to an inhalation system and its use for administering an active ingredient into the respiratory tract of a subject.

[0002] More specifically, the present invention relates to a system for inhaling an aerosol produced by a mesh nebulizer, the system making it possible to reduce the deposition of aerosol on the face of the subject while ensuring efficient pulmonary deposition. STATE OF THE ART

[0003] To deliver active ingredients into a subject's respiratory tract (or airways), to humidify a subject's airways, or to administer a substance for preclinical or clinical testing, one technique is to use inhalation systems. These inhalation systems transform a liquid into fine droplets (aerosol) using a nebulizer. These droplets are then inhaled by the subject to enter the respiratory tract. This technique is commonly referred to as aerosol therapy.

[0004] However, known inhalation systems are not satisfactory.

[0005] Indeed, nebulization efficiency is determined by measuring the amount of aerosol introduced into the nebulizer and comparing it to the amount of aerosol that is deposited in the subject's airways. Known inhalation systems are not very effective in pediatrics and show a large variation in efficiency during a nebulization session due to several factors.

[0006] First, some systems allow aerosol inhalation only through the subject's mouth or nose. This aerosol delivery is inefficient because droplet-free air can be inhaled through the subject's nose or mouth when not connected to the nebulizer, thereby reducing the total amount of aerosol inhaled.

[0007] Then, some systems use a chamber or a mechanical structure like a Hood bell to expose the subject's head to an aerosol. They allow inhalation of the aerosol through the subject's mouth and / or nose. This aerosol distribution is inefficient because the aerosol produced in this large exposure volume is lost on the walls of the system and the subject's face. Only a small fraction of the aerosol produced in the chamber is inhaled by the subject.

[0008] Third, some inhalation systems include a face mask covering a subject's mouth and nose. The nebulizer is connected to the face mask by an opening oriented in a relatively horizontal direction as described, for example, in European patent application EP2804647A1. However, for these known systems, a non-negligible quantity of droplets is deposited on the subject's face and therefore does not enter the subject's respiratory tract. In addition, the aerosol deposited on the face can have side effects from a cutaneous or ophthalmological point of view. This effect is even more significant when the subject is in a lying or semi-sitting position because gravity then directs the droplets directly onto the subject's face. However, the lying or semi-sitting position is used almost systematically in infants and in anesthetized subjects.

[0009] In addition, most known masks include a significant dead volume at the mask level that limits the penetration of the aerosol into the deep respiratory tract of the subject, which implies a deposition of the aerosol mainly in the upper respiratory tract and, to a small extent, in the lungs. This effect is particularly noted in subjects who have a low inhalation volume (for example, children). Moreover, in some cases, this inhalation volume is lower than the volume of the mask. Some nebulization systems project the aerosol directly into the mask in order to overcome the problem of dead volume of the mask. Although these systems are efficient in terms of efficiency, they are associated with a significant deposition on the face of the subject.

[0010] In addition, during the expiratory phase, a significant proportion of droplets is expelled from the mask and is lost into the ambient air, thus causing a reduction in the quantity of respirable droplets but also contamination of the ambient air.

[0011] Furthermore, known systems lead to the deposition of the aerosol on the internal walls of the mask due to the condensation effect. The aerosol droplets thus deposited and lost will not contribute to the deposition of F aerosol in the respiratory tract.

[0012] Finally, the low efficiency of known inhalation systems can also be caused by the type of nebulizer used. Indeed, most nebulizers used in known systems have a low efficiency involving the presence of a high proportion (up to 50%) of residual liquid in the nebulizer at the end of the nebulization or aerosol therapy session.

[0013] Thus, none of the nebulization systems known to date can ensure both high pulmonary efficiency, deep pulmonary deposition and low deposition on the subject's face.

[0014] The aim of the invention is to provide a system which makes it possible to avoid one or more of these problems by promoting the inhalation of aerosol with greater efficiency of deposition in the lower respiratory tract (the lungs) and / or by reducing the deposition of droplets on the face of the subject in a standing or lying position.

[0015] The invention therefore relates to an inhalation system comprising a mask body covering the nose and mouth of the subject. A mesh nebulizer is connected to the mask body through an inhalation conduit which is oriented vertically, the aerosol being generated at a higher altitude than the mask body. This allows an accumulation of aerosol droplets in the inspiration conduit during the expiratory phase and then an entry, during the inspiratory phase, into the respiratory tract of the subject without accumulation of aerosol in the mask body. The mask is further connected to a one-way valve allowing the expiration of air outside the mask. SUMMARY

[0016] An inhalation system comprising a mesh nebulizer configured to generate droplets and a face mask comprising: A mask body configured to cover the nose and mouth of a subject when said mask body is placed on the subject and bounded by a mask edge defining a surface characterized by a midplane including a mask center, A first opening comprising an inspiration duct comprising: ■ a first end whose intersection with the mask body defines a surface comprising an inspiration center forming, with the mask center, a direction of the first opening, ■ a first inlet connected to the sieve nebulizer, the latter being configured to generate aerosol droplets inside the inspiration conduit, and ■ a second inlet comprising a one-way valve allowing communication from the outside of the inhalation system to the inside of the inspiration conduit, A second opening comprising an exhalation conduit comprising a first end whose intersection with the mask body defines a surface comprising an exhalation center forming, with the mask center, a direction of the second opening, the exhalation conduit comprising a second end connected to a one-way valve allowing communication from the inside of the mask body to the outside of the inhalation system, and wherein the direction of the first opening and the direction of the second opening form an opening angle greater than 45°, preferably greater than 90°.

[0017] Closing the inspiration duct by the nebulizer allows the aerosol droplets to be generated directly in the duct through which the air will be inspired. This allows all aerosol droplets to be carried away during inspiration and reduces aerosol deposition on the subject's face.

[0018] Using an inlet with a one-way valve connected to the inspiration conduit allows air to be inhaled only through the inspiration conduit, which improves aerosol transport to the subject's airways. In addition, during the exhalation phase, air cannot exit the mask through the inspiration conduit. This creates a volume of stagnant air in the inspiration conduit during the expiratory phase. Aerosol is therefore generated and accumulated in this stagnant air during the expiratory phase before being inhaled by the subject.

[0019] The distance between the two openings of the mask, i.e. between the opening for aerosol inhalation and the opening for exhalation, is proportional to the opening angle. A sufficient distance created by an opening angle greater than 45° allows the volume of the mask to be emptied and the aerosol remaining in the mask to be expelled at the end of the breathing cycle using the air exhaled by the subject in order to avoid the creation of unventilated areas which would concentrate the aerosol and encourage its deposition on the subject's face.

[0020] The use of a sieve nebulizer allows, thanks to the absence of gas injection into the aerosol and its low residual volume, to obtain a higher yield than other known nebulizers, thus leading to an increase in the efficiency of deposition in the lower respiratory tract (lungs).

[0021] Additionally, the face mask covering the subject's nose and mouth allows for simultaneous treatment of the upper and lower respiratory tract as the subject can inhale through both the nose and mouth.

[0022] Finally, the use of a one-way valve in the exhalation conduit allows for faster triggering of the one-way valve in the inspiration conduit because air can only enter through the inspiration conduit. Thus, the inspiration of outside air is done only through the inhalation conduit connected to the first opening of the mask and therefore only through the conduit containing the aerosol. The volume of the inhalation conduit corresponding to the volume less than or equal to the volume alveolar: tidal volume from which the anatomical dead volume (volume of the mouth and trachea) is removed, this allows an increase in the efficiency of deposition in the respiratory tract by inhalation of a volume comprising the largest proportion of aerosol.

[0023] According to another advantageous aspect of the invention, the first end and the first inlet of the inspiration conduit define an oriented axis, the oriented axis forming, with a vertical axis, a distribution angle of less than 45°, preferably less than 20°, more preferably less than 10°, when the face mask is placed on the subject, the first inlet being located above the first end.

[0024] The vertical orientation of the inspiration conduit and the positioning of the second end of the inhalation conduit above the first end of the inhalation conduit allows the aerosol to be generated at a higher altitude than the first end of the inhalation conduit. In order to reach the mask body, the droplets thus generated must descend along the inspiration conduit. It was surprisingly found by the inventors that the aerosol droplets accumulate in the inspiration conduit during the expiratory phase without entering the mask body. The aerosol concentration in the inspiration conduit is therefore greater near the first end compared to the second end.Then, during the inspiratory phase, the one-way valve connected to the inlet of the inspiration duct opens allowing the aspiration of air into the inspiration duct thus carrying the accumulated droplets directly into the respiratory tract of the subject without causing deposit on the face of the subject. The proximity of the first end to the nose and / or mouth of the subject and the concentration gradient in the duct promote the rapid penetration of the aerosol into the respiratory tract with a low aeraulic dead volume. The system according to the invention therefore has a high efficiency and makes it possible to deliver droplets (particles) of a size between 10 nm and 10 pm, and more particularly particles whose size is between 0.5 pm and 5 pm.

[0025] According to another advantageous aspect of the invention, the oriented axis forms, with the direction of the first opening, an orientation angle, the inhalation system further comprising a steering element configured to allow a change in the steering angle.

[0026] This allows the system to be used on both seated and lying subjects. The orientation of the inhalation tube relative to the vertical can be adapted to suit the subject's sitting or lying position.

[0027] According to another advantageous aspect of the invention, the inspiration conduit has an inspiration length measured parallel to the axis oriented between the inspiration center and the first inlet. The second inlet of the inspiration conduit comprising the one-way valve is positioned at a certain distance from the inlet of the inspiration center, this distance being between 70% and 100% of the inspiration length, preferably between 90% and 100% of the inspiration length.

[0028] The inlet including the one-way valve is therefore positioned close to the second end which is connected to the nebulizer. Thus, when the valve is triggered during the inspiratory phase, the inspired air enters the inspiration conduit near the second end and therefore transports a large part of the droplets towards the subject's respiratory tract.

[0029] According to another advantageous aspect of the invention, the inspiration length is between 2 cm and 15 cm and preferably between 2 cm and 6 cm.

[0030] Indeed, an inspiration tube that is too short would not allow the phenomenon of droplet accumulation to be generated: the aerosol would then be projected directly into the mask. Conversely, an inspiration tube that is too long would not correspond to the subject's inspiratory volume and would not allow for complete rinsing of the tube after each inhalation, rinsing limiting the accumulation of aerosol in the tube.

[0031] According to another advantageous aspect of the invention, the screen nebulizer comprises a nebulization conduit connected to an orifice of a nebulization chamber and to the first inlet, the nebulization conduit having a nebulization length measured between said orifice of the nebulization chamber and the first inlet, the nebulization length being between 0.1 cm and 5 cm, preferably between 0.5 cm and 1 cm.

[0032] This is particularly advantageous when the nebulizer is eccentric relative to the longitudinal axis of inspiration around which the inspiration conduit extends. Indeed, a nebulization conduit that is too long implies gravity impaction of the droplets on the surface of the nebulization conduit before entering the inspiration conduit.

[0033] According to another advantageous aspect of the invention, the inspiration conduit and the nebulization conduit together form an inspiration chamber having a volume of between 5 mL and 100 mL, preferably between 20 mL and 40 mL. This volume can be adapted according to the alveolar volume of the individual to be treated.

[0034] According to another advantageous aspect of the invention, the one-way valve of the inspiration conduit is included in an inlet conduit connected to the second inlet, the inspiration conduit and the inlet conduit together forming an inspiration chamber having a volume of between 5 mL and 100 mL, preferably between 20 mL and 40 mL. This volume can be adapted according to the alveolar volume of the individual to be treated.

[0035] Indeed, an inspiration duct with too large a volume would imply too large an aeraulic dead volume and would reduce the sensitivity of the one-way valve triggering (pressure drop). It would also reduce the effectiveness of pulmonary targeting due to a poor aerosol concentration gradient. An inspiration duct volume that is too small would generate a phenomenon of coalescence and condensation of droplets on the walls of the duct and would promote an inertial impaction phenomenon in the upper airways at the time of inhalation by excessive acceleration of the particles.

[0036] According to another advantageous aspect of the invention, the inspiration conduit is configured to allow rotation of the first inlet around a longitudinal inspiration axis around which said inspiration conduit extends.

[0037] This allows the nebulizer to be oriented so that droplets are generated downward in a direction close to gravity without changing the distribution angle.

[0038] According to another advantageous aspect of the invention, the inspiration duct opens into the nasal part of the mask body.

[0039] According to another advantageous aspect of the invention, the exhalation duct opens into the mouth part of the mask body.

[0040] According to another advantageous aspect of the invention, the expiration conduit has a longitudinal dimension of less than 2 cm, preferably less than 1 cm.

[0041] Indeed, a small exhalation duct allows, thanks to the reduction in the total volume of the mask, a faster triggering of the one-way valve (reduced pressure loss in the entire inhalation system) and improves pulmonary targeting due to the aerosol concentration gradient.

[0042] According to another advantageous aspect of the invention, the volume of the face mask is less than 300 mL.

[0043] Indeed, this volume of air corresponds to the average volume of air inhaled by an individual with each inspiration and can also correspond to the alveolar volume. This makes it possible to reduce the dead volume of the mask and therefore increase the proportion of aerosol inhaled.

[0044] According to another advantageous aspect of the invention, the inspiration conduit is connected to a source of dry gas.

[0045] This limits the condensation of water vapor on the droplets, thus preventing deposits on the internal surface of the face mask.

[0046] Additionally, the invention also relates to a method of administering a product into the respiratory tract of a subject comprising the steps of: Supply of the inhalation system as described above, Introduction of an active ingredient in liquid form into the screen nebulizer, Installation of the system on the subject's nose and mouth, preferably so that the first inlet is located above the first end, Generation in the inhalation duct of an aerosol by the screen nebulizer.

[0047] The method makes it possible to generate the aerosol at a higher altitude than the first end of the inhalation conduit, thus causing a depression zone inside the inhalation conduit preventing the aerosol generated during said exhalation phase from entering the mask body.

[0048] Use of the system may also include positioning the subject in a supine position prior to aerosol generation. For example, the subject may be lying down in an environment that provides containment of the microbiological risk. DEFINITIONS

[0049] In the present invention, the terms below are defined as follows:

[0050] "MMAD" or "Mass Median Aerodynamic Diameter" refers to the median value of the diameter of the aerosol droplets produced by the nebulizer. This size can be measured, for example, by a cascade impactor.

[0051] “Mouth part of a mask” refers to the part of a face mask that, when worn by a subject, includes the subject’s mouth. In other words, the mouth part is the part located below the subject’s nose.

[0052] "Nasal portion of a mask" refers to the portion of a face mask that, when worn by a subject, includes the subject's nose. In other words, the nasal portion is the portion above the subject's mouth.

[0053] "Nebulization efficiency" refers to the ratio between the amount of liquid deposited in the respiratory tract (lower and upper) in the form of aerosol at the end of a nebulization or aerosol therapy session and the amount of liquid introduced into the nebulizer before the start of the session.

[0054] "Lung efficiency" refers to the ratio of the amount of liquid deposited in the lower airways (the lungs) as an aerosol at the end of nebulization or aerosol therapy session and the quantity of liquid introduced into the nebulizer before the start of the nebulization session.

[0055] “Mask rinsing” concerns the expulsion of all droplets from the mask body during the expiratory phase.

[0056] “Volume of a mask” refers to the sum of the volume of the mask body (completed by an average surface defined by the mask edge) and the volume of the first and second openings, each completed by an average surface defined by the edge of its end not opening into the mask body.

[0057] "Dead volume of a face mask" or "mask dead volume" refers to the volume of a face mask that is not breathed in by the subject wearing the face mask during the inspiration phase.

[0058] "Aeraulic dead volume" refers to the volume subtended between the first end of the inhalation conduit and the orifice (nostrils or mouth) through which the subject wearing the face mask inhales. In other words, it is the volume defined by the airflow lines followed by the air breathed by the subject during the inspiration phase. In other words, it is the first volume of inspired air that does not contain aerosol. The aeraulic dead volume is less than the mask dead volume. DESCRIPTION OF FIGURES

[0059] Other characteristics and advantages of the present invention will emerge from the description given below, with reference to the appended drawings which illustrate exemplary embodiments thereof which are not limiting in nature. In the figures:

[0060] Figure 1 shows the inhalation system according to one embodiment of the invention as it is positioned on the subject's face during use.

[0061] Figure 2 is a representation of the system seen from the side according to one embodiment of the invention for use on a subject in a seated or standing position.

[0062] Figure 3 is a representation of the system seen from the side according to one embodiment of the invention for use on a subject in a lying position.

[0063] Figure 4 is an enlargement of the inhalation conduit as shown in Figure 3.

[0064] Figure 5 is a representation of the system seen from the front according to one embodiment of the invention.

[0065] Figure 6 is a representation of the phenomenon of aerosol accumulation towards the first end of the inhalation conduit and the release of the aerosol during inspiration.

[0066] Figure 7 is a representation of the system seen from the side according to one embodiment of the invention for use on a subject in a seated or standing position, the system being connected to a source of dry gas.

[0067] Figure 8 shows the evolution of the aerosol concentration (in percentage) for the invention (solid black line) and the system described in the article by Cabrera et al. (dashed line) as well as the inspiratory flow rate of the animal model (dotted line) as a function of the inspired volume (in milliliter - mL).

[0068] Figure 9 shows positron emission tomography deposit images for different anatomical sections.

[0069] Figure 10 shows the aerosol deposition on the face of three models (as a percentage of aerosol loaded in the nebulizer) with the system according to one embodiment of the invention (black discs) and with the device disclosed in European patent application EP2804647A1 (black stars).

[0070] Figure 11 is a representation of the system seen from the side according to an embodiment of the invention for use on a subject in a lying position, the nebulizer being eccentric relative to the longitudinal axis of inspiration around which the inspiration conduit extends. DETAILED DESCRIPTION

[0071] The following detailed description will be better understood when read in conjunction with the drawings. For purposes of illustration, the system is shown in preferred embodiments. It should be understood, however, that the invention is not limited to the arrangements, structures, features, embodiments, and aspects illustrated. The drawings are not to scale and are not intended to limit the scope of the claims to the embodiments shown. Accordingly, it should be understood that where features recited in the appended claims are followed by reference signs, such signs are included solely for the purpose of enhancing the intelligibility of the claims and do not limit the scope of the claims in any way.

[0072] The present invention relates to an inhalation system 100 comprising a mesh nebulizer 103 and a face mask.

[0073] A nebulizer transforms liquids into a cloud of fine droplets (aerosol). The droplets formed are typically less than 10 μm in size. The operation of sieve nebulizers is based on the passage of a liquid through the holes in the sieve to generate droplets with a diameter roughly equivalent to the diameters of the holes in the sieve. Sieve nebulizers can be static or vibrating sieves. In the case of a static sieve nebulizer, the mechanical force applied to the liquid to ensure the passage of the liquid through the sieve can be implemented using a vibrating piezoelectric quartz. The piezoelectric quartz can also be associated with the sieve. In the case of a vibrating sieve nebulizer, the piezoelectric quartz is associated with the sieve and sets the sieve in motion. The vibration creates an extrusion effect and projects the liquid through the holes, thus producing a calibrated aerosol.The use of a 103 sieve nebulizer avoids the injection of additional gas into the aerosol, and advantageously allows a nebulization efficiency superior to other known nebulizers (pneumatic nebulizer for example) thus leading to an increase in the efficiency of deposition in the respiratory tract.

[0074] The face mask comprises a mask body 102, a first opening and a second opening. The face mask is for example shown in Figures 1 to 5.

[0075] The mask body 102 is configured to cover the nose and mouth of a subject when the system is placed on (or worn by) a subject (Figure 1). Wearing the mask allows the mask body 102 to be virtually separated into two parts which are defined according to the part of the face covered by each of them. Thus, as shown in Figure 1, the mask body 102 comprises a nasal part (checkered in Figure 1) covering, when the mask is worn by a subject, the subject's nose and a buccal part (dotted in Figure 1) covering, when the mask is worn by a subject, the subject's mouth. In other words, the buccal part is the part located below the subject's nose while the nasal part is the part located above the subject's mouth.

[0076] Wearing the mask during use also makes it possible to associate a vertical direction V defined as oriented in the direction of gravity with the structure of the face mask. Thus, from this absolute definition (direction of gravity), it is possible to match the vertical direction V to certain anatomical orientations, depending on the configuration of the mask. For example, when the mask is in a “standing” configuration as shown in Figure 2 (i.e. when the mask is configured to be worn by a subject in a sitting or standing position)^ the vertical direction V corresponds substantially to the direction connecting the nose and the mouth of the subject.When the mask is in a "reclining" configuration as shown in Figure 3 or 4 (i.e., when the mask is configured to be worn by a subject in a reclining position), the vertical direction V corresponds substantially to the direction connecting the face and the face to the back of the skull (the occipital). When the mask is in a "semi-reclining" configuration (i.e., when the mask is configured to be worn by a subject in a semi-sitting or semi-reclining position), the vertical direction V corresponds substantially to the direction connecting the forehead to the nape of the neck of the subject.

[0077] The mask body 102 is delimited by a mask edge which can be defined as the portion of the mask body 102 coming into contact with a subject's face when worn. Advantageously, the mask edge can be an element added to the mask body 102 and made from a flexible material. For example, the The soft material can be silicone or other soft elastomer, or an inflatable bead to adapt to the shape of the face. This increases the seal of the mask and therefore reduces contamination of the outside air by the aerosol, ensures the proper functioning of the one-way valves and increases the efficiency of aerosol deposition in the subject's respiratory tract.

[0078] The mask edge defines a surface characterized by a mean plane S (in gray in Figures 2 and 3). Thus, the mask body 102 and the mean plane S define an inner (or internal) part and an outer (or external) part of the face mask. The mask body 102 has a volume measured as the volume of the inner part of the mask body 102. This volume is preferably less than 300 mL in order to limit the dead volume of the mask. For example, this volume is less than 300 mL for an adult and less than 30 mL for an infant. The mean plane S comprises a mask center C. The mask center C is a point belonging to the mean plane S located at the mathematical center of gravity of the mask edge. In addition, the mask body 102 can also be characterized by a vertical plane, substantially perpendicular to the mean plane S and passing through the axis of symmetry of the subject's face.Preferably, the mask body 102 has a symmetry with respect to the vertical plane as shown in Figure 1 or 5. In this case, the mask center C is located on the intersection between the vertical plane and the mean plane S.

[0079] The first opening comprises a conduit 104, also called an inspiration or nebulization conduit. This first opening allows in particular the passage of outside air towards the inside of the mask during inspiration by the subject. The inspiration conduit 104 has, by definition, two ends and extends along a longitudinal inspiration axis passing through these two ends. Thus, the inspiration conduit 104 comprises a lateral face extending around the longitudinal inspiration axis and connecting the two ends which can be perpendicular to the longitudinal inspiration axis. The inspiration conduit 104 can be a prism. The inspiration conduit 104 can be cylindrical. The inspiration conduit 104 can have a truncated cone shape.

[0080] The end opening into the mask body 102 - the first end 104a - forms, with the latter, an intersection defining a surface comprising an inspiration center C1 forming, with the mask center C, a direction of the first opening N1. As shown in Figures 2 and 3, the direction of the first opening N1 preferably forms an angle greater than 10° and less than or equal to 90° with the mean plane S, preferably between 10° and 75°. The direction of the first opening N1 is also preferably included in the vertical plane perpendicular to the mean plane S as shown in an illustrative manner in Figure 5. Advantageously, the inspiration conduit 104 opens near the nose or mouth of the subject in order to reduce the aeraulic dead volume which promotes the rapid penetration of the aerosol into the respiratory tract. The inspiration conduit 104 preferably opens into the nasal part of the mask body 102.

[0081] The inspiration conduit 104 also comprises a first inlet 104b connected to a mesh nebulizer 103 so that the nebulizer 103 closes this first inlet 104b. Thus, the mesh nebulizer 103 is in fluid connection with the interior of the mask body 102 through the inspiration conduit 104 in which the mesh nebulizer 103 generates the droplets. The mesh nebulizer 103 is advantageously positioned outside the mask which allows intervention on the mesh nebulizer 103 during use of the inhalation system 100. In addition, this external positioning makes it possible to maintain a compact shape for the mask body 102, so as to limit its volume.

[0082] The mesh nebulizer 103 comprises a nebulization chamber 103b in which the droplets are generated. The droplets are then delivered via an orifice located on the wall of the nebulization chamber 103b. This orifice may be directly connected to the first inlet 104b of the inspiration conduit 104. Alternatively, the mesh nebulizer 103 may comprise a nebulization conduit 103a connected to the orifice and to the first inlet 104b. The nebulization conduit 103a has a nebulization length measured between the orifice of the nebulization chamber 103b and the first inlet 104b. The nebulization length may be between 0.1 cm and 5 cm, preferably between 0.5 cm and 1 cm. This low length is particularly advantageous when the nebulizer is eccentric relative to the longitudinal inspiration axis around which the inspiration conduit extends. Indeed, a nebulization conduit that is too long involves gravity impaction of the droplets on the surface of the nebulization conduit before entering the inspiration conduit. In addition, the small size of the nebulization conduit 103a allows a reduction in the total volume of the mask and therefore a reduction in the pressure drop. The inspiration conduit 104 and the nebulization conduit 103a together form an inspiration chamber. The volume of the inspiration chamber is for example between 5 mL and 50 mL, preferably between 20 mL and 40 mL and can be adapted according to the individual.

[0083] The first end 104a and the first inlet 104b of the inspiration conduit 104 define an axis oriented L. The inspiration conduit 104 has an inspiration length LI measured parallel to the axis oriented L between the inspiration center Cl and the first inlet 104b as shown in FIG. 4. The inspiration length LI is preferably between 2 cm and 15 cm and preferably between 2 cm and 6 cm.

[0084] The first inlet 104b may be aligned with the longitudinal axis of inspiration, thus corresponding to the second end of the inspiration conduit 104 not connected to the mask body as shown in Figures 2 and 3. Alternatively, the first inlet 104b may be eccentric relative to the longitudinal axis of inspiration and positioned along the lateral face of the inspiration conduit 104 as shown in Figure 11. In this alternative embodiment, the first inlet 104b is preferably positioned near the second end of the inspiration conduit 104 not connected to the mask body in order to maximize the inspiration length LI and therefore maximize the volume of the inspiration conduit 104 that can be occupied by the droplets.

[0085] The inspiration conduit 104 further comprises a second inlet 104c connected to a one-way valve 1091. When the first inlet 104b is aligned with the longitudinal axis of inspiration, the second inlet 104c is preferentially positioned on the lateral face of the inspiration conduit 104. When the first inlet 104b is eccentric relative to the longitudinal axis of inspiration, the second inlet 104c may correspond to the second end of the inspiration conduit 104 not connected to the mask body. The one-way valve 1091 allows communication from the outside of the system 100 to the inside of the inspiration conduit 104.

[0086] The one-way valve 1091 can be positioned in an inlet conduit 107 connected to the second inlet 104c. The inspiration conduit 104 and the inlet conduit 107 together form an inspiration chamber. The volume of the inspiration chamber is for example between 5 mL and 50 mL, preferably between 20 mL and 40 mL and can be adapted according to the individual.

[0087] The resistance of a valve to opening (to trigger) is expressed as the ratio between the pressure (inspiration or expiration) in cm of water (cmthO) and the flow rate (inspiration or expiration) in liters per minute (L / min). The one-way valve 1091 has a resistance preferably less than 1 cmH20 / (L / min) and ideally less than 0.1 cmH20 / (L / min).

[0088] The second inlet 104c of the inspiration conduit 104 is preferably positioned at an inlet distance E from the inspiration center Cl measured between the inspiration center Cl and the second inlet 104c. The inlet distance E may be between 70% and 100% of the inspiration length LI, preferably between 90% and 100% of the inspiration length LI.

[0089] The inspiration conduit 104 may be connected to a dry gas source 300 such as a dry air or dry oxygen tank. The dry gas source 300 may be a pressurized cylinder connected directly to the face mask via, for example, a channel 350, preferably a corrugated conduit or hose, connected to the second inlet 104c as shown for example in FIG. 7. In an alternative embodiment, for example in a hospital environment, the dry gas source 300 is a central tank. The second inlet 104c is then connected via, for example, a corrugated conduit and a wall-mounted pressure regulator to one of the air outlets of the central tank. The connection between the gas source 300 and the second inlet 104c is configured so that the gas at the end of the channel 350 connected with the second inlet 104c is at a pressure lower than the resistance of the one-way valve 1091. The corrugated pipe being connected on the one hand to the second inlet 104c and being left to the open air on the other hand by a vent 350a. Thus during the expiratory phase, the gas enters the entire tube 350. The vent 350a being left to the open air, the resistance of the valve 1091 applies a greater resistance than the vent 350a to not allow the penetration of the gas through the opening 104c. During the inspiratory phase, the inspiratory valve opens and the gas contained in the tube 350 enters the inspiratory tube via the inspiratory valve 1091. The use of dry air or dry oxygen is advantageous because it allows more effective rinsing of the mask during inspiration. Indeed, the dry gas limits the condensation of water vapor on the aerosol droplets to prevent deposition on the internal wall of the mask body 102. This therefore makes it possible to reduce the loss of aerosol and to increase the efficiency of the deposition of the aerosol in the respiratory tract of the subject.The addition of dry gas also helps reduce droplet size through evaporation to allow efficient inhalation and deposition in the lungs.

[0090] When the face mask is placed on the subject, the oriented axis L forms, with the vertical axis V, a distribution angle D. The distribution angle D is preferably less than 45°. The distribution angle D is preferably less than 20°. The distribution angle D is preferably less than 10°. The oriented axis L also forms, with the direction of the first opening NI, an orientation angle O shown in Figure 4. The orientation angle O is therefore determined by the distribution angle D and the angle between the direction of the first opening N 1 and the mean plane S . Thus, the orientation angle O is preferably between 10° and 80° in the “lying down” configuration and preferably between 0° and 55° in the “standing up” configuration. Even more preferably, the orientation angle O is substantially equal to 45° in the “lying down” configuration.

[0091] When the face mask is placed on the subject, the first inlet 104b is located above the first end 104a as more specifically shown in Figure 4. The term "above" therefore means at a higher altitude along the vertical axis V.

[0092] The combination between the verticality of the oriented axis L and the position of the first inlet 104b above the first end 104a makes it possible to reduce the deposition of droplets on the subject's face, even in the lying position. Indeed, the closure of the inspiration conduit 104 by the nebulizer 103 makes it possible to generate the aerosol droplets directly in the conduit through which the air will be inspired. Thanks to the one-way valve 1091 connected to the inspiration conduit 104, the air cannot exit the mask through the inspiration conduit 104 during the expiration phase. Thus, this creates a volume of stagnant air in the inspiration conduit 104 during the expiratory phase. The aerosol is therefore generated and accumulated in this stagnant air during the expiratory phase before being inspired by the subject during the inspiratory phase by triggering the one-way valve 1091, which makes it possible to carry away all the droplets generated during the expiratory phase.The inventors have surprisingly found that the vertical positioning of the inspiration conduit 104 with the first inlet 104b above the first end 104a further improves the accumulation of droplets in the inspiration conduit 104. Indeed, the aerosol droplets generated at the first inlet 104b accumulate towards the first end 104a without entering the body of the mask 102. This phenomenon is shown diagrammatically in Figure 6. During the expiratory phase (left part of Figure 6), the one-way valve 1091 is closed. The mesh nebulizer generates, in the inhalation conduit 104, the aerosol droplets (represented by the points in Figure 6) which, by the force of gravity, descend from the first inlet 104b closed by the nebulizer towards the first end 104a. The aerosol droplets accumulate in the inspiration conduit 104 without entering the mask body 102.At the end of the expiratory phase, the aerosol concentration in the inspiration duct 104 is therefore greater near the first end 104a compared to the first inlet 104b. Then, during the inspiratory phase (right part of FIG. 6), the one-way valve 1091 connected to the second inlet 104c of the inspiration duct 104 opens allowing the suction of air (represented by the arrow in the inspiration duct) and thus carrying the accumulated droplets towards the inside of the mask body 102. The droplets following the inspired air flow, they are directly carried into the respiratory tract of the subject without causing any deposit on the subject's face.The volume inhaled by the subject therefore comprises a first more concentrated part coming from the volume close to the first end 104a and a second less concentrated part coming from the volume close to the first inlet 104b promoting deep pulmonary deposition and limiting losses in. the dead volume of the mask and the aeraulic dead volume. This concentration gradient is therefore created directly by the arrangement between the first end and the first inlet and by the vertical orientation of the inhalation conduit 104. In other words, the generation of the aerosol at a higher altitude than the first end of the inhalation conduit 104 allows the creation of a depression zone inside the inhalation conduit 104 preventing the aerosol generated during said exhalation phase from entering the mask body. This creation of a depression zone is all the more marked when the orientation of the inhalation conduit 104 is close to verticality.Indeed, a distribution angle D greater than 45° would have the effect of reducing the concentration gradient in the inhalation conduit 104, would increase sedimentation in the inhalation conduit 104 and would not create a depression zone inside the inhalation conduit 104 which would not prevent the generated aerosol from entering the mask body during the exhalation phase. An angle between 45° and 10°, for example a distribution angle D less than 20°, allows the creation of a depression zone but in a non-optimized manner because a large proportion of the generated particles sediment inside the inhalation conduit 104.A distribution angle D of less than 10° makes it possible to create a depression zone and a maximum concentration gradient between the first end and the first inlet in order to prevent the penetration of the aerosol generated into the mask body during the expiration phase while guaranteeing almost zero sedimentation in the inhalation conduit 104.

[0093] In one embodiment, the inhalation system 100 further comprises a steering element configured to allow a modification of the orientation angle O formed between the oriented axis L and the direction of the first opening NI. This steering element therefore advantageously makes it possible to maintain a constant distribution angle D, preferably less than 10°, between the oriented axis L and the vertical V when the subject moves from the standing / sitting position to the lying position or vice versa. In other words, the steering element makes it possible to move the face mask from the “lying” configuration to the “standing” configuration and vice versa. The steering element also makes it possible to place the face mask in the “semi-lying” configuration but also in any intermediate configuration. Indeed, when moving, for example, from the “lying” configuration to the "standing", the angle between the direction of the first opening NI and the mean plane S remains constant. In order to ensure that the distribution angle D is kept below 10°, the opening angle O must be modified.

[0094] The steering element may include a gyroscope and a processor for analyzing data collected by the gyroscope to automatically maintain the verticality of the oriented axis L. In another example, the steering element may include a mechanical element, such as a screw, gear, ring nut, or ball joint, to manually change the orientation angle O.

[0095] The inspiration conduit 104 may be configured to allow rotation of the first inlet 104b about a longitudinal inspiration axis. This makes it possible to orient the mesh nebulizer 103 so that the droplets are generated in a direction close to gravity (i.e. downwards) without changing the distribution angle. This makes it possible to use a single mask for different subject positions close to each other.

[0096] The second opening comprises a conduit 108, also called an exhalation conduit. This second opening allows in particular the passage of the air included in the mask body 102 towards the outside of the mask during exhalation by the subject. The exhalation conduit 108 has, by definition, two ends between which a length is measured. The exhalation conduit 108 can be a prism. The exhalation conduit 108 can be cylindrical. The exhalation conduit 108 can be only a hole in the mask body 102, the length of the conduit being the thickness of the mask body 102. The end of the exhalation conduit 108 opening into the mask body 102 - the first end - forms, with the latter, an intersection defining a surface comprising an exhalation center C2 forming, with the mask center C, a direction of the second opening N2.As shown in Figures 2 and 3, the direction of the second opening N2 preferably forms an angle greater than or equal to 0° and less than or equal to 90°, preferably between 10° and 75°, with the mean plane S. The direction of the second opening N2 is also preferably included in the vertical plane perpendicular to the mean plane S as in Figure 5. The conduit. expiration 108 preferentially opens into the mouth part of the mask body 102.

[0097] As shown in Figures 2 and 3, the second end of the exhalation conduit 108 is connected to a one-way valve 109E allowing communication from the inside of the mask body 102 to the outside. Thus, when air is inspired during the inspiratory phase, only the one-way valve 1091 connected to the second inlet 104c of the inspiration conduit 104 is open. Air can therefore only enter the mask body 102 through the inspiration conduit 104, thus allowing better control of the inspired aerosol concentration. The one-way valve 109E preferably has a resistance of less than 1 cmH20*min / L.

[0098] The longitudinal dimension of the exhalation conduit 108 is for example less than 2 cm, preferably less than 1 cm. The small size of the exhalation conduit 108 allows, thanks to the reduction in the total volume of the mask (reduction in pressure loss), faster triggering of the one-way valve 109E.

[0099] In an advantageous embodiment, the second end of the exhalation conduit 108 is connected to a filter. In a specific embodiment, the filter is an absolute expiratory filter retaining fine droplets during exhalation. This is advantageous because the filter helps protect the outside air from aerosol contamination during exhalation.

[0100] The one-way valve 109E and the filter may be connected separately or simultaneously to the exhalation conduit 108. In one embodiment, only the one-way valve 109E is connected to the exhalation conduit 108. In another embodiment, the one-way valve 109E and the filter are connected to the exhalation conduit 108. In this embodiment, the filter may be positioned upstream of the one-way valve 109E, i.e., between the one-way valve 109E and the interior of the mask body 102. This protects the valve 109E from contamination by aerosol droplets and from potential malfunction following its clogging.

[0101] As shown for example in Figures 2 and 3, the direction of the first opening NI and the direction of the second opening N2 form an opening angle a greater than 45°, preferably greater than 90°. The first and second openings are therefore positioned at distant locations on the mask body 102. Consequently, the inspiration and expiration conduits (104, 108) intersect the mask body 102 at distant locations. The distance between the first and second openings advantageously makes it possible to rinse the mask using the air exhaled by the subject in order to avoid the creation of unventilated zones which would concentrate the aerosol and promote its deposition on the subject's face.

[0102] The mask volume is defined as the sum of the volume defined by the mask body 102 and the mean plane S and the volume of each of the conduits (103a, 104, 107, 108). A low mask volume allows for faster triggering of the opening (triggering) of the valves (1091, 109E). For example, the mask volume can be reduced by decreasing the length of the conduits (103a, 104, 107, 108), mainly the nebulization conduit 130a, the exhalation conduit 108 and / or the inlet conduit 107 because the length of the inspiration conduit 104 must be sufficient to ensure the accumulation of droplets.

[0103] In a specific embodiment, the volume of the mask is substantially equal to or less than the lung capacity of an average subject. For example, for an adult human, the volume of the mask may be less than 300 mL while for a child, the volume of the mask may be less than 100 mL, preferably close to 50 mL.

[0104] For example, the mask and conduits are made of a material such as polypropylene PP, polyethylene PE or polyetheretherketone PEEK. The mask and conduits are preferably phthalate-free and / or polyvinyl chloride PVC-free. The mask and conduits are preferably made of a material that is not likely to become electrostatically charged.

[0105] The invention also relates to a use of the system 100 described above for administering a product into the respiratory tract of a subject.

[0106] The first step in use is to introduce a liquid active ingredient into the 103 mesh nebulizer. The active ingredient may be a test product or a marker, used in clinical or research trials. In this case, minimizing the dispersion of the product outside the mask is important, and efficient - quantitative - administration of the product allows for the use of smaller quantities of hazardous products.

[0107] The active ingredient may be in the form of a solution or suspension with a non-soluble particle size of less than 5 pm, and preferably less than 2 pm.

[0108] The subject is in a sitting, standing, semi-sitting / semi-lying or lying position. The subject is for example placed in an environment ensuring biological containment. Preferably, the system 100 in a “standing”, “lying” or “semi-lying” configuration corresponding to the position of the subject is then installed on the nose and mouth of the subject. In the embodiment in which the system 100 comprises a steering element, the direction of the inhalation conduit 104 can be adapted so that the oriented axis L has a distribution angle D of less than 10° and the nebulizer is at a higher altitude than the first end 104a of the inhalation conduit 104.

[0109] The mesh nebulizer 103 generates, preferably continuously, an aerosol comprising the introduced active ingredient. An advantage of using the mesh nebulizer is that it allows the aerosol flow rate and droplet size to be adapted to the subject. Thus, in a specific embodiment, the flow rate of the nebulizer is between 0.01 and 1 mL / minute and / or the size of the aerosol droplets produced is between 0.1 and 10 microns. Preferably, the aerosol flow rate is between 0.05 and 0.5 mL / minute, optimally between 0.05 and 0.1 mL / minute. Furthermore, and independently of the flow rate of the nebulizer, the size of the aerosol droplets produced is preferably between 0.5 and 5 microns, optimally between 2 and 5 microns. This is advantageous because the use of these flow rate ranges limits the loss of aerosol through condensation of droplets on the internal wall of the mask.Additionally, these droplet size ranges are small enough to allow for better deposition efficiency in the lower airways thereby increasing lung efficiency.

[0110] The continuous generation of the aerosol allows the system 100 of the present invention to be used in the most efficient manner possible. Indeed, as explained above, during the exhalation phase, the aerosol droplets generated in the conduit 104 will accumulate towards the first end 104a. Continuous generation of the aerosol makes it possible to create this accumulation phenomenon in a continuous and optimal manner, thus minimizing the number of droplets escaping from the inspiration conduit 104.

[0111] Upon inspiration, the one-way valve 1091 of the second inlet 104c opens and outside air is inspired into the inspiration conduit 104. The contents of the accumulated inspiration conduit 104 are then entrained by the inspired air and the aerosol droplets are inhaled to deposit in the subject's respiratory tract.

[0112] During expiration, the volume contained in the mask is rinsed by the exhaled air and then expelled from the mask body 102 through the exhalation conduit 108. This expelled air can be filtered by the filter which is optionally connected to the exhalation conduit 108. Thanks to the presence of the one-way valve 1091 at the second inlet 104c of the inspiration conduit, the air exhaled by the subject does not enter the inspiration conduit 104 and does not prevent the generation and accumulation of droplets in the inspiration conduit 104.

[0113] Thanks to the configuration of the inhalation system 100, it is advantageously possible to use the same system for the successive administration of two substances because the nebulizer 103 is accessible from outside the mask body 102. Thus, for example, the system 100 makes it possible to administer a product and its antidote by aerosol. The antidote can be administered before or after the administration of the product. The use of the same system 100 makes it possible to obtain a similar deposition between the two substances and therefore to evaluate the topical efficacy.

[0114] Thus, the invention also relates to a method for determining a topical efficacy of an antidote using the system 100 described above.

[0115] The first step of the method is to introduce a first substance in liquid form into the screen nebulizer 103. In a first embodiment of the method, the substance is a product. In a second embodiment of the method, the substance is an antidote.

[0116] The subject is in a sitting, standing, semi-sitting / semi-lying or lying position. The subject is for example placed in an environment ensuring biological containment. Preferably, the system 100 in a “standing”, “lying” or “semi-lying” configuration corresponding to the position of the subject is installed on the nose and mouth of the subject. Alternatively, the subject may be placed in a sitting, standing, semi-sitting / semi-lying or lying position corresponding to the configuration of the system 100 to be used. In the embodiment in which the system 100 comprises a steering element, the direction of the inhalation conduit 104 may be adapted so that the oriented axis L has a distribution angle D of less than 10° and the nebulizer is at a higher altitude than the first end 104a of the inhalation conduit 104.

[0117] The mesh nebulizer 103 generates, preferably continuously, an aerosol comprising the first introduced substance. In a specific embodiment, the flow rate of the nebulizer is between 0.01 and 1 mL / minute and / or the size of the aerosol droplets produced is between 0.1 and 10 microns. Preferably, the aerosol flow rate is between 0.05 and 0.5 mL / minute, optimally between 0.05 and 0.1 mL / minute. Furthermore and independently of the flow rate of the nebulizer, the size of the aerosol droplets produced is preferably between 0.5 and 5 microns, optimally between 2 and 5 microns.

[0118] At the end of the inhalation session of the first substance, a second substance is introduced into the nebulizer 103. The second substance is the counterpart of the first substance. In the first embodiment of the method, the second substance is an antidote to the previously introduced product. In a second embodiment of the method, the second substance is a product for which the previously introduced antidote is intended to neutralize the effects.

[0119] The second substance is introduced into the same nebulizer 103 connected to the same face mask as that used for nebulizing the first substance. Advantageously, the second substance may be introduced into the nebulizer 103 without that the inhalation system 100 is disconnected from the subject. Thus, the two nebulization sessions are carried out under the same breathing conditions and positioning of the face mask on the subject.

[0120] The screen nebulizer 103 generates, preferably continuously, an aerosol comprising the second introduced substance. In a specific embodiment, the flow rate of the nebulizer and the particle size are identical to the nebulization of the first substance. EXAMPLE

[0121] The present invention will be better understood by reading the following example which illustrates the invention in a non-limiting manner. Materials and methods

[0122] According to the invention, the inhalation system 100 used in this example comprises a screen nebulizer 103 and a face mask including: A mask body 102, An inspiration conduit 104 whose first inlet 104b aligned with the longitudinal axis of inspiration is closed by the screen nebulizer 103 configured to continuously generate aerosol droplets inside the inspiration conduit 104 and the second inlet 104c is positioned on the lateral face of the inspiration conduit 104, An exhalation duct 108.

[0123] The direction of the first opening NI and the direction of the second opening N2 form an opening angle a of 90°, and the oriented axis L forms, with the vertical axis V, a distribution angle D of 0°.

[0124] The mesh nebulizer comprises a vibrating membrane producing a 4 micron MMAD radioactive aerosol at a flow rate of 0.1 mL / minute.

[0125] The 100 system is placed over the nose and mouth of an animal model in a supine position. The animal models breathe a tidal volume of 25 mL at a rate of 30 breaths per minute. The inspiration chamber has a volume of 22 mL and a length of 6 cm.

[0126] The effectiveness of the system 100 according to the invention is compared to that of the system described in the article by Cabrera et al., the system described in European patent application EP2804647A1 as well as three commercial nebulizers: Micro cirrus™, Sidestream™ and NL20®. Results

[0127] The system described in Cabrera's article is the system shown in Figure 4 (Face mask number 1) of the article by Cabrera M, Le Pennec D, Le Guellec S, Pardessus J, Ehrmann S, MacLoughlin R, Heuzé-Vourc'h N, Vecellio L. Influence of mesh nebulizer characteristics on aerosol delivery in non-human primates. Eur J Pharm Sci. 2023.

[0128] Figure 8 shows the simulation of the normalized concentration (expressed in percent) as a function of the volume V' inspired by the model in mL (and therefore over the inhalation time) for the invention (solid black line) and the system described in the article by Cabrera et al. (dashed line) as well as the inspiratory flow rate (unitless) of the animal model (dotted line). The calculations were performed according to the method described in the article by Vecellio L, Kippax P, Rouquette S, Diot P. Influence of realistic airflow rate on aerosol generation by nebulizers. Int J Pharm. 2009 April 17, 371(1-2): 99-105. At the highest inspiratory flow rates, the system described in the article by Cabrera et al. involves the inhalation of a high concentration of aerosol, thus promoting impaction in the upper respiratory tract.Conversely, the system 100 according to the invention delivers a high concentration of aerosol at the start of inhalation, i.e. at the lowest inspiratory flow rates, thus limiting the impaction phenomenon in the upper respiratory tract and allowing the administration of larger particles into the lungs.

[0129] The first part of the inhaled volume (0 to 17 mL) corresponds to the volume that enters the lungs while the second part of the inhaled volume (18-25 mL) corresponds to the volume that enters the upper respiratory tract at the end of inspiration. Figure 8 clearly shows that the invention promotes pulmonary penetration compared to the state of the art: the second part of the volume inhaled by the animal model at the end of inspiration is much less rich in aerosol compared to the state of the art. The system according to the invention therefore causes less loss in the upper airways. In addition, the first milliliters of inhaled air (0-10 mL) do not contain aerosol when using the system according to the state of the art, which corresponds to the aeraulic dead volume.Consequently, the system according to the state of the art does not allow effective penetration of the aerosol into the deep lung (alveoli), whereas the system 100 according to the invention generates a higher concentration in the first volumes of inhaled air (very low dead air volume) allowing increased alveolar penetration. Thus, the system 100 according to the invention makes it possible to improve the pulmonary and alveolar penetration of the inhaled aerosol in the animal model in comparison with the system(s) according to the state of the art.

[0130] The deposition results in the airways are also measured by scintigraphic imaging. The deposition result after using the system 100 according to the invention is compared to the deposition results after using three commercial materials: Micro Cirrus™, Sidestream™ and NL20®. The results are summarized in Table 1.The first column of Table 1 lists the systems used, the second column lists the MMAD size of the particles produced in microns, the third column lists the pulmonary deposition as the ratio in percent between the mass of substance deposited in the lower airways and the mass of substance deposited in the entire airways, the fourth column lists the variability of deposition as the ratio in percent between F standard deviation and the mean deposition, the fifth column lists the nebulization efficiency in percent measured after 10 minutes of nebulization and defined as the ratio between the mass of substance deposited in the airways and the mass of substance loaded into the nebulizers. The sixth column lists the flow rate result as the ratio between the volume deposition of the substance in the airways and the nebulization time. [Table 1]

[0131] These results confirm a significant nebulization efficiency with the system 100 according to the invention compared to commercial nebulizers: 56% versus 5.7% for a nebulizer producing a similar MMAD with the Sidestream™ system. Pulmonary targeting is improved compared to other systems thanks to the aerosol bolus effect. Pulmonary deposition is 3%, 10% and 17% respectively for droplets of 13.9 microns, 3.2 microns and 0.4 microns MMAD with state-of-the-art systems (respectively NL20®, Sidestream™ and Micro Cirrus™) while it is 35% with the system 100 according to the invention generating a droplet size of 3.9 microns MMAD. This is all the more marked for a similar aerosol size MMAD of 3.2 microns with the Sidestream™ system and 3.9 microns with the 100 system of the invention, the pulmonary deposition is 10% with the Sidestream™ system compared to 35% with the 100 system of the invention.

[0132] The use of the system 100 of the invention advantageously makes it possible, thanks to the high deposition yield that it generates, to evaluate the deposition in the respiratory tract of the subject of a radiopharmaceutical substance by nuclear medical imaging. The deposition images by positron emission tomography (PET Scan) representing different anatomical sections (figure 9) demonstrate penetration of the aerosol into all of the lungs of the animal model.

[0133] Finally, in Figure 10, the deposition on the face of three animal models (aerosol deposition on the face expressed as a percentage of aerosol loaded in the nebulizer) is compared between the T-shaped device disclosed in European patent application EP2804647A1 (represented by stars in Figure 10) and the system 100 of the present invention (represented by discs). The dead volumes of the masks are identical and the flow rates and MMAD are identical. The results clearly demonstrate a reduction in aerosol deposition on the face of the animal models thanks to the system 100 according to the invention.

[0134] Consequently, the system 100 according to the invention allows a reduction in the deposition on the face of the subject, a greater deposition in the entire lower respiratory tract (greater pulmonary efficiency) even for larger droplets, and allows a higher concentration of aerosol in the first inhaled volumes of air. These results are applicable to the use of the system 100 according to the invention on a human being. DIGITAL REFERENCES 100 - Inhalation system / / 102 - mask body / / 103 - mesh nebulizer / / 103a - Nebulization conduit / / 103b - Nebulization chamber / / 104 - inhalation conduit / / 104a - first end / / 104b - first inlet / / 104c - second inlet II 107 - inlet conduit / / 108 - exhalation conduit / / 1091 - one-way valve of the inhalation conduit / / 109E - one-way valve of the exhalation conduit / / 300 - dry gas source / / 350 - channel / / 350a - vent UC - mask center / / Cl - center of inspiration / / C2 - center of expiration II D - distribution angle II E - entry distance II L - oriented axis / / LI - length of inspiration / / NI - direction of the first opening / / N2 - direction of the second opening II O - orientation angle / / S - medium plane UN - vertical axis / / V' - inspired volume II a - opening angle

Claims

CLAIMS 1. An inhalation system (100) comprising a mesh nebulizer (103) configured to generate droplets and a face mask comprising: A mask body (102) configured to cover the nose and mouth of a subject when said mask body (102) is placed on the subject and delimited by a mask edge defining a surface characterized by a mean plane (S) comprising a mask center (C) belonging to the mean plane (S) and located at the mathematical center of gravity of the mask edge, A first opening comprising an inspiration conduit (104) comprising: ■ a first end (104a) whose intersection with the mask body (102) defines a surface comprising an inspiration center (Cl) forming, with the mask center (C), a direction of the first opening (NI), and ■ a first inlet (104b) connected to the screen nebulizer (103), the latter being configured to generate aerosol droplets inside the inspiration conduit (104), ■ a second inlet (104c) comprising a one-way valve (1091) allowing communication from the outside of the system (100) to the inside of the inspiration conduit (104), A second opening comprising an exhalation conduit (108) comprising a first end whose intersection with the mask body (102) defines a surface comprising an exhalation center (C2) forming, with the mask center (C), a direction of the second opening (N2), the exhalation conduit (108) comprising a second end connected to a one-way valve (109E) allowing communication from the inside of the mask body (102) to the outside of the inhalation system (100), and wherein the direction of the first opening (NI) and the direction of the second opening (N2) form an opening angle (a) greater than 45°, preferably greater than 90°.

2. The inhalation system (100) according to claim 1, wherein the first end (104a) and the first inlet (104b) of the inspiration conduit (104) define an oriented axis (L), the oriented axis (L) forming, with a vertical axis (V) oriented in the direction of gravity, a distribution angle (D) of less than 45°, preferably less than 20°, more preferably less than 10°, when the face mask is placed on the subject, the first inlet (104b) being located above the first end (104a).

3. The inhalation system (100) according to claim 1 or 2 wherein the oriented axis (L) forms, with the direction of the first opening (NI), an orientation angle (O), the inhalation system (100) further comprising a direction element configured to allow a modification of the orientation angle (O).

4. The inhalation system (100) according to any one of claims 1 to 3 wherein the inspiration conduit (104) has an inspiration length (LI) measured parallel to the oriented axis (L) between the inspiration center (Cl) and the first inlet (104b), and the second inlet (104c) of the inspiration conduit (104) comprising the one-way valve (1091) is positioned at an inlet distance (E) from the inspiration center (Cl), the inlet distance (E) being between 70% and 100% of the inspiration length (LI), preferably between 90% and 100% of the inspiration length (LI).

5. The system (100) according to claim 4, wherein the inspiration length (LI) is between 2 cm and 15 cm, preferably between 2 cm and 6 cm.

6. The system (100) according to any one of claims 1 to 5, wherein the screen nebulizer (103) comprises a nebulization conduit (103a) connected to an orifice of a nebulization chamber (103b) and to the first inlet (104b), the nebulization conduit (103a) having a nebulization length measured between said orifice of the nebulization chamber (103b) and the first inlet (104b), the nebulization length being between 0.1 cm and 5 cm, preferably between 0.5 cm and 1 cm.

7. The inhalation system (100) according to claim 6 wherein the inspiration conduit (104) and the nebulization conduit (103a) together form an inspiration chamber having a volume of between 5 mL and 100 mL, preferably between 20 mL and 40 mL.

8. The system (100) according to any one of claims 1 to 7, wherein the inspiration conduit is configured to allow rotation of the first inlet (104b) around a longitudinal inspiration axis around which said inspiration conduit (104) extends.

9. The inhalation system (100) according to any one of claims 1 to 8 wherein the one-way valve (1091) of the inspiration conduit (104) is included in an inlet conduit (107) connected to the second inlet (104c), the inspiration conduit (104) and the inlet conduit (107) together forming an inspiration chamber having a volume of between 5 mL and 100 mL, preferably between 20 mL and 40 mL.

10. The inhalation system (100) according to any one of claims 1 to 9 wherein the inspiration conduit (104) opens into the nasal part of the mask body (102).

11. The inhalation system (100) according to any one of claims 1 to 10 wherein the exhalation conduit (108) opens into the mouth part of the mask body (102).

12. The inhalation system (100) according to any one of claims 1 to 11, wherein the exhalation conduit (108) has a longitudinal dimension of less than 2 cm, preferably less than 1 cm.

13. The inhalation system (100) according to any one of claims 1 to 12, wherein the volume of the face mask is less than 300 mL.

14. The inhalation system (100) according to any one of claims 1 to 13, wherein the inspiration conduit (104) is connected to a source of dry gas.

15. A method of administering a product into the respiratory tract of a subject, the method comprising: - Providing the inhalation system (100) according to any one of claims 1 to 14, Introducing an active ingredient in liquid form into the screen nebulizer, Installing the inhalation system (100) on the nose and mouth of the subject, preferably so that the first inlet (104b) is located above the first end (104a), Generation of an aerosol in the inhalation duct by the screen nebulizer.

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