Spray system

Abstract

The invention provides a spray system comprising a reservoir, a two-fluid spray nozzle, a dispenser mounted on the reservoir, and a wet gas source designed to inject a controlled wet gas into the reservoir.

Description

NEBULIZATION SYSTEM FIELD OF THE INVENTION

[0001] The present invention relates to a nebulization system and its use for generating a stable aerosol over time which has a high concentration, a wide range of droplet sizes and using liquids over a wide range of viscosity. STATE OF THE ART

[0002] A liquid aerosol is a two-phase mixture comprising droplets and a gas, which is most commonly air. This aerosol can be used in the context of particle sensor calibration, in a laboratory research context, in a medical context by administering this aerosol into the respiratory tract (or airways) of a subject - for example during an aerosol therapy session or during a toxicology study - or in a breathing simulation context.

[0003] Particle sensors are typically calibrated during construction by measuring the target particle concentration in a given volume. Whether for initial or control calibration, a reproducible, stable, and accurate source of particle dispersion is required.

[0004] Breathing simulators can simulate, for example, airborne contamination of an environment or between multiple subjects. The aerosol concentration must be precisely controlled to determine the simulation parameters.

[0005] In the research or medical context, the study of the effect of inhaled aerosols on the respiratory tract in aerosol therapy or toxicology requires controlling and knowing the quantity of active ingredient deposited in the respiratory tract. This quantity is calculated based, in particular, on the concentration of active ingredient in the aerosol.

[0006] In this study context, the regulatory texts impose a stability of the concentration in order to produce an aerosol whose concentration of active ingredient varies by less than 20% (relative variation) in the exposure chambers. Since the duration of exposure during a study can be several hours, it is necessary to achieve an aerosol generation with a concentration stable over time.

[0007] However, known nebulization systems are not satisfactory.

[0008] Indeed, a first known system is pneumatic nebulization which uses a source of compressed gas injected continuously into a nebulization chamber (or nebulizer) containing the liquid to be nebulized. The liquid is then atomized, forming droplets suspended in the air of the nebulization chamber. During nebulization, a recycling and evaporation phenomenon occurs within the nebulizer reservoir which results in an increase in the concentration of active ingredient in the liquid to be nebulized contained in the reservoir over time.

[0009] Indeed, the liquid to be nebulized is a solution comprising an active ingredient whose saturated vapor pressure is lower than the solvent (usually water) in which it is mixed. Thus, the atmosphere in the nebulization chamber formed by the injected gas will have the effect of evaporating the solvent more quickly than the active ingredient. As a result, the concentration of active ingredient in the liquid to be nebulized will increase as the solvent evaporates. The aerosol droplets have (at their creation) the same concentration of active ingredient as the liquid to be nebulized. Thus, the concentration of active ingredient in the droplets will also increase during nebulization. In addition, during the transport of the droplets towards the nebulizer outlet, the evaporation phenomenon continues to occur on the latter, which will further increase the concentration of active ingredient in the droplets until they are inhalation.

[0010] In addition, the geometric arrangement of certain types of pneumatic nebulizers such as Pari (registered trademark) or Sidestream (registered trademark) nebulizers generating an aerosol flow towards the liquid in the reservoir, promotes the impaction of droplets in the liquid contained in the reservoir. A larger volume of liquid promotes more droplet impaction in comparison a smaller volume of liquid in the reservoir. As a result, the flow rate and particle size increase over time as the liquid is nebulized gradually (decreasing the volume of liquid contained in the reservoir). These types of nebulizers therefore do not allow for the generation of a stable aerosol over time.

[0011] Another known system is a Blam system which consists of bringing the liquid to be nebulized into the nebulizer by a pump with a continuous and constant flow rate. The gas conveyed with a constant flow rate atomizes the injected liquid. A selection is then made on the droplets so that only the small droplets are transported out of the nebulizer to be inhaled. The largest droplets are directed out of the nebulization chamber and are intended to be eliminated. This system avoids recycling and evaporation of the liquid before nebulization. However, this system generates a very low concentration of liquid aerosol (0.001 mg / m 3 - 0.01g / m 3 in mass concentration of droplets) and produces a large amount of waste (typically more than 98% of the aerosol is eliminated).

[0012] Finally, some known systems use vibrating sieve technology. The liquid to be nebulized in contact with the sieve is then expelled through the sieve orifices to mix with the gas. The droplet concentrations produced are higher than with the Blam system. However, this system has problems with clogging of the sieve orifices which can alter its operation and therefore the droplet flow and consequently the concentration of active ingredient over time. In addition, the sieve nebulizer cannot nebulize solutions with high viscosity or droplets smaller than 2 μm unlike the pneumatic nebulizer.

[0013] There is therefore a need for a nebulization system that can avoid one or more of these problems by promoting the generation of an aerosol with a stable substance concentration (active ingredient or particles) over time, as well as a wide range of droplet sizes and / or using liquids over a wide range of viscosity.

[0014] The aim of the invention is to provide a nebulization system comprising a reservoir capable of receiving a liquid to be nebulized comprising a two-fluid nozzle as well as a source of humid gas injecting a gas of controlled humidity into the reservoir. SUMMARY

[0015] For this purpose, the present invention relates to a nebulization system comprising: a) A device comprising: ■ A reservoir comprising a gas nozzle defining a nebulization axis and comprising a first opening located inside the reservoir, the reservoir being capable of receiving a liquid to be nebulized, ■ A nebulizing nozzle superimposed on the gas nozzle comprising a second opening, ■ A dispenser mounted on the reservoir, the dispenser being aligned with the nebulizing axis to convey the aerosol out of the reservoir, the nebulizing nozzle and the gas nozzle forming a two-fluid nebulizing nozzle comprising: ■ A gas channel inside the gas nozzle, ■ A liquid channel between the nebulizing nozzle and the gas nozzle, and ■ A nebulization zone at the intersection of the gas channel and the liquid channel, the outlet of the nebulization zone corresponding to the second opening, and b) A source of wet gas which feeds the gas channel so as to inject a wet gas of controlled humidity into the reservoir, the injection of wet gas making it possible to draw the liquid to be nebulized into the liquid channel.

[0016] Indeed, the geometry of the device and the injection of humid gas of controlled humidity allows the production of a high concentration aerosol (0.1-1 g / m 3 in droplet mass concentration) presenting a wide range of droplet sizes (50 nm-10 microns) and implementing liquids over a wide range of viscosity (0.1-200 cP). In addition, this limits the evaporation of the liquid and droplets in the tank, which prevents the concentration of the substance contained in the aerosol from increasing over time.

[0017] According to another advantageous aspect, the invention has the following characteristics taken in isolation or in combination: at least one part of the distributor has an angle of between 30° and 70° relative to the nebulization axis; the two-fluid nebulization nozzle comprises a deflector located at the outlet of the nebulization zone.

[0018] Indeed, both embodiments make it easier to select droplets based on their size. The use of the deflector also allows for additional fragmentation of the droplets and therefore an increase in yield.

[0019] According to another advantageous aspect of the invention, the first opening has a first size and the second opening has a second size greater than the first size, the first opening being aligned with the second opening and the first opening and the second opening being perpendicular to the nebulization axis.

[0020] In fact, this difference in size makes it possible to optimize the quantity of aerosol produced and the size of the droplets.

[0021] According to another advantageous aspect, the invention has the following characteristics taken in isolation or in combination: the first size is between 0.1 mm and 1 mm and the second size is between 0.2 mm and 2 mm; the nebulization nozzle has an internal wall and the gas nozzle has an external wall, the internal wall being spaced 0.2 mm to 2 mm from the external wall; the device is configured to heat the liquid to be nebulized; the device is made of stainless steel; the humid gas source comprises a gas source and a humidification device connected to the gas source and the gas nozzle, the humidification device being configured to humidify a gas from the gas source; the humidification device is a nebulizer; the humidification device comprises a heating plate; the humidification device comprises an outlet filter; the humidification device is a bubbler; the humidification device is configured to heat the gas.

[0022] In addition, the invention also relates to an aerosol therapy system comprising the nebulization system according to one of the above embodiments fluidically connected to a face mask.

[0023] The invention also relates to a breathing simulator configured to simulate the expiratory phase of a breath, the breathing simulator comprising the nebulization system in which the device is configured to heat the liquid to be nebulized.

[0024] The invention therefore allows a more reliable simulation of human breathing by heating the liquid to a temperature close to the temperature of a human body, for example 37°C.

[0025] The invention also relates to a toxicological study system comprising the nebulization system according to one of the above embodiments fluidly connected to a nasal mask or to a whole body enclosure.

[0026] The invention also relates to a calibration device configured to generate an aerosol with a stable particle concentration, the calibration device comprising a calibration chamber defining a calibration volume in which the particle concentration is stable over time, the calibration chamber comprising the nebulization system according to one of the embodiments above and being capable of accommodating a sensor configured to detect said particles.

[0027] Finally, the invention also relates to a method for generating an aerosol comprising the steps of: Provide the nebulization system according to one of the above embodiments, Introduce a liquid to be nebulized into the tank, Provide, from the wet gas source, wet gas with a constant pressure between 0.1 bar and 10 bar and a controlled humidity of relative humidity greater than 60%, Inject the humidity-controlled wet gas into the tank via the gas channel. DEFINITIONS

[0028] In the present invention, the terms below are defined as follows: "Two-fluid nebulizing nozzle" relates to an arrangement of two nozzles allowing the aspiration of the liquid to be nebulized by the Venturi effect. This effect is produced when two nozzles are superimposed so as to create a gap between the inner wall of the outer nozzle and the outer wall of the inner nozzle. Thus, when the outer nozzle is partially immersed in a liquid and a gas is injected into the inner nozzle, a vacuum is created in the gap allowing the aspiration of the liquid. "Substance concentration" refers, for an aerosol, to the concentration of substance (active ingredient or particles) - dissolved or dispersed in the droplets. This concentration can be established at the nebulizer outlet or at the time of inhalation by a subject or during calibration of a sensor. This concentration is the quantity of substance (in grams) contained in the air (in m 3 ). "Droplet mass concentration" refers, for an aerosol, to the mass of aerosol droplets (in grams) contained in the air (in m 3 ). “Large droplet” refers to a droplet with a diameter greater than or equal to 5 pm. “Small droplet” refers to a droplet with a diameter smaller than or equal to 5 pm. BRIEF DESCRIPTION OF THE FIGURES

[0029] 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 in any limiting nature. In the figures:

[0030] Figure 1 shows a nebulization system according to one embodiment of the invention.

[0031] Figure 2 shows the geometry of the nebulization device according to one embodiment of the invention.

[0032] Figure 3 shows the operation of the system according to the invention.

[0033] Figure 4 shows the nebulizing device including a deflector (137).

[0034] Figure 5 shows the nebulizing device in which the distributor (120) is inclined.

[0035] Figure 6 shows the nebulization system in which the humidification device (210) is a nebulizer.

[0036] Figure 7 compares the variation in the concentration of active ingredient as a function of the duration of nebulization with a device of the prior art and a device according to an embodiment of the invention.

[0037] Figure 8 shows the efficiency of aerosol deposition in the respiratory tract. DETAILED DESCRIPTION

[0038] Figure 1 shows a nebulization system comprising a device 100 and a wet gas source 200.

[0039] Device 100 includes: A tank 111 comprising a gas nozzle 113, A nebulizing nozzle 130 superimposed on the gas nozzle 113, and a distributor 120 mounted on the tank 111.

[0040] The reservoir 111 is capable of receiving a liquid to be nebulized.

[0041] The liquid may include, for example, one or more substances. For example, the substance may be an active ingredient that will act on the respiratory tract or a marker that will be injected into the subject's respiratory tract as part of clinical tests or research. The active ingredient may be diluted in a solvent, preferably sterile physiological saline (NaCl 0.9%). The substance may, for example, include a type of particle that will be detected by the sensor to be calibrated. The (insoluble) particles may be precipitated in a solvent, preferably water (H2O). The particles will, during nebulization, be included in solvent droplets.

[0042] The nozzles of the device (the gas nozzle 113 and the nebulizing nozzle 130) are conventional nozzles or pipes of preferably cylindrical shape having an internal wall, an external wall and two ends.

[0043] One end of the gas nozzle 113 is located inside the reservoir. This end is partially closed and comprises a first opening 113o. The gas nozzle 113 defines a nebulization axis Z which corresponds to the longitudinal axis of the nozzle. The gas nozzle 113 and the reservoir 111 are preferably formed in a single piece.

[0044] The nebulizing nozzle 130 located in the reservoir 111 is superimposed on the gas nozzle 113 in the sense that the nebulizing nozzle 130 surrounds, over part of its length, the gas nozzle 113. The gas nozzle 113 is preferably centered in the nebulizing nozzle 130.

[0045] Both ends of the nebulizing nozzle 130 are located inside the tank. One end of the nebulizing nozzle 130 comprises a second opening 130o. The nebulizing nozzle 130 is superimposed on the gas nozzle 113 so that the two ends comprising the openings (113o, 130o) are juxtaposed.

[0046] In one embodiment, the first opening 113o has a first size and the second opening 130o has a second size preferably larger than the first size. These openings are shown in detail in Figure 2. The openings can be of any shape. The size of an opening then corresponds to their largest dimension. The openings are preferably circular; the size then corresponds to the diameter. For example, the first size is between 0.1 mm and 1 mm while the second size is between 0.2 mm and 2 mm. Preferably, the first size is between 0.2 mm and 0.8 mm and the second size is between 0.3 mm and 1.6 mm. The first opening 113o is aligned with the second opening 130o and the two openings are preferably aligned on the nebulization axis Z.The first opening 113o and the second opening 130o are preferably perpendicular to the nebulization axis Z.

[0047] The inner wall of the nebulizing nozzle 130 and the outer wall of the gas nozzle 113 are preferably spaced 0.2 mm to 2 mm apart from each other.

[0048] The nebulizing nozzle 130 and the gas nozzle 113 thus form a two-fluid nebulizing nozzle as shown in FIG. 2 comprising: a gas channel 132 (represented by dashed lines) inside the gas nozzle 113, a liquid channel 134 (represented by solid lines) between the nebulizing nozzle 130 and the gas nozzle 113, and a nebulizing zone 131 (represented by dotted lines) at the intersection of the gas channel 132 and the liquid channel 134.

[0049] The nebulizing nozzle 130 is arranged so that a gap is present between the end not including the opening 130o and the internal surface of the reservoir 111 to allow the liquid to enter the liquid channel 130.

[0050] The two-fluid nebulizing nozzle allows, when the system is used, to create a Venturi effect, the operation of which will be described later. The liquid is then sucked through the liquid channel 134 to the nebulization zone 131 as represented by the arrows 460 in Figure 3. The liquid is then fragmented into droplets by the gas flow injected into the gas channel 132. The liquid is said to be atomized or nebulized to form the aerosol. The droplets exit the nebulization zone 131 through the second opening 130o. The device described above makes it possible to create droplets with a size between 10 nm and 100 pm. Thus, the size range of the droplets created extends over four orders of magnitude. This order of magnitude can be regulated, among other things, with the gas flow rate.

[0051] The distributor 120 is a channel comprising two ends. The distributor may be an orifice passing through one of the walls of the reservoir 111; the height of the channel then corresponds to the thickness of the wall that it passes through. The distributor 120 is mounted on the reservoir 111. Thus, one of the ends of the distributor 120 is connected to the reservoir 111. The distributor 120 is aligned with the nebulization axis Z to convey the aerosol out of the reservoir. In other words, the axis connecting the two ends of the distributor 120 is superimposed on the nebulization axis Z. The alignment of the distributor 120 with the nebulization axis Z allows a more direct path of the droplets towards the outlet of the device 100 (the end of the distributor 120 which is not connected to the reservoir 111). droplets experience less impact on the edges of the device 100 during their journey towards the exit. Therefore, in aerosol therapy or toxicology, a larger quantity of droplets is delivered to the subject, which reduces the nebulization time. For example, the section of the distributor 120 is larger than the section of the gas nozzle 113.

[0052] The dimensions of the reservoir 111 are configured so that the smallest droplets are conveyed out of the reservoir 111 by the dispenser 120 while the larger droplets, which therefore have greater kinetic energy, impact the walls of the dispenser 120 and then fall back into the reservoir 111. This therefore reduces the amount of waste because the larger droplets will be reused. Consequently, this sizing makes it possible to dispense all the droplets that have a size smaller than a limit determined by said sizing. Thus, this makes it possible to select the droplets according to their size in order to better adjust the mass concentration of the dispensed aerosol droplets and / or to better control the transport of the droplets without evaporation towards the subject.

[0053] In order to refine the selection of droplet sizes that will be dispensed and to increase the efficiency of the nebulization, the two-fluid nebulization nozzle may include a deflector 137 located at the outlet of the nebulization zone 131 as shown in Figure 4. The deflector 137 advantageously has a dual role: first, it allows for additional fragmentation of the droplets, thereby increasing the number of droplets having the appropriate size to exit the reservoir 111. Second, it allows for finer selection of the droplet size. Indeed, the deflector also allows the trajectory of the droplets to be deflected towards the edges (lateral surface) of the reservoir 111. Thus, droplets having high kinetic energy will impact the surface of the reservoir 111. These droplets will therefore accumulate on the surface of the reservoir 111 and will return to the reservoir 111 just like the large droplets.Thus, the deflector 137 makes it possible to distribute finer droplets and follow the trajectory leading them outside the tank.

[0054] To further refine the selection of droplet sizes that will be dispensed, at least a portion of the dispenser 120 may have an angle A of between 30° and 70°, preferably between 45° and 60°, relative to the nebulization axis Z as shown in Figure 5. Thus, droplets that have high kinetic energy will impact the surface of the dispenser 120. These droplets will therefore accumulate on the surface of the dispenser 120 and return to the reservoir 111 just like the large droplets. Thus, the angle A of the dispenser 120 advantageously makes it possible to distribute only droplets that have a size within a certain range allowing them to follow the trajectory of the curvature of the dispenser 120. This embodiment can be combined with the presence of a deflector 137.

[0055] According to the invention, the source of wet gas 200 supplies the gas channel 132 so as to inject a wet gas 440 of controlled humidity into the reservoir 111. Controlling the humidity of the injected gas advantageously allows the generation of an aerosol having a stable concentration of the substance over time at the outlet of the device 100. Indeed, the injection of wet gas has the effect of saturating (or tending towards saturation of) the atmosphere of the reservoir with humidity. Thus, the phenomenon of evaporation of the solvent contained in the liquid to be nebulized or in the droplets is slowed down or even stopped. Consequently, the concentration of substance in the aerosol becomes stable.Indeed, controlling the humidity of the injected gas firstly makes it possible to avoid the evaporation of the solvent contained in the liquid to be nebulized, which would lead to the evaporation of the solvent contained in the liquid to be nebulized and consequently to an increase in the concentration of the substance in the reservoir over time. In addition, the humid gas limits the evaporation of the water contained in the aerosol droplets. This evaporated solvent would then condense on the walls of the nebulizer and return to the liquid to be nebulized and consequently reduce the concentration of substance in the reservoir (dilution). The introduction of a humid gas of controlled humidity therefore makes it possible to maintain the concentration of the liquid to be nebulized constant over time because the droplets that fall back into the reservoir maintain a concentration equal to that of the liquid to be nebulized. This therefore advantageously makes it possible to produce an aerosol with a high concentration of substance (0.1-1 g / m.3 ) with a wide range of droplet sizes (10 nm-10 microns) and implementing liquids over a wide viscosity range (up to 200 cP). Compared to known systems for which the concentration can reach 0.01 g / m 3 , the system according to the invention makes it possible to increase the concentration of at least a factor of 10. The size of the droplets does not appear to depend on the relative humidity of the wet gas.

[0056] In the case of aerosol therapy or toxicological studies, in addition to stability of the concentration of the substance at the outlet of the device 100 over time, the system according to the invention also makes it possible to maintain constant the concentration of the substance between the outlet of the device 100 and the entry into the airways of the subject. Indeed, the atmosphere in which the droplets are conveyed being saturated with humidity, the phenomenon of evaporation of the solvent contained in the conveyed droplets is limited which guarantees a concentration of each droplet entering the respiratory tract of the subject equal to the concentration in the liquid to be nebulized.If the atmosphere into which the droplets are delivered is not close to humidity saturation, the solvent in the delivered aerosol droplets would evaporate and consequently the droplets would have a smaller size and a greater concentration than the liquid to be nebulized when inhaled by a subject.

[0057] The system described in international application WO 2015 / 189290 is known. This document describes humidity control for maintaining mucociliary clearance levels in the patient's airways in order to improve the efficiency and reliability of aerosol delivery. Unlike the invention, this document does not seek to obtain a stable concentration of active ingredient over time. Indeed, this document teaches the ventilation of a subject with the objective of maintaining a constant humidity level close to saturation at the nebulizer outlet (and not in the reservoir as is the case in the invention) regardless of the parameters of the liquid to be nebulized. The concentration of substance in the aerosol can also be modified in order to maintain a target humidity at the nebulizer outlet.To achieve a constant humidity level at the nebulizer outlet, this document teaches that the atmosphere in the reservoir must not be saturated in order to allow the evaporation of the solution to complete the humidity level to obtain 100% gas humidity at the nebulizer outlet. This evaporation of the liquid to be nebulized is precisely what the invention seeks to avoid because, as explained previously, evaporation of the liquid to be nebulized implies a variation in the concentration of the substance in the liquid to be nebulized over time.

[0058] The humid gas source 200 may include a gas source 220 and a humidification device 210 connected to the gas source 220 and the gas nozzle 113 as shown in Figure 3.

[0059] The gas source 220 distributes a gas 420 to the humidification device 210. The gas may, for example, be a dry gas. The gas is preferably air. The gas source 220 may, for example, be a pressurized gas cylinder or a compressor.

[0060] The humidification device 210 is configured to humidify the gas from the gas source 220. The thus humidified gas 440 therefore has a controlled humidity. The humid gas 440 is then conveyed to the gas channel 132 via a pipe 217 connected to the gas nozzle 113 in order to create the aerosol droplets having the advantageous characteristics presented above.

[0061] The humidification device 210 may for example be a nebulizer as shown in FIG. 6. The gas from the gas source 220 is conveyed to the inlet of the nebulizer 210 by a pipe 215. The liquid included in the nebulizer of the humidification device 210 is preferably water.

[0062] Alternatively, the humidification device 210 may be a bubbler in order to humidify the gas by micro-bubbling.

[0063] The humidification device 210 may further comprise an outlet filter, preferably an absolute filter made of fiberglass for example, retaining for example 99.95% of droplets with a diameter greater than 0.3 μm. The filter is low resistance and can be changed when it is saturated with water droplets. The filter is positioned between the humidification device 210 and the gas nozzle 113. The filter, by definition, makes it possible to block the water droplets (or other humidification liquid) and to allow only water in vapor form to pass through.

[0064] The humidification device 210 can also be integrated into the gas source 220 as is the case in a medical compressor.

[0065] The gas source 220 may be configured to heat the gas 440. The heating may occur before or after humidification of the gas 440. For example, in aerosol therapy or toxicology, the gas 440 may be heated to a temperature corresponding to the temperature of a subject breathing the aerosol generated by the device 100. In another example, when simulating breathing, the gas 440 may be heated to a temperature corresponding to the temperature of the subject whose breathing is being simulated. In order to heat the gas 440, the humidification device 210 may further comprise a heating plate.

[0066] In addition, the liquid to be nebulized may also be heated. For example, the liquid to be nebulized may be heated to a temperature corresponding to the temperature of a subject breathing the aerosol generated by the device 100. In order to heat the liquid to be nebulized, the device 100 may for example be made of a thermally conductive material which is heated by an external heat source. For example, the device 100 may be made of stainless steel and placed in a liquid heated to the desired temperature (water bath). The temperature to which the gas 440 and / or the liquid to be nebulized is heated is for example approximately 37°C in order to correspond to the body temperature of a human being.

[0067] The nebulizer may also include an additional system for supplying liquid to be nebulized via a drip or syringe pump system. In this case, the liquid is supplied to the nebulizer reservoir using a thin tube passing through the distributor 120. The use of a syringe pump with a flow rate equivalent to the nebulization flow rate thus makes it possible to avoid the need for significant sizing of the reservoir 111 of the nebulizer and to operate it without limitation over time.

[0068] In aerosol therapy, the system according to the invention can be connected to a face mask covering the subject's nose and / or mouth or to a breathing tube placed in the subject's mouth. In toxicology, the system according to the invention can be connected to a nose-only system configured to deliver the aerosol to the subject's nose or to a whole-body system configured to accommodate the subject's entire body so that the subject can breathe naturally through the nose or mouth. Advantageously, the system allows, by generating an aerosol that is stable over time and during distribution, to know precisely the quantity of aerosol deposited in the subject's respiratory tract. In addition, the system allows nebulizing solutions with high concentration, high viscosity and small droplet size.

[0069] By virtue of the sizing of the device 100 and the injection of humid gas 440 of controlled humidity into the reservoir 111, the nebulization system can be used to simulate the exhalation process of a subject, for example a human being. Indeed, the system according to the invention generates droplets whose size, speed and density reproduce the flow of droplets created naturally during the exhalation of a subject by tearing droplets from the mucus of the respiratory tract. In addition, when the gas source 220 is configured to heat the gas 440 or when the liquid to be nebulized is heated, the simulation of the exhalation of a subject is all the more precise as the gas 440 or the liquid to be nebulized is heated to the temperature of the subject whose exhalation process is simulated. Thus, the system according to the invention can for example be used to simulate the phenomenon of contamination by generating droplets in the manner of exhalation.The system can therefore be included in a breathing simulator configured to simulate the expiratory phase of breathing in order, for example, to study the airborne contamination process.

[0070] The stability of the substance concentration over time also makes it possible to calibrate particle sensors. Indeed, when the nebulization system is included in a calibration device, the calibration device can be configured to produce an environment comprising a stable concentration of particles, dispersed in droplets, to be measured by the sensor over time. The calibration device comprises a calibration chamber defining a calibration volume in which the particle concentration is stable over time. The calibration chamber comprises the nebulization system and is configured to accommodate a sensor allowing the quantitative or qualitative measurement of the number of particles or to detect the particles in a given volume.The nebulization system advantageously allows the sensor to be easily calibrated at different times, for example, between several measurements, after each measurement or after a given duration of use. Indeed, the calibration is advantageously homogeneous over time thanks to. to the maintenance, by the system, of a constant concentration of particles dispersed in droplets over time.

[0071] The invention also relates to a use of the system described above for generating an aerosol.

[0072] The first step in the method of generating an aerosol is to introduce a liquid to be nebulized into the reservoir 111. The reservoir 111 is preferably filled until the surface of the liquid to be nebulized is above the end of the nebulizing nozzle 130 not including the opening 130o.

[0073] The second step consists of providing, from the wet gas source 200, a wet gas with a constant pressure of between 0.1 bar and 10 bar, preferably between 0.5 bar and 5 bar and a controlled humidity of relative humidity greater than 60%, preferably greater than 70%.

[0074] This humid gas of controlled humidity is then injected into the reservoir 111 via the gas channel 132. The injection is preferably carried out continuously, that is to say, at a constant flow rate. Indeed, the continuous injection makes it possible to generate a mass concentration of droplets in the atmosphere of the reservoir 111 which is continuous. Combined with the concentration of substance which is constant in the droplets thanks to the injection of humid gas of controlled humidity, this leads to further stabilizing the concentration of substance at the outlet of the reservoir.

[0075] During use, the reservoir 111 is preferably held so that the nebulization axis Z is substantially vertical and the distributor 120 is positioned above the two-fluid nebulization nozzle. Thus, when a gas flow is injected into the gas channel 132 into the reservoir 111, a vacuum is created by the Venturi effect in the liquid channel 134. The liquid to be nebulized is then drawn through the liquid channel 134, as shown by the arrows 460 in FIG. 3, to the nebulization zone 131 in which the liquid is atomized by the wet gas 440. EXAMPLES

[0076] Experimental tests measuring the effectiveness of the system according to the invention have been carried out. Example 1: Stability of substance concentration over time

[0077] In this example, the concentration of substance generated with a system according to the invention and with a known system are compared. The liquid to be nebulized is a solution of water and fluorescein - the active ingredient - with a viscosity of 1 cP.

[0078] The system according to the invention comprises a deflector 137. The first opening 113o has a diameter of 0.7 mm while the second opening 130o has a diameter of 1.3 mm.

[0079] The humidification device is a nebulizer with a filter at its outlet. The humid gas is air humidified with water. The relative humidity of the humid gas injected into the gas channel is set at 72% ± 2%.

[0080] The known system comprises the same nebulization device as the system according to the invention. The liquid to be nebulized is atomized by a flow of non-humidified gas. The relative humidity of the gas injected into this nebulizer is 12% ± 1%.

[0081] The concentration of the active ingredient (fluorescein) distributed is measured for both systems. The variation of the concentration (y-axis) is shown in Figure 7 as a function of the nebulization time in minutes (x-axis). The concentration measured for the known system is represented by the dotted line while the concentration by the system according to the invention is shown by the solid line.

[0082] The concentration of active ingredient using the system according to the invention shows a low variation compared to the concentration generated by the known system which increases from the first minutes of use. In addition, the variation of the concentration of active ingredient generated by the system according to the invention remains below the regulatory relative concentration variation of 20% for aerosol test studies. Example 2: Aerosol deposition efficiency in the respiratory tract

[0083] In this example, the aerosol deposition efficiency (nebulization efficiency) in the respiratory tract using a system according to the invention is measured. The liquid to be nebulized is a radioactive solution - the radioactive compound is the active ingredient.

[0084] The system of the invention used is the same as in Example 1.

[0085] The system is used on a model for 10 minutes. At the end of the nebulization session, the efficiency of aerosol deposition in the model's airways is measured by scintigraphic imaging.

[0086] Figure 8 shows satisfactory deposition in the airways. Thus, this shows that the aerosol is well delivered to the airways. DIGITAL REFERENCES 100 - Nebulizing Device / / 111 - Reservoir / / 113 - Gas Nozzle / / 113o - First Opening / / 120 - Distributor / / 130 - Nebulizing Nozzle / / 130o - Second Opening / / 131 - Nebulizing Zone / / 132 - Gas Channel / / 134 - Liquid Channel / / 137 - Deflector / / 200 - Wet Gas Source / / 210 - Humidifying Device / / 215 - Hose / / 217 - Hose / / 220 - Gas Source / / 420 - Gas Elux / / 440 - Humidity Controlled Wet Gas Elux / / 460 - Liquid Suction by Venturi Effect / / A - Distributor Angle / / Z - Nebulizing Axis

Claims

CLAIMS 1. A nebulization system comprising: a) A device (100) comprising: ■ A reservoir (111) comprising a gas nozzle (113) defining a nebulization axis (Z) and comprising a first opening (113o) located inside the reservoir (111), the reservoir (111) being capable of receiving a liquid to be nebulized, ■ A nebulizing nozzle (130) superimposed on the gas nozzle (113) comprising a second opening (130o), ■ A dispenser (120) mounted on the reservoir (111), the dispenser (120) being aligned with the nebulization axis (Z) to convey the aerosol out of the reservoir, the nebulization nozzle (130) and the gas nozzle (113) forming a two-fluid nebulization nozzle comprising: ■ A gas channel (132) inside the gas nozzle (113), ■ A liquid channel (134) between the nebulizing nozzle (130) and the gas nozzle (113), and ■ A nebulization zone (131) at the intersection of the gas channel (132) and the liquid channel (134), the outlet of the nebulization zone corresponding to the second opening (130o), and b) A source of wet gas (200) which supplies the gas channel (132) so as to inject a wet gas (440) of controlled humidity into the reservoir (111), the injection of wet gas (440) making it possible to suck the liquid to be nebulized into the liquid channel (134).

2. The nebulization system according to claim 1 wherein at least a portion of the distributor (120) has an angle (A) of between 30° and 70° relative to the nebulization axis (Z).

3. The nebulization system according to any one of claims 1 to 2 wherein the two-fluid nebulization nozzle comprises a deflector (137) located at the outlet of the nebulization zone (131).

4. The nebulization system according to any one of claims 1 to 3 wherein the first opening (113o) has a first size and the second opening (130o) has a second size greater than the first size, the first opening (113o) being aligned with the second opening (130o) and the first opening (113o) and the second opening (130o) being perpendicular to the nebulization axis (Z).

5. The nebulization system according to claim 4 wherein the first size is between 0.1 mm and 1 mm and the second size is between 0.2 mm and 2 mm.

6. The nebulization system according to any one of claims 1 to 5 wherein the nebulization nozzle (130) has an inner wall and the gas nozzle (113) has an outer wall, the inner wall being spaced 0.2 mm to 2 mm from the outer wall.

7. The nebulization system according to any one of claims 1 to 6 wherein the humid gas source (200) comprises a gas source (220) and a humidification device (210) connected to the gas source (220) and the gas nozzle (113), the humidification device (210) being configured to humidify a gas from the gas source (220).

8. The nebulization system according to claim 7 wherein the humidification device (210) is a nebulizer.

9. The nebulization system of claim 7 or 8 wherein the humidification device (210) comprises an outlet filter.

10. The nebulization system of any one of claims 1 to 9 wherein the wet gas source (200) is configured to heat the gas (440).

11. The nebulization system according to any one of claims 1 to 10 wherein the device (100) is configured to heat the liquid to be nebulized, the device (100) preferably being made of stainless steel.

12. An aerosol therapy system comprising the nebulization system according to any one of claims 1 to 11 fluidly connected to a face or nasal mask.

13. A toxicological study system comprising the nebulization system according to any one of claims 1 to 11 fluidly connected to a nasal mask or a whole body enclosure.

14. A breathing simulator configured to simulate the expiratory phase of a breath, the breathing simulator comprising the nebulization system according to any one of claims 1 to 11.

15. A calibration device configured to generate an aerosol of stable particle concentration, the calibration device comprising a calibration chamber defining a calibration volume in which the particle concentration is stable over time, the calibration chamber comprising the nebulization system according to any one of claims 1 to 11 and being capable of accommodating a sensor configured to detect said particles.

16. Method for generating an aerosol comprising the steps of: Providing the nebulization system according to any one of claims 1 to 11, Introduce a liquid to be nebulized into the tank (111), Provide, from the wet gas source (200), a wet gas with a constant pressure between 0.1 bar and 10 bar and a controlled humidity of relative humidity greater than 60%, Inject the humidity-controlled wet gas into the reservoir (111) via the gas channel (132).

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