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Title:
JET AEROSOL DISPENSER
Document Type and Number:
WIPO Patent Application WO/2018/127591
Kind Code:
A1
Abstract:
Jet aerosol dispenser (1) comprising a jet nebulizer (2), a gas inlet pipe (3) and an aerosol outlet pipe (5), the gas inlet pipe (3) and the aerosol outlet pipe (5) being connected to the jet nebulizer (2), wherein the jet nebulizer (2) comprises a baffle (12), a gas injector (9) and a liquid injector (10), the gas injector (9) having a diameter smaller than the liquid injector (10) diameter and being arranged to enable expulsion of the gas coming from the gas inlet pipe (3) and a liquid drug (21) present in the jet nebulizer (2) through the baffle (12) to provide the aerosol, the gas injector (9) having an outlet (16) of a diameter between 0.2 mm and 0.5 mm wherein the jet aerosol dispenser (1) further comprises a control system (6) configured to control injection of gas in the gas inlet pipe (3) at a flow rate less than 4 L/min, and wherein the aerosol outlet pipe (5) terminates with a nasal cannula (4).

Inventors:
VECELLIO NONE, Laurent (INSERM U 1100, Centre d'étude des pathologies respiratoires10 Boulevard Tonnelé, TOURS CEDEX, 37032, FR)
REMINIAC, Francois (INSERM U 1100, Centre d'étude des pathologies respiratoires Faculté de médecin, 10 Boulevard Tonnelé TOURS CEDEX, 37032, FR)
EHRMANN, Stephan (INSERM U 1100, Centre d'étude des pathologies respiratoires Faculté de médecin, 10 Boulevard Tonnelé TOURS CEDEX, 37032, FR)
Application Number:
EP2018/050377
Publication Date:
July 12, 2018
Filing Date:
January 08, 2018
Export Citation:
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Assignee:
INSERM (INSTITUT NATIONAL DE LA SANTÉ ET DE LA RECHERCHE MÉDICALE) (101 rue de Tolbiac, PARIS, 75013, FR)
UNIVERSITE DE TOURS (60 Rue du Plat d'Etain, TOURS, 37000, FR)
CENTRE HOSPITALIER REGIONAL UNIVERSITAIRE DE TOURS (2 boulevard Tonnellé, TOURS, 37000, FR)
International Classes:
A61M11/06; A61M16/06; A61M16/08; A61M16/10; A61M16/16; A61M16/20
Attorney, Agent or Firm:
CABINET PLASSERAUD (Immeuble Le Rhone Alpes, 235 Cours Lafayette, LYON, 69006, FR)
Download PDF:
Claims:
Claims

1. Jet aerosol dispenser (1 ) for administering drug to a patient, the jet aerosol dispenser (1 ) comprising a jet nebulizer (2), a gas inlet pipe (3) and an aerosol outlet pipe (5), the gas inlet pipe (3) and the aerosol outlet pipe (5) being connected to the jet nebulizer (2), characterized in that the jet nebulizer (2) comprises a baffle (12), a gas injector (9) and a liquid injector (10), the gas injector (9) having a diameter smaller than the liquid injector (10) diameter and being arranged to enable expulsion of the gas coming from the gas inlet pipe (3) and a liquid drug (21 ) present in the jet nebulizer (2) through the baffle (12) to provide the aerosol, the gas injector (9) having an outlet (16) of a diameter between 0.2 mm and 0.5 mm, preferably between 0.25 mm and 0.4 mm, in that the jet aerosol dispenser (1 ) further comprises a control system (6) configured to control injection of gas in the gas inlet pipe (3) at a flow rate less than 4 L/min, and in that

the aerosol outlet pipe (5) terminates with a nasal cannula (4).

2. Jet aerosol dispenser (1 ) according to claim 1 , wherein the nasal cannula (4) extends to a free end having an internal diameter between 1 mm and 7 mm, preferably between 2 mm and 4 mm.

3. Jet aerosol dispenser (1 ) according to any one of claims 1 and 2, further comprising a support element (20) arranged on the aerosol outlet pipe (5) to define an insertion orientation of the nasal cannula (4).

4. Jet aerosol dispenser (1 ) according to claim 3, wherein the support element (20) has a contact surface intended to contact the face of the patient between the nostrils and the superior lip of the patient in an utilization position, the nasal cannula (4) forming an angle between 45° and 90°, preferably between 70° and 90°, with a plan in which the contact surface of the support element (20) extends when the nasal cannula is in the utilization position.

5. Jet aerosol dispenser (1 ) according to any of claims 1 to 4, wherein the flow rate of injected gas is between

I .5 L/min and 2.5 L/min.

6. Jet aerosol dispenser (1 ) according to any one of claims 1 to 5, wherein the control system (6) is a gas cylinder adjusting valve, a compressor or a terminal unit for medical gases valve.

7. Jet aerosol dispenser (1 ) according to any one of claims 1 to 6, wherein the aerosol outlet pipe (5) has a length between 30 cm and 400 cm.

8. Jet aerosol dispenser (1 ) according to any one of claims 1 to 7, wherein the aerosol outlet pipe (5) has a diameter between 1 mm and 20 mm. 9. Jet aerosol dispenser (1 ) according to any one of claims 1 to 8, wherein an expiratory one way valve (18) is placed between the nasal cannula (4) and the aerosol outlet pipe (5), allowing fluid exhaust.

10. Jet aerosol dispenser (1 ) according to any one of claims 1 to 9, wherein the nasal cannula (4) has a nostril shape allowing an airtight engagement with nostrils.

I I . Jet aerosol dispenser (1 ) according to any one of claims 1 to 10, comprising a humidifier (14) connected to a heated wire (15). 12. Jet aerosol dispenser (1 ) according to claim 1 1 , wherein the humidifier (14) is placed between an aerosol exit port (13) of the jet nebulizer (2) and the nasal cannula (4).

13. Jet aerosol dispenser (1 ) according to any one of claims 1 1 and 12, wherein the heated wire (15) is placed inside the aerosol outlet pipe (5), at an exit port (26) of the humidifier (14).

14. Jet aerosol dispenser (1 ) according to any one of claims 1 1 to 13, wherein the heated wire (15) has a diameter between 1 mm and 12 mm.

Description:
Jet aerosol dispenser

The present invention relates to the field of jet aerosol delivery circuit and jet aerosol delivery apparatus adapted for administering drug.

More precisely, the present invention relates to jet aerosol dispensers for administering drug to a patient.

An aerosol is defined as a mixture of particles suspended in gas. These particles can have a size between a few nanometers and tens of micrometers. The aerosol dispensers in the medical field aim at transforming a liquid drug into an aerosol that can be inhaled by the patient.

Generally, aerosol dispensers are composed of a chamber enclosing a reservoir filled with liquid drug, a nebulizer, an inlet pipe and an outlet pipe. Commonly, the aerosol is delivered to the lungs of a patient through a front-end device connected to the outlet pipe. The front-end device enables the patient to inhale the aerosol. The nebulizer enables the formation of an aerosol. The liquid drug contained in the reservoir of the aerosol dispenser passes through the nebulizer, which separates the liquid drug into a plurality of microscopic droplets to form an aerosol. There are two main different types of nebulizers. The first type is the mesh nebulizer. The mesh nebulizer comprises a vibrating electrical piezo component that causes a mesh to vibrate. The liquid drug passes through the holes of the mesh, which separates it into a plurality of microscopic droplets to form an aerosol. The second type is the jet nebulizer. The jet nebulizers are much cheaper than the mesh nebulizers (thirty times cheaper). They are widely used in hospitals. A jet nebulizer is commonly made of plastic. Jet nebulization was the first technical operation developed for aerosol production. It uses gas flow either from a compressor or from a central gas supply. The gas passes through a small aperture in the nebulizer in order to pick up and atomize the liquid drug. The aerosol generated by atomization contains large and small droplets, and is driven to a baffle. Large droplets are impacted by the baffle and forced onto the side of the nebulizer to be recycled in liquid form in a reservoir. More than 90% of the droplets produced by atomization are selected and recirculate in the nebulizer to be recycled in the liquid-drug reservoir. Small droplets are transported out of the nebulizer by the gas to be inhaled by the patient. The drug mass loaded in the nebulizer is greater than that delivered as an aerosol to the patient. Part of the drug mass is trapped in the nebulizer as residual mass and another significant part is lost in the form of aerosol particles in the ambient air during exhalation as leakage (Vecellio L, 2006, breathe).

To cure lung illnesses in hospitals, aerosol therapy is often used. Commonly, the nebulizer delivers aerosol with a high flow rate of 8 liters per minutes. For non-pediatric patient, a mouthpiece is recommended to deposit the drug directly into the lungs with minimum nose deposition. The nose is a more effective filter than the mouth. Thus, inhalation through the mouth is the preferred route for aerosol delivery to the lungs (Eur Respir J. 201 1 Jun;37(6):1308-31. doi: 10.1 183/09031936.00166410. Epub 201 1 Feb 10. What the pulmonary specialist should know about the new inhalation therapies. Laube BL, Janssens HM, de Jongh FH, Devadason SG, Dhand R, Diot P, Everard ML, Horvath I, Navalesi P, Voshaar T, Chrystyn H). For pediatric patients, it is difficult to use this type of device, since they are not able to breathe exclusively with their mouth. A facemask is then used to deliver the aerosol to these patients.

However, the use of a facemask involves three main problems. First, it can be complicated for a child to wear a facemask during the nebulization time. Indeed, during inhalation, children are frequently crying or being distressed, which leads to a low level of pulmonary deposition (J Aerosol Med. 2007;20 Suppl 1 :S78-83; Facemasks and aerosol delivery in vivo. Erzinger S1 , Schueepp KG, Brooks-Wildhaber J, Devadason SG, Wildhaber JH; Arch Dis Child. 1999 Aug;81 (2):163-5. Crying significantly reduces absorption of aerosolised drug in infants, lies R1 , Lister P, Edmunds AT.).

Secondly, the aerosol delivered by the facemask can deposit on the face of the child. More particularly, the aerosol can deposit close to the eyes of the patient, which can lead to a cataract or glaucoma, depending on the delivered drug. (J Aerosol Med. 2007;20 Suppl 1 :S78-83; Facemasks and aerosol delivery in vivo. Erzinger S1 , Schueepp KG, Brooks-Wildhaber J, Devadason SG, Wildhaber JH; Pediatr Pulmonol. 2004 May;37(5):447-52. Facemasks and facial deposition of aerosols. Sangwan S1 , Gurses BK, Smaldone GC.)

Finally, the facemasks are most effective when the patient inhales with his mouth. However, a young child naturally inhales by his nose and he is not able to inhale with his mouth only. The upper respiratory tracts of young children are very small. Because of these three facts, a facemask does not permit to a great amount of drug to be delivered to the lungs of a young child. In fact, only a small amount of drug passes the nose and pharynx of the patient if the patient is a child.

However, the facemask, if we ignore the three disadvantages exposed above, is still considered as efficient to cure lung illnesses by aerosol therapy. The amount of aerosol deposit in the patient's lungs remains satisfactory.

Another device for delivering product in inhalation therapy is a nasal cannula. The nasal cannula is generally not recommended in aerosol therapy to cure lung illnesses. Indeed, the biggest particles are mainly deposited in the upper airway when using nasal cannula. It comes from the fact that, when entering the nostrils at a high speed, the biggest particles crash against the turbinate, for example. It follows that nasal cannula is preferable for targeting the nasal cavities (Escabasse et al, 2014).

A description of the invention is presented below.

In a first aspect, the invention relates to a jet aerosol dispenser comprising a jet nebulizer, a gas inlet pipe and an aerosol outlet pipe, the gas inlet pipe and the aerosol outlet pipe being connected to the jet nebulizer, wherein the jet nebulizer comprises a baffle, a gas injector and a liquid injector, the gas injector having a diameter smaller than the liquid injector diameter and being arranged to enable expulsion of the gas coming from the gas inlet pipe and a liquid drug present in the jet nebulizer through the baffle to provide the aerosol, the gas injector having an outlet of a diameter between 0.2 mm and 0.5 mm, preferably between 0.25 mm and 0.4 mm,

wherein the jet aerosol dispenser further comprises a control system configured to control injection of gas in the gas inlet pipe at a flow rate less than 4L/min,

and wherein the aerosol outlet pipe terminates with a nasal cannula.

The present invention proposes a jet aerosol dispenser with a nasal cannula termination that allows an amount of drug deposit in the patient's lung as satisfactory as the amount deposited by using a facemask, despite large particles produced by the jet nebulizer.

The use of a nasal cannula solves the problems caused by the use of facemasks. The nasal cannula is well tolerated by young children, and there is no deposition of the aerosol on the face of the patient. Besides, the low flow rate of 4 L/min of the outgoing aerosol reduces the aerosol deposition in the nose by impaction. Moreover, it reduces aerosol losses in ambient air and increases the amount of drug deposition into the lungs of the young patient.

The nebulizer performance is related to the gas flow rate and the gas pressure. The small diameter of the gas injector enables the aerosol generation at low flow rates (2 L/min for example). Using a standard jet nebulizer (with a standard gas injector diameter larger than 0.5 mm) at low flow rate (2 L/min for example) does not permit aerosol generation or it generates a too low aerosol output and a high particle size and consequently a higher duration of nebulization time not compatible with standard drug treatment (from 1 mL to 5 mL of liquid drug filled in the nebulizer reservoir).

Below, we will detail some additional aspects of the invention.

The diameter of the end of the nasal cannula has an impact on the aerosol velocity and thus on the aerosol deposition in the nasal cavities. Using a nasal cannula with an internal diameter as large as possible will improve the lung deposition. This diameter depends on the anatomy nostrils of the patient. The nasal cannula may then extend to a free end having an internal diameter between 1 mm and 7 mm, preferably between 2 mm and 4 mm.

In another aspect, the flow rate of the injected gas is between 1.5L/min and 2.5L/min.

In another aspect, the control system is a gas cylinder adjusting valve, a compressor, or a terminal unit for medical gases valve.

In another aspect, the jet nebulizer is filled with a liquid drug.

In another aspect, the gas inlet pipe is connected to the gas injector.

In another aspect, the aerosol outlet pipe is connected to an aerosol exit port of the jet nebulizer. In another aspect, the aerosol outlet pipe has a length between 30 cm and 400 cm.

The length of the aerosol outlet pipe leads to the deposition of the biggest particles along the pipe. Thereby, there is less particles impaction in the patient's nose, which enables a greater amount of drug deposition in the lungs of a patient.

In another aspect, the aerosol outlet pipe has a diameter between 1 mm and 20 mm.

In another aspect, the jet aerosol dispenser further comprises a support element arranged on the aerosol outlet pipe to define an insertion orientation of the nasal cannula.

The support element may have a contact surface intended to contact the face of the patient between the nostrils and the superior lip of the patient in an utilization position, the nasal cannula forming an angle between 45° and 90°, preferably between 70° and 90°, with a plan in which the contact surface of the support element extends when the nasal cannula is in the utilization position. In other words, an outlet at the free end of the nasal cannula has a central axis forming an angle between 45° and 90°, preferably between 70° and 90°, with a plan in which the contact surface of the support element extends. The nasal cannula directs the aerosol flow into the patient respiratory tracts. The angle of the insertion can lead to a great amount of aerosol deposition in the patient's nose, or a great amount of aerosol deposition in the patient's lungs. In this case, the aerosol flow is directed towards the lower part of the nasal cavities (under the turbinates), which enhances the amount of aerosol deposition in the lungs.

In another aspect, an expiratory one way valve is placed between the nasal cannula and the aerosol outlet pipe, allowing a fluid exhaust. in another aspect, the nasal cannula has a nostril shape, allowing an airtight engagement with nostrils.

In another aspect, the jet aerosol dispenser comprises a humidifier connected to a heated wire.

In another aspect, the humidifier is placed between the aerosol exit port of the jet nebulizer and the nasal cannula.

In another aspect, the heated wire is placed inside the aerosol outlet pipe, at the exit port of the humidifier.

The heated wire may have a diameter between 1 mm and 12 mm. The drawings in the figures will now be briefly described. Figure 1 is a schematic view representing an aerosol dispenser according to a first embodiment,

Figure 2 is a schematic view representing an aerosol dispenser according to a second embodiment, Figure 3 is a schematic view representing an aerosol dispenser according to a third embodiment,

Figures 4 - 10 illustrate some tests results.

Below is a detailed description of several embodiments of the invention, with examples and with references to the drawings.

Figure 1 shows a jet aerosol dispenser 1 according to an exemplary embodiment of the invention. The jet aerosol dispenser comprises a jet nebulizer 2 and a gas source 22. As an illustration, the gas source 22 is represented by a gas bottle as an example. The jet nebulizer 2 is connected to the gas source via a gas inlet pipe 3. The jet aerosol dispenser also comprises a patient interface such as a nasal cannula 4. The nasal cannula 4 is connected to the jet nebulizer 2 via an aerosol outlet pipe 5. The nasal cannula 4 extends from an end portion of the aerosol outlet pipe 5 to a free end provided with an outlet.

The jet nebulizer 2 contains liquid drug 21 intended for nebulization. The jet nebulizer 2 may have a variety of different shapes and sizes. For example, in some exemplary embodiment, the jet nebulizer 2 may have a pseudo hexagonal shape in cross sectional section. In top-down view, the jet nebulizer 2 may be cylindrical.

The jet nebulizer 2 can be decomposed in two parts. The first part is a reservoir 7 and the second part is a lid 8. The jet nebulizer 2, once filled with liquid drug 21 and in position, has a lower portion characterized by the reservoir 7, and an upper portion characterized by the lid 8. It also presents a substantially vertical main axis AA, relative to which the terms lower, upper, side, horizontal and vertical are applied to the jet aerosol dispenser as a whole. Due to gravity, the liquid drug 21 will be located in the reservoir 7. The connections between the jet nebulizer 2 and the gas inlet pipe 3 and between the jet nebulizer 2 and the aerosol outlet pipe 5 are placed respectively at the bottom and at the top of the jet nebulizer 2, on the central axis AA. The gas inlet pipe 3 is inserted in the reservoir 7 to assure the sealing. The lower part of the reservoir 7 surrounds the inserted termination of the gas inlet pipe 3 and it rises inside the reservoir 7 to form a tube inside the jet nebulizer 2. This tube forms the gas injector 9. The gas injector 9 has substantially the same diameter as the gas inlet pipe 3. The outlet 16 of the gas injector 9 extends radially towards the central axis AA, so as to have a diameter smaller than the diameter of the entire gas injector 9.

A liquid injector 10 surrounds the gas injector 9 inside the reservoir 7. The liquid injector 10 extends radially towards the central axis AA. The diameter of the liquid injector 10 is larger than the diameter of the gas injector 9 with a small space 1 1 between the liquid and gas injectors allowing the sucking of the liquid drug. The diameter of the outlet 19 of the liquid injector 10 is substantially larger than the outlet 16 of the gas injector 9.

The gas inlet pipe 3 receives compressed gas from the gas source at a 2L/min flow rate. The compressed gas comes from a gas source. For example, the gas source is a gas cylinder, a gas terminal unit or coming from a compressor. The flow rate of the compressed gas is regulated by a control system 6. The control system 6 can be a valve comprised in the gas source to regulate the gas flow rate, or it can be a compressor with a constant gas flow rate.

The gas can for example be compressed air or oxygen. The gas injector 9 pressurizes the gas. At this point, the compressed gas increases in velocity. It creates an underpressure and the liquid drug 21 is sucked up to the space 1 1 between the gas injector 9 and the liquid injector 10 and then is ejected through the outlet 19.

The liquid drug 21 is carried away with gas stream towards the baffle 12. The liquid drug 21 is cut-off in a plurality of droplets by the impaction on the impingement surface 17 of the baffle 12. Larger particles are impacted on the reservoir 7 surface to be recycled in a liquid drug 21 , and then nebulized again. The smallest droplets then arrive to the aerosol exit port 13 of the jet nebulizer 2 in aerosol form. The droplets, still carried by the gas stream, enter the aerosol outlet pipe 5 at a flow rate less than 4L/min, more particularly at a flow rate between 1.5 and 2.5L/min, and reach the patient nostrils via a nasal cannula at the same flow rate. In the following description, and with no intention to limit, the flow rate will be equal to 2L/min. In another embodiment of the present invention, as illustrated on figure 3, a humidifier 14 is placed between the aerosol exit port 13 and the aerosol outlet pipe 5. The humidifier comprises a tank 27 filled with water, an entry port 25 and an exit port 26. The entry port 25 is connected to the aerosol exit port 13 by a connection 23. The exit port 26 is connected to the aerosol outlet pipe 5. The humidifier is connected to a heated wire 15, which is inserted in the aerosol outlet pipe 5. The aerosol passes through the humidifier 14 and around the heated wire 15 before entering the aerosol outlet pipe 5. The humidifier 14 and the heated wire 15 ensure the comfort of the patient when he inhales the aerosol and they avoid the dryness of the respiratory mucosa. Indeed, the heated wire 15 raises the temperature of the particles to a temperature of approximately 37°C, which is the temperature of a human body. In the embodiments, the jet aerosol dispenser 1 comprises a support element 20. The support element 20 is placed on the aerosol outlet pipe 5, just before the nasal cannula 4. The support element 20 can be an insert piece of plastic, substantially thin. The support element 20 indicates the suitable direction for the insertion of the nasal cannula 4 in the nostrils of the patient. In utilization position, the support element 20 has a contact surface laying on the face of the patient between the nostrils and the superior lip of the patient. In the utilization position, the nasal cannula forms an angle between 45° and 90°, preferably between 70° and 90°, with a plan BB in which the contact surface of the support element 20 extends, as shown on figure 8. More specifically, the outlet at the free end of the nasal cannula 4 has a central axis forming an angle between 45° and 90°, preferably between 70° and 90°, with the plan BB. With such configuration, the aerosol is directed towards the bottom of the nasal cavities. The bottom of the nasal cavities is relatively flat, what permits to reduce nasal deposition and increase the aerosol deposition into the patient lungs.

To support the chosen insertion angle of the nasal cannula, the Applicant realized a plurality of tests, illustrated in reference with the figure 4. The tests have been made with the aerosol dispenser of the invention, but with different types of nasal cannula. Three insertion angles for the nasal cannula have been tested: 0°, 45° and 90°. The abscissa corresponds to the insertion angle of the nasal cannula in degree (DEG); the ordinates are the percentage of aerosol deposition in the lungs of a patient (DEP PUL). It appears that much more aerosol is deposited in the lungs when the nasal cannula is inserted with an angle between 45° and 90° in the patient's nostrils.

In another embodiment, the nasal cannula 4 has a nostril shape to avoid the aerosol loss when the nasal cannula 4 is inserted in the patient's nostrils. The nasal cannula 4 is nostril shaped to enhance the airtight of the nasal cannula 4 when it is inserted into the nostrils of the patient. Theoretically, such shape enhances the amount of aerosol deposition into the patient's lungs because patient inhale by the mouth when the inspiratory flowrate is higher than the nebulizer gas flowrate. It reduces the particle velocity in the nasal cavities, and so the impaction and it reduces aerosol losses during patient expiratory phase due to the reduction of aerosol dead space (nasal cavity is full of aerosol and is ready for the next inhalation phase). As shown in figure 2, when nasal cannula shape is airtight, the jet aerosol dispenser 1 comprises a valve 18 to control the aerosol flow passage in the aerosol outlet pipe 5. More precisely, the valve 18 is open when a positive pressure is applied in the nasal cannula, for example during the patient expiratory phase by the nose or by the mouth for an older child or an adult, to permit aerosol exhaust. It avoids over pressure in nasal cavities if the nasal cannula is in airtight contact with the nostrils, in addition with the closing soft palate. The valve 18 may be disposed at any location between the aerosol outlet pipe 5 and the nasal cannula 4. For example, the valve 18 can be made in soft plastic material with a shape memory form. For example, the valve is close when the patient inhales by the mouth or by the nose, and the valve is open when the patient exhales by the nose or by the mouth (for older children and adults). The present invention proposes a jet aerosol dispenser designed to enable a massive deposition of the particles contained in the aerosol generated by a jet nebulizer into the lungs of an infant or toddler, and also for older children or adults. The 2L/min flow rate induces two major advantages in the aerosol delivery for infants and toddlers. A low flow rate, such as 2L/min, reduces the nasal impaction phenomena. The nasal impaction phenomena happens when particles enters the nostrils of a patient at a high flow rate. The particles cannot follow the airstream because of their velocity and the curvatures of the nasal cavities. So the particles crash against the nasal cavities and deposit in the respiratory upper tracts, such as turbinate, ethmoids, or larynx.

The second advantage resides in the fact that toddlers and infants have an instantaneous respiratory flow greater than 2L/min. Hence, the patient, when inhaling, reduces the velocity of the aerosol coming into his nasal cavities, which reduces the deposit in nasal cavities. Moreover, during the expiratory phase of the patient, there is less loss of aerosol than with a flow rate of 8L/min. However, a flow rate between 1.5 and 2.5L/min presents the same advantages as those exposed above. The aerosol output and particle size are directly correlated to the gas flow rate. A lower flow rate does not allow the nebulization process or it increases the nebulization time with a non-relevant inhalation duration.

The above array shows the interest of choosing a flow rate between 1.5 and 2.5L/min. the first column indicates the flow rate, the second column indicates the size of the particles, the third column indicates the output drug flow rate and the fourth column indicates the requisite duration of the nebulization to be efficient.

It appears that for a very low flow rate (0.5L/min), the size of the deposited particles is very high, but the duration of the nebulization is well too long to be satisfactory. In contrary, a flow rate between 1.5 and 2.5L/min enables a short duration of the nebulization and the particles with a great size can also deposit in the lungs. The use of large particles (6.4μιη MMAD) enables an amount of lung deposition comparable to that obtained by using a facemask, with a nebulizer at 2.6μιη MMAD (2.6 m being the recommended MMAD for young children).

The Applicant also did some tests whose results corroborate the chosen gas flow rate values. As illustrated on the graphic figure 6, with the gas flow rate as abscissa DEB and the percentage of aerosol deposit as ordinates DEP (expressed in term of nebulizer charge), with the high flow rate (typically 8L/min), there is much more deposit on the patient nose and much less deposit in the lungs PUL comparatively to the use of a jet aerosol dispenser of the present invention delivering an aerosol at a less flow rate. More precisely, there is, on average, only 1 % of aerosol deposit in the lungs for an 8L/min gas flow rate. In contrary, for a gas flow rate between 0.5 and 2L/min, the amount of aerosol deposited in the patient lungs is on average equal to 3%.

In other hand, the amount of aerosol deposit in the head and nasal cavities (ORL) system of a patient reaches 7% for an aerosol dispenser at 8L/min when it does not exceed 5% for an aerosol dispenser with a gas flow rate between 0.5 and 2L/min. Figure 9 shows the fraction of lost aerosol in ambient air according to the nebulizer gas flow rate. On figure 9, the simulation has been made for newborns' ventilation system : Inhaled gas volume = 25mL

Ratio between inspiration time and expiration time = 35/65

Respiratory cycle : 40cycles/min

In ordinates, there is the percentage of generated aerosol lost during the expiratory phase of the patient, and in abscissa the nebulizer's gas flow rate (L/min). It appears that there is generally a great amount of aerosol loss during the expiratory phases of the patient. However, the percentage of loss is moderate for a 2L/min gas flow rate, compare to the percentage of loss for a 8L/min gas flow rate (only 65% for the 2L/min gas flow rate and 90% for the 8L/min gas flow rate). The diameter of the outlet 16 of the gas injector 9 is between 0.2 and 0.5 millimeters, preferably between

0.25 mm and 0.4 mm. This small diameter involves the creation of liquid sucking from space 1 1 allowing the atomization and the small particles of liquid drug 21 in the aerosol. Using a larger diameter of the outlet 16 does not permit the nebulization. As shown on figure 10 (ordinates: diameter of the gas injector, abscissa: gas flow rate), for a gas flow rate less than 4L/min, the diameter of the outlet 16 of the gas injector is preferably between 0.2 and 0.5mm. These results have been defined for a pressure interval between 700mbar (for a pressure less than that value, there is no nebulization) and 2000mbar (the standard technology does not permit the use of a greater pressure). Since the pressure must remain constant and so is the chosen gas flow rate for a nebulizer, the diameter has to be chosen to keep these values constant. These results come from a mathematical formula developed from the Bernoulli equation.

The length and the diameter of the aerosol outlet pipe 5 are chosen so as to enable the entering of the smallest particles into the patient's nostrils. The length is between 30 cm and 400 cm and the diameter is between 1 and 20 mm. Due to these values, the biggest particles deposit in the aerosol outlet pipe 5 and spread among the surface of the aerosol outlet pipe 5. The liquid drug 21 thus deposited is not expulsed through the nasal cannula 4, which avoids their deposition in the nasal cannula 4. Only the smallest particles enter the patient nostrils, which leads to a great amount of deposition into the patient lungs. The Applicant also drove some tests concerning the length of the aerosol outlet pipe 5. All the tests have been made with an aerosol dispenser of the present invention but with different aerosol outlet pipes, as illustrated on the graphic figure 5, with the length of the aerosol outlet pipe as abscissa L and the percentage of aerosol deposit as ordinates DEP. The graphic illustrates that, for a small length of the aerosol outlet pipe, typically 2cm, there is much more aerosol deposit in the ORL system of the patient (nose, head,...) than in the lungs PUL (five times higher). Besides, there is less than 1 % of aerosol deposit in the lungs of the patient.

Otherwise, the amount of aerosol deposit in the patient's lungs reaches 1 % for a length of 1 m50. With such length, the amount of aerosol deposit in the lungs is higher than the amount of aerosol deposit in the ORL system of the patient.

Finally, the Applicant made a comparison between the aerosol dispenser of the present invention and some aerosol dispensers already present in the market. There are two other aerosol dispensers. The first one is the "Cirrus 2" (commercialized by Intersurgical, Fontenay sous bois, France) jet nebulizer with a child face mask. The second one is the "Hudson" (commercialized by Teleflex Medical, Le Faget, France) jet nebulizer with a child face mask. The aerosol dispenser used for the comparison is an aerosol dispenser of the present invention, which presents the following characteristics:

Oxygene flow rate: 2L/min,

Nasal cannula diameter:2mm,

Insertion angle: 90°,

Aerosol outlet pipe length: 1.50m

Gas injector outlet diameter; 0.30mm.

The aerosol dispensers have been tested on two different "monkey groups" referenced as (1 ) and (2). Different drugs have also been tested. First, the jet aerosol dispenser of the type of the third embodiment of the present invention has been tested. The average amount of aerosol deposit in the lungs of the monkey patient (1 ) is equal to 0.85%, while the amount of deposit in the ORL system of the patient is on average equal to 3.73%. Concerning the Cirrus 2 aerosol dispenser, the amount of aerosol deposit in the lungs of the monkey patient (1 ) is equal to 0.71 %, while the amount of deposit in the ORL system of the patient is on average equal to 7.37%. For the "Hudson" device, amount of aerosol deposit in the lungs of the monkey patient (2) is equal to 0.74%, while the amount of deposit in the ORL system of the patient is on average equal to 1.22%. Finally, the jet aerosol dispenser has been tested without a humidifier and the amount of aerosol deposit in the lungs of the monkey patient (2) is equal to 1.27%, while the amount of deposit in the ORL system of the patient is on average equal to 0.94%.

The last line presents some scintigraphic images of aerosol deposit in the patient body. The upper part is the ORL system of the patient, while the lower part is the patient's lungs. The more the stain is large and white, the more is the amount of aerosol deposit at this stain. For example, the white large stain in the upper part of the scintigraphic image of the Cirrus 2 nebulizer corresponds to the 7.37% of aerosol deposition in the ORL system, The results strictly show that the characteristics of the jet aerosol dispenser of the present invention enable a higher amount of aerosol deposit in the lungs, while the amount of aerosol deposition on the ORL system is reduced in term of quantity and in term of surface deposition (no facial deposition).

Below, we will now describe a possible way of operating an embodiment of the invention. In a first place, a jet aerosol dispenser, as described above, is provided. The reservoir of the jet aerosol dispenser has to be filled with liquid drug 21. Such liquid drug 21 can be corticoids or any other drugs prescribed for lung diseases. The nasal cannula is inserted into the patient's nostrils, according to the orientation as defined using the support element. In a second place, a compressed gas must be provided, for example from a gas cylinder or from terminal units in hospitals. The injected gas flow rate is controled. It can be controlled by an adjusting valve, comprised on a gas bottle for example, that has to be set so as to inject compressed gas at a flow rate less or equal to 2L/min. It can also be a compressor set to a constant flow rate. The compressed gas enters the gas inlet pipe. When the compressed gas reaches the gas injector, the small aperture of the outlet of the gas injector induces an underpressure. The underpressure enables the suction of the liquid drug 21 into the gas injector. This is called a Venturi effect. The liquid drug 21 is then carried by the flow stream of the compressed gas through the impingement surface of the baffle, placed just above the gas injector. The liquid drug 21 is separated in a plurality of microscopic and submicronic droplets. The smallest particles are carried by the air stream to the exit port of the jet nebulizer, whereas the biggest particles are recycled into the reservoir. The small diameter of the gas injector encourages the creation of small particles and the aerosol output.

The smallest droplets, mixed with the gas, form the aerosol. The aerosol is transported in the aerosol outlet pipe of the jet nebulizer and is delivered to the patient through a nasal cannula. The length and the diameter of the aerosol outlet pipe enable the deposition of the biggest particles along the inner surface of the aerosol outlet pipe. Then, the patient only inhales the smallest particles that can be carried away by the airstream into his lungs.

According to the jet aerosol dispenser used by the patient, the inspiratory flow can be limited by airtight nasal cannulas in the nostril. A one-way expiratory valve is then added to permit the patient expiratory phase by his nose or his mouth.

Of course, the invention is not limited to the example embodiments described above; it extends to other variants.

For example, the jet aerosol dispenser 1 can be mobile to be used in the patient's house.

References:

Jet aerosol dispenserl Space 1 1 Liquid drug 21

Jet nebulizer 2 Baffle 12 Gas source 22

Gas inlet pipe 3 Aerosol exit port 13 Connection 23

Nasal cannula 4 Humidifier 14 Water 24

Aerosol outlet pipe 5 Heated wire 15 50 Entry port 25

Control system 6 Outlet of gas injector 16 Exit port 26

Reservoir 7 Impingement surface 17 Tank 27

Lid 8 Valve 18

gas injector 9 Outlet of liquid injector 19

Liquid injector 10 Support element 20