ES2642217T3 - Supply device - Google Patents

Description

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Supply device Description

[0001] The present invention relates to a delivery device for delivering a substance, in particular, one of a liquid, such as a suspension or solution, or a powder containing a medicament, especially systemic or topical pharmaceuticals, or a vaccine for the nasal airway of a subject.

[0002] Referring to Figure 13, the airways 1 comprise two nasal cavities separated by the nasal septum, whose airways 1 include numerous ostia, such as the paranasal sinus ostia 3 and the tube ostia 5, and olfactory cells , and is bordered by the nasal mucosa. The nasal airway 1 can communicate with the nasopharynx 7, the oral cavity 9 and the lower airway 11, the nasal airway 1 being in selective communication with the anterior region of the nasopharynx 7 and the oral cavity 9 by opening and closing the Oropharyngeal veil 13. Veil 13, which is often referred to as the soft palate, is illustrated in a continuous line in the closed position, as is achieved by providing a certain positive pressure in the oral cavity 9, as is achieved in exhalation. through the oral cavity 9, and in dashed line in the open position.

[0003] There are many nasal conditions that require treatment. One such condition is nasal inflammation, specifically rhinitis, which can be allergic or non-allergic and is often associated with infection and prevents normal nasal function. As an example, allergic and non-allergic inflammation of the nasal airways can typically affect between 10 and 20% of the population, with nasal congestion of the erectile tissues of the nasal turbinate, tearing, secretion of aqueous mucus, Sneezing and itching the most common symptoms. As you will understand, nasal congestion prevents nasal breathing and promotes oral breathing, which leads to snoring and sleep disorders. Other nasal conditions include nasal polyps that arise from the paranasal sinuses, hypertrophic adenoids, secretory otitis media, sinus disease and the reduction of smell.

[0004] In the treatment of certain nasal conditions, topical administration of medications is particularly preferable, where the nasal mucosa is the first pathological pathway, such as in the treatment or relief of nasal congestion. Medications that are commonly topically administered include decongestants, antihistamines, cromoglycates, steroids and antibiotics. At present, among the known anti-inflammatory pharmaceutical products, topical steroids have been shown to have an effect on nasal congestion. Topical decongestants have also been suggested for use in relieving nasal congestion. The treatment of hypertrophic adenoids and chronic secretory otitis media using topical decongestants, steroids and anti-microbial agents, although somewhat controversial, has also been proposed. In addition, topical administration of pharmaceutical products has been used to treat or at least alleviate the symptoms of inflammation in the anterior region of the nasopharynx, sinuses and auditory tubes.

[0005] Medications can also be administered systematically through the nasal route, allowing the nasal route a good route of administration for the systematic administration of pharmaceutical products, such as hormones, for example, oxytocin and calcitonin, and analgesics. , such as anti-migraine compositions, such as high blood flow and the large surface area of the nasal mucosa advantageously allows rapid systemic absorption.

[0006] It is also expected that the nasal administration will be advantageous for the administration of medicaments that require a rapid onset of action, for example, analgesics, antiemetics, insulin, antiepileptics, sedatives and hypnotics, and also other pharmaceutical products, for example, cardiovascular drugs. The nasal administration is expected to provide a rapid onset of action, at a rate similar to that of injection and at a much faster rate than that of oral administration. In fact, for the treatment of many acute conditions, nasal administration is advantageous compared to oral administration, since gastric stasis can further delay the onset of action after oral administration.

[0007] It is also expected that the nasal administration can provide an effective route of administration for the administration of proteins and peptides such as that produced by modern biotechnological techniques. For such substances, the metabolism in the intestines and the first pass effect on the liver represent significant obstacles to reliable and economically efficient administration.

[0008] In addition, nasal administration using the nasal administration device of the present invention is expected to be effective in the treatment of many common neurological diseases, such as Alzheimer's, Parkinson's, psychiatric diseases and intracerebral infections, where it is not possible using existing techniques. The nasal administration device of the present invention allows administration to the olfactory region, whose region is in the upper region of the nasal cavities and represents the only region where it is possible to circumvent the

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blood-brain barrier (BBB) and allow communication with the cerebrospinal fluid (CSF) and the brain.

[0009] In addition, it is expected that the nasal device of the present invention will allow for effective administration of vaccines.

[0010] Apart from the administration of medicaments, the irrigation of the nasal mucosa with liquids, in particular saline solutions, is commonly practiced to eliminate particles and secretions, as well as to improve the mucociliary activity of the nasal mucosa. These solutions can be used in combination with active pharmaceutical products.

[0011] For any type of drug administration, precise and responsible dosing is essential, but it is of particular importance in relation to the administration of potent drugs that have a narrow therapeutic window, drugs with potentially serious adverse effects, and drugs for the treatment of serious and life-threatening diseases. For some conditions, it is essential to individualize the dosage to the particular situation, for example, in the case of diabetes mellitus. For diabetes and, in fact, for many other conditions, the dosage of the pharmaceutical product is preferably based on real measurements in real time.

[0012] At present, blood samples are used more frequently, but the analysis of the molecules in the exhalation breath of the subjects has been proposed as an alternative to blood tests for various conditions. Breath analysis is currently used to diagnose conditions such as Helicobacter pylori infections that cause gastric ulcers.

[0013] WO-A-00/51672 discloses a delivery device for delivering a substance, in particular a medicament, in a bidirectional flow through the nasal cavities, that is, an air flow passing in a pit nasal, around the posterior margin of the nasal septum and in the opposite direction of the other nostril. This bidirectional air flow acts advantageously to stimulate the sensory nerves of the nasal mucosa, therefore conditioning the subject for administration and providing a more comfortable administration situation.

[0014] WO-A-2004/103447 discloses a delivery device and method of administration of substance, in particular a vaccine, to a mucous surface in the oral cavity of a subject, the device comprising: a unit of mouthpiece to be held in the mouth of a subject, in which the mouthpiece unit is configured such that, in the exhalation or exhalation attempted by the subject, a pressure develops in the oral cavity, which is as to close the oropharyngeal veil of the subject; and an oral outlet unit, including at least one outlet from which the substance is in use supplied to a mucosal surface within the subject's oral cavity.

[0015] WO-A-1990/011791 discloses an intermittent oxygen delivery system for delivering oxygen to a first nasal receptacle of a nasal cannula in response to patient exhalation detected through a second nostril that is afsla of the administration of oxygen to the first nostril.

[0016] An object of the present invention is to provide an alternative administration device to provide the administration of substance to the nasal airway of the subject. The present intervention provides a delivery device for supplying the substance to a nasal airway of a subject, the delivery device comprising: at least one nasal nozzle unit for insertion into a nasal cavity of a subject and comprising a piece of nose for mounting to the respective nostril of the subject; and at least one administration unit that is operative to deliver a substance through the unit of at least one piece of nose into the nasal cavity of the subject, wherein the supply unit of at least one includes a supply unit of substance for supplying a substance and a drive unit that is operable to operate the substance supply unit in response to the generation of a predetermined pressure or flow rate by nasal exhalation by the subject.

[0017] In one embodiment, the substance supply unit is configured to deliver an aerosol spray.

[0018] In one embodiment, the aerosol sprayer is a liquid aerosol.

[0019] In another embodiment, the aerosol sprayer is a powder aerosol.

[0020] In another embodiment, the substance supply unit is configured to deliver a jet of liquid.

[0021] In a further embodiment the substance supply unit is configured to

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Supply a jet of dust.

[0022] In one embodiment, the nose piece is configured to provide a fluid tight seal with that of a nasal orifice of the subject.

[0023] In one embodiment, the drive unit includes a pressure sensor to detect the pressure in the nose piece and the drive of the substance supply unit in response to the predetermined pressure.

[0024] In another embodiment the drive unit includes a flow sensor to detect the flow rate in the nose piece and the drive of the substance supply unit in response to the predetermined flow rate.

[0025] In a further embodiment, the drive unit includes a pressure sensor to detect the pressure in the nozzle and is operative to allow manual operation of the substance supply unit only in response to the detection of the pressure sensor of The default pressure.

[0026] In a further embodiment, the drive unit includes a flow sensor to detect the flow rate in the nose piece and is operative to allow manual operation of the substance supply unit only in response to the flow sensor. of detection of the predetermined flow rate.

[0027] In one embodiment, the substance supply unit is configured to deliver substance with sufficient force to be directed to a posterior region of the nasal cavity, and to be carried away by a flow of exhalation air through the other cavity. nasal.

[0028] In another embodiment, the substance supply unit is configured to administer substance in the nasal cavity, and can be extracted from the nasal cavity by a flow of exhalation air through the other nasal cavity.

[0029] In one embodiment, the delivery device comprises: the first and second nasal bridge units to be installed in the respective nostrils of the subject, in which the substance supply unit is in fluid communication with the first nozzle unit nasal such that the substance is in use supplied to the nasal cavity and the drive unit is in fluid communication with the second unit of the outlet nose piece.

[0030] In one embodiment, the administration unit includes a filter unit that is in fluid communication with the second unit, outlet nose piece.

[0031] In one embodiment the drive unit includes a release mechanism that is manually operable to unlock the drive unit to make the drive unit operational in response to nasal exhalation by the subject.

[0032] In one embodiment, the release mechanism comprises a mobile element that is manually operated between a first configuration, the lock in which the drive unit is locked and prevents operation in response to nasal exhalation by the subject, and a second unlocked configuration in which the drive unit is unlocked and allows operation in response to nasal exhalation by the subject.

[0033] In one embodiment, the mobile element in use extends into the other nasal cavity, such that the other nostril of the subject is closed when the mobile element is in the unlock configuration.

[0034] Preferred embodiments of the present invention will now be described by way of example only with reference to the accompanying drawings, in which:

Figure 1 illustrates a nasal administration device according to a first embodiment of the present invention;

Figures 2 (a) to (c) illustrate a mode of operation of the nasal administration device of Figure 1;

Figures 3 (a) to (c) illustrate another mode of operation of the nasal administration device of Figure 1;

Figure 4 illustrates a nasal administration device according to a second embodiment of the present invention;

Figures 5 (a) to (c) illustrate an operation mode of the nasal administration device of Figure 4;

Figures 6 (a) to (c) illustrate another mode of operation of the nasal administration device

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of Figure 4;

Figure 7 illustrates a nasal administration device according to a third embodiment of the present invention;

Figures 8 (a) to (c) illustrate a mode of operation of the nasal administration device of Figure 7;

Figures 9 (a) to (c) illustrate another mode of operation of the nasal administration device of Figure 7;

Figure 10 illustrates a nasal administration device according to a fourth embodiment of the present invention;

Figures 11 (a) to (c) illustrate a mode of operation of the nasal administration device of Figure 10;

Figures 12 (a) to (c) illustrate another mode of operation of the nasal administration device of Figure 10;

Figure 13 schematically illustrates a nasal administration device according to a fifth embodiment of the present invention;

Figure 14 illustrates the delivery device of Figure 13 where operative to administer a dose of substance in the nasal airway of the subject; Y

Figure 15 schematically illustrates the anatomy of the upper respiratory tract of a human subject.

[0035] Figures 1 to 3 illustrate a nasal administration device according to a first embodiment of the present invention.

[0036] The administration device comprises a nasal nozzle unit 21 for installation in a nostril of a subject, and a delivery unit 23 for the administration of substance through the nasal nozzle unit 21 in the nasal cavity in response to exhalation by the subject through the nasal airway.

[0037] The nasal nozzle unit 21 includes a nose piece 25 through which the substance is supplied in the subject's nasal cavity.

[0038] In this embodiment the nose piece 25 comprises a tubular, conical-conical element that is configured in such a way as to be inserted into a nostril, and in a preferred embodiment provide a fluid tight seal with the nostril

[0039] In an alternative embodiment the nose piece 25 may comprise an annular element that is configured in such a way as to engage the nostrils of a nostril, and in a preferred embodiment provide a fluid-tight seal with the hole. nasal.

[0040] The supply unit 23 includes a substance supply unit 27 for delivering a dose of a substance, in this embodiment a measured dose of a substance, and a drive unit 29, in this embodiment a drive breathing unit , which is in fluid communication with the nose piece 25 and is operative to operate the substance supply unit 27 in response to the generation of a predetermined pressure or flow rate by exhalation by the subject through the nasal airway .

[0041] In this embodiment, the substance supply unit 27 comprises a liquid supply unit for supplying a liquid substance through the nose piece 25.

[0042] In another embodiment, the substance supply unit 27 could comprise a powder supply unit for the administration of a powdered substance through the nose piece 25.

[0043] In this embodiment, the substance supply unit 27 comprises an aerosol generator for delivering an aerosol of the substance through the nose piece 25.

[0044] In an alternative embodiment the substance supply unit 27 could comprise a jet generator to deliver a jet of the substance through the nozzle 25. In this embodiment, the substance comprises a medicament, but the substance could be any type of another substance, such as a vaccine.

[0045] In this embodiment, the substance supply unit 27 comprises a pump unit, here a mechanical pump unit.

[0046] In an alternative embodiment the substance supply unit 27 may comprise an electrically operated pump unit.

[0047] In another embodiment, the substance supply unit 27 could comprise a nebulizer for delivering an aerosol, either as a liquid or powder aerosol, to the nose piece 25.

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[0048] In this embodiment the drive unit 29 includes a pressure sensor to detect the pressure in the nose piece 25 and the drive of the substance supply unit 27 in response to the generation of a predetermined pressure.

[0049] In another embodiment the drive unit 29 could include a flow sensor for the detection of a flow through the nose piece 25 and the drive of the substance supply unit 27 in response to the detection of a predetermined flow.

[0050] An operation mode of the administration device described above will now be described below with reference to Figures 2 (a) to (c) of the accompanying drawings.

[0051] The subject first prepares the administration unit 23, in this embodiment by loading a deflection element, the nose piece 25 is fitted to a nostril, as illustrated in Figure 2 (a), and the subject is exhaled later through his nasal airway.

[0052] In this embodiment, where the nasal cavity is closed, in exhalation through the nasal airway, a pressure develops in the nasal cavity to which the delivery device is mounted and an exhalation air flow is develops through the other nasal cavity, as illustrated in Figure 2 (b). As illustrated in Figure 2 (b), the pressure that develops in a nasal cavity acts to extend the nasal valve therein, thereby facilitating the administration of substance to posterior regions of the nasal airway. In the generation of a predetermined pressure in the nose piece 25, the drive unit 29 acts to drive the substance supply unit 27 to deliver substance through the nose piece 25 and into a nasal cavity, as illustrated in Figure 2 (c).

[0053] In one embodiment, the substance supply unit 27 is configured to administer substance with sufficient force to be directed to a posterior region of the nasal cavity, and to be carried away by the exhalation air flow through the Another nasal cavity In this way, the substance is dragged around the nasal septum, making it possible to improve administration to the posterior region of the nasal airway.

[0054] In an alternative embodiment the substance supply unit 27 may be configured to deliver the substance in the nose piece 25, whose substance becomes resident in the nasal cavity and is removed, in the form of the Venturi effect, in the exhalation air flow through the other nasal cavity. In this way, the substance is supplied around the nasal septum, allowing to improve administration to the posterior region of the nasal airway.

[0055] In one embodiment, and when necessary, the delivery device may be used to administer the substance to the respective nasal cavities of the subject by repeating the administration operation.

[0056] Another mode of operation of the administration device described above will now be described below with reference to Figures 3 (a) to (c) of the accompanying drawings.

[0057] The subject first prepares the administration unit 23, in this embodiment by loading a deflection element, the nose piece 25 is fitted to a nostril, as illustrated in Figure 3 (a), and the subject exhales later through his nasal airway.

[0058] In this embodiment, where the one nasal cavity is open to allow a flow, in exhalation through the nasal airway, a pressure develops in the nasal cavity to which the delivery device is mounted and a flow exhalation air develops through the other nasal cavity, as illustrated in Figure 3 (b). As illustrated in Figure 3 (b), the pressure that develops in the nasal cavity acts to expand the nasal valve, thereby facilitating the administration of substance to posterior regions of the nasal airway.

[0059] In the generation of a predetermined flow in the nose piece 25, the drive unit 29 acts to drive the substance supply unit 27 to deliver substance through the nose piece 25 and into the nasal cavity, as It is illustrated in Figure 3 (c).

[0060] In one embodiment, the substance supply unit 27 is configured to administer substance with sufficient force to be directed to a posterior region of the nasal cavity, and to be carried away by the exhalation air flow through the Another nasal cavity In this way, the substance is dragged around the nasal septum, making it possible to improve administration to the posterior region of the nasal airway.

[0061] In an alternative embodiment the substance supply unit 27 may be configured to deliver the substance in the nose piece 25, which becomes a resident substance in the

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nasal cavity and is extracted, in the form of the Venturi effect, in the flow of exhalation air through the other nasal cavity. In this way, the substance is supplied around the nasal septum, allowing to improve administration to the posterior region of the nasal airway.

[0062] In one embodiment, and when necessary, the delivery device may be used to administer the substance to the respective nasal cavities of the subject by repeating the administration operation.

[0063] Figures 4 to 6 illustrate a nasal administration device according to a second embodiment of the present invention.

[0064] The administration device of this embodiment is quite similar to the supply device of the first embodiment described above, and therefore, in order to avoid unnecessary duplication of the description, only the differences will be described in detail, being similar parts designated by similar reference signs.

[0065] The administration device of this embodiment differs from the first embodiment described above in that it comprises first and second nasal bridge units 21a, 21b, each including a nose piece 25, for mounting to the respective nostrils of the subject the substance supply unit 27 being in fluid communication with the first inlet nose piece unit 21a such that the substance is supplied in the nasal cavity and the drive unit 29 which is in fluid communication with the second unit of outlet nose piece 21b.

[0066] In this embodiment the administration unit 23 also further comprises a filter unit 31 that is in fluid communication with the second outlet nose piece unit 21b, such as to trap any substance that otherwise leaves the Another nostril.

[0067] An operation mode of the administration device described above will now be described below with reference to Figures 5 (a) to (c) of the accompanying drawings.

[0068] The subject first prepares the administration unit 23 in this embodiment by loading a deflection element, the nozzles 25 of the nose piece units 21a, 21b being adapted to the respective nostrils, as illustrated in Figure 5 (a), and then exhale through your nasal airway.

[0069] In this embodiment, when the nasal cavity is closed, in exhalation through the nasal airway, a pressure develops in the nasal cavity to which the delivery device is mounted and an exhalation air flow is develop through the other nasal cavity, as illustrated in Figure 5 (b). As illustrated in Figure 5 (b), the pressure that develops in the nasal cavity acts to expand the nasal valve, thereby facilitating the administration of substance to posterior regions of the nasal airway. In generating a predetermined flow through the other nasal cavity as detected by the drive unit 29, the drive unit 29 acts to drive the substance supply unit 27 to deliver substance through the nose piece 25 of the inlet nasal nozzle unit 21a and in the nasal cavity, as illustrated in Figure 5 (c).

[0070] In one embodiment, the substance supply unit 27 is configured to administer substance with sufficient force to be directed to a posterior region of the nasal cavity, and to be carried away by the exhalation air flow through the Another nasal cavity In this way, the substance is dragged around the nasal septum, making it possible to improve administration to the posterior region of the nasal airway.

[0071] In an alternative embodiment the substance supply unit 27 may be configured to deliver the substance in the nose piece 25 of the inlet nasal nozzle unit 21a, whose substance becomes a resident in the nasal cavity and is removed , in the manner of the Venturi effect, in the flow of exhalation air through the other nasal cavity. In this way, the substance is supplied around the nasal septum, making it possible to improve administration to the posterior region of the nasal airway.

[0072] Another mode of operation of the administration device described above will be described below with reference to Figures 6 (a) to (c) of the accompanying drawings.

[0073] The subject first prepares the administration unit 23, in this embodiment by loading a deflection element, it adapts to the nozzles 25 of the tool mouth units 21a, 21b to the respective nostrils, such as It is illustrated in Figure 6 (a), and then exhales through its nasal airway.

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[0074] In this embodiment, where a nasal cavity is open to allow a flow, in exhalation through the nasal airway, a pressure develops in the nasal cavity to which the delivery device is mounted and a flow of exhalation air develops through the other nasal cavity, as illustrated in Figure 6 (b). As illustrated in Figure 6 (b), the pressure that develops in the nasal cavity acts to expand the nasal valve, thereby facilitating the administration of substance to posterior regions of the nasal airway. In generating a predetermined flow through the other nasal cavity as detected by the drive unit 29, the drive unit 29 acts to drive the substance supply unit 27 to deliver substance through the nose piece 25 of the inlet nasal nozzle unit 21a and in the nasal cavity, as illustrated in Figure 6 (c).

[0075] In one embodiment, the substance supply unit 27 is configured to administer substance with sufficient force to be directed to a posterior region of the nasal cavity, and to be carried away by the exhalation air flow through the Another nasal cavity In this way, the substance is dragged around the nasal septum, making it possible to improve administration to the posterior region of the nasal airway.

[0076] In an alternative embodiment the substance supply unit 27 may be configured to deliver the substance in the nose piece 25 of the inlet nasal nozzle unit 21a, whose substance becomes a resident in the nasal cavity and is removed , in the manner of the Venturi effect, in the flow of exhalation air through the other nasal cavity. In this way, the substance is supplied around the nasal septum, making it possible to improve administration to the posterior region of the nasal airway.

[0077] Figures 7 to 9 illustrate a nasal administration device according to a third embodiment of the present invention.

[0078] The administration device comprises a nasal nozzle unit 121 for installation in a nostril of a subject, and a delivery unit 123 which is operable to deliver the substance through the nasal nozzle unit 121 in the cavity subject's nasal

[0079] The nasal nozzle unit 121 includes a nose piece 125 through which the substance is supplied into the subject's nasal cavity.

[0080] In this embodiment the nose piece 125 comprises a tubular, conical-conical element that is configured in such a way as to be inserted into a nostril, and in a preferred embodiment provide a fluid tight seal with the nostril

[0081] In an alternative embodiment the nose piece 125 could comprise an annular element that is configured to engage the nostrils of the nostril, and in a preferred embodiment provide a fluid tight seal with the nostril.

[0082] The delivery unit 123 includes a substance supply unit 127 for delivering a dose of a substance, in this embodiment a measured dose of a substance, and an actuation unit 129, in this embodiment a manual actuation unit, which is in fluid communication with the nose piece 125 and configured to allow the manual operation of the substance supply unit 127 only in response to the generation of a predetermined pressure or the flow rate by exhalation by the subject through the pathway nasal.

[0083] In this embodiment, the substance supply unit 127 comprises a liquid supply unit for supplying a liquid substance through the nose piece 125.

[0084] In another embodiment, the substance supply unit 127 may comprise a powder supply unit for the administration of a powdered substance through the nozzle 125.

[0085] In this embodiment, the substance supply unit 127 comprises an aerosol generator for delivering an aerosol of the substance through the nozzle 125.

[0086] In an alternative embodiment, the substance supply unit 127 could comprise a jet generator for administering a jet of the substance through the nozzle 125.

[0087] In this embodiment, the substance comprises a medicament, but the substance could be any type of other substance, such as a vaccine.

[0088] In this embodiment, the substance supply unit 127 comprises a pump unit, here a mechanical pump unit.

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[0089] In an alternative embodiment the substance supply unit 127 may comprise an electrically operated pump unit.

[0090] In another embodiment, the substance supply unit 127 could comprise a nebulizer for delivering an aerosol, either as a liquid or powder aerosol, to the nose piece 125.

[0091] In this embodiment the drive unit 129 includes a pressure sensor to detect the pressure in the nose piece 125 and is configured to allow manual operation of the substance supply unit 127 only in response to the generation of a default pressure.

[0092] In another embodiment the drive unit 129 could include a flow sensor for the detection of a flow through the nose piece 125 and be configured to allow manual operation of the substance supply unit 127 only in response to Detection of a predetermined flow.

[0093] An operation mode of the administration device described above will now be described below with reference to Figures 8 (a) to (c) of the accompanying drawings.

[0094] The subject first prepares the administration unit 123, in this embodiment by loading a deflection element, the nose piece 125 is fitted to a nostril, as illustrated in Figure 8 (a), and the subject exhales later through his nasal airway.

[0095] In this embodiment, where the nasal cavity is closed, in exhalation through the nasal airway, a pressure develops in the nasal cavity to which the delivery device is mounted and an exhalation air flow is develops through the other nasal cavity, as illustrated in Figure 8 (b). As illustrated in Figure 8 (b), the pressure that develops in the nasal cavity acts to expand the nasal valve, thereby facilitating the administration of substance to posterior regions of the nasal airway.

[0096] In the generation of a predetermined pressure in the nose piece 125, the drive unit 129 is configured such that it is manually operable. In this embodiment the drive unit 129 provides an indication to the user, typically as one or more of an audible, visual or tactile indication, when the predetermined pressure is generated in the nose piece 125.

[0097] Then, the user operates the substance supply unit 127 to deliver substance through the nose piece 125 and into the nasal cavity, as illustrated in Figure 8 (c).

[0098] In one embodiment, the substance supply unit 127 is configured to administer substance with sufficient force to be directed to a posterior region of the nasal cavity, and to be carried away by the exhalation air flow through the Another nasal cavity In this way, the substance is dragged around the nasal septum, allowing improved administration to the posterior region of the nasal airway.

[0099] In an alternative embodiment the substance supply unit 127 may be configured to administer substance in the nose piece 125, which becomes a resident substance in the nasal cavity and is removed, in the manner of the Venturi effect, in the exhalation air flow through the other nasal cavity. In this way, the substance is supplied around the nasal septum, allowing to improve administration to the posterior region of the nasal airway.

[0100] In one embodiment, and when necessary, the delivery device may be used to administer the substance to the respective nasal cavities of the subject by repeating the administration operation.

[0101] Another mode of operation of the administration device described above will be described below with reference to Figures 9 (a) to (c) of the accompanying drawings.

[0102] The subject first prepares the administration unit 123, in this embodiment by loading a deflection element, the nose piece 125 is fitted to a nostril, as illustrated in Figure 9 (a), and the subject exhales later through his nasal airway.

[0103] In this embodiment, where the one nasal cavity is open to allow a flow through it, in exhalation through the nasal airway, a pressure develops in the nasal cavity to which the delivery device is mounted and an exhalation air flow develops through the other nasal cavity, as illustrated in Figure 9 (b). As illustrated in Figure 9 (b), the pressure that develops in the nasal cavity acts to enlarge the nasal valve, thereby facilitating the

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administration of substance to posterior regions of the nasal airway.

[0104] In the generation of a predetermined flow in the nose piece 125, the drive unit 129 is configured such that it is manually operable. In this embodiment the drive unit 129 provides an indication to the user, typically as one or more of an audible, visual or tactile indication, when the predetermined flow rate is generated in the nose piece 125.

[0105] The user then drives the substance supply unit 127 to deliver substance through nose piece 125 and into the nasal cavity, as illustrated in Figure 9 (c).

[0106] In one embodiment, the substance supply unit 127 is configured to administer substance with sufficient force to be directed to a posterior region of the nasal cavity, and to be carried away by the exhalation air flow through the Another nasal cavity In this way, the substance is dragged around the nasal septum, allowing improved administration to the posterior region of the nasal airway.

[0107] In an alternative embodiment the substance supply unit 127 may be configured to administer substance in the nose piece 125, which becomes a resident substance in the nasal cavity and is removed, in the form of the Venturi effect, in the exhalation air flow through the other nasal cavity. In this way, the substance is supplied around the nasal septum, allowing to improve administration to the posterior region of the nasal airway.

[0108] In one embodiment, and when necessary, the delivery device may be used to administer the substance to the respective nasal cavities of the subject by repeating the administration operation.

[0109] Figures 10 to 12 illustrate a nasal administration device according to a fourth embodiment of the present invention.

[0110] The administration device comprises a nasal nozzle unit 221 for installation in a nostril of a subject, and a supply unit 223 for delivering a substance through the nasal nozzle unit 221 into the nasal cavity in response to the generation of a predetermined pressure or rate for the exhalation flow through the subject through the nasal airway.

[0111] The nasal nozzle unit 221 includes a nose piece 225 through which the substance is supplied in the subject's nasal cavity.

[0112] In this embodiment the nose piece 225 comprises a tubular, conical-conical element that is configured in such a way as to be inserted into a nostril, and in a preferred embodiment provide a fluid tight seal with the nostril

[0113] In an alternative embodiment the nose piece 225 could comprise an annular element that is configured such as to engage the nostrils of a nostril, and in a preferred embodiment provide a fluid tight seal with the nostril. The supply unit 223 includes a substance supply unit 227 for delivering a dose of a substance, in this embodiment a measured dose of a substance, and a drive unit 229, in this embodiment a drive breathing unit, which is in fluid communication with the nose piece 225 and operative to operate the substance supply unit 227 in response to exhalation or at least exhalation attempted by the subject through the nasal airway.

[0114] In this embodiment, the substance supply unit 227 is configured to deliver substance with sufficient force to be directed to a posterior region of the nasal cavity.

[0115] In this embodiment, the substance supply unit 227 comprises a liquid supply unit for supplying a liquid substance through the nozzle 225.

[0116] In another embodiment, the substance supply unit 227 could comprise a powder supply unit for the administration of a powdered substance through the nozzle 225.

[0117] In this embodiment, the substance supply unit 227 comprises an aerosol generator for delivering an aerosol of the substance through the nozzle 225.

[0118] In an alternative embodiment the substance supply unit 227 comprises a jet generator for supplying a jet of the substance through the nozzle 225.

[0119] In this embodiment, the substance comprises a medication, but the substance could be

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any type of other substance, such as a vaccine.

[0120] In this embodiment, the substance supply unit 227 comprises a pump unit, here a mechanical pump unit.

[0121] In an alternative embodiment the substance supply unit 227 may comprise an electrically driven pump unit.

[0122] In another embodiment, the substance supply unit 227 could comprise a nebulizer for delivering an aerosol, either as a liquid or powder aerosol, to nose piece 225.

[0123] The drive unit 229 includes a release mechanism 233, which is manually operable to unlock the drive unit 229, such as to make the drive unit 229 operative in response to exhalation or at least attempt to exhale through of the nasal airway.

[0124] In this embodiment the release mechanism 233 comprises a mobile element 235, which is manually operable between a first, blocking state, as illustrated, for example, in Figures 11 (a) and 12 (a), in that the actuation unit 229 is locked to prevent operation in response to exhalation or at least attempt to exhale through the nasal airway, and a second unlocked state, as illustrated, for example, in Figures 11 ( b) or 12 (b), in which the drive unit 229 is unlocked to allow operation in response to exhalation or attempted exhalation through the nasal airway.

[0125] In this embodiment the drive unit 229 includes a pressure sensor to detect the pressure in the nose piece 225 and the drive of the substance supply unit 227 in response to the generation of a predetermined pressure.

[0126] In another embodiment the drive unit 229 could include a flow sensor for the detection of a flow through the nose piece 225 and the operation of the substance supply unit 227 in response to the detection of a flow predetermined.

[0127] An operation mode of the administration device described above will now be described below with reference to Figures 11 (a) to (c) of the accompanying drawings.

[0128] The subject first prepares the administration unit 223, in this embodiment by loading a thrust element, and then adjusting the nose piece 225 to a nostril such that the movable element 235 of the release mechanism 233 extends, in this embodiment, at least to the other nasal cavity, as illustrated in Figure 11 (a).

[0129] The subject then acts to close the other nasal cavity, in this embodiment by pinching the external nostrils of the nostrils, and the applied force F acts to move the movable member 235 of the release mechanism 233 of the locked configuration to the unlocked configuration, as illustrated in Figure 11 (b), in which configuration the drive unit 229 is in the operational state.

[0130] The subject then exhales through their nasal airways, as illustrated in Figure 11 (b).

[0131] In this embodiment, where the nasal cavity is closed, on exhalation through the nasal airway, or at least trying to exhale through the nasal airway, a pressure develops in both nasal cavities. As illustrated in Figure 11 (b), the pressure that develops in a nasal cavity acts to expand the nasal valve, thereby facilitating the subsequent administration of substance to posterior regions of the nasal airway. In generating a predetermined pressure in the nose piece 225, the actuation unit 229 acts to operate the substance supply unit 227 to deliver substance through the nose piece 225 and into the nasal cavity, as illustrated in Figure 11 (c). Due to the positive pressure that develops in the nasal airway by attempt of exhalation, the substance administered remains within the nasal airway, with any residual substance that is washed from the nasal airway in the release of the force F applied in the withdrawal of the administration device.

[0132] In one embodiment, and when necessary, the delivery device may be used to administer the substance to the respective nasal cavities of the subject by repeating the administration operation.

[0133] Another mode of operation of the administration device described above will be described below with reference to Figures 12 (a) to (c) of the accompanying drawings.

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[0134] The subject first prepares the administration unit 223, in this embodiment by loading a thrust element, and then adjusting the nose piece 225 to a nostril such that the movable element 235 of the release mechanism 233 extends, in this embodiment, at least to the other nasal cavity, as illustrated in Figure 12 (a).

[0135] The subject then acts to close the other nasal cavity, pinching in this embodiment the external nostrils of the nostrils, and the applied force F acts to move the movable member 235 of the release mechanism 233 of the locked configuration to the unlocked configuration, as illustrated in Figure 12 (b), in which configuration the drive unit 229 is in the operational state.

[0136] The subject then exhales through their nasal airways, as illustrated in Figure 12 (b).

[0137] In this embodiment, where the nasal cavity is partially open to allow a flow through it, which provides an indication to the subject of the establishment of adequate exhalation, in exhalation through the nasal airway, a small flow is develops through the nasal cavity to which the delivery device is equipped and a pressure develops in the nasal airway. As illustrated in Figure 12 (b), the pressure that develops in the nasal cavity acts to expand the nasal valve, thereby facilitating the subsequent administration of substance to subsequent regions of the nasal airway. In the generation of a predetermined flow rate through the nose piece 225, the drive unit 229 acts to drive the substance supply unit 227 to deliver substance through the nose piece 225 and into the nasal cavity, as is illustrated in Figure 12 (c). Due to the positive pressure that develops in the nasal airway by attempt of exhalation, the substance administered remains substantially within the nasal airway, washing any residual substance from the nasal airway in the release of the force F applied in the withdrawal of the administration device.

[0138] In one embodiment, and when necessary, the delivery device may be used to administer the substance to the respective nasal cavities of the subject by repeating the administration operation.

[0139] Figures 13 and 14 illustrate a nasal administration device according to a fifth embodiment of the present invention.

[0140] The administration device comprises a housing 315, and a nose piece unit 317 for mounting in a nasal cavity of a subject and in which the subject exhales nasally to actuate the delivery device in response to the generation of a predetermined pressure or flow rate through nasal exhalation. The nasal nozzle unit 317 comprises a nose piece 320, in this embodiment a trunk-conical element, to guide the nasal nozzle unit 317 into a nasal cavity of the subject and which is configured both to provide a seal to the fluids with the nostrils of the nostril and at least obstruct, in this embodiment, the nasal passage in a position, substantially corresponding in this embodiment in a position to the nasal valve, thereby obstructing the anterior third of the nasal cavity and leaving the back of two thirds of the nasal cavity open, as illustrated in Figure 14.

[0141] In this embodiment the nose piece 320 is also mechanically configured to open the nasal valve, thereby facilitating access to the two posterior thirds of the nasal cavity.

[0142] The nasal nozzle unit 317 further comprises an outlet unit 321 for the administration of substance in the nasal cavity of the subject.

[0143] In this embodiment the output unit 321 comprises a communication channel 323 that is in fluid communication with the nasal cavity of the subject, such as to allow the nasal exhalation to be detected through the generation of an increase in the pressure therein, and a mouthpiece 325 to deliver a measured dose of substance in the subject's nasal cavity.

[0144] In this embodiment, the nozzle 325 is configured to administer a jet, such as a substance column, either of liquid or powder.

[0145] In an alternative embodiment, the nozzle 325 may be configured to deliver an aerosol spray of the substance, either liquid or powder, as in the embodiments described above.

[0146] The administration device further comprises a substance supply unit 329 for the administration of measured doses of the substance, which is fluidly connected to the nozzle

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325 to supply the substance from the nasal nozzle unit 317, in this embodiment as a jet.

[0147] In this embodiment, the substance supply unit 329 comprises a mechanical supply pump.

[0148] In this embodiment, the substance supply unit 329 is a multiple dose unit for delivering a plurality of measured doses of the substance. In another embodiment the substance supply unit 329 may be a single dose unit for the administration of a single measured dose of the substance.

[0149] The substance supply unit 329 can be prepared beforehand, in this embodiment by loading an elastic element, and includes a release mechanism triggered by respiration 331 which, when triggered by nasal exhalation, releases the elastic element and drives the substance supply unit 329 to deliver a measured dose of the substance through the nozzle 325.

[0150] In this embodiment the release mechanism 331 is configured to produce the action of the substance supply unit 329 in the generation of a predetermined pressure in the communication channel 323, which is developed in response to nasal exhalation.

[0151] The generation of a high pressure in the nasal cavity acts to expand the posterior region of the nasal cavity, and also acts to force the substance into the ducts and channels that lead to the sinuses, which can, for example, be blocked by the inflammation of the mucosa and polyps.

[0152] The operation of the administration device will be described below with reference to Figure 14 of the accompanying drawings.

[0153] The nasal nozzle unit 317 is first inserted into one of the nasal cavities of a subject until the nose piece 320 abuts the nostrils of the nostril, such as to establish a tightness with the same seal a the fluids, at which point the distal end of the outlet unit 321 extends about 2 cm in the subject's nasal cavity, such as to activate and expand the nasal valve.

[0154] Next, the subject begins to exhale through the nasal route, whose exhalation acts to generate an increase in the pressure in the nasal cavity. In this embodiment, the subject's mouth can be closed, or the mouth can remain open and the tongue is positioned such that oral exhalation is prevented, as illustrated in Figure 14.

[0155] In this embodiment, when the pressure developed in the communication channel 323 reaches a predetermined value, the release mechanism 331 is triggered to operate the substance supply unit 329 to deliver a measured dose of the substance to the mouthpiece 325 and in the nasal cavity of the subject, here as a jet.

[0156] In this embodiment, the administration device is configured such that at least 50% of the dose deposited as initially in the nasal cavity is deposited in a region of the nasal cavity that is posterior to the nasal valve, and At least 30% of the dose deposited as initially in the nasal cavity is deposited in an upper posterior region of the nasal cavity that is posterior to the nasal valve and above the lower meatus.

[0157] In preferred embodiments, the administration device is configured such that at least 55%, more preferably at least 60%, even more preferably at least 65% and still more preferably 70% of the dose deposited as initially in the nasal cavity is deposited in the posterior region of the nasal valve.

[0158] In preferred embodiments, the administration device is configured such that at least 35%, more preferably at least 40%, even more preferably at least 45% and still more preferably 50% of the dose deposited as initially in the nasal cavity is deposited in the upper posterior region of the nasal cavity.

[0159] In this embodiment, where the delivery device is a multiple dose device, the device is ready for later use after priming of the pump unit 329.

[0160] In an alternative embodiment, the nozzle 325 may be configured to supply a plurality of liquid jets.

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[0161] In one embodiment, the contralateral nostril may be partially or totally obstructed, such as to promote the generation of elevated pressure in the nasal cavity in which the substance is to be administered. In one embodiment, the contralateral nostril may be obstructed by the application of a pressure to the lateral nostril of the contralateral nostril. In another embodiment, the nasal nozzle unit 317 may include a second nose piece 320 that is configured to be mounted in the other nostril of the subject, such as to obstruct it.

[0162] Finally, it will be understood that the present invention has been described in its preferred embodiments and can be modified in many different ways without departing from the scope of the invention as defined by the appended claims.

[0163] For example, in one modification, the supply device of the first described embodiment can be modified to include first and second tool mouth units 21 that are fluidly connected to the administration unit 23. In one embodiment, The administration device could include first and second administration units 23 that allow the supply of different substances to the nasal airway.

[0164] In another modification, the administration devices of the second and fourth embodiments could be modified such as to be manually operable in the form of the third described embodiment.

Claims (14)

5 10 fifteen twenty 25 30 35 40 Four. Five fifty 55 60 65 Claims 1. A delivery device for the administration of substance to a nasal airway of a subject, the delivery device comprising: at least one nasal nozzle unit (21; 21a; 121; 221; 317) for insertion into a nasal cavity of a subject and comprising a nose piece (25; 125; 225; 320) for installation in the pit respective nasal of the subject; Y at least one supply unit (23; 123; 223) that is operative to deliver a substance through at least one nasal nozzle unit (21; 21a; 121; 221; 317) in the subject's nasal cavity, in the that the at least one supply unit (23; 123; 223) includes a substance supply unit (27; 127; 227; 329) for supplying a substance and a drive unit (29; 129; 229; 331) that It is operable to operate the substance supply unit (27; 127; 227; 329), characterized in that the drive unit (29; 129; 229; 331) is operable to drive the unit of substance (27; 127; 227; 329) in response to the generation of a predetermined pressure or the flow rate by nasal exhalation by the subject 2. The administration device of claim 1, wherein the substance supply unit (27; 127; 227; 329) is configured to deliver an aerosol spray. 3. The administration device of claim 2, wherein the aerosol sprayer is one of a liquid aerosol or a powder aerosol. 4. The administration device of claim 1, wherein the substance supply unit (27; 127; 227; 329) is configured to administer one of a liquid jet or a powder jet. 5. The delivery device of any of claims 1 to 4, wherein the nose piece (25; 125; 225; 320) is configured to provide a fluid tight seal with that of a nasal orifice of the subject. 6. The delivery device of any of claims 1 to 5, characterized in that the drive unit (29; 129; 229; 331) includes a pressure sensor for detecting the pressure in the nose piece (25; 125; 225 ; 320) and operate the substance supply unit (27; 127; 227; 329) in response to the predetermined pressure. 7. The delivery device of any one of claims 1 to 5, characterized in that the drive unit (29; 129; 229; 331) includes a flow sensor for detecting the flow rate in the nosepiece (25; 125 ; 225; 320) and the operation of the substance supply unit (27; 127; 227; 329) in response to the predetermined flow rate. The delivery device of any one of claims 1 to 5, characterized in that the drive unit (29; 129; 229; 331) includes a pressure sensor for detecting the pressure in the nose piece (25; 125; 225 ; 320) and is operative to allow manual operation of the substance supply unit (27; 127; 227; 329) only in response to the pressure sensor the detection of the predetermined pressure. 9. The delivery device of any one of claims 1 to 5, characterized in that the drive unit (29; 129; 229; 331) includes a flow sensor for detecting the flow rate in the nosepiece (25; 125 ; 225; 320) and is operative to allow manual operation of the substance supply unit (27; 127; 227; 329) only in response to the flow sensor detecting the predetermined flow rate. 10. The delivery device of any of claims 1 to 9, comprising: first and second tool mouth units (21a, 21b) for mounting to the respective nostrils of the subject, in which the substance supply unit (27) is in fluid communication with the first nose piece unit ( 21a) in such a way that the substance is in use delivered in a nasal cavity and the drive unit (29) is in fluid communication with the second output nose piece unit (21b). 11. The administration device of claim 10, wherein the at least one administration unit (23) includes a filter unit (31) that is in fluid communication with the second outlet nose piece unit (21b ). 12. The administration device of any of claims 1 to 9, characterized in that the 5 10 fifteen twenty 25 30 35 40 Four. Five fifty 55 60 65 drive unit (229) includes a release mechanism (233) that is manually operable to unlock the drive unit (229) to make the drive unit (229) operative in response to nasal exhalation by the subject. 13. The administration device of claim 12, wherein the release mechanism (233) comprises a mobile element (235) that is manually operable between a first configuration, the lock in which the drive unit (229) is locked and prevents operation in response to nasal exhalation by the subject, and a second configuration, unlocked in which the drive unit (229) is unlocked and allows operation in response to nasal exhalation by the subject. 14. The administration device of claim 13, wherein the movable member (235) in use extends into the other nasal cavity, such that the other nostril of the subject is closed when the movable element (235) is in the unlocked configuration.