MXPA99010549A - Inhaler for powdered medicaments - Google Patents

Abstract

A device for applying a powdered or particulate substance to a mucous membrane in a nostril comprises a tubular body (10) similar to a drinking straw. The tubular body has opposite end parts forming a mouthpiece (11) and a nasal piece (12) to be inserted between the lips and into the nostril, respectively, of a user. The mouthpiece (11) and the nasal piece (12) are interconnected by a bent or a bendable, preferably corrugated part (13). A dose of a powdered or particulate substance arranged within the tubular body (10) is transferred to the nostril when the user blows into the mouthpiece (11). A part of the mouthpiece is preferably deflated or compressed between a pair of fingers (35) of the user. The compressed part (34) is released when the user has started to blow forcefully into the compressed mouthpiece part which is thereby inflated. It has been found that the user will automatically close the connection between the nostrils and the throat by the uvula when blowing.

Description

DUST HANDLER FOR POWDER DRUGS FIELD OF THE INVENTION The present invention concerns a method for introducing a powder or particulate substance into a person's nostril or orifices. It is known to disperse the powder or particulate substance in a flow of air that is created by compressing a rubber bulb disposed at one end of a tube or hose having a free opposite end, which can be inserted into the nostril .

BACKGROUND OF THE INVENTION The present invention provides such a method for introducing a powder or particulate substance into a person's orifice or nostril, said method comprising a dose of the substance within an interior cavity of a tubular body, inserting a first open end of the tubular body communicating with the interior cavity between the lips of the person, inserting a second open end of the tubular body communicating with the interior cavity in said nostril, and blowing into the first open end of the tubular body so of creating a flow of air through the interior cavity of the tubular body to transfer the substance to the nostril. REF. 31919 In the method according to the invention, the person or patient being treated creates the necessary air flow through the inner cavity of the tubular member by means of its expiratory breath. It has been found that the user will automatically close the connection between the nostrils and the throat through the uvula when it is blowing. Accordingly, the powder or particulate substance is substantially impeded from penetrating the trachea and esophagus of the user. Accordingly, in order to use the method according to the invention, almost the total amount of the substance blown into the nostril is applied to the mucous membrane inside the nostril.

The method according to the invention can be carried out by means of a tubular body which has been shaped such that an open end thereof can be inserted between the lips of the user while the opposite open end is inserted into the hole nasal of the user. The said second opposite open end of the tubular body can be bifurcated in such a way that a pair of adjacent open ends can be inserted in the nostrils of the user.

Prior to the insertion of the opposite ends of the tubular body in the mouth and the nostril, respectively, a suitable dose of any kind of a suitable type of an active substance is inserted into the inner cavity of the tubular body. This substance can for example be an active substance or vaccine against allergic reactions, such as allergy against pollen, animal hair, etc. Such substance or vaccine can be composed for the individual user. The substance can, alternatively, be any pharmaceutical or other product to be applied to the mucous membrane inside a nasal orifice, such as an antihistamine.

When a user or patient is about to insert the first open end of the tubular body in his mouth the patient's breathing can cause the first open end of the tubular body to be unintentionally exposed to slight suction or overpressure. This can cause unintentional movement of the powdered substance or particles inside or outside the tubular body. The risk of such unintentional movement of the powder or particulate substance can be minimized when at least one vent opening is defined in the wall of the tubular body at or adjacent said first open end. However, when the user or patient has inserted the first open end between the lips and is ready to blow through the tubular body the vent opening will be covered by the lips or is located in the oral cavity of the user.

At least one restriction in the cross section can be formed inside the cavity of the tubular body in such a way that the dose of powder or particulate substance is disposed towards the end of the restriction in relation to the direction of the air flow that transfers the powder or particulate substance to the nostril. Such restriction in the cross section will stimulate the patient or user to blow more energetically on the tubular body. further, the speed of the air flow in the throat or trachea defined by the restriction, will be relatively high which can help to obtain a good dispersion of the powder substance or particles in the air flow. When a vent opening as well as a restriction are formed in or adjacent to the first open end of the tubular body the restriction is preferably disposed towards the end of the vent opening.

When used in a method according to the invention, the efficiency of the tubular body can be further increased by defining the restriction by effective restriction means so that they are movable between a first restriction position and a second position in which the restriction defined by the means of restriction is substantially smaller. Such effective restriction means may result and move from the first restricting position to the second non-restriction or minor restriction position when in the pressure difference, between the interior of the cavity towards the beginning of the restriction means and towards the end. of the restriction means on the outer side of the tubular body, a predetermined value has been obtained. This means that a sudden energetic flow of air can be created when the restriction medium is moving from its first to its second position.

The present invention also concerns a device for applying a powder or particulate substance to a mucous membrane of a nasal orifice of a user of the device, said device comprising a tubular body defining an interior flow passage extending longitudinally between a nasal piece (12) and a first end of the tubular body to be inserted in the nostril of the user and a second end opposite said body, and the device according to the invention is characterized in that the second end of the tubulat body defines a part buccal to be inserted into the lips of the user, the length and shape of the tubular body that is such that the nasal piece and the mouthpiece can at the same time be placed in the nostril and between the lips, respectively, of the user, means of which the user can blow at the end of the buccal part of the flow passage and transport the powder or particulate substance s arranged in the flow passage of the tubular body to the nostril in a dispersed condition.

The tubular body can have any suitable shape that allows the buccal piece and the nasal piece to be correctly inserted in the mouth and in the nasal orifice, respectively, of the user.

In this way, for example, it was obtained when the tubular body comprises an intermediate curve or flexible section.

This means that the tubular body can have or can be given an angular shape. As for example, the tubular body or at least an intermediate part thereof can be made of a deformable or flexible material. Alternatively, the curve and / or the flexible section may comprise wrinkles extending adjacent or peripherally allowing the tubular body to be evenly curved when made from a relatively rigid material. It has been found that the depressions and inner ridges of the folds extending transversely to the air flow stimulate the atomization of the particulate substance and the dispersion of the substance in the air flowing through the passage of the air flow. This effect is improved when the folds have a substantially dentate external contour when viewed in a longitudinal, axial section. This means that the bottom of the depressions and peaks of the ridges of the folds are relatively sharp.

The device according to the invention is preferably of the disposable type. Accordingly, the device may comprise a dose of powder or particulate substance disposed in the flow passage. When the device has been used once and the substance has been transferred to the mucous membrane of a nasal orifice or to the nostrils of a person, the device can be discarded. Said substance can be of any type that can advantageously be introduced into a nasal orifice dispersed in an air flow, such as an active substance or allergy vaccine, a pharmaceutical product or a medicament.

When the tubular body contains a dose of the powder or particulate substance, the free opposite end of the buccal piece and the nasal piece, respectively, are preferably sealed or closed by closure means, which are removed or opened prior to the use of the device. Such a closure means may be a membrane that could be removed or broken. In the preferred embodiment, however, the closure means comprises at least one removable plug disposed at the free ends of the mouth piece and the nosepiece, respectively. In this way, the tubular body can be closed by means of a closing plug disposed at each of the opposite ends. However, when the tubular body has a flexible intermediate section, the mouthpiece and nasal piece may be coextensive and have their free ends placed closely adjacent prior to use of the device. This means that the tubular body can be substantially in the form of * U ", and the narrow adjacency of the free ends can then be closed by a common plug with interval.

The external and internal transverse sections of the tubular body may vary along the length of the tubular body. In the preferred embodiment, however, the tubular body has a substantially uniform internal cross-sectional shape and an exterior shape along its length. In this way, the device according to the invention can be elaborated very simply and can be shaped similarly to a straw.

In order to obtain a good dispersion of a particulate or powder substance in the air flow through the passage for air flow the velocity of the air must be relatively high. Accordingly, the passage for the air of the tubular body preferably has a cross-sectional area not exceeding 75 mm2 and preferably not more than 70 mm2. In a preferred embodiment the cross-sectional areas of the passage for the flow not to exceed 50 mm2 and which is preferably 7-35 mm2 or approximately 20 mm ".

The device according to the invention may additionally comprise at least one vent opening defined in the tubular body at or adjacent said first end. The device according to the invention can additionally comprise restriction means comprising at least one restriction in the cross section of the inner cavity of the tubular body, and a dose of powder or particulate substance can then be placed towards the end of said medium of restriction before the device is used. This means that the air flowing through the tubular body when a user is blowing through the buccal part thereof, will pass the restriction means before the dose of powder or particulate substance passes.

As previously discussed, the restriction means are preferably efficient as long as they are movable between a first restriction position and a second non-restriction or position of least restriction. Such effective restraining means may comprise a fin which in said first position covers at least part of the cross section of the inner cavity of the tubular body and which can be deflected and moved to a lower restriction position. Alternatively, an efficient restriction means may comprise a valve of a position of any kind having a valve body that is inclined towards a closure or restriction position and that can be moved towards a smaller restriction opening or position when the force of Tilting is overcome by a pressure generated in the first open end or buccal part of the tubular body when a user or patient is blowing on it. The valve body of the valve of one position can be in the form of a fin or the like.

Preferably, the device according to the invention does not comprise parts that are separated from the tubular body because such separate parts could not only increase the manufacturing cost of the device according to the invention, but could also involve a risk for the user. Accordingly, the flap whether it forms part of a valve of a single position or not, is preferably an integral part of the wall of the tubular body. Thus, for example, it is obtained when the flap is separated from the wall of the tubular body and internally bent in the inner cavity of the tubular body so as to define a vent opening immediately towards the start of the flap. The opening is preferably formed in or immediately adjacent to the mouthpiece so that the opening can be covered by the of the user or is located in the oral cavity of the user who blows through the tubular body. Alternatively, the flap may extend into the interior cavity or at the open end of the tubular body from the free edge of the mouthpiece.

In the preferred embodiment, however, the restriction means comprise compressible or internally perforable parts in the wall of the tubular body. Such compressible parts of the wall can be longitudinal sections of the tubular body having a smaller wall thickness and / or made of a more flexible or elastic material than the remaining parts of the tubular body. In the preferred mode, however, the wall of the tubular body has substantially the same characteristics throughout the total extension of the tubular body. In such a case the tubular body may be compressible throughout its entire extension and the "compressible parts" or "pierceable portions" may be marked, for example by means of different colors, impressions, protuberances, roughness, or the like, or the "compressible parts" may be defined by dotted lines, or the like. When a user or patient is using the preferred embodiment of the device according to the invention to transfer a powdery or particulate substance into his nostril or nostril he can grasp the "compressible parts" of the tubular body between his thumb and forefinger and compress, contract or deflate such parts. When the user has inserted the nasal piece of the device into his orifice and placed the mouth piece between his lips he can blow energetically on the mouthpiece to generate a high pressure in it. It can then release the compressible parts so that the compressed parts are suddenly inflated and expanded so that the air can flow freely through the unobstructed inner cavity of the tubular body. The pressure that is established in the oral cavity when the user is blowing while the compressible parts are deformed causes the uvula to efficiently close the connection between the nostril and the throat.

It could be understood that the restriction means can comprise any other kind of means adapted to move from its first restricting position to its second position of least restriction or non-restriction when a user is blowing at the first end of the tubular body in a manner of creating a pressure difference between said first and second ends of the tubular body exceeding a predetermined value.

The method and device according to the invention can also be used to introduce a gel-like substance into a nasal orifice. This means that the powder or particulate substance can be replaced by such a gel-like active substance.

The invention further provides a device for dispersing a powdery or particulate substance in an air flow, said device comprising a tubular body defining a flow passage for a dose of active substance in powder or particulate disposed in the passage of flow, the tubular body having a mouthpiece at one end to be inserted between the lips of a user so that it can blow into or inhale through the mouth piece end of the flow passage so as to disperse said dose of substance powder or particulate in the air flowing through the flow passage, and the device according to the invention is characterized in that the restriction means of the cross section which is disposed toward the beginning of the flow passage of the dose of substance moving active between a first closure or restriction position and a second position where there is no restriction or there is substantially less restriction, is defined by the restriction means, the restriction means which is adapted to move from its first restriction position to its second position of least restriction when a user is blowing at the end of the buccal part of the tubular body in such a manner that a pressure difference is created between said mouthpiece and nasal piece ends of the tubular body exceeding a predetermined value. Such a device can be used not only to transport a powder or particulate product to a nasal orifice, but also as an inhaler. The tubular body and restriction means may be of any type described herein.

The invention will now be described further with reference to the drawings, in Figures 1-3 are illustrated the use of three different embodiments of the device according to the invention, Figure 4 is an enlarged side view of the device shown in Fig. 3, Figures 5-8 illustrate further embodiments of the device according to the invention Figure 9 is a cross section of the device of Figure 8 shown on an amplified scale, Figures 10 and 11 illustrate two additional embodiments of the device according to the invention, Figure 12 shows, on an enlarged scale, a side view of a modality of the buccal part of the device according to the invention provided with vent openings, Figure 13 shows another embodiment of the buccal part that has vent opening and a flap that extends inside the cavity of the mouthpiece, Figure 14 is a modality of the mouthpiece with a flap extending from the free edge of the mouthpiece, Figure 15 shows a further embodiment of the mouthpiece having a vent opening and a part of the wall of the tube that extends into the interior cavity of the mouthpiece, Figure 16 is another embodiment of the mouthpiece containing a separation of a one-way valve, Figure 17 shows a modality of the buccal piece that has internally contractable parts of the wall, Figure 18 is a side view illustrating how a device with a mouthpiece as shown in Figure 17 is grasped by a user, Figure 19 illustrates how the device shown in Figure 18 can be inserted into the nostril and between the lips of a user, and Figure 20 shows the same as in Figure 19, but when the user blows through the mouthpiece.

Figure 1 illustrates how a device according to the invention can be used to introduce a dose of a powder or particulate substance into a user's nostril. The device 10 shown in Figure 1 is a tubular body, which can be integrally formed of a rubber, cellulose material, glass or plastic, for example by blow molding. The device is preferably of the disposable type and comprises at opposite ends a buccal piece 11 to be inserted between the lips of the user and a nasal piece 12 to be inserted into a nostril of the user respectively. The mouth piece 11 and the nose piece 12 are interconnected by an intermediate part 13. In the embodiment shown in Figure 1, the intermediate part is substantially formed as an arc of a circle.

The tubular body forming the device 10 can have any suitable cross-sectional shape. When the shape of the cross section is circular, the inner diameter of the wall can, for example, be 3-8 mm. The tubular device 10 may contain a dose 14 of a powder or particulate substance. Prior to the use of the device, the opposite open ends of the tubular body are closed by a pair of removable plugs or any other type of closure means, which can be pierced or removed.

When the device shown in Figure 1 is to be used, the closure means is removed from the opposite end of the tubular device. Subsequently, the mouth piece 11 and the nose piece 12 are inserted between the lips and in the nostril of the user, respectively, as shown in figure 1. Then the user blows through the mouth piece 11 so that the substance powder 14 is dispersed in the air flowing through the tubular device and is transferred to the nostril.

The tubular device 10 shown in Figure 2 is similar to that shown in Figure 1, but the intermediate part 13 is shaped differently. It would be understood that this intermediate piece can have any other appropriate shape.

Figures 3 and 4 illustrate one embodiment of the device according to the invention which is composed of more parts. Thus in Figures 3 and 4, the intermediate part 13 defines an interior cavity 15 open in connections for receiving the mouth piece 11 and the nose piece or pieces 12 formed separately, respectively. The intermediate part 13 shown in figures 3 and 4 can be formed of plastic material by blow molding and the mouthpiece 11 and the nosepiece 12 can be portions of right tube made of glass or plastic material. As these tube portions are interchangeable mounted in the intermediate part 13, they are preferably disposable while the intermediate part can be reused.

As shown in Figure 4, the device may comprise a pair of nose pieces 12 and a single mouthpiece 11. Alternatively, the device may comprise only one nose piece. The inner cavity 15 of the intermediate part 13 is preferably shaped in such a way as to create turbulence in the air flowing through the cavity as well as to cause dispersion of the powdery or particulate substance in the air flowing through the device. Tubular when used.

The tubular device shown in Fig. 5 is integrally formed, for example of glass or plastic, and is of disposable type containing a dose 14 of a powder or particulate substance. Accordingly, prior to use the opposite ends of the tubular body 10 are closed by plugs or other removable locking means (not shown) as explained above. In Figure 5, the intermediate part 13 has a helical shape with one or more turns or threads to improve the dispersion of the powdered substance in the air flowing through the tubular device 10 when it is used.

Figure 6 shows the embodiment of the tubular device 10 according to the invention, which has a shape similar to a straw. The device comprises substantially opposite rectilinear portions forming the mouthpiece 11 and the nose piece 12, respectively. These rectilinear end portions are interconnected by an integrally formed intermediate portion 13 with a plurality of peripherally extending folds, preferably of the type having relatively pointed peaks and planar portions. Because of these folds, the intermediate part is flexible and the folds also cause turbulence in the air flowing through the tubular device. Therefore, the dispersion of the powder or particulate substance in the flowing air is improved, as previously explained. Prior to use, the tubular device may contain a dose 14 of substance, and the opposite ends of the device may be closed as explained above.

The tubular device 10 according to the invention preferably comprises means for creating turbulence in order to improve the dispersion of the powder or particulate substance in the flow of air flowing through the device. Figure 7 shows an embodiment in which a screw threaded element 16 made for example of metal or plastic has been arranged in the tubular device. The threaded element can extend anywhere along the tubular device. In Figure 7, the threaded element 16 extends along substantially the entire length of the device 10. The tubular element can, for example, be made of a film of flexible material, such as a plastic film. The opposite ends of the tubular element can then be closed by a thermal seal. Prior to use the sealed opposite ends of the tubular body are cut.

The tubular device 10 can be made by any suitable method of production. Although extrusion is preferred because it is relatively inexpensive, the vacuum formed can be used. Figures 8 and 9 show an embodiment that has been developed by thermally welding a pair of the vacuum formed parts separately, together along the longitudinally extending opposing folds. The embodiment shown in Figure 10 can be made of a relatively rigid material, such as plastic or glass, with the exposed appearance of a deformable material, such as flexible plastic or rubber. In the later case, the tubular device can be formed by extrusion as a substantially straight long tube. which is curved in the way previously exposed to use.

The embodiment shown in Figure 10 can be made of a relatively rigid material, such as plastic or glass with the exposed shape or a deformable material, such as flexible plastic or rubber. In the later case the tubular device can be formed by extrusion as a substantially straight long tube which is curved in the manner previously exposed to use.

Figure 11 shows a modality intended to be used several times. The tubular device 10 that can be manufactured by injection molding is divided into two parts comprising the mouth piece 11 and the nosepiece 12, respectively. These two pieces can be adapted together or telescopically interconnected so that a capsule 18 containing a dose of a powder or particulate substance can be inserted in the intermediate part. 13. The device may contain puncture needles or a blade that automatically opens the capsule when the two separate parts are closed. In the embodiment shown in figure 11 an opening 9 for insertion of the capsule 18 is formed in the walls of the intermediate part 13. The intermediate part 13 is surrounded by a cover element 20 which can be rotated around the intermediate part between a position in which the opening 19 is exposed, and a position in which the opening is closed. A spring acting by piercing or cutting the element 21 can automatically open the capsule 18, when the covering element has been moved from its closed position.

Figs. 12-17 diagrammatically illustrate various embodiments of the free outer end of the mouthpiece 11. In Fig. 12 a pair of diagonally arranged opposing apertures 22 are formed in the wall of the mouthpiece closely adjacent to the free end of the mouthpiece 11. If a person or patient inadvertently exhales in or inhales through the open end of the mouthpiece 11 when preparing the device for use, the respiratory air flowing through the open end of the mouthpiece 11 can pass through. the opening 22. However, when the user has placed the free end of the mouthpiece 11 between the lips so that the opening 22 is covered or located within the oral cavity and is blowing forcefully the openings 22 will not influence the air flowing through the interior of the cavity of the tubular body 10.

Figure 13 illustrates an embodiment in which an opening 23 is formed by cutting a flap 24 from the wall of the mouthpiece 11 in such a way that the flap 24 is nevertheless connected to the wall of the tubular element via a part in hinge 25 of the inner end of the opening 23. The wing 24 has been curved in the tubular element so that it extends through the inner cavity of the tubular element and is partially restricted to the passage therethrough. If the user inhales or exhales slightly through the open end of the mouthpiece 11 this will not have or have a small effect through the opening 23 and the flap 24. However, when the user has placed the free end of the mouthpiece between the lips and blows energetically at the open end of the mouthpiece, the wing 24 acts suddenly and opens the passage of the flow through the tubular body 10. This creates a strong pressure pulse so that the powder or particulate product 14 It is efficiently dispersed in the air flow and blown into the user's nostril.

In the embodiment of Figure 14, the flap 24 is connected to the mouthpiece 11 via a hinge part located on the free edge of the mouthpiece 11. Otherwise, the embodiment set forth in Figure 14 functions substantially as illustrated. in figure 13.

Figure 15 shows a modality in which a vent opening 26 is formed in mouth piece 11 by cutting a pair of spaced incisions, parallel to the wall of the mouthpiece and by pushing a part of the wall similar to a strip 27 defined between the incisions internally in the interior cavity of the mouthpiece 11. Accordingly, the part of the wall 27 forms a flow that obstructs the element. The embodiment set forth in Figure 15 functions in a manner similar to the embodiment set forth in Figures 13 and 14.

Fig. 16 discloses a mode in which a single-position loose valve 28 comprising an annular seat valve 29 and a mobile valve body similar to a fin 30 have been mounted on the mouthpiece 11 adjacent to the free end thereof . The valve of a position 28 prevents air from flowing through the tubular body 10 in the wrong direction if the patient mistakenly inhales through the tubular body instead of blowing on the mouthpiece 11.

In addition, the valve member 30 may be biased towards its closing position by resilient or resilient forces such that the valve of a position opens only when a predetermined pressure difference is generated through the valve of a position 28. .

Figure 17 shows a buccal part 10 comprising a valve 31 operable manually. This manually operable valve 31 is formed by oppositely disposed deformable wall portions 32 which can, for example, be defined by dim lines or curved lines 33. When the opposite directed compression forces indicated by arrows 34 in Figure 17 are applied to the mouth piece 11 by a pair of fingers 35 (see figure 18) a restriction or throat 36 is formed in mouthpiece 11. This restriction 36 inadvertently prevents the flow of air through the tubular body by unintentional suction or blow action.

When a device 10 according to the invention having a mouthpiece 11 as illustrated in Figure 17 is to be used the deformable wall portions 32 of the device are gripped between a pair of fingers 35 as illustrated in Figure 18 in such a way that a restriction 36 is formed. After that, the mouth piece 11 and the nasal piece 12 are placed between the lips and in the nostril of the user, respectively, as illustrated in Figure 19, while the deformable parts 32 they are still compressed. When the user is blowing energetically on the buccal part the deformable parts 32 are released as illustrated in Figure 20. The pressure that has been generated at the entrance of the mouthpiece 10 is sufficient to suddenly inflate the deformed portions of the wall. so that they recover their initial position. An energetic and sudden flow of air through the tubular device 10 is thus created. The dose 14 of powdered or particulate product is then dispersed in and entrained by the air flow, so the powdered or particulate substance is transported to the nostril.

EXAMPLE The deposition patterns and elimination characteristics of a powder substance after administration from two devices that differ was evaluated.

Introduction The time taken for a formulation to be eliminated from the nose can be altered by depositing the formulations in the different regions of the nose. The embouchure of the nose is a non-ciliated region, therefore, drugs that are released at the mouth of the nose will remain in the nasal cavity for longer periods of time compared to those administered in the respiratory and olfactory regions of the nose. It is possible that the use of different administration devices could produce enormously different elimination times for the same drug formulations. In this example, one embodiment of the device according to the invention such as that shown in FIG. 6 (hereinafter referred to as "device of the invention") was compared with a conventional device for nasal release of dry powder (hereinafter referred to as "advance in the specialty" with reference to the nasal cycle.

The nasal cycle is a well-recognized phenomenon that produces rhythmic alterations of unilateral nasal resistance and airflow. To effectively investigate the nasal release of medications it is important to have information about the nasal cycle of each volunteer, since the nasal cycle can have an effect on the elimination of mucociliarity.

Methods In order to study the elimination characteristics and deposition patterns produced by the different administration devices, radiolabeled powder was administered to a group of six healthy human volunteers according to a design through two full days of study with one week between each treatment. .

Before administering each volunteer, peak nasal inspiration flow measurements of each nostril were performed. The data obtained were used to plot the cyclic rhythm of each volunteer, facilitating the administration of the formulations in the open nostril.

Advance in Specialty The volunteers took deep breaths through the nasal orifice that has the device in the open nostril embouchure. The content of the device (10 mg, approximately 1 MBq) was released on the mucosal surface of the open nostril.

Invention Volunteers placed in the long portion of the device at the mouth of the nose and closed their mouth around the shortest portion. A rapid, forceful breath released the contents of the device (10 mg, approximately 1 Mbq) to the mucosal surface of the open nostril.

The deposition and subsequent 'elimination of the different nasal release systems was followed by gamma scintigraphy, using a Maxi Camera II Gamma Camera (General Electric). The position of the volunteers nose was fixed on the gamma camera collimator using a specially designated tempered one. Static side views (60 seconds in duration) were taken directly after dosing and at appropriate time intervals for 180 minutes after administration. The images were recorded for subsequent analysis and quantification.

Results The quantification of the volunteers' data involved defining regions of interest around the nasal cavity and throat. The counting ratio of each region of interest (ROI), corrected for decay and radioactive background, was then expressed as a counting ratio greater than one minute, typically the image recorded in the ROI nasal cavity immediately after dosing. That is, the highest count ratio was assigned to 100% values, which were then used to calculate the% of values for the counting proportions of the extemporaneous points.

In this way the elimination of nasal cavity formulations was evaluated as a decrease in the percentage of activity against time for each volunteer. Using this elimination data, the time taken for 50% of the formulation to be eliminated from the ROI nasal cavity was calculated for each volunteer. In addition, the deposition patterns produced by the device were evaluated by defining an area of interest around the initial deposition site and counting the covered cell calculator.

Identification Advance in the Device of Volunteers Specialty Invention T50 Area of T50 Area of (min) Deposition (min) Deposition (cells) (cells) 001 170 41 158 35 004 43 48 171 56 005 123 37 153 29 007 84 36 101 28 009 110 34 139 25 010 144 36 48 27 Average 112 39 128 33 SE ± ± 18 ± 2 ± l ± 5 Conclusions / Observations . The Invention Device and Advancement in the Specialty have produced elimination times and deposition areas that are not significantly different from one another.

The device of the invention emptied very well, only an intense blowing of air was required to completely empty the devices. In comparison, Advance in the Specialty that often required two breath admissions to manage all the content.

. It is believed that the Invention Device will require a simple flow valve to be fully effective. The devices are emptied so that once the long tract is placed in the nostril any admission of breath around the short tract is sufficient to cause the device to empty incorrectly in the mouth.

The volunteers reported less irritation of the mucous membranes after the use of the Devices of the Invention.

It would be understood that other embodiments could be elaborated within the scope of the present invention. Accordingly, any of the features set forth in relation to the embodiments shown in the drawings could be exchanged or combined in any way.

Claims (92)

1. A method for introducing a powder or particulate substance into a nasal orifice of a person, said method is characterized in that it comprises, arranging a dose of the substance in an interior cavity of a tubular body, inserting a first open end of the tubular body communicating with the interior cavity between the person's lips, inserting a second open end of the tubular body communicating with the interior cavity in said nostril, and blowing at the first open end of the tubular body in order to create a flow of air through the inner cavity of the tubular body to transport the substance to the nostril.

2. A method according to claim 1, characterized in that the tubular body has an outer contour cross section of substantially uniform shape along its extension.

3. A method according to claim 1 or 2, characterized in that the tubular body has an interior contour cross-section of substantially uniform shape along its extension.

4. A method according to any of claims 1-3, characterized in that the tubular body comprises an intermediate curve and / or a flexible section.

5. A method according to claim 4, characterized in that the curve and / or the flexible section comprises folds extending adjacent, peripherally.

6. A method according to claim 5, characterized in that the folds have a substantially dentate external contour when viewed in a longitudinal, axial section.

7. A method according to any one of claims 2-6, characterized in that the tubular body is shaped similar to a straw.

8. A method according to any of claims 1-7, characterized in that the inner cavity of the tubular body has a cross-sectional area not exceeding 75 mm ^

9. A method according to claim 8, characterized in that the cross-sectional area of the inner cavity does not exceed 70 mm.

10. A method according to claim 9, characterized in that the cross-sectional area of the interior cavity does not exceed 50 mm2-

11. A method according to claim 10, characterized in that the cross-sectional area of the inner cavity is from 7 to 35 mm 2

12. A method according to claim 11, which is characterized in that the cross-sectional area of the inner cavity is approximately 20 pun ".

14. A method according to any of claims 1-12, characterized in that the active substance in powder form or in particles is an active substance against allergic reactions of the person.

14. A method according to any of claims 1-12, characterized in that the powder or particulate substance is a pharmaceutical product.

15. A method according to claim 14, characterized in that the powder or particulate substance is an antihistamine.

16. A method according to any of claims 1-15, characterized in that at least one vent opening is defined in the wall of the tubular body at or adjacent said first open end.

17. A method according to any of claims 1-15, characterized in that at least one restriction in the cross-section is formed in the inner cavity of the tubular body, the dose of particulate or powder that is disposed toward the end of the restriction.

18. A method according to claims 16 and 17, characterized in that the restriction is disposed toward the end of said at least one vent opening.

19. A method according to claim 17 or 18, which is characterized in that the restriction is defined by mobile efficient restriction means between a first restriction position and a second restriction position in which the restriction defined by the restriction means is substantially lower .

20. A method according to claim 19, characterized in that the restriction means comprises a fin covering at least part of the cross section of the interior cavity in said first position.

21. A method according to any of the claims 17-20, which is characterized in that the restriction means comprises a valve of one position.

22. A method according to claim 20 or 21, which is characterized in that the fin is an integral part of the wall of the tubular body.

23. A method according to claims 18 and 22, * which is characterized in that the flap is separated from the wall of the tubular body and internally bent in the inner cavity of the tubular body so as to define a vent opening immediately towards the beginning of the flap .

24. A method according to claims 20 and 22, characterized in that the fin extends into the inner cavity of the tubular body from the free edge of said first end of the tubular body.

25. A method according to claim 19, characterized in that the restriction is made by compressing or perforating a longitudinal section of the wall of the tubular body.

26. A method according to any of claims 19-25, characterized in that the restriction means is moved from its first restricting position to its second position of least restriction when a user is blowing at the first open end of the tubular body in a manner of creating a pressure difference between said first and second open ends of tubular body exceeding a predetermined value.

27. A device for applying a powder or particulate substance to a mucous membrane in the nostril of a user of the device, said device comprising a tubular body defining an interior flow passage extending longitudinally between a nasal part (12) in a first end of the tubular body to be inserted in the user's nostril and a second end of said body, which is characterized in that the second end of the tubular body defines a buccal piece to be inserted between the lips of the user, the extension and the shape of the tubular body being such that the nasal piece and the mouthpiece can at the same time be placed in the hole nasal and between the lips, respectively, of the user, by means of which the user can blow at the end of the buccal part of the flow passage and transport the powdery or particulate substance disposed in the flow passage of the tubular body to the orifice nasal in a dispensed condition.

28. A device according to claim 27, characterized in that the tubular body comprises an intermediate curve and / or a flexible section.

29. A device according to claim 28, characterized in that the curve and / or the flexible section comprises folds extending adjacent, peripherally.

30. A device according to claim 29, characterized in that the folds have a contour -egged suit when viewed in a longitudinal, axial section.

31. Device according to claim 28, characterized in that the curved section comprises a helical part having one or more turns or threads.

32. A device according to claim 28, characterized in that the curved section comprises a separate part that forms connections therein for removably receiving a separate mouth piece and at least one separate nose piece.

33. A device according to any of claims 28-32, characterized in that the curved section can be opened so as to allow the insertion of a capsule containing a dose of said substance into the tular body, means that it is provided for cutting or pierce the wall of the capsule when it is inserted into the tubular body.

34. A device according to any of claims 27-33, further comprising a dose of a powder or particulate substance disposed in the flow passage.

35. A device according to claim 34, characterized in that the powder or particulate substance is an active substance against allergy.

36. A device according to claim 34, characterized in that the powder or particulate substance is a pharmaceutical of the type to be administered to a nasal mucous membrane.

37. A device according to any of claims 34-36, characterized in that the opposite free ends of the mouth piece and the nasal piece, respectively, are sealed or closed by closing means, which are removed or opened prior to the use of the device. .

38. A device according to claim 37, characterized in that the closure means comprises at least one removable covering element, disposed on the free ends of the buccal part and the nasal part, respectively.

39. A device according to any of claims 28-30 and 34-38, characterized in that the intermediate section of the tubular body is flexible, the mouthpiece and nasal piece co-extending and having their free ends placed adjacent closely prior to use of the device.

40. A device according to claim 39, characterized in that the closely adjacent free ends are closed by a common closure element.

41. A device according to any of claims 27-40, characterized in that the tubular body has an external contour of substantially uniform cross section along its extension.

42. A device according to any of claims 27-41, characterized in that the tubular body has an internal contour of substantially uniform cross section along its extension.

43. A device according to claims 41 or 42, characterized in that the tubular body is shaped similar to a straw.

44. A device according to any of claims 27-43, characterized in that the flow passage of the tubular body has a cross-sectional area not exceeding 75 mm2.

45. A device according to claim 44, characterized in that the areas of the flow passage cross sections do not exceed 70 mm.

46. A device according to claim 45, characterized in that the areas of the cross sections of the flow passage do not exceed 50 m.

47. A device according to claim 46, characterized in that the areas of the cross sections of the flow passage are 7 - 35 mm ?.

48. A device according to claim 47, characterized in that the areas of the cross sections of the flow passage are approximately 20 mm.

49. A device according to any of claims 27-48, further comprising means for inducing turbulence in the tubular body.

50. A device according to claim 49, characterized in that the turbulence induction means comprise a helical element similar to a thread disposed in the tubular body.

51. A device according to any of claims 27-50, further comprising at least one vent opening defined in the wall of the tubular body at or adjacent to the buccal part of said first end.

52. A device according to any of claims 27-50, further comprising restricting means forming at least one restricting cross section in the inner cavity of the tubular body, a dose of powder or particulate substance which is disposed towards the end of said restriction means before the device is used.

53. A device according to claims 51 and 52, characterized in that the restriction is located towards the end of the aforementioned vent opening.

54. A device according to claim 52 or 53, characterized in that the restriction means are designed to be moved between a first restriction position and a second position in which the restriction defined by the restriction means is substantially smaller.

55. A device according to claim 54, characterized in that the restriction means comprises a fin which in said first position covers at least part of the cross section of the inner cavity of the tubular body.

56. A device according to any of claims 52-55, characterized in that the restriction means comprises a one-way valve.

57. A device according to claim 55 or 56, characterized in that the fin is an integral part of the wall of the tubular body.

58. A device according to claims 55 and 57, characterized in that the fin is separated from the wall of the tubular body and bent internally in the cavity of the tubular body so as to define a vent opening immediately towards the start of the fin.

59. A device according to claim 55 and 57, characterized in that the fin extends into the interior cavity of the tubular body of the free leaf of the mouthpiece.

60. A device according to claim 52, characterized in that the restriction means comprises compressible or pierceable interior parts of the wall of the tubular body.

61. A device according to any of claims 54-60, characterized in that the restriction means are adapted to move from its first restricting position to its second position of least restriction when a user is blowing at the second end of the tubular body of means of creating a pressure difference between said first and second ends of the tubular body exceeding a predetermined value.

62. A device for dispersing a powder or particulate substance in an air flow, said device comprising a tubular body defining a flow passage therein and a dose of powder or particulate active substance disposed in the flow passage, the tubular body having a mouthpiece at one end to be inserted into the user's lips so that the user can blow on or inhale through the mouthpart end of the flow passage so as to disperse said dose of substance in the mouthpiece. dust or particles in the air that flows through the flow passage, is characterized in that the cross section of the restriction means is arranged in the flow passage towards the start of the dose of active substance, the restriction means which is moved between a first closure or restriction position and a second position substantially less or no restriction, is defined by the restriction means, the restriction means which are adapted to move from its first restricting position to its second position of least restriction when a user is blowing at the end of the mouthpiece of the tubular body of way to create a pressure difference between said ends of the buccal part and the nasal part of the tubular body exceeding a predetermined value.

63. Device according to claim 62, characterized in that the tubular body comprises a curved retainer and / or a flexible section.

64. A device according to claim 63, characterized in that the curve and / or the flexible section comprises folds extending peripherally, axially.

65. A device according to claim 64, characterized in that the folds have a substantially toothed outline when viewed in a longitudinal, axial section.

66. A device according to claim 63, characterized in that the curved section comprises a helical part having one or more turns or threads.

67. A device according to claim 63, characterized in that the curved section comprises a separate part that forms connections thereto by withdrawing a separate mouth piece and at least one separate nose piece.

63. A device according to any of claims 63-67, characterized in that the curved section can be opened in order to allow the insertion of a capsule containing a dose of said substance into the tubular body, which means is provided by cutting or pierce the wall of the capsule when it is inserted into the tubular body.

69. A device according to any of claims 62-68, which is characterized in that the powder or particulate substance is an active substance against allergy.

70. A device according to claims 62-69, characterized in that the powder or particulate substance is a pharmaceutical of the type to be administered in a nasal mucosa membrane.

71. A device according to any of claims 62-70, characterized in that the opposite free ends of the buccal piece and the nasal piece, respectively, are sealed or closed by means of closure, which are removed or opened prior to the use of the device. device.

72. A device according to claim 71, characterized in that the closure means comprises at least one removable plug element disposed at the free ends of the mouth piece and the nosepiece, respectively.

73. A device according to any one of claims 62-72, characterized in that the intermediate section of the tubular body is flexible, the mouthpiece and nasal piece co-extending and having their free ends placed closely adjacent prior to the use of the device. .

74. Device according to claim 73, characterized in that the closely adjacent free ends are closed by a common integral plugging member.

75. Device according to any of claims 62-74, characterized in that the tubular body has an external contour of substantially uniform cross-sectional shape along its extension.

76. A device according to any of claims 62-75, which is characterized in that the tubular body has an internal contour of cross-section of susbtancially uniform shape along its extension.

77. A device according to claim 75 or 76, characterized in that the tubular body is shaped similar to a straw.

78. A device according to any of claims 62-77, characterized in that the flow passage of the tubular body has a cross-sectional area not exceeding 75 mpu.

79. A device according to claim 78, characterized in that those of the cross section of the flow passage do not exceed 70 mrri2.

80. A device according to claim 79, characterized in that the cross-sectional areas of the flow passage do not exceed 50 mma.

81. A device according to claim 80, characterized in that the cross-sectional areas of the flow passage are 7-35 mm2.

82. A device according to claim 81, characterized in that the cross-sectional areas of the flow passage are approximately 20 mm2.

83. A device according to any of claims 27-48, further comprising a means of inducing turbulence in the tubular body.

84. A device according to claim 83, characterized in that the turbulence induction means comprises a helical element similar to a thread disposed in the tubular body.

85. A device according to any of claims 62-84, characterized in that it additionally comprises at least one vent opening in the wall of the tubular body at or adjacent to the buccal part of said first end.

86. A device according to claim 85, characterized in that the restriction means is located towards the end of at least one mentioned vent opening.

87. A device according to any of claims 62-86, characterized in that the restriction means comprises a fin in the first mentioned position covering at least part of the cross section of the inner cavity of the tubular body.

88. A device according to any of claims 62-87, characterized in that the restriction means comprises a one-way valve.

89. A device according to claim 87, characterized in that the fin is an integral part of the wall of the tubular body.

90. A device according to claim 87 and 89, characterized in that the flap is separated from the wall of the tubular body and curved internally in the inner cavity of the tubular body so as to define a vent opening immediately towards the start of the flap.

91. A device according to claims 87-89, characterized in that the fin extends into the inner cavity of the tubular body of the free edge of the mouthpiece.

92. A device according to any of claims 62-86, characterized in that the restriction means comprises compressible or pierceable interior parts of the wall of the tubular body.