Dry powder inhaler

Abstract

The dry powder inhaler comprises an inhalation channel (8) connected to a mouthpiece (4), a container (7) for storing the powder drug, a deaggregation device (25) having a vortex chamber (26) disposed at an end of the inhalation channel (8), and a metering device (14) comprising a shuttle (16) having a dosing recess (15). The shuttle (16) is movable between a filling position in which the dosing recess (15) is aligned with the opening (17) of the container (7) and an inhalation position in which the dosing recess (15) is aligned with the vortex chamber (26). The opening (17) of the container (7) is elongated along a major axis (Y-Y), the dosing recess (15) is elongated along a principal axis (X-X), and when the shuttle (16) is in the filling position, an edge (27) of the opening (17) of the container (7) surrounds the dosing recess (15).

Description

Technical Field

[0001] The present invention relates to a dry powder inhaler, i.e., a device for dispensing a powder pharmaceutical formulation by inhalation. The device is in particular a portable multi-dose breath-actuated dry powder inhaler without propellant gas, comprising a metering device for dispensing the dose delivered from the drug container.

Background Art

[0002] An inhaler is a hand-held portable device for delivering a drug directly to the lungs. One classification of inhalers is the passive dry powder inhaler (DPI). A passive DPI is a patient-driven device where the act of inhaling through the device draws the powdered formulation of the drug into the airways. DPIs are well known as devices for drug delivery to the lungs for the treatment of lung and systemic diseases. They are generally divided into: i) single-dose (unit-dose) inhalers for the administration of individual doses of the active ingredient(s) contained in capsules or blisters that are pierced by the patient immediately before use and loaded into the device; ii) pre-metered multi-dose inhalers containing a series of blisters or capsules containing the active ingredient(s) formulation; or iii) reservoir inhalers containing a larger amount of the powdered formulation of the active ingredient(s) corresponding to multiple doses that are metered from a storage unit immediately before inhalation.

[0003] The following Patent Document 1 by the same applicant discloses a reservoir inhaler (Type iii), which is a dry powder inhaler comprising a casing including a lower shell and an integral cover pivotally connected to the lower shell. The lower shell defines a mouthpiece, and the integral cover is movable between a closed position where the mouthpiece is surrounded and hidden by the integral cover and an open position where the mouthpiece is exposed for use. The lower shell houses a container for storing the powder drug, a metering member having a dosing recess to be filled with a single dose of the powder drug, and an inhalation channel communicating with the mouthpiece. The dosing recess is cup-shaped and exhibits a circular edge. The metering member is movable between a filling position and an inhalation position. In the filling position, the dosing recess is aligned with the opening of the container so as to be filled with a single dose of the powder drug by gravity, and in the inhalation position, the dosing recess is aligned with a volute chamber connected to the inhalation channel to enable inhalation of the single dose of the powder drug contained in the dosing recess. The powder inhaler further comprises a protection member, which is slidably movable on the metering member between a closed position where the protection member covers the dosing recess of the metering member when the metering member is in the inhalation position and an open position where the protection member exposes the dosing recess to enable inhalation of the single dose of the powder drug contained in the dosing recess. The protection member is connected to an inhalation actuating mechanism such that when the inhalation suction force exerted by the user exceeds a predetermined level, the inhalation actuating mechanism moves the protection member from its closed position to its open position.

[0004] Patent Documents 2 and 3 by the same applicant disclose dry powder inhalers (reservoir inhalers) similar to the inhaler of Patent Document 1. The following Non-Patent Document 1 also discloses a dry powder inhaler (NEXThaler (registered trademark) DPI) by the applicant.

[0005] The dosing recesses of the cited prior art documents have a spherical cup shape with a circular edge (in the top view) and are typically configured to accommodate a powder drug dose of 5 mg to 10 mg. This means that the DPI is configured to deliver such a dose through each inhalation.

[0006] However, it may be necessary to deliver a dose of the powder drug that is greater than the dose delivered by prior art inhalers for each inhalation, for example a dose greater than 10 mg.

[0007] The applicant has recognized that in the case of doses greater than 10 mg, the prior art systems can be subject to several drawbacks, and that increasing the diameter or height of the edge of the spherical cup-shaped dosing recess can imply modifications to other components of the known DPI, and that such components should be newly designed and manufactured through specially made molds.

Prior Art Documents

Patent Documents

[0008]

Patent Document 1

Patent Document 2

Patent Document 3

Non-Patent Documents

[0009]

Non-Patent Document 1

Summary of the Invention

[0010] An object of the present invention is to provide a type iii dry powder inhaler (reservoir inhaler) capable of delivering a dose greater than the dose delivered by the prior art, for example a dose greater than 10 mg, preferably without changing and / or redesigning most of the components of the known DPI.

[0011] It is also an object of the present invention to provide a dry powder inhaler capable of delivering a higher dose while maintaining or enhancing the delivery efficiency of a known DPI.

[0012] In particular, it is an object of the present invention to provide a dry powder inhaler that enables a larger dosing recess to be completely filled with a powder drug dispensed from a container by gravity.

[0013] It is also an object of the present invention to provide a dry powder inhaler capable of completely emptying the dosing recess and ensuring the discharge and delivery of the full dose through the mouthpiece.

[0014] At least one of the above objects is substantially achieved by a dry powder inhaler according to one or more of the appended claims and / or the following aspects.

[0015] According to a first independent aspect, a dry powder inhaler comprises a casing having a mouthpiece, an inhalation channel housed in the casing and connected to the mouthpiece, a container housed in the casing for storing a powder drug, the container having an opening, a de - agglomerator having a vortex chamber disposed at an end of the inhalation channel opposite the mouthpiece, a metering device comprising a shuttle having a dosing recess formed in one face, the shuttle being movable between a filling position and an inhalation position, in the filling position, the dosing recess being aligned with and facing the opening of the container so as to be filled with a single dose of the powder drug, and in the inhalation position, the dosing recess being aligned with the vortex chamber and the inhalation channel to enable inhalation of a single dose of the powder drug contained in the dosing recess through the mouthpiece, comprising In the above figure, the openings of the containers are elongated along their respective major axes, the dosing recesses are elongated along their respective major axes, and when the shuttle is in the filling position, the edges of the openings of the containers surround the dosing recesses.

[0016] The dry powder inhaler (DPI) of the present invention is a reservoir inhaler (type iii) that contains a powder formulation of a large amount of active ingredient(s) corresponding to multiple doses that are metered from a storage unit (container) immediately before inhalation.

[0017] The shape of the dosing recess according to the present invention enables the dosing recess to receive a larger dose of powder drug from the container than the dose contained in the spherical cup-shaped dosing recess of the prior art, and to contain such a dose of powder drug.

[0018] The shape of the dosing recess according to the present invention enables the dosing recess to be completely filled because no part of the dosing recess is located outside the edge of the opening of the container.

[0019] The present invention enables only the shape of the dosing recess to be changed, i.e., only the mold for the shuttle to be changed, and the other components of the known DPI to be left unchanged.

[0020] Thus, the present invention enables a DPI that can deliver a larger amount of powder drug to be manufactured by using mostly the same elements of the prior art DPI and only a limited number of different elements, and by fully utilizing existing production lines.

[0021] Other aspects of the present invention are disclosed below.

[0022] In a second aspect according to aspect 1, the direction of movement of the shuttle between the filling position and the inhalation position, and the aforementioned major axis, delimit an angle of 90° therebetween, and the aforementioned major axis and major axis delimit a first angle other than 0° therebetween.

[0023] In a third aspect according to aspect 2, the aforementioned first angle is between 10° and 30°, and optionally, the aforementioned first angle is 20°.

[0024] In a fourth aspect according to any of the previous aspects 1 to 3, the deagglomeration device has two air inlet openings in the vortex chamber, and the aforementioned two air inlets are arranged on both sides of the vortex chamber along a tangential or substantially tangential inflow direction to form an air vortex in the aforementioned vortex chamber. At the suction position, the dosing recess faces the vortex chamber and is completely enclosed within the vortex chamber. Optionally, the dosing recess has opposing ends arranged along the main axis. At the suction position, each of the opposing ends of the dosing recess is located next to one of the air inlets.

[0025] In a fifth aspect according to aspect 4, the diametrical line connecting the two air inlets and the main axis define a second angle other than 0° between them.

[0026] In a sixth aspect according to aspect 4 or 5, the deagglomeration device comprises two curved walls having recesses facing each other. The two curved walls are staggered to delimit the vortex chamber and the two tangential air inlets. Optionally, the diametrical line passing through the free end of each of the curved walls and the main axis define a second angle other than 0° between them.

[0027] In a seventh aspect according to aspect 5 or 6, the diametrical line is parallel to the major axis, and the first angle is equal to the second angle.

[0028] In an eighth aspect according to any of the previous aspects 4 to 7, each of the opposing ends of the dosing recess is arranged downstream of each air inlet with respect to the air inflow entering from the aforementioned tangential air inlet.

[0029] In a ninth aspect according to any of aspects 5 to 7 or aspect 8, when according to any of aspects 5 to 7, the vortex chamber is configured to form a clockwise air vortex, the main axis is rotated clockwise with respect to the diameter line, or the vortex chamber is configured to form a counterclockwise air vortex, and the main axis is rotated counterclockwise with respect to the diameter line.

[0030] In a tenth aspect according to aspect 6 or any of aspects 7 to 9, when according to aspect 6, at the inhalation position, the dosing recess is included in a base circle having a diameter "d" provided by a segment extending between the free ends of the two curved walls.

[0031] In an eleventh aspect according to any of aspects 1 to 10, the edge of the opening of the container is substantially elliptical, or the edge of the opening of the container has two major arched sides and two minor straight sides.

[0032] In a twelfth aspect according to any of aspects 1 to 11, the periphery of the dosing recess comprises two parallel straight lines connected by two arcs, the two parallel straight lines being parallel to the main axis, or the periphery of the dosing recess is oval or elliptical and the main axis is the major axis of the ellipse.

[0033] In a thirteenth aspect according to any of aspects 1 to 12, the dosing recess has a volume for a powder drug of more than 10 mg, optionally more than 15 mg, optionally 20 mg, optionally between 20 mg and 30 mg.

[0034] In a fourteenth aspect according to any of aspects 1 to 13, the dosing recess has a length L measured along the main axis and a width W measured perpendicular to the main axis, and optionally the ratio of L / W is greater than 1, optionally between 1.4 and 1.8, for example 1.6.

[0035] In a 15th aspect according to any of aspects 1 to 14, a protective member is provided between the shuttle and the vortex chamber. When the shuttle is in the inhalation position, the protective member is slidably movable between a closed position and an open position on or above the shuttle. In the closed position, the protective member completely covers the dosing recess to prevent communication between the dosing recess and the vortex chamber. In the open position, the protective member leaves the dosing recess exposed to the vortex chamber.

[0036] The shape and position of the dosing recess relative to the vortex chamber are such that when the shuttle is in the inhalation position and the protective member is in the open position, the single-dose powder drug contained in the dosing recess is entrained by the air flow and guided through the inhalation channel to the mouthpiece, ensuring that the dosing recess is completely emptied.

[0037] In a 16th aspect according to aspect 6 or 10, each curved wall is an arc of the circumference, optionally a semi - circumference.

[0038] In a 17th aspect according to aspect 10, the width "p" of each air inlet measured along the segment extending between the free ends of the two curved walls is between d / 6 and d / 4, and optionally, the width "p" is d / 5.

[0039] In an 18th aspect according to aspect 10 or 17, when the shuttle is in the inhalation position, the first minimum distance "s1" between the periphery of the dosing recess and the curved wall is between d / 12 and d / 8, and optionally, the first minimum distance "s1" is d / 10.

[0040] In a 19th aspect according to one or more of the previous aspects 6, 10, 17 or 18, the de - agglomeration device comprises a base wall having a through - opening for receiving the powder drug from the dosing recess when the shuttle is in the inhalation position.

[0041] In a 20th aspect according to the previous aspects, the two curved walls extend from the base wall and surround or delimit the through - opening.

[0042] In a 21st aspect according to one or more of the previous aspects 6, 10, or 17 - 20, the end of the inhalation channel on the side opposite the mouthpiece is arranged near or between two curved walls.

[0043] In a 22nd aspect according to one or more of the previous aspects 6, 10, or aspects 17 - 21, each of the two curved walls has a radius "R", the two curved walls each have a center, and the aforementioned centers are staggered from each other by a distance "Δ", and optionally, both centers are located on a diameter line.

[0044] In a 23rd aspect according to the previous aspect, in the case of aspect 17, considering the thickness "t" of the curved wall, Δ = t + p and d = 2R - Δ.

[0045] In a 24th aspect according to one or more of the previous aspects, the inhalation channel and the vortex chamber share a common central axis.

[0046] In a 25th aspect according to aspect 11 or aspect 12, in the case of aspect 11, the two small straight sides at the edge of the opening are parallel to the moving direction of the shuttle.

[0047] In a 26th aspect according to aspect 12, the two arcs around the administration recess define the opposite ends of the administration recess.

[0048] In a 27th aspect according to aspect 12 or 26, when aspect 12 is according to aspect 10, when the shuttle is in the filling position, the second minimum distance "s2" between the periphery of the administration recess and the edge of the container opening is between d / 12 and d / 8, and optionally, the second minimum distance "s2" is d / 10.

[0049] In a 28th aspect according to aspect 14, the length L is between 8 mm and 12 mm.

[0050] In a 29th aspect according to aspect 14 or 28, the width W is between 4 mm and 6 mm.

[0051] In a 30th aspect according to the previous aspects 10 and 14, the ratio of L / d is between 0.8 and 0.95, and optionally, it is 0.9.

[0052] In a 31st aspect according to the previous aspects 10 and 14 or according to aspect 30, the ratio of W / d is between 0.4 and 0.8, and optionally, it is 0.6.

[0053] In a 32nd aspect according to any of the previous aspects, the container comprises a drug chamber configured to store or be configured to store the powdered drug and having the aforementioned opening.

[0054] In a 33rd aspect according to the previous aspect, the drug chamber is shaped at least partially like a hopper converging towards the opening.

[0055] In a 34th aspect according to aspect 32 or 33, the container comprises a desiccant chamber configured to store or be configured to store a desiccant.

[0056] In a 35th aspect according to the previous aspect, a permeable membrane separates the desiccant chamber from the drug chamber.

[0057] In a 36th aspect according to aspect 15, the protective member is a plate.

[0058] In a 37th aspect according to aspect 15 or 36, the width of the protective member measured along the major axis is greater than the size of the dosing recess measured along the aforementioned major axis.

[0059] In a 38th aspect according to aspect 15 or 36 or 37, an inhalation actuating mechanism is connected to the protective member and is configured to move the protective member from its closed position to its open position when the inhalation suction force exerted by the user through the mouthpiece exceeds a predetermined level.

[0060] In the 39th aspect according to the previous aspect, the inhalation actuating mechanism includes an inhalation actuating member, which is optionally in the shape of a flap, a connecting member, and an elastic element disposed on the connecting member. When an inhalation suction force exceeding a predetermined value exists, the inhalation actuating member is moved from a first position to a second position, and the protection member is connected to the protection member through the connecting member so that the protection member is moved from a closed position to an open position.

[0061] In the 40th aspect according to any of the previous aspects, the dry powder inhaler further includes a powder drug.

[0062] In the 41st aspect according to any of the previous aspects, the dry powder inhaler further includes a cover that can engage with the casing to close the mouthpiece.

[0063] In the 42nd aspect according to the previous aspect, the shuttle is mechanically connected to the cover such that an opening of the cover beyond the range of rotational movement from the closed position moves the shuttle from the filling position to the inhalation position, and closing of the cover returns the shuttle from the inhalation position to the filling position.

[0064] In the 43rd aspect according to any of the previous aspects, the dry powder inhaler is the same as or similar to the device disclosed in any of the above Patent Documents 1 to 3 and Non-Patent Document 1, except for the shape and size of the dosing recess.

[0065] In the 43rd aspect according to any of the previous aspects, the powder drug is a pharmaceutical composition.

[0066] In the 44th aspect according to the previous aspect, the pharmaceutical composition includes one or more phosphodiesterase-4 (PDE-4) inhibitors.

[0067] In the 45th aspect according to the previous aspect, the phosphodiesterase-4 (PDE-4) inhibitor is selected from the group consisting of tanimilast, cilomilast, roflumilast, tetomilast, oglemilast, apremilast, piclamilast, and salts thereof.

[0068] In a 46th aspect according to aspect 43 or 44, the pharmaceutical composition comprises tanimilast, or the phosphodiesterase-4 (PDE-4) inhibitor to be administered is tanimilast.

[0069] According to a 47th aspect, a method of treating a respiratory disease comprises administering a delivery dose through an inhaler according to any of the previous aspects.

[0070] In a 48th aspect according to the previous aspects, the delivery dose is more than 10 mg.

[0071] In a 49th aspect according to aspect 47 or 48, the delivery dose is a pharmaceutical composition.

[0072] In a 50th aspect according to the previous aspects, the pharmaceutical composition comprises one or more phosphodiesterase-4 (PDE-4) inhibitors.

[0073] In a 51st aspect according to the previous aspects, the phosphodiesterase-4 (PDE-4) inhibitor is selected from tanimilast, cilomilast, roflumilast, tetomilast, oglemilast, apremilast, piclamilast, and salts thereof.

[0074] In a 52nd aspect according to aspect 49 or 50, the pharmaceutical composition comprises tanimilast, or the phosphodiesterase-4 (PDE-4) inhibitor to be administered is tanimilast.

[0075] A 53rd aspect relates to the use of any of the previous inhalers 1-46 in the treatment of respiratory diseases.

[0076] In a 54th aspect according to aspect 52 or 53, the powder drug comprises tanimilast.

[0077] Aspect 55 relates to a pharmaceutical composition for use in a method of treating a respiratory disease, the pharmaceutical composition being a powder drug, and the method comprising administering the pharmaceutical composition through an inhaler according to any of the preceding aspects 1 to 46.

[0078] In a 56th aspect according to aspect 55, the pharmaceutical composition comprises one or more phosphodiesterase-4 (PDE-4) inhibitors selected from tanimilast, cilomilast, roflumilast, tetomilast, oglemilast, apremilast, piclamilast, and salts thereof.

[0079] In a 57th aspect according to aspect 56, the phosphodiesterase-4 (PDE-4) inhibitor to be administered is tanimilast.

[0080] In a 58th aspect according to any of aspects 55 to 57, the method comprises administering a delivery dose of the pharmaceutical composition greater than 10 mg per actuation.

[0081] In a 59th aspect according to any of the previous aspects, the dosing recess has a volume greater than 10 mm 3 optionally greater than 20 mm 3 optionally greater than 25 mm 3 The dosing recess has a volume of 10 mm 3 to 50 mm 3 optionally 20 mm 3 to 40 mm 3 or optionally 25 mm 3 to 35 mm 3 and may have a volume.

[0082] Further features and advantages will become more apparent from a detailed description of preferred but non-exclusive embodiments of the dry powder inhaler according to the present invention.

Brief Description of the Drawings

[0083]

Figure 1

Figure 2A

Figure 2B

Figure 2C

Figure 3

Figure 4

Figure 5A

Figure 5B

Figure 6

Figure 7

Figure 8

Figure 9

Figure 10

DETAILED DESCRIPTION OF THE INVENTION

[0084] Referring to the accompanying drawings, FIGS. 1, 2A, 2B, and 2C show a dry powder inhaler 1 according to the present invention. These non-limiting examples of the dry powder inhaler 1 may be similar to the inhalers disclosed in International Publication No. WO 2004 / 012801, International Publication No. WO 2016 / 000983, and International Publication No. WO 2021 / 105440 by the same applicant, or the paper "Expert Opin. Drug Deliv. (2014) 11(9), 1497-1506" by Corradi M. et al.

[0085] The dry powder inhaler 1 comprises a casing 2 and a cover 3 pivotally or rotatably connected to the casing 2. As can be understood from FIG. 1, the cover 3 can be opened to expose a mouthpiece 4 through which the user can inhale the powdered drug. An air intake opening 5 is formed in the casing 2 at the upper front side of the mouthpiece 4.

[0086] The casing 2 is a closed shell made of a thermoplastic material (e.g., ABS and polycarbonate) and comprises a side surface, an upper surface, and a lower surface (upper and lower with respect to the orientation of the powder inhaler 1 in FIGS. 1, 2A - 2C).

[0087] The mouthpiece 4 projects from the upper surface and has a frustoconical outer shape that tapers towards an opening 6 made at the top (smaller base) of the mouthpiece 4.

[0088] The cover 3 is hinged to the casing 2 and is rotatable between a closed position shown in FIG. 2A and an open position shown in FIGS. 1, 2B, and 2C. In the closed position, the cover 3 surrounds the mouthpiece 4, and in the open position, the cover 3 is pulled away from the mouthpiece 4 to expose the aforementioned mouthpiece 4 for use.

[0089] The powder inhaler 1 comprises a container 7 for storing the powdered drug, an inhalation channel 8 connected to the opening 6 of the mouthpiece 4, and a dispensing device 9 (FIGS. 2A - 2C). The inhalation channel 8 has a first opening connected to the mouthpiece 4 and a second opening opposite the first opening. All these elements are part of a sub - assembly 10 shown in FIG. 3 and are housed in the casing 2.

[0090] As shown in FIGS. 2A - 2C, the container 7 is a container containing an integral desiccant.

[0091] The container 7 comprises a drug chamber 11 for storing the powdered drug and a desiccant chamber 12 for storing a desiccant for absorbing moisture that may have entered the drug chamber 11.

[0092] The desiccant chamber 12 is separated from the drug chamber 11 by a separate permeable membrane 13. This permeable membrane 13 has a permeability different from that of either the desiccant or the drug to the external environment. The permeability of the membrane 13 can be achieved, for example, by making the membrane 13 of a material different from that of the main body of the container 7 and / or a section thinner than the main body of the container 7. A foil may be used to seal both the drug chamber 11 and the desiccant chamber 12. The container 7, particularly the drug chamber 11, is filled with a powder drug in an amount corresponding to multiple doses, for example, up to 100 to 200 doses, or is configured to be filled with such an amount of powder drug. For example, the powder drug is a pharmaceutical composition.

[0093] The desiccant is housed in a housing that can be inserted into the desiccant chamber 12, or the desiccant is in the form of a single tablet that can be inserted into the desiccant chamber 12. The desiccant is a material having pores of uniform size, for example, an alkali salt of aluminosilicate, a so-called zeolite, or aluminophosphate, or porous glass, or activated carbon, or a molecular sieve made of artificial zeolite, or contains such a molecular sieve. The molecular sieve is configured to absorb small molecules such as water molecules. The desiccant may be silica gel.

[0094] The dispensing device 9 includes a metering device 14 having a dosing recess 15. The metering device 14 shown in the attached figure has a plate-like shape and includes a shuttle 16 provided with the aforementioned dosing recess 15, and the dosing recess 15 is formed on the surface of the shuttle 16.

[0095] The dispensing device 9 is movable between an idle state (Figure 2A) and a trigger state (Figure 2C) with respect to the container 7 and the inhalation channel 8. In the idle state, the dosing recess 15 communicates with the opening 17 of the container 7 so as to be filled with a single dose of powder drug. In the trigger state, the dosing recess 15 communicates with the inhalation channel 8 to enable inhalation of the single dose of powder drug contained in the dosing recess 15 through the mouthpiece 4.

[0096] As shown in FIGS. 2A, 2B, 2C, 3, and 5A - 5B, the drug chamber 11 is at least partially shaped like a hopper having walls converging towards the opening 17.

[0097] The shuttle 16 is disposed between the sub - assembly 10 and the bottom wall of the casing 2. The shuttle 16 is shaped like a plate made of a single piece of plastic, for example, acrylonitrile - butadiene - styrene copolymer (ABS).

[0098] The shuttle 16 is slidably movable between a filling position (FIG. 2A) and an inhalation position (FIGS. 2B and 2C) along the movement direction F. The filling position corresponds to the idle state of the metering device 14. At the filling position, the dosing recess 15 aligns with and faces the opening 17 of the container 7 so as to be filled with a single dose of powder drug. The inhalation position corresponds to the armed state (described in detail later) (FIG. 2B) and the trigger state of the metering device 14 (FIG. 2C). At the inhalation position, the dosing recess 15 aligns with the inhalation channel 8.

[0099] The shuttle 16 is mechanically connected to the cover 3 such that an opening of the cover beyond the range of rotational movement from the closed position moves the shuttle 16 from the filling position to the inhalation position. Closing of the cover 3 returns the shuttle 16 from the inhalation position to the filling position.

[0100] As shown in FIGS. 2A, 2B, and 2C, a spring 36 is interposed between the bottom wall of the casing 2 and the shuttle 16 and is configured to press the shuttle 16 against the opening 17 of the container 7 when the shuttle 16 is in the filling position. The shuttle 16 slides relative to the spring 36 when moving between the filling position and the inhalation position.

[0101] The metering device 14 further comprises a protection member 18 provided between the shuttle 16 and the suction channel 8. The protection member 18 is a plate disposed between the second opening of the suction channel 8 and the shuttle 16. The protection member 18 is parallel to the shuttle 16 and is slidably movable between a closed position and an open position on or above the shuttle 16.

[0102] In the closed position, the protection member 18 is shifted rearwardly towards the second opening of the suction channel 8 and the container 7. In the closed position, the rear portion of the protection member 18 can at least partially close the second opening of the suction channel 8. In the open position, the protection member 18 is shifted forwardly towards the wall of the casing 2. In the open position, the rear portion of the protection member 18 keeps the second opening of the suction channel 8 open. The protection member 18 is in the closed position when the shuttle 16 is in the filling position (FIG. 2A). The protection member 18 may be moved between the closed position and the open position when the shuttle 16 is in the suction position (FIGS. 2B and 2C).

[0103] Thus, the metering device 14 is configured to assume the three different states (idle, ready, trigger) described above, which are defined by the positions of the shuttle 16 and the protection member 18.

[0104] In the idle state (Figure 2A), the shuttle 16 is in the filling position and the protection member 18 is in the closed position. The protection member 18 does not cover the dosing recess 15. The dosing recess 15 communicates with the opening of the container 7 to receive a drug dose. In the ready state (Figure 2B), the shuttle 16 is in the inhalation position and the protection member 18 is in the closed position. The protection member 18 covers the dosing recess 15. The protection member 18 prevents the powder drug contained in the dosing recess 15 from entering the inhalation channel 8 and from being lost if the powder inhaler 1 rotates or moves in an inclined position before the inhalation operation or if the user blows air into the mouthpiece 4. In the trigger state (Figure 2C), the shuttle 16 is in the inhalation position and the protection member 18 is in the open position. The protection member 18 does not cover the dosing recess 15, thereby exposing the dosing recess 15 to the inhalation channel 8 so that the user can inhale the single-dose powder drug contained in the dosing recess 15.

[0105] The dispensing device 9 further comprises a breathing or inhalation actuation mechanism 19 connected to the protection member 18 (Figures 2A, 2B, 2C). The inhalation actuation mechanism 19 comprises an inhalation actuation member 20 having a flap-like shape, a connecting member 21, and an elastic element 22 (spring) disposed on the connecting member 21.

[0106] When there is an inhalation suction force exceeding a predetermined value, the flap 20 is connected to the protection member 18 through the connecting member 21 so that the movement of the flap 20 from the first position to the second position moves the protection member 18 from the closed position to the open position. The flap 20 is disposed near the air intake opening 5 inside the casing 2. In the first position (FIG. 2A), the flap 20 separates the air intake opening 5 from the inhalation channel 8 and is located in the main air flow path. The flap 20 provides resistance and gives positive feedback when the user blows air into the device. In the second position (FIG. 2C), the flap 20 is rotated relative to the first position to open the air intake opening 5 and to allow air to flow from the air intake opening 5 into the inhalation channel 8 and out of the mouthpiece 4. The elastic element 22 is arranged such that the aforementioned elastic element 22 holds the flap 20 in its first position. When the shutter 16 is pushed forward by opening the cover 3, the elastic element 22 is compressed and charged so that the flap 20 can pivot or rotate from the first position to the second position when there is a sufficiently high inhalation suction force in the inhalation channel 8, that is, pivot downward relative to the first position, and the reset force exerted on the flap 20 is released.

[0107] The flap 20 is hinged to the casing 2 to rotate between the first position and the second position about respective axes of rotation that are substantially perpendicular to the main axis A-A of the inhalation channel 8. The connecting member 21 is also hinged to the casing 2 to rotate between its respective first and second positions about respective axes of rotation that are substantially perpendicular to the main axis A-A of the inhalation channel 8.

[0108] The connecting member 21 comprises an arm (not shown) that projects towards the flap 20 and engages the flap 20 such that a clockwise rotation of the flap 20 from the first position to the second position causes a counterclockwise rotation of the connecting member 21 from its respective first position to its respective second position.

[0109] The connecting member 21 comprises an extension portion 23 that engages an opening formed in the protective member 18 so that when the connecting member 21 moves from its respective first position to its respective second position, the protective member 18 is moved from the closed position to the open position, and vice versa.

[0110] The extension portion 23 of the connecting member 21 is also movably disposed in a longitudinal opening 24 formed in the shuttle 16 along the longitudinal direction of the shuttle 16 such that while the aforementioned extension portion 23 can move freely in the longitudinal opening 24, the movement of the shuttle 16 from the inhalation position to the filling position causes the extension portion 23 of the connecting member 21 to abut against the edge of the longitudinal opening 24 to return the connecting member 21 to its initial first position.

[0111] The dry powder inhaler 1 further comprises a deagglomeration device 25 connected to the second end of the inhalation channel 8 opposite the mouthpiece 4. The deagglomeration device 25 is also part of the sub-assembly 10.

[0112] The deagglomeration device 25 delimits a vortex chamber 26 and is configured such that the vortex chamber 26 generates a cyclonic air flow resulting in a strong velocity gradient. The protective member 18 is slidable on the shuttle 16 between the closed position and the open position of the protective member 18. In the closed position, the protective member 18 covers the dosing recess 15, and in the open position, when the metering device 14 is in the inhalation position, the protective member 18 exposes the dosing recess 15 to the deagglomeration device 25 and the inhalation channel 8 so that a single dose of powder drug can be inhaled through the deagglomeration device 25, the inhalation channel 8, and the mouthpiece 4.

[0113] The powder inhaler 1 may further comprise a dose counting unit not shown in the embodiments of the accompanying drawings. The dose counting unit is housed in the casing 2 and is connected to both the inhalation actuating mechanism 19 and the closing of the cover 3 after a valid inhalation has occurred. The casing 2 may further comprise a window or opening for displaying the number of administrations performed or the number of administrations remaining in the container 7, which number is counted by the dose counting unit.

[0114] As shown in the top views of FIGS. 5A, 5B, and 9, the opening 17 of the container 7 is elongated along the major axis Y - Y, and the aforementioned major axis Y - Y is perpendicular to the moving direction F of the shuttle 16. In other words, the opening 17 has a size measured along the aforementioned major axis that is larger than the size measured along the moving direction F of the shuttle 16.

[0115] The edge 27 of the opening 17 is located in a plane parallel to the surface of the shuttle 16 where the dosing recess 16 is made (FIGS. 3, 5A, 5B, 9). The edge 27 is formed by two large arch - shaped sides 17a and two small straight sides 17b. The two small straight sides 17b are of the same length and are parallel to the moving direction F of the shuttle 16. Each of the two large arch - shaped sides 17a connects the ends of the two small straight sides 17b. The two large arch - shaped sides 17a have recesses facing each other. The edge 27 of the opening 17 looks like an oval with truncated ends.

[0116] Although not shown, in other embodiments, the edge 27 of the opening 17 may be elliptical or substantially elliptical.

[0117] The de - agglomeration device 25 comprises a casing 28 having a side wall 29 and a base wall 30 (see FIG. 3), and the vortex chamber 26 is delimited inside the aforementioned casing 28.

[0118] As shown in FIGS. 4, 5A, 5B, and 10, the de - agglomeration device 25 comprises two curved walls 31 protruding from the base wall 30 of the sub - assembly 10. The two curved walls 31 have recesses facing each other and delimit the vortex chamber 26. Each curved wall 31 has a thickness t and is shaped like a semi - circumference with a radius R. The centers of the two curved walls 31 are arranged on a common diameter line Z - Z and are staggered from each other by a distance Δ (FIG. 10). The diameter line Z - Z is perpendicular to the moving direction F of the shuttle 16 and is thus parallel to the major axis Y - Y.

[0119] The two curved walls 31 extend from the base wall 30 and surround or delimit the through opening 32 formed in the aforementioned base wall 30 (Figs. 2A, 2B, 2C).

[0120] Each of the two curved walls 31 has an end connected to the respective side wall 29 and the opposite free end 33. The diameter d provided by the segment extending between the free ends 33 of the two curved walls 31 may be considered as the diameter of the volute chamber 26.

[0121] Each free end 33 and the adjacent side wall 29 delimit an air inlet 34 opening into the volute chamber 26. The two air inlets 34 are arranged on both sides of the volute chamber along a tangential or substantially tangential inflow direction in order to form an air vortex in the aforementioned volute chamber 26. In other words, the air flow entering from each of the two air inlets 34 is guided tangentially with respect to the circle centered on the volute chamber 26.

[0122] The width p of each air inlet 34 measured along the segment extending between the free ends 33 of the two curved walls 31 is between d / 6 and d / 4. For example, the width p is d / 5.

[0123] The relationships between the radius R, the distance Δ, the width p, the diameter d, and the thickness t are as follows. Δ = t + p d = 2R - Δ

[0124] A recess 35 delimited between the side wall 29 and the radially outer surfaces of the two curved walls 31 can be put into fluid communication with the air intake opening 5 through the breathing or suction actuating mechanism 19.

[0125] As shown in Figs. 2A, 2B, and 2C, the second end of the suction channel 8 on the side opposite to the mouthpiece 4 is arranged between the two curved walls 31 and opens into the volute chamber 26. The suction channel 8 and the volute chamber 26 share a common central axis.

[0126] When the user exerts an inhalation suction force exceeding a predetermined value, the protection member 18 moves from the closed position to the open position. In the open position, the protection member 18 keeps the dosing recess 15 exposed to the volute chamber 26. Air flows into the recess 35 through the air intake opening 5, into the volute chamber 26 through the air inlet 34, then into the inhalation channel 8 and out of the mouthpiece 4. The single-dose powder drug contained in the dosing recess 15 is entrained by the swirling air flow and guided through the inhalation channel 8 to the mouthpiece 4.

[0127] As is apparent from the above, the internal mechanism and function of the powder inhaler 1 disclosed above may be substantially the same as those disclosed in International Publication No. WO 2004 / 012801, International Publication No. WO 2016 / 000983, or International Publication No. WO 2021 / 105440 by the same applicant.

[0128] The main differences with respect to these documents are the shape, size, and position of the dosing recess 15, as detailed below.

[0129] According to the present invention, as shown in the top views of FIGS. 5A, 5B, 6, and 9, the dosing recess 15 does not exhibit a circular periphery. Instead, the dosing recess 15 of the present invention is elongated along its respective major axis X-X. The dosing recess 15 may be cup-shaped.

[0130] The periphery of the dosing recess 15 may be oval or elliptical, and the major axis X-X is the major axis of the ellipse. Otherwise, as shown in the accompanying FIGS. 5A-9, the periphery of the dosing recess 15 comprises two parallel straight lines connected by two arcs, and the two parallel straight lines are parallel to the major axis X-X. The two arcs around the dosing recess 15 define both ends of the dosing recess 15 arranged along the major axis X-X. The dosing recess has a length L measured along the major axis X-X and a width W measured perpendicular to the major axis X-X, and the ratio of L / W is greater than 1, preferably between 1.4 and 1.8, for example 1.6.

[0131] Furthermore, the main axis X-X and the major axis Y-Y define a first angle β other than 0° therebetween. The aforementioned first angle β may be about 20°.

[0132] As shown in FIG. 9, the size around the dosing recess 15 is such that when the shuttle 16 is in the filling position, the edge 27 of the opening 17 of the container 7 surrounds the dosing recess 15, or in other words, the periphery of the dosing recess 15 is surrounded by or sealed within the edge 27 of the opening 17. In this way, the dosing recess 15 is completely filled with the powdered drug flowing from the opening 17.

[0133] This shape of the dosing recess 15 enables it to receive and accommodate a larger dose of powdered drug from the opening 17 of the container 7 than the dose accommodated in a prior art spherical cup-shaped dosing recess. For example, the length L is between 8 mm and 12 mm, the width W is between 4 mm and 6 mm, and the volume of the dosing recess 15 according to the present invention is greater than 15 mg, for example, 20 mg. For example, the dosing recess 15 is larger than 20 mm 3 greater, for example, about 30 mm 3 or about 32 mm 3 and may have a volume of.

[0134] In the inhalation position and when the protective member 18 is in the open position, the dosing recess 15 faces the swirl chamber 26 and is completely located within the swirl chamber 26. In particular, the dosing recess 15 is included in a base circle having a diameter d (FIG. 10). A diameter line Z-Z passing through each free end 33 of the curved wall 31 and connecting the two air inlets 34 defines a second angle γ together with the main axis X-X, and this second angle γ is equal to the first angle β, that is, other than 0°, for example, 20°.

[0135] Each of the two ends of the dosing recess 15 is located adjacent to one of the air inlets 34 and is arranged downstream of each air inlet 34 with respect to the air inflow entering from the tangential air inlet 34 described above. In the illustrated embodiment, the swirl chamber 26 is configured to form a clockwise air vortex, and the main axis X-X is rotated clockwise by a second angle γ with respect to the diameter line Z-Z. Although not shown, in other embodiments, the swirl chamber 26 may be configured to form a counterclockwise air vortex, and the main axis X-X will be rotated counterclockwise with respect to the diameter line Z-Z.

[0136] When the shuttle 16 is in the inhalation position, the first minimum distance s1 between the periphery of the dosing recess 15 and the curved wall 31 is between d / 12 and d / 8. For example, the first minimum distance s1 is d / 10. In the attached FIG. 10, the first minimum distance s1 is measured along the diameter line Z-Z.

[0137] When the shuttle 16 is in the filling position, the second minimum distance s2 between the periphery of the dosing recess 15 and the edge 27 of the opening 17 of the container 7 is between d / 12 and d / 8. For example, the second minimum distance s2 is d / 10.

[0138] The ratio of L / d is between 0.8 and 0.95, for example 0.9, and the ratio of W / d is between 0.4 and 0.8, for example 0.6. In the attached FIG. 9, the second minimum distance s2 is between one of the two large arched sides 17a of the edge 27 and one of the two arcs of the periphery of the dosing recess 15.

[0139] The shape and position of the dosing recess 15 with respect to the swirl chamber 26 ensure that when the shuttle 16 is in the inhalation position and the protection member 18 is in the open position, the swirling air in the swirl chamber 26 completely empties the dosing recess 15. The elongated shape of the dosing recess 15 and the relative position of the dosing recess 15 with respect to the air inlet 34 of the swirl chamber 26 make it possible to collect all the powder drug from the dosing recess 15 and send the aforementioned powder drug to the inhalation channel 8.

[0140] Furthermore, the width of the protective member 18 measured along the major axis Y-Y is larger than the size of the dosing recess 15 measured along the aforementioned major axis Y-Y, and the length of the protective member 18 measured along the moving direction F is larger than the size of the dosing recess 15 measured along the aforementioned moving direction F. As a result, any leakage of the powder drug from the dosing recess 15 before inhalation is prevented.

[0141] The dry powder inhaler 1 according to the present invention can be used with any pharmaceutical composition that can be dispensed through the DPI at a delivery dose of more than 10 mg per actuation.

[0142] In particular, the dry powder inhaler 1 according to the present invention can be used for the treatment of respiratory diseases that require a delivery dose of a pharmaceutical composition of more than 10 mg per actuation.

[0143] In a preferred embodiment, the powder drug stored in the container 7 of the dry powder inhaler 1 according to the present invention is a pharmaceutical composition containing one or more phosphodiesterase-4 (PDE-4) inhibitors selected from the group consisting of tanimilast, cilomilast, roflumilast, tetomilast, oglemilast, apremilast, piclamilast, and salts thereof, or other suitable active ingredients. In a more preferred embodiment, the powder drug is a pharmaceutical composition containing tanimilast.

Explanation of Reference Numerals

[0144] 1 Powder inhaler 2 Casing 3 Cover 4 Mouthpiece 5 Air intake opening 6 Opening of the mouthpiece 7 Container 8 Inhalation channel 9 Dispensing device 10 Sub-assembly 11 Drug chamber 12 Desiccant chamber 13 Permeable membrane 14 Metering device 15 Dosing recess 16 Shuttle 17 Opening of the container 17a Large arch-shaped side 17b Small straight side 18 Protective member 19 Breathing or inhalation actuating mechanism 20 Inhalation actuating member or flap 21 Connecting member 22 Elastic element 23 Extension part 24 Longitudinal opening 25 Disaggregation device 26 Vortex chamber 27 Edge of the opening 28 Casing 29 Side wall 30 Base wall 31 Two curved walls 32 Through opening 33 Free end of the side wall 34 Air inlet 35 Depression 36 Spring F Moving direction of the shuttle Y-Y Major axis X-X Main axis β First angle γ Second angle Δ Distance s1 First minimum distance s2 Second minimum distance

Claims

1. A casing (2) having a mouthpiece (4), The suction channel (8) is housed in the casing (2) and connected to the mouthpiece (4), A container (7) is housed in the casing (2) for storing powdered drugs and has an opening (17), A deagglutination device (25) having a vortex chamber (26) located at the end of the suction channel (8) opposite to the mouthpiece (4), A measuring device (14) comprising a shuttle (16) having a dosing recess (15) formed on one surface, wherein the shuttle (16) is movable between a filling position and an inhalation position, and in the filling position, the dosing recess (15) is aligned with and faces the opening (17) of the container (7) so as to be filled with one dose of the powder drug, and in the inhalation position, the dosing recess (15) is aligned with the vortex chamber (26) and the inhalation channel (8) so as to enable inhalation of the one dose of powder drug contained in the dosing recess (15) through the mouthpiece (4), A dry powder inhaler equipped with, In a top view, the opening (17) of the container (7) is elongated along the main axis (Y-Y), the administration recess (15) is elongated along the main axis (X-X), and when the shuttle (16) is in the filling position, the edge (27) of the opening (17) of the container (7) surrounds the administration recess (15), wherein the dry powder inhaler is provided.

2. The dry powder inhaler according to claim 1, wherein the direction of movement (F) of the shuttle (16) between the filling position and the inhalation position and the main axis (Y-Y) divide a 90° angle between them, and the main axis (X-X) and the main axis (Y-Y) divide a first angle (β) other than 0° between them.

3. The dry powder inhaler according to claim 2, wherein the first angle (β) is between 10° and 30°.

4. The dry powder inhaler according to claim 1, wherein the deagglomeration device (25) has two air inlets (34) opening into the vortex chamber (26), the two air inlets (34) being positioned on both sides of the vortex chamber (26) along a tangential or substantially tangential inflow direction to form an air vortex in the vortex chamber (26), and in the inhalation position, the dosing recess (15) is facing the vortex chamber (26) and completely sealed within the vortex chamber (26), the dosing recess (15) having opposing ends positioned along the main axis (X-X), and in the inhalation position, each of the opposing ends of the dosing recess (15) is located next to one of the air inlets (34).

5. The dry powder inhaler according to claim 4, wherein the diameter line (Z-Z) and the main axis line (X-X) connecting the two air inlets (34) divide each other by a second angle (γ) other than 0°.

6. The dry powder inhaler according to claim 4, wherein the deagglomerating device (25) comprises two curved walls (31) having opposite recesses, the two curved walls (31) are staggered to separate the vortex chamber (26) and the two tangential air inlets (34), and a diameter line (Z-Z) and a principal axis line (X-X) passing through the free ends (33) of the curved walls (31) separate a second angle (γ) other than 0° between them.

7. The dry powder inhaler according to claim 5, wherein the diameter line (Z-Z) is parallel to the main axis line (Y-Y), and the first angle (β) is equal to the second angle (γ).

8. The dry powder inhaler according to claim 4, wherein each of the opposing ends of the administration recess (15) is positioned downstream of the air inlet (34) with respect to the air inflow entering from the air inlet (34).

9. The dry powder inhaler according to claim 5, wherein the vortex chamber (26) is configured to form a clockwise air vortex and the main axis (X-X) is rotated clockwise with respect to the diameter line (Z-Z), or the vortex chamber (26) is configured to form a counterclockwise air vortex and the main axis (X-X) is rotated counterclockwise with respect to the diameter line (Z-Z).

10. The dry powder inhaler according to claim 6, wherein, at the inhalation position, the administration recess (15) is contained within a base circle having a diameter (d) given by a segment extending between the free ends (33) of the two curved walls (31).

11. The dry powder inhaler according to claim 1, wherein the edge (27) of the opening (17) of the container (7) is substantially elliptical, or the edge (27) of the opening (17) of the container (7) has two large arched sides and two small straight sides.

12. The dry powder inhaler according to claim 1, wherein the periphery of the administration recess (15) comprises two parallel lines connected by two arcs, and the two parallel lines are parallel to the main axis (X-X), or the periphery of the administration recess (15) is oval or elliptical, and the main axis (X-X) is the major axis of the ellipse.

13. The dry powder inhaler according to claim 1, wherein the administration recess (15) has a capacity for the powder drug of more than 10 mg, optionally more than 15 mg, and optionally 20 mg.

14. The aforementioned administration recess (15) is 20 mm ３ Larger volume than that, optional 20 mm ３ ~40mm ３ The volume, or optionally 25 mm ３ ~35mm ３ A dry powder inhaler according to claim 1, having the volume of [a certain volume].

15. The dry powder inhaler according to claim 1, wherein the administration recess (15) has a length (L) measured along the main axis (X-X) and a width (W) measured perpendicular to the main axis (X-X), and the ratio of L / W is greater than 1 and optionally between 1.4 and 1.

8.

16. The dry powder inhaler according to claim 1, further comprising a protective member (18) provided between the shuttle (16) and the vortex chamber (26), wherein when the shuttle (16) is in the inhalation position, the protective member (18) is slidably movable on or above the shuttle (16) between a closed position and an open position, in the closed position the protective member (18) completely covers the administration recess (15) to prevent communication between the administration recess (15) and the vortex chamber (26), and in the open position the protective member (18) leaves the administration recess (15) exposed to the vortex chamber (26).

17. The dry powder inhaler according to claim 1, comprising the powder drug, wherein the powder drug is a pharmaceutical composition comprising one or more phosphodiesterase-4 (PDE-4) inhibitors selected from the group consisting of tanimilast, shiromilast, roflumilast, tetomimilast, ogremilast, apremilast, picramiralast, and salts thereof.

18. The dry powder inhaler according to claim 17, wherein the pharmaceutical composition comprises Tanimilast.

19. A pharmaceutical composition for use in a method of treating a respiratory disease, wherein the pharmaceutical composition is a powder drug, and the method comprises the step of administering the pharmaceutical composition through a dry powder inhaler according to any one of claims 1 to 18.

20. A pharmaceutical composition for use according to claim 19, comprising one or more phosphodiesterase-4 (PDE-4) inhibitors selected from tanimilast, shiromilast, roflumilast, tetomimilast, ogremilast, apremilast, picramiralast, and salts thereof.

21. The pharmaceutical composition for use according to claim 20, wherein the phosphodiesterase-4 (PDE-4) inhibitor administered is tanimilast.

22. The pharmaceutical composition for use according to claim 19, wherein the method comprises the step of administering a delivery dose of the pharmaceutical composition greater than 10 mg per operation.

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