Dry powder inhaler

Abstract

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

Description

Technical Field

[0001] The present invention relates to a dry powder inhaler, ie a device for dispensing a powdered medicament preparation by inhalation. The device is in particular a portable multi-dose breath-actuated dry powder inhaler without propellant gas, the dry powder inhaler being equipped with a metering device for dispensing a dose delivered from a medicament container. Background Art

[0002] An inhaler is a handheld portable device that delivers medication directly to the lungs. One type of inhaler is a passive dry powder inhaler ("DPI"). A passive DPI is a patient-driven device in which a powder formulation of a medicament is inhaled into the respiratory tract by the action of inhaling through the device. DPIs are recognized as devices that deliver medication to the lungs to treat pulmonary and systemic diseases. DPIs can generally be divided into: i) single-dose (unit dose) inhalers for administering a single dose of active ingredient / active ingredients contained in a capsule or blister that is loaded into the device and pierced by the patient immediately before use; ii) pre-metered multi-dose inhalers, which contain a series of blisters or capsules with active ingredient / active ingredient formulations or iii) reservoir inhalers, which contain a large amount of powder formulation corresponding to multiple doses of active ingredient / active ingredients, and the powder formulation is metered from a storage unit before inhalation.

[0003] Document WO 2004 / 012801 under the same applicant's name discloses a kind of storage inhaler (type iii), it is a dry powder inhaler and comprises a shell with a lower housing and an integral cover that is pivotally connected to this lower housing.The lower housing defines a mouthpiece and the integral cover can move between a closed position and an open position, in which the mouthpiece is sealed and hidden by the integral cover, and in the open position, the mouthpiece is exposed for use.The lower housing accommodates a container for storing powdered medicament, a metering member of a quantitative distribution recess with a certain dose of powdered medicament to be filled and an inhalation passage communicated with the mouthpiece.The quantitative distribution recess is cup-shaped and has a circular edge.The metering member can move between a filling position and an inhalation position, in which the quantitative distribution recess is aligned with the opening of the container, so that a certain dose of powdered medicament is filled by gravity, and in which the quantitative distribution recess is aligned with the vortex chamber that is connected to the inhalation passage, so that a certain dose of powdered medicament included in the quantitative distribution recess can be sucked. The powder inhaler further comprises a protective member which can be slidably moved on the metering member between a closed position in which it covers the dosing recess of the metering member if the metering member is in the inhalation position and an open position in which it exposes the dosing recess, thereby enabling a dose of the powdered medicament contained in the dosing recess to be inhaled. The protective member is coupled to the inhalation-activated mechanism in such a way that the inhalation-activated mechanism moves the protective member from its closed position to its open position if there is an inhalation suction force applied by the user exceeding a predetermined level.

[0004] Documents WO 2016 / 000983 and WO 2021 / 105440 under the name of the same applicant disclose a dry powder inhaler (storage inhaler) similar to the dry powder inhaler of WO2004 / 012801. The applicant's paper "Expert Opin. Drug Deliv. (2014) 11 (9), 1497-1506, Corradi M. et al." also discloses a dry powder inhaler ( DPI).

[0005] The dosing recess of the cited prior art document has a spherical cup shape with rounded edges (in top view) and is typically configured to accommodate a 5 mg to 10 mg dose of powdered medicament. This means that the DPI is configured to deliver such a dose with each inhalation.

[0006] However, it may be desirable to deliver powdered medicaments in doses greater than those delivered by prior art inhalers, for example greater than 10 mg per inhalation.

[0007] The applicant has recognised that for doses above 10 mg, the prior art systems may have some disadvantages and that increasing the rim diameter or height of the spherical cup-shaped dosing recess may mean modifications to other components of the known DPI, which should be redesigned and produced by tailor-made moulds. Summary of the invention

[0008] The object of the present invention is to provide a type iii (reservoir inhaler) dry powder inhaler capable of delivering higher doses than those delivered by the prior art, for example above 10 mg, preferably without changing and / or redesigning most of the components of known DPIs.

[0009] Another object of the present invention is to provide a dry powder inhaler that is capable of delivering larger doses while maintaining or enhancing the delivery efficiency of known DPIs.

[0010] In particular, it is an object of the present invention to provide a dry powder inhaler which allows complete filling of a larger dosing recess with powdered medicament dispensed from a container by gravity.

[0011] Another object of the present invention is to provide a dry powder inhaler which enables complete emptying of the dosing recess and ensures expulsion and delivery of the entire dose through the mouthpiece.

[0012] 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.

[0013] According to a first independent aspect, a dry powder inhaler comprises:

[0014] - a housing having a mouthpiece;

[0015] - an inhalation channel housed in the housing and connected to the mouthpiece;

[0016] - a container received in the housing for storing a powdered medicament, the container having an opening;

[0017] - a deagglomerator having a vortex chamber at the end of the suction channel opposite the mouthpiece;

[0018] a metering device comprising a shuttle device having a dosing recess formed in a surface of the shuttle device, wherein the shuttle device is movable between a filling position, in which the dosing recess is aligned with and faces an opening of the container for filling with a dose of powdered medicament, and an inhalation position, in which the dosing recess is aligned with the vortex chamber and the inhalation channel for enabling the dose of powdered medicament comprised in the dosing recess to be inhaled through the mouthpiece;

[0019] Therein, in top view, the opening of the container is elongated along a respective long axis and the dosing recess is elongated along a respective main axis; wherein the edge of the opening of the container surrounds the dosing recess when the shuttle device is in the filling position.

[0020] The dry powder inhaler (DPI) of the present invention is a reservoir inhaler (type iii) which contains a large amount of powder formulation corresponding to multiple doses of active ingredient / active ingredients, which is metered from a storage unit (container) just before inhalation.

[0021] The shape of the dosing recess according to the invention allows receiving and containing a larger dose of powdered medicament from a container than can be contained in a spherical cup-shaped dosing recess of the prior art.

[0022] The shape of the dosing recess according to the invention allows complete filling of said dosing recess, since no part of the dosing recess is located outside the edge of the opening of the container.

[0023] The invention allows to change only the shape of the dosing recess, ie the mould for the shuttle device, and to keep the other parts of the known DPI unchanged.

[0024] Thus, the present invention allows the manufacture of a DPI capable of delivering larger quantities of powdered medicament by employing most of the same elements of the prior art DPIs and only a limited number of different elements and by fully utilizing existing production lines.

[0025] Other aspects of the invention are disclosed as follows.

[0026] In a second aspect according to aspect 1, the direction of movement of the shuttle device between the filling position and the intake position defines an angle of 90° with the long axis therebetween, and the main axis and the long axis define a first angle other than 0° therebetween.

[0027] In aspect 3 according to aspect 2, the first angle is between 10° and 30°, optionally, the first angle is 20°.

[0028] In a 4th aspect according to any one of the aforementioned aspects 1 to 3, the deagglomerator has two air inlets opening in the vortex chamber, and the two air inlets are arranged on opposite sides of the vortex chamber and along a tangential or substantially tangential inflow direction to form an air vortex in the vortex chamber; in the suction position, the metering recess faces the vortex chamber and is completely enclosed in the vortex chamber; optionally, the metering recess has opposite ends positioned along the main axis, and in the suction position, each of the opposite ends of the metering recess is close to one of the air inlets.

[0029] In a fifth aspect according to aspect 4, a diameter line connecting the two air inlets and the main axis define a second angle therebetween which is not 0°.

[0030] In a 6th aspect according to aspect 4 or 5, the deagglomerator comprises two curved walls having concave cavities facing each other, the two curved walls being staggered with each other and defining a vortex chamber and the two tangential air inlets; optionally, a diameter line passing through the free end of each of the curved walls and the main axis define a second angle between the two that is not 0°.

[0031] In a 7th aspect according to aspect 5 or aspect 6, the diameter line is parallel to the long axis and the first angle is equal to the second angle.

[0032] In an 8th aspect according to any one of the aforementioned aspects 4 to 7, each of the opposite ends of the dosing recess is located downstream of the corresponding air inlet with respect to the intake air entering through the tangential air inlet.

[0033] In aspect 9 according to any one of aspects 5 to 7 or according to aspect 8 when aspect 8 is subordinate to any one of aspects 5 to 7, the vortex chamber is configured to form a clockwise air vortex and the main axis rotates clockwise relative to the diameter line, or the vortex chamber is configured to form a counterclockwise air vortex and the main axis rotates counterclockwise relative to the diameter line.

[0034] In a 10th aspect according to aspect 6 or according to any one of aspects 7 to 9 when aspects 7 to 9 are dependent on aspect 6, in the inhalation position the dosing recess is contained within a base circle having a diameter "d" given by a segment extending between the free ends of the two curved walls.

[0035] In an 11th aspect according to any one of aspects 1 to 10, the edge of the opening of the container is substantially oval or the edge of the opening of the container has two main arcuate sides and two secondary straight sides.

[0036] In the 12th aspect according to any one of aspects 1 to 11, the periphery of the quantitative distribution recess includes two parallel straight lines connected by two arcs, and the two parallel straight lines are parallel to the main axis, or the periphery of the quantitative distribution recess is oval or elliptical, and the main axis is the long axis of the ellipse.

[0037] In a 13th aspect according to any one of aspects 1 to 12, the dosing recess has a capacity of greater than 10 mg, optionally greater than 15 mg, optionally 20 mg, optionally including between 20 mg and 30 mg of powdered medicament.

[0038] In a 14th 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; optionally the ratio L / W is greater than 1, optionally between 1.4 and 1.8, such as 1.6.

[0039] In a 15th aspect according to any one of aspects 1 to 14, a protective member is arranged between the shuttle device and the vortex chamber; when the shuttle device is in the suction position, the protective member can be slidably moved on or above the shuttle device between a closed position and an open position; in the closed position, the protective member completely covers the metering recess and prevents communication between the metering recess and the vortex chamber; in the open position, the protective member exposes the metering recess to the vortex chamber.

[0040] When the shuttle device is in the inhalation position and the protective member is in the open position, the shape of the dosing recess and its position relative to the vortex chamber ensure that the dosing recess is completely emptied so that a dose of powdered medicament contained in the dosing recess is entrained by the air flow and guided to the mouthpiece through the inhalation channel.

[0041] In the 16th aspect according to aspect 6 or aspect 10, each curved wall is a circumferential arc, optionally a semi-circumferential arc.

[0042] 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, optionally, the width "p" is d / 5.

[0043] In an 18th aspect according to aspect 10 or aspect 17, when the shuttle device 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, optionally, the first minimum distance "s1" is d / 10.

[0044] In a 19th aspect according to one or more of the preceding aspects 6, 10, 17 or 18, the deagglomerator comprises a base wall having a through hole for receiving the powdered medicament from the dosing recess when the shuttle device is in the inhalation position.

[0045] In a 20th aspect according to the preceding aspect, the two curved walls extend from the base wall and surround or define the through hole.

[0046] In the 21st aspect according to one or more of the aforementioned aspects 6, 10 or 17 to 20, an end of the suction passage opposite to the mouthpiece is placed close to or between the two curved walls.

[0047] In aspect 22 according to one or more of aspects 6, 10 or 17 to 21, each of the two curved walls has a radius "R", the two curved walls have respective centers, and the centers are staggered by a distance "Δ"; optionally, each center is on a diameter line.

[0048] In the 23rd aspect according to the aforementioned aspect when the aforementioned aspect is dependent on aspect 17, given the thickness "t" of the curved wall: Δ=t+p and d=2R-Δ.

[0049] In a 24th aspect according to one or more of the preceding aspects, the suction channel and the swirl chamber share a common central axis.

[0050] In the 25th aspect according to aspect 11 or according to aspect 12 when aspect 12 is dependent upon aspect 11, the two minor straight sides of the edge of the opening are parallel to the movement direction of the shuttle device.

[0051] In a 26th aspect according to aspect 12, the two arcs of the periphery of the dosing recess define opposite ends of the dosing recess.

[0052] In aspect 27 according to aspect 12 or according to aspect 26 when aspect 12 is dependent on aspect 10, when the shuttle device is in the filling position, the second minimum distance "s2" between the periphery of the dosing recess and the edge of the opening of the container is between d / 12 and d / 8, optionally, the second minimum distance "s2" is d / 10.

[0053] In a 28th aspect according to aspect 14, the length L is between 8 mm and 12 mm.

[0054] In aspect 29 according to aspect 14 or aspect 28, the width W is between 4 mm and 6 mm.

[0055] In a 30th aspect according to the aforementioned aspect 10 and aspect 14, the ratio L / d is between 0.8 and 0.95, optionally 0.9.

[0056] In the 31st aspect according to the aforementioned aspects 10 and 14 or according to aspect 30, the ratio W / d is between 0.4 and 0.8, optionally 0.6.

[0057] In a 32nd aspect according to any one of the preceding aspects, the container comprises a medicament chamber storing or configured to store a powdered medicament and having said opening.

[0058] In a 33rd aspect according to the preceding aspect, the medicament chamber is at least partially shaped like a hopper converging toward the opening.

[0059] In a 34th aspect according to aspect 32 or aspect 33, the container comprises a desiccant chamber storing or configured to store a desiccant.

[0060] In a 35th aspect according to the preceding aspect, the permeable membrane separates the desiccant chamber from the drug chamber.

[0061] In the 36th aspect according to aspect 15, the protection member is a plate.

[0062] In a 37th aspect according to aspect 15 or aspect 36, the width of the protection member measured along the long axis is greater than the dimension of the dosing recess measured along the long axis.

[0063] In aspect 38 according to aspect 15 or aspect 36 or aspect 37, the inhalation-activated mechanism is connected to the protective member and is configured to move the protective member from its closed position to its open position if there is an inhalation suction force applied by the user through the mouthpiece exceeding a predetermined level.

[0064] In aspect 39 according to the preceding aspects, the suction-actuated mechanism comprises: an suction-actuated member, which is optionally shaped like a wing; a connecting member; and an elastic element arranged on the connecting member; the suction-actuated member is connected to the protective member via the connecting member, so that if there is an inhalation suction force exceeding a predetermined value, the suction-actuated member moves from a first position to a second position, thereby causing the protective member to move from a closed position to an open position.

[0065] In a 40th aspect according to any one of the preceding aspects, the dry powder inhaler further comprises a powdered medicament.

[0066] In a 41st aspect according to any one of the preceding aspects, the dry powder inhaler further comprises a cover engageable with the housing to close the mouthpiece.

[0067] In aspect 42 according to the preceding aspects, the shuttle device is mechanically connected to the cover so that opening of the cover beyond the range of rotational movement from the closed position causes the shuttle device to move from the filling position to the intake position, and closing of the cover causes the shuttle device to move from the intake position back to the filling position.

[0068] In a 43rd aspect according to any one of the preceding aspects, except for the shape and size of the metering recess, the dry powder inhaler is the same or similar to the device disclosed in WO 2004 / 012801 or WO 2016 / 000983 or WO 2021 / 105440 or the paper "Expert Opin. Drug Deliv. (2014) 11 (9), 1497-1506, Corradi M. et al."

[0069] In a 43rd aspect according to any one of the preceding aspects, the powdered medicament is a pharmaceutical composition.

[0070] In a 44th aspect according to the preceding aspects, the pharmaceutical composition comprises one or more phosphodiesterase-4 (PDE-4) inhibitors.

[0071] In a 45th aspect according to the previous aspects, the phosphodiesterase-4 (PDE-4) inhibitor is selected from the group consisting of tanimilast, cilomilast, roflumilast, tetomilast, olemide, apremilast, piramidolast and salts thereof.

[0072] In a 46th aspect according to aspect 43 or aspect 44, the pharmaceutical composition comprises tanimilast or the administered phosphodiesterase-4 (PDE-4) inhibitor is tanimilast.

[0073] According to a 47th aspect, a method of treating a respiratory disease comprises administering a dose delivered by an inhaler according to any one of the preceding aspects.

[0074] In a 48th aspect according to the preceding aspects, the delivered dose is greater than 10 mg.

[0075] In a 49th aspect according to aspect 47 or aspect 48, the delivered dose is a pharmaceutical composition.

[0076] In a 50th aspect according to the preceding aspects, the pharmaceutical composition comprises one or more phosphodiesterase-4 (PDE-4) inhibitors.

[0077] In a 51st aspect according to the previous aspects, the phosphodiesterase-4 (PDE-4) inhibitor is selected from tanimilast, cilomilast, roflumilast, tetomilast, olemide, apremilast, piramidolast and salts thereof.

[0078] In aspect 52 according to aspect 49 or aspect 50, the pharmaceutical composition comprises tanimilast or the administered phosphodiesterase-4 (PDE-4) inhibitor is tanimilast.

[0079] Aspect 53 relates to use of the inhaler according to any one of Aspects 1 to 46 for treating respiratory diseases.

[0080] In a 54th aspect according to aspect 52 or aspect 53, the powdered medicament comprises tanimilast.

[0081] Aspect 55 relates to a pharmaceutical composition for use in a method of treating a respiratory disease, wherein the pharmaceutical composition is a powdered medicament and wherein the method comprises administering the pharmaceutical composition through an inhaler according to any one of aspects 1 to 46 above.

[0082] In aspect 56 according to aspect 55, the pharmaceutical composition comprises one or more phosphodiesterase-4 (PDE-4) inhibitors selected from tanimilast, cilomilast, roflumilast, tetomilast, olemide, apremilast, piramidolast and salts thereof.

[0083] In a 57th aspect according to aspect 56, the phosphodiesterase-4 (PDE-4) inhibitor administered is tanimilast.

[0084] In a 58th aspect according to any one of aspects 55 to 57, the method comprises administering a delivered dose of the pharmaceutical composition greater than 10 mg per actuation.

[0085] In a 59th aspect according to any one of the preceding aspects, the dosing recess has a diameter greater than 10 mm. 3 , optionally greater than 20mm 3 , optionally larger than 25mm 3 The dosing recess may have a volume of 10 mm 3 Up to 50mm 3 , optionally 20mm 3 Up to 40mm 3 or optionally 25mm 3 Up to 35mm 3 The volume.

[0086] Further features and advantages will become clear from the detailed description of a preferred but non-exclusive embodiment of a dry powder inhaler according to the invention. BRIEF DESCRIPTION OF THE DRAWINGS

[0087] Figure 1 shows a 3D view of a dry powder inhaler in an open configuration according to the present invention;

[0088] Figure 2A , Figure 2B and Figure 2C are in different states Figure 1 A cross-sectional view of a dry powder inhaler;

[0089] Figure 3 yes Figure 1 An exploded view of some of the components of the dry powder inhaler;

[0090] Figure 4 Shows Figure 3 A 3D view of one of the components;

[0091] Figure 5A and Figure 5B are in different states Figure 4 A top view of a component;

[0092] Figure 6 Shows Figure 3 a 3D top view of another component;

[0093] Figure 7 Shows Figure 6 3D bottom view of the component;

[0094] Figure 8 Shows Figure 6 a cross-sectional view of a component;

[0095] Fig. 9 yes Figure 5B an enlarged top view of a portion of;

[0096] Fig.10 yes Figure 5A An enlarged top view of another part of the device. DETAILED DESCRIPTION

[0097] With reference to the accompanying drawings, Figure 1 , Figure 2A , Figure 2B , Figure 2C An embodiment of a dry powder inhaler 1 according to the present invention is shown. These non-limiting examples of dry powder inhalers 1 may be similar to the inhalers disclosed in documents WO 2004 / 012801, WO 2016 / 000983 and WO 2021 / 105440 or the paper "Expert Opin. Drug Deliv (2014) 11 (9), 1497-1506, Corradi M. et al." by the same applicant.

[0098] The dry powder inhaler 1 comprises a housing 2 and a cover 3 pivotally or rotatably coupled to the housing 2. Figure 1As can be seen in FIG. 2 , the cover 3 can be opened to reveal a mouthpiece 4 through which a user can inhale a powdered medicament. At the front upper side of the mouthpiece 4, an inhalation opening 5 is formed in the housing 2.

[0099] The housing 2 is a closed shell made of thermoplastic material (e.g., ABS and polycarbonate) and includes lateral sides, an upper side, and a lower side (relative to the Figure 1 , FIG. 2A to FIG. 2C Orientation of the powder inhaler 1 (upper and lower).

[0100] The mouthpiece 4 protrudes from the upper side and has the outer shape of a truncated cone tapering towards an opening 6 formed in the top part (smaller base) of the mouthpiece 4 .

[0101] The cover 3 is hinged to the housing 2 and can be Figure 2A The closed position shown and Figure 1 , Figure 2B and Figure 2C The cover 3 can be rotated between an open position shown, in which the cover 3 surrounds the mouthpiece 4, and an open position in which the cover 3 is spaced apart from the mouthpiece 4 to expose the mouthpiece 4 for use.

[0102] The powder inhaler 1 comprises a container 7 for storing a powdered medicament, an inhalation channel 8 connected to an opening 6 of a mouthpiece 4, and a dispensing device 9 (FIG. 2). The inhalation channel 8 has a first opening connected to the mouthpiece 4 and a second opening opposite to the first opening. All these elements are part of a subassembly 10 housed in the housing 2, such as Figure 3 shown.

[0103] like FIG. 2A to FIG. 2C As shown, container 7 is a container with an integrated desiccant.

[0104] The container 7 includes a medicine chamber 11 storing a powdered medicine and a desiccant chamber 12 storing a desiccant for absorbing moisture that may have entered the medicine chamber 11 .

[0105] The desiccant chamber 12 is separated from the medicament chamber 11 by a separate permeable membrane 13. The permeability of the permeable membrane 13 is different from the permeability of the desiccant or medicament to the external environment. The permeability of the membrane 13 can be achieved, for example, by making it from a different material from the body of the container 7 and / or making it have a thinner section than the body of the container. The foil can be used to seal both the medicament chamber 11 and the desiccant chamber 12. The container 7, in particular the medicament chamber 11, is filled with or configured to be filled with a certain amount of powdered medicament corresponding to a plurality of doses (e.g., up to 100 doses to 200 doses). For example, the powdered medicament is a pharmaceutical composition.

[0106] The desiccant is contained 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 or includes a molecular sieve made of a material having pores of uniform size, such as an alkaline salt of an aluminosilicate (called a zeolite) or an aluminophosphate or porous glass or activated carbon or an artificial zeolite. The molecular sieve is configured to absorb small molecules, such as water molecules. The desiccant can also be silica gel.

[0107] The dispensing device 9 comprises a metering device 14 having a dosing recess 15. The metering device 14 shown in the figures comprises a shuttle 16 which is shaped like a plate and is provided with said dosing recess 15 formed in the face of the shuttle 16.

[0108] The dispensing device 9 can be in an idle state ( Figure 2A ) and the trigger state ( Figure 2C ), in the idle state, the dosing recess 15 is connected to the opening 17 of the container 7 so as to be filled with a certain dose of powdered medicine, and in the triggered state, the dosing recess 15 is connected to the inhalation channel 8 so as to enable the certain dose of powdered medicine contained in the dosing recess 15 to be inhaled through the mouthpiece 4.

[0109] The medicament chamber 11 is at least partially formed as a hopper having walls converging toward the opening 17, such as Figure 2A , Figure 2B , Figure 2C , Figure 3 and Figure 5.

[0110] The shuttle 16 is placed between the subassembly 10 and the base wall of the housing 2. The shuttle 16 is shaped like a plate made of a single piece of plastic, such as acrylonitrile butadiene styrene (ABS).

[0111] The shuttle device 16 can be moved along the direction of movement F in the filling position ( Figure 2A ) and suction position ( Figure 2B and Figure 2C ). The filling position corresponds to an idle state of the metering device 14, wherein the dosing recess 15 is aligned with and faces the opening 17 of the container 7 so as to be filled with a dose of the powdered medicament. The inhalation position corresponds to a standby state ( Figure 2B ) and the trigger state ( Figure 2C ), wherein the metering recess 15 is aligned with the intake channel 8.

[0112] The shuttle 16 is mechanically coupled to the lid 3 so that opening of the lid 3 beyond the rotational motion range from the closed position causes the shuttle 16 to move from the filling position to the suction position. Closing of the lid 3 causes the shuttle 16 to move back from the suction position to the filling position.

[0113] like Figure 2A , Figure 2B and Figure 2C As shown, the spring 36 is interposed between the base wall of the housing 2 and the shuttle 16 and is configured to push the shuttle 16 against the opening 17 of the container 7 when the shuttle 16 is in the filling position. When the shuttle 16 moves between the filling position and the suction position, the shuttle slides relative to the spring 36.

[0114] The metering device 14 further includes a protective member 18 disposed between the shuttle device 16 and the suction channel 8. The protective member 18 is a plate disposed between the second opening of the suction channel 8 and the shuttle device 16. The protective member 18 is parallel to the shuttle device 16 and is slidably movable on or above the shuttle device 16 between a closed position and an open position.

[0115] In the closed position, the protective member 18 moves backwards towards the second opening of the suction channel 8 and towards the container 7. In the closed position, the rear part of the protective member 18 can at least partially close the second opening of the suction channel 8. In the open position, the protective member 18 moves forwards towards the wall of the housing 2. In the open position, the rear part of the protective member 18 opens the second opening of the suction channel 8. When the shuttle device 16 is in the filling position ( Figure 2A ), the protective member 18 is in the closed position. When the shuttle device 16 is in the suction position ( Figure 2B and Figure 2C ), the protective member 18 can be moved between a closed position and an open position.

[0116] The metering device 14 is therefore configured to assume the three different states described above (idle, standby, triggered), and these states are determined by the positions of the shuttle device 16 and the protective member 18 .

[0117] In idle state ( Figure 2A ), the shuttle device 16 is in the filling position and the protective member 18 is in the closed position. The protective member 18 does not cover the dosing recess 15. The dosing recess 15 is connected to the opening of the container 7 to receive the dose of the medicament. In the standby state ( Figure 2B), the shuttle device 16 is in the inhalation position and the protective member 18 is in the closed position. The protective member 18 covers the dosing recess 15. In the case where the powder inhaler 1 in the tilted position before the inhalation maneuver rotates or moves or if the user blows into the mouthpiece 4, the protective member 18 prevents the powdered medicament contained in the dosing recess 15 from entering the inhalation channel 8 and preventing the powdered medicament from being lost. In the triggered state ( Figure 2C ), the shuttle device 16 is in the inhalation position and the protective member 18 is in the open position. The protective 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 a dose of the powdered medicament contained in the dosing recess 15.

[0118] The dispensing device 9 also includes a breathing or inhalation-activated mechanism 19 ( Figure 2A , Figure 2B , Figure 2C ). The inhalation-activated mechanism 19 comprises a flap-shaped inhalation-activated member 20 , a coupling member 21 and an elastic element 22 (spring) arranged on the coupling member 21 .

[0119] The flap 20 is coupled to the protective member 18 by a coupling member 21 so that if there is an inhalation suction exceeding a predetermined value, the flap 20 moves from the first position to the second position, thereby causing the protective member 18 to move from the closed position to the open position. The flap 20 is placed inside the housing 2 and close to the suction opening 5. In the first position ( Figure 2A ), the fin 20 separates the inhalation opening 5 from the inhalation channel 8 and is located in the main airflow path. If the user blows into the device, the fin 20 provides resistance, thereby giving positive feedback. In the second position ( Figure 2C ), the flap 20 rotates relative to the first position to open the suction opening 5 and allow air to flow through the suction opening 5 into the suction channel 8 and out of the mouthpiece 4. The elastic element 22 is arranged so that it holds the flap 20 in its first position. When the shuttle device 16 is pushed forward by opening the cover 3, the elastic element 22 is compressed and loaded, and the restoring force exerted on the flap 20 is released, so that if there is a sufficiently high suction suction in the suction channel 8, the flap 20 can be pivoted or rotated from the first position to the second position pivoted downward relative to the first position.

[0120] The flap 20 is hinged to the housing 2 for rotation between a first position and a second position about a respective rotation axis substantially perpendicular to the main axis AA of the suction channel 8. The coupling member 21 is also hinged to the housing 2 for rotation between a respective first position and a second position about a respective rotation axis substantially perpendicular to the main axis AA of the suction channel 8.

[0121] The coupling member 21 includes an arm (not shown) that projects toward the flap 20 and engages with the flap 20 such that clockwise rotation of the flap 20 from the first position to the second position causes the coupling member 21 to rotate counterclockwise from its respective first position toward its respective second position.

[0122] The coupling member 21 includes an extension 23 that engages with an opening formed in the protective member 18 to move the protective member 18 from the closed position to the open position when the coupling member 21 moves from its respective first position to its respective second position, and vice versa.

[0123] The extension 23 of the connecting member 21 is also movably arranged in a longitudinal opening 24 formed in the shuttle device 16 along the longitudinal direction of the shuttle device, so that the extension 23 can move freely in the longitudinal opening 24, and the movement of the shuttle device 16 from the suction position to the filling position causes the extension 23 of the connecting member 21 to abut against the edge of the longitudinal opening 24, thereby moving the connecting member 21 back to its initial first position.

[0124] The dry powder inhaler 1 further comprises a deagglomerator 25 which is coupled to a second end of the inhalation channel 8 opposite to the mouthpiece 4. The deagglomerator 25 is also part of the subassembly 10.

[0125] The deagglomerator 25 defines a vortex chamber 26 and is configured such that it generates a cyclonic airflow resulting in a strong velocity gradient. The protective member 18 is slidable on the shuttle device 16 between its closed position, in which it covers the dosing recess 15, and its open position, in which, when the metering member 14 is in the inhalation position, the protective member exposes the dosing recess 15 to the deagglomerator 25 and the inhalation channel 8, so that a dose of the powdered medicament can be inhaled through the deagglomerator 25 and the inhalation channel 8 and the mouthpiece 4.

[0126] The powder inhaler 1 may further comprise a dose counting unit (not shown in the embodiment of the drawings) contained in the housing 2 and coupled to the inhalation-activated mechanism 19 and the closure of the cap 3 after an effective inhalation has taken place. The housing 2 may further comprise a window or opening for displaying the number of doses taken or the number of doses remaining in the container 7, which number is counted by the dose counting unit.

[0127] like Figure 5A , Figure 5B and Fig. 9 As shown in the top view of , the opening 17 of the container 7 is elongated along the long axis YY, and the long axis YY is perpendicular to the movement direction F of the shuttle device 16. In other words, the opening 17 has a size measured along the long axis, which is greater than the size measured along the movement direction F of the shuttle device 16.

[0128] The edge 27 of the opening 17 lies in a plane parallel to the face of the shuttle 16 in which the dosing recess 16 is formed ( Figure 3 , Figure 5A , Figure 5B , Fig. 9 ). The edge 27 is formed by two main arched sides 17a and two secondary straight sides 17b. The two secondary straight sides 17b have the same length and are parallel to the movement direction F of the shuttle device 16. Each of the two main arched sides 17a connects the ends of the two secondary straight sides 17b. The two main arched sides 17a have concave cavities facing each other. The edge 27 of the opening 17 looks like an oval with a truncated end.

[0129] In other embodiments not shown, the edge 27 of the opening 17 may be elliptical or substantially elliptical.

[0130] The deagglomerator 25 includes a housing 28 having a side wall 29 and a base wall 30 (see Figure 3 ), and the vortex chamber 26 is defined inside the housing 28.

[0131] like Figure 4 , Figure 5A , Figure 5B and Fig.10 As shown, the deagglomerator 25 comprises two curved walls 31 protruding from the base wall 30 of the subassembly 10. The two curved walls 31 have concave cavities facing each other and define the vortex chamber 26. Each curved wall 31 has a thickness t and is shaped as a semicircle with a radius R. The centers of the two curved walls 31 are located on a common diameter line ZZ and are offset from each other by a distance Δ( Fig.10 ). The diametrical line ZZ is perpendicular to the direction of movement F of the shuttle device 16 and is therefore parallel to the long axis YY.

[0132] The two curved walls 31 extend from the base wall 30 and surround or define a through hole 32 ( Figure 2A , Figure 2B , Figure 2C ).

[0133] Each of the two curved walls 31 has an end connected to the respective side wall 29 and an opposite free end 33. The diameter d given by the segment extending between the free ends 33 of the two curved walls 31 can be considered as the diameter of the vortex chamber 26.

[0134] Each free end 33 and the adjacent side wall 29 define an air inlet 34 opening in the vortex chamber 26. The two air inlets 34 are arranged on opposite sides of the vortex chamber and along a tangential or substantially tangential inflow direction to form an air vortex in the vortex chamber 26. In other words, the airflow entering through each of the two air inlets 33 is directed tangentially relative to a circle centered at the vortex chamber 26.

[0135] The width p of each air inlet 34 measured along the section 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.

[0136] The relationship between radius R, distance Δ, width p, diameter d and thickness t is as follows:

[0137] Δ=t+p

[0138] d=2R-Δ

[0139] The hollow portion 35 defined between the side wall 29 and the radially outer surface of the two curved walls 31 may be in fluid communication with the air inlet opening 5 via the breath- or inhalation-actuated mechanism 19 .

[0140] like Figure 2A , Figure 2B and Figure 2C As shown, the second end of the suction channel 8 opposite the mouthpiece 4 is placed between said two curved walls 31 and opens into the vortex chamber 26. The suction channel 8 and the vortex chamber 26 share a common central axis.

[0141] When the user applies an inhalation suction force exceeding a predetermined value, the protective member 18 moves from the closed position to the open position. In the open position, the protective member 18 exposes the dosing recess 15 to the vortex chamber 26. The air flows through the inhalation opening 5, enters the hollow portion 35, passes through the air inlet 34, enters the vortex chamber 26, then enters the inhalation channel 8 and flows out of the mouthpiece 4. A dose of powdered medicament contained in the dosing recess 15 is entrained in the rotating airflow and is guided to the mouthpiece 4 through the inhalation channel 8.

[0142] As is apparent from the above, the internal mechanism and functions of the powder inhaler 1 disclosed above may be substantially the same as those of the powder inhalers disclosed in documents WO 2004 / 012801, WO 2016 / 000983 or WO 2021 / 105440 of the same applicant.

[0143] The main differences with respect to these documents are the shape, size and positioning of the dosing recess 15, as will be described in detail below.

[0144] According to the present invention, Figure 5A , Figure 5B , Figure 6 and Fig. 9 As shown in the top view of , the dosing recess 15 does not have a circular periphery. In contrast, the dosing recess 15 of the present invention is elongated along the corresponding main axis XX. The dosing recess 15 can be cup-shaped.

[0145] The shape of the periphery of the quantitative dispensing recess 15 can be oval or elliptical, and the main axis XX is the long axis of the ellipse. Fig. 9 As shown, the perimeter of the dosing recess 15 comprises two parallel straight lines connected by two arcs, and the two parallel straight lines are parallel to the main axis XX. The two arcs of the perimeter of the dosing recess 15 define opposite ends of the dosing recess 15 located along the main axis XX. The dosing recess has a length L measured along the main axis XX and a width W measured perpendicular to the main axis XX, and the ratio L / W is greater than 1, preferably between 1.4 and 1.8, for example 1.6.

[0146] Furthermore, the major axis XX and the major axis YY define therebetween a first angle β which is different from 0°. The first angle β may be about 20°.

[0147] The perimeter of the dosing recess 15 is dimensioned such that when the shuttle device 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 perimeter of the dosing recess 15 is surrounded by or enclosed within the edge 27 of the opening 17, such as Fig. 9 As shown. In this way, the metering recess 15 is completely filled with the powdered medicine flowing out from the opening 17.

[0148] This shape of the dosing recess 15 allows receiving and accommodating a larger dose of powdered medicament from the opening 17 of the container 7 than the dose contained in the spherical cup-shaped dosing recess of the prior art. For example, the length L is between 8 mm and 12 mm, the width W is between 4 mm and 6 mm, and the capacity of the dosing recess 15 according to the present invention is greater than 15 mg and is, for example, 20 mg. For example, the dosing recess 15 may have a length greater than 20 mm. 3 Volume, for example, about 30 mm 3 or about 32mm 3 The volume.

[0149] In the inhalation position and when the protective member 18 is in the open position, the dosing recess 15 faces the vortex chamber 26 and is completely located in the vortex chamber 26. In particular, the dosing recess 15 is contained within a base circle having a diameter d ( Fig.10). The diameter line ZZ passing through the free end 33 of each of the curved walls 31 and connecting the two air inlets 34 defines with the main axis XX a second angle γ which is equal to the first angle β, ie not 0°, for example equal to 20°.

[0150] Each of the opposite ends of the dosing recess 15 is adjacent to one of the air inlets 34 and is located downstream of the corresponding air inlet 34 relative to the air entering through the tangential air inlet 34. In the illustrated embodiment, the vortex chamber 26 is configured to form a clockwise air vortex, and the main axis XX is rotated clockwise by a second angle γ relative to the diameter line ZZ. In other embodiments not shown, the vortex chamber 26 can be configured to form a counterclockwise air vortex and the main axis XX will rotate counterclockwise relative to the diameter line ZZ.

[0151] When the shuttle device 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. Fig.10 , the first minimum distance s1 is measured along the diameter line ZZ.

[0152] When the shuttle 16 is in the filling position, a 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.

[0153] The ratio L / d is between 0.8 and 0.95, for example 0.9 and the ratio W / d is between 0.4 and 0.8, for example 0.6. Fig. 9 In the embodiment of the present invention, the second minimum distance s2 is between one of the two main arcuate sides 17 a of the edge 27 and one of the two arcs of the periphery of the dosing recess 15 .

[0154] When the shuttle device 16 is in the inhalation position and the protective member 18 is in the open position, the shape and position of the dosing recess 15 relative to the vortex chamber 26 ensure that the dosing recess 15 is completely emptied due to the rotation of air in the vortex chamber 26. The elongated shape of the dosing recess 15 and its relative position relative to the air inlet 34 of the vortex chamber 26 allow all the powdered medicament to be collected from the dosing recess 15 and delivered into the inhalation channel 8.

[0155] In addition, the width of the protective member 18 measured along the long axis YY is greater than the size of the metering dispensing recess 15 measured along the long axis YY, and the length of the protective member 18 measured along the movement direction F is greater than the size of the metering dispensing recess 15 measured along the movement direction F, so as to prevent any powdered medicine from leaking from the metering dispensing recess 15 before inhalation.

[0156] The dry powder inhaler 1 according to the invention can be used with all pharmaceutical compositions that can be dispensed by a DPI in a delivered dose greater than 10 mg per actuation.

[0157] In particular, the dry powder inhaler 1 according to the present invention may be used for the treatment of respiratory diseases, where a delivered dose of the pharmaceutical composition of more than 10 mg per actuation is required.

[0158] In a preferred embodiment, the powdered medicament stored in the container 7 of the dry powder inhaler 1 according to the present invention is a pharmaceutical composition comprising one or more phosphodiesterase-4 (PDE-4) inhibitors or other suitable active ingredients selected from the group consisting of tanimilast, cilomilast, roflumilast, tetomilast, olemide, apremilast, piramidolast and salts thereof. In a more preferred embodiment, the powdered medicament is a pharmaceutical composition comprising tanimilast.

[0159] Reference numerals

[0160] Powder inhaler1

[0161] Shell 2

[0162] Cover 3

[0163] Mouth Part 4

[0164] Air intake opening 5

[0165] Mouth opening 6

[0166] Container 7

[0167] Suction channel 8

[0168] Dispensing device 9

[0169] Subassembly 10

[0170] Pharmacy 11

[0171] Drying room 12

[0172] Permeable membrane 13

[0173] Metering device 14

[0174] Ration recess 15

[0175] Shuttle device 16

[0176] Opening of container 17

[0177] Main arch side 17a

[0178] Secondary straight side 17b

[0179] Protection member 18

[0180] Breathing or inhalation actuated mechanism 19 Inhalation actuated member or flap 20 Coupling member 21

[0181] Elastic element 22

[0182] Extension 23

[0183] Longitudinal opening 24

[0184] Depolymerizer 25

[0185] Vortex chamber 26

[0186] Edge of opening 27

[0187] Housing 28

[0188] Sidewall 29

[0189] Base wall 30

[0190] Two arc-shaped walls 31

[0191] Through hole 32

[0192] The free end 33 of the side wall has an air inlet 34

[0193] Hollow part 35

[0194] Spring 36

[0195] Movement direction of the shuttle device F

[0196] Long axis YY

[0197] Main axis XX

[0198] The first angle β

[0199] The second angle γ

[0200] Distance Δ

[0201] The first minimum distance s1

[0202] The second minimum distance s2

Claims

1. A dry powder inhaler, comprising: - a housing (2) having a mouthpiece (4); - an inhalation channel (8) housed in the housing (2) and connected to the mouthpiece (4); - a container (7) received in the housing (2) for storing a powdered medicament, the container (7) having an opening (17); - a deagglomerator (25) having a vortex chamber (26) located at the end of the suction channel (8) opposite the mouthpiece (4); a metering device (14) comprising a shuttle device (16) having a metering recess (15) formed in a face of the shuttle device (16), wherein the shuttle device (16) is movable between a filling position, in which the metering recess (15) is aligned with and faces the opening (17) of the container (7) for filling with a dose of powdered medicament, and an inhalation position, in which the metering recess (15) is aligned with the vortex chamber (26) and the inhalation channel (8) for enabling the dose of powdered medicament contained in the metering recess (15) to be inhaled through the mouthpiece (4); wherein, in a top view, the opening (17) of the container (7) is elongated along a corresponding long axis (YY), and the dosing recess (15) is elongated along a corresponding main axis (XX); wherein, when the shuttle device (16) is in the filling position, the edge (27) of the opening (17) of the container (7) surrounds the dosing recess (15).

2. The inhaler according to claim 1, characterized in that The direction (F) of movement of the shuttle device (16) between the filling position and the suction position defines an angle of 90° with the main axis (YY) therebetween, and wherein the main axis (XX) defines a first angle (β) with the long axis (YY) therebetween which is not 0°.

3. The inhaler according to claim 2, characterized in that The first angle (β) is between 10° and 30°.

4. The inhaler according to any one of claims 1 to 3, characterized in that The deagglomerator (25) has two air inlets (34) opening into the vortex chamber (26), the two air inlets (34) being arranged on opposite sides of the vortex chamber (26) and along a tangential or substantially tangential inflow direction to form an air vortex in the vortex chamber (26); wherein, in the suction position, the metering recess (15) faces the vortex chamber (26) and is completely enclosed in the vortex chamber (26); wherein the metering recess (15) has opposite ends positioned along the main axis (XX); wherein, in the suction position, each of the opposite ends of the metering recess (15) is close to one of the air inlets (34).

5. The inhaler according to claim 4, characterized in that A diametric line (ZZ) connecting the two air inlets (34) and the main axis (XX) defines a second angle (γ) therebetween which is different from 0°.

6. The inhaler according to claim 4, characterized in that The deagglomerator (25) comprises two curved walls (31) with concave cavities facing each other, the two curved walls (31) are staggered with each other and define the vortex chamber (26) and the two tangential air inlets (34); wherein a diameter line (ZZ) passing through the free end (33) of each of the curved walls (31) and the main axis (XX) define between them a second angle (γ) that is not 0°.

7. The inhaler according to claim 5 or 6, characterized in that The diametrical line (ZZ) is parallel to the long axis (YY) and the first angle (β) is equal to the second angle (γ).

8. An inhaler according to any one of claims 4 to 7, characterized in that Each of the opposite ends of the dosing recess (15) is located downstream of the corresponding air inlet (34) with respect to the intake air entering through the air inlet (34).

9. An inhaler according to any one of claims 5 to 7, or according to claim 8 when it is dependent on any one of claims 5 to 7, characterized in that The vortex chamber (26) is configured to form a clockwise air vortex and the main axis (XX) rotates clockwise relative to the diameter line (ZZ); or, wherein the vortex chamber (26) is configured to form a counterclockwise air vortex and the main axis (XX) rotates counterclockwise relative to the diameter line (ZZ).

10. The inhaler according to claim 6, characterized in that In the inhalation position, the dosing recess (15) is contained within a base circle, the diameter (d) of which is given by the segment extending between the free ends (34) of the two curved walls (31).

11. The inhaler according to any one of claims 1 to 10, characterized in that The edge (27) of the opening (17) of the container (7) is substantially elliptical; or wherein the edge (27) of the opening (17) of the container (7) has two main arched sides and two secondary straight sides.

12. An inhaler according to any one of claims 1 to 11, characterized in that The periphery of the dosing recess (15) comprises two parallel straight lines connected by two arcs, the two parallel straight lines being parallel to the main axis (XX); or wherein the periphery of the dosing recess (15) is oval or elliptical and the main axis (XX) is the long axis of the ellipse.

13. An inhaler according to any one of claims 1 to 12, characterized in that The dosing recess (15) has a capacity of more than 10 mg, optionally more than 15 mg, optionally 20 mg of powdered medicament.

14. An inhaler according to any one of claims 1 to 13, characterized in that The quantitative dispensing recess (15) has a diameter greater than 20 mm. 3 , optionally 20mm 3 Up to 40mm 3 , or optionally 25mm 3 Up to 35mm 3 The volume.

15. An inhaler according to any one of claims 1 to 14, characterized in that The dosing recess (15) has a length (L) measured along the main axis (XX) and a width (W) measured perpendicular to the main axis (XX); wherein the ratio L / W is greater than 1, optionally between 1.4 and 1.

8.

16. An inhaler according to any one of claims 1 to 15, further comprising a protective member (18) arranged between the shuttle device (16) and the vortex chamber (26); when the shuttle device (16) is in the inhalation position, the protective member (18) can slide on or above the shuttle device (16) between a closed position and an open position; characterized in that In the closed position, the protective member (18) completely covers the dosing recess (15), thereby preventing communication between the dosing recess (15) and the vortex chamber (26); wherein, in the open position, the protective member (18) exposes the dosing recess (15) to the vortex chamber (26).

17. An inhaler according to any one of claims 1 to 16, containing a powdered medicament, characterized in that The powdered medicine is a pharmaceutical composition comprising one or more phosphodiesterase-4 (PDE-4) inhibitors selected from the group consisting of tanimilast, cilomilast, roflumilast, tetomilast, olemide, apremilast, piramidolast and salts thereof.

18. The inhaler according to claim 17, characterized in that The pharmaceutical composition includes tanimilast.

19. A pharmaceutical composition for use in a method for treating a respiratory disease, characterized in that: The pharmaceutical composition is a powdered medicament and wherein the method comprises administering the pharmaceutical composition via an inhaler according to any one of claims 1 to 18.

20. The pharmaceutical composition for use according to claim 19, characterized in that The pharmaceutical composition comprises one or more phosphodiesterase-4 (PDE-4) inhibitors selected from tanimilast, cilomilast, roflumilast, tetomilast, olemilast, apremilast, piramidolast and salts thereof.

21. The pharmaceutical composition for use according to claim 20, characterized in that The phosphodiesterase-4 (PDE-4) inhibitor administered was tanimilast.

22. The pharmaceutical composition for use according to any one of claims 19 to 21, characterized in that The method comprises administering a delivered dose of the pharmaceutical composition greater than 10 mg per actuation.

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