Respiratory delivery devices

Abstract

This disclosure provides a respiratory delivery device. In particular, this disclosure provides a delivery device used to administer particulate drugs to the target airways and lungs via inhalation. The delivery device may be suitable for emergency medical use for the delivery of active pharmaceutical ingredients, including epinephrine.

Description

Technical Field

[0006] , , , ,

[0001] The present disclosure relates to a respiratory delivery device. More specifically, the present disclosure relates to a delivery device for use in administering particulate medicaments to the airway of a subject.

Background Art

[0002] In some medical conditions, it may be desirable to administer medicaments to a subject via the airway. For this purpose, an inhaler such as a dry powder inhaler (DPI) can be used.

[0003] A dry powder inhaler (DPI) combined with inhaled dry powder is used in the treatment of diseases such as respiratory diseases, cardiovascular diseases, diabetes, obesity, and cancer, or symptoms associated with these and other diseases (e.g., nausea, vomiting, pain, and inflammation), by delivering a consistent dose of pharmacological medicaments to the patient's airway through inhalation.

[0004] Existing inhalers are typically inefficient with respect to the delivered dose. This typically limits the use of the inhaler to non-emergency applications where a reduced dose is acceptable. Thus, new strategies for the respiratory administration of medicaments would be desirable. It would be particularly desirable to develop a new respiratory delivery device that provides improved efficiency with respect to the delivered dose.

[0005] Any discussion of the documents, acts, materials, devices, articles, etc. included herein is not to be construed as an admission that any or all of these matters form part of the prior art or were common general knowledge in the relevant art of the present disclosure as if they had existed prior to the priority date of each of the appended claims.

Summary of the Invention

[0006] In a first aspect, the present disclosure is in a device for the delivery of a composition to the airway of a subject, the device having a body defined about a central axis, Fluids are in communication, A composition receptacle adapted to receive a composition capsule containing the composition, A dispersion chamber defined by at least one wall having at least one opening inside, located substantially adjacent to a composition receptacle, Equipped with a gas outlet, At least one opening is continuous with an inlet path extending between the at least one opening and a gas inlet that allows gas to enter the device, the gas inlet being formed in the body of the device substantially adjacent to the dispersion chamber.

[0007] In another aspect, the disclosure relates to a device for delivering a composition to a target airway, the device having a body defined around a central axis, Fluids are in communication, A composition receptacle adapted to receive a composition capsule containing the composition, A dispersion chamber defined by at least one wall having two openings inside, located substantially adjacent to a composition receptacle, Equipped with a gas outlet, Each of the two openings is continuous with an inlet path extending between the respective opening and the respective gas inlet, which allows gas to enter the device, and the gas inlet is formed in the body of the device substantially adjacent to the dispersion chamber. The inlet path extends between the gas inlet and two openings in at least one wall of the dispersion chamber, in a plane substantially perpendicular to the central axis.

[0008] In the embodiment, at least one wall of the dispersion chamber has a distal end defining a first plane adjacent to the composition receptacle and a proximal end defining a second plane, which is closer to the gas outlet than the distal end, and the gas inlet is formed in a region of the device body that overlaps with the region formed between the first plane and the second plane.

[0009] In the embodiment, the inlet path extends in a plane substantially perpendicular to the central axis between the gas inlet and at least one opening in at least one wall of the dispersion chamber.

[0010] In the embodiment, the cross-sectional area of ​​the inlet path decreases as it moves from the gas inlet towards at least one opening.

[0011] In the embodiment, at least one wall of the dispersion chamber is continuous with a wall that at least partially defines an inlet path. One wall of the inlet path may be a first inlet path wall that is at least partially tangent to at least one wall of the dispersion chamber. The first inlet path wall may be tangent to at least one wall of the dispersion chamber, and the second inlet path wall that at least partially defines the inlet path may not be tangent to at least one wall of the dispersion chamber.

[0012] In this embodiment, the inlet path extends substantially between the first plane and the second plane.

[0013] In one embodiment, at least one opening in at least one wall of the dispersion chamber is two openings, each opening having an inlet path extending between the opening and its respective gas inlet.

[0014] In the embodiment, the gas inlet defines a gas inlet axis that extends between both gas inlets. Preferably, the gas inlet axis extends between the gas inlet openings within the body or housing of the device.

[0015] In this embodiment, each inlet path extends at a certain angle with respect to the gas inlet axis.

[0016] In this embodiment, each inlet path extends at an angle of 20 to 70 degrees with respect to the gas inlet axis.

[0017] In the embodiment, each of the one or more inlet paths has a point of maximum contraction in front of their associated openings in at least one wall.

[0018] In an embodiment, the maximum contraction point is a contraction of the cross-sectional area of the inlet path.

[0019] In an embodiment, the maximum contraction point is located near each opening of at least one wall of the dispersion chamber relative to each gas inlet.

[0020] In an embodiment, the maximum contraction point is located adjacent to each opening of at least one wall of the dispersion chamber, and optionally, the maximum contraction point is not located directly adjacent to each opening of at least one wall of the dispersion chamber.

[0021] In an embodiment, the angle of the gas inlet upon entry into the dispersion chamber is from about 25 to about 60 degrees.

[0022] In an embodiment, the dispersion chamber is adapted to receive a composition for delivery to a subject and to disperse the composition into the gas flow between one or more gas inlets and a gas outlet for delivery to the subject's airway.

[0023] In an embodiment, the gas outlet is coaxial with a central axis. The central axis may pass through the center point of the gas outlet and reach the base of the device. In some embodiments, the central axis passes through the center point of the gas outlet and passes through substantially the center point or substantially the central region of the dispersion chamber. The gas outlet may comprise a tubular body defining a lumen configured to allow a flow of the dispersed composition therethrough, and the lumen extends along the central axis. In some embodiments, the lumen of the gas outlet is symmetric about the central axis. The dispersion chamber may be symmetric about the central axis. In some embodiments, the composition receptacle, the dispersion chamber, and the gas outlet are aligned with the central axis. The gas inlet may be formed in a portion of the body of the device that is substantially parallel to the central axis.

[0024] In an embodiment, the gas outlet is a mouthpiece.

[0025] In an embodiment, the dispersion chamber is adapted to promote rotational movement or swirling of the composition capsules within the dispersion chamber.

[0026] In an embodiment, the dispersion chamber is a vortex chamber.

[0027] In an embodiment, the device further comprises one or more primers and a cap that engages and displaces the one or more primers and is configured to pierce the composition capsule upon removal of the cap. The cap may move relative to the body substantially along or parallel to the central axis.

[0028] In an embodiment, each of the one or more primers comprises a cam follower and an associated pin or blade, and the cap comprises one or more cams positioned to engage and displace the respective primers to pierce the composition capsule upon removal of the cap. The associated pin of the primer may be received in a bore defined in the body of the device, and the bore is configured to minimize or eliminate an air flow through the bore.

[0029] In an embodiment, the one or more primers are two primers, and each of the primers comprises a cam follower connected to a pin or blade.

[0030] In an embodiment, the cam followers of the one or more primers prevent the cap from being replaced once the cap is removed.

[0031] In an embodiment, the device further comprises a degglomerator positioned substantially adjacent to the dispersion chamber and between the dispersion chamber and the gas outlet.

[0032] In an embodiment, the degglomerator is a screen or mesh.

[0033] In the embodiment, the cap comprises a cap top having one or more elongated members that extend from the cap top to the composition receptacle and are adapted to hold the composition capsule in place.

[0034] In the embodiment, the device further comprises a base having a capsule sheet adapted to position the composition capsules within a composition receptacle.

[0035] In the embodiment, the composition capsule is held in place for puncture by one or more primers between a capsule sheet formed on a base and one or more elongated members extending from the cap top of the cap.

[0036] The main body of the device may include a bump portion that partially defines at least one of the inlet paths, and the bump portion includes a ramp that changes the gradient of each inlet path.

[0037] The inlet path may comprise a first inlet channel having a first bump portion and a second inlet channel having a second bump portion, wherein the first and second bump portions are identical.

[0038] The bump portion may comprise a peak and a trailing edge oriented toward the dispersion chamber, and the transition between the ramp, peak, and trailing edge is configured to minimize flow separation of the fluid flowing through one of the inlet channels.

[0039] The bump sections may be configured to reduce the cross-sectional area of ​​each inlet passage. The bump sections may be configured to gradually reduce and increase the cross-sectional area of ​​each inlet passage between the gas inlet and the opening.

[0040] At least one of the inlet passages may be tapered between the gas inlet and the opening. The tapered portion may cause the inlet passage to contract in a first plane, and the bump portion may cause the inlet passage to contract in a second plane, such that (i) the first and second planes are not parallel, or (ii) the first and second planes are parallel.

[0041] The gas inlet may be substantially formed within a region of the device body formed between a first plane and a second plane, such that it is defined by the distal and proximal ends of the wall of the dispersion chamber.

[0042] Throughout this specification, the word “comprise,” or variations such as “comprises” or “comprising,” shall be understood to imply the inclusion of a specified element, integer, or step, or group of elements, integers, or steps, but not to imply the exclusion of any other element, integer, or step, or group of elements, integers, or steps.

[0043] It will be understood that the indefinite articles "a" and "an" are not interpreted as single indefinite articles, nor as excluding more than one or more than one object that the indefinite article refers to. For example, "one" gas inlet includes one gas inlet, one or more gas inlets, or multiple gas inlets. [Brief explanation of the drawing]

[0044] [Figure 1] This shows an exploded perspective view of a device according to one embodiment of the present disclosure. [Figure 2A] Figure 1 shows a perspective view of the device in the loaded state. [Figure 2B] Figure 1 shows a front cross-sectional view of the device in the loaded state. The cross-sectional view is taken along section AA shown in Figure 2A. [Figure 3A] Figure 1 shows a perspective view of the device in operation. [Figure 3B]Figure 1 shows a front cross-sectional view of the device in operation. The cross-sectional view is taken along the cross-section CC shown in Figure 3A. [Figure 4A] Figure 1 shows a perspective view of the main body of the device according to one embodiment of the present disclosure. [Figure 4B] Figure 4A shows an enlarged view of a portion of the perspective view of the main body. [Figure 4C] Figure 4A shows a top view of the main body. [Figure 4D] Figure 4A shows a cross-sectional view of the main body of the device. [Figure 4E] This is an enlarged view of the upper part of Figure 4D, showing the inclination of the gas inlet to the dispersion chamber. [Figure 5] This is a graphical representation of particle delivery using this device and a standard RS01 comparator. [Modes for carrying out the invention]

[0045] Respiratory delivery of therapeutic drugs may be suitable for a variety of applications. These include applications where the target is typically conscious and responsive, such as the administration of powdered epinephrine, vaccines, antibiotics, and insulin.

[0046] The delivery compositions referred to herein, though not limited to them, are typically in the form of a dry powder. As used herein and as will be understood by those skilled in the art, “dry powder” generally refers to a particulate drug form for respiratory delivery, which is typically delivered or preferred for delivery in the absence of a propellant.

[0047] The compositions described herein (e.g., dry powder or particulate pharmaceuticals) preferably contain at least one “active ingredient,” i.e., a biologically active ingredient. Dry powder or particulate pharmaceuticals may be in the form of one or more pure or substantially pure active ingredients. Alternatively, dry powder or particulate pharmaceuticals may contain, as is well known in the art, one or more pharmaceutically acceptable ingredients in addition to one or more active ingredients, such as fillers, excipients, or diluents. For a non-limiting overview of dry powder formulations, those skilled in the art should refer to Telko and Hickey (2005) 'Dry Powder Inhaler Formulation', Respiratory Care, 50(9), 1209-1227, which is incorporated herein by reference. It will be understood that activators and / or compositions containing activators may be alternatively referred to as “pharmaceuticals.”

[0048] One aspect of the present disclosure provides a device for administering a composition into the airway of a target. Figures 1 to 4E show a typical embodiment of the device of this aspect, device 1000. Device 1000 is configured for one-sided operation, i.e., operation by negative pressure, such as achieved by inhalation by the user.

[0049] Figure 1 shows an exploded perspective view of device 1000 according to an embodiment of the present disclosure, which partially comprises a body 1050, a first gas inlet 1100, a second gas inlet 1150, an outlet 1200, a primer 1600, a cap 1800 having a cap body 1810 and a cap top 1820, and a base 1900.

[0050] Figure 2A shows a perspective view of device 1000 of Figure 1 in a loaded state, and Figure 2B shows a front cross-sectional view of device 1000 of Figure 1 in a loaded state, where the cross-sectional view is taken along cross-section AA shown in Figure 2A. As depicted in Figure 2B, device 1000 is defined around a central axis BB.

[0051] As best seen in Figures 1 and 4A, the body 1050 comprises a first wall 1052 and a second wall 1054 surrounding a hollow internal region. As best depicted in Figure 4C, in the outer region of the body 1050, the first and second walls 1052 and 1054 are spaced apart to create a first spaced region 1060 and a second spaced region 1070. The body 1050 is formed from plastic, which can be changed as desired. For example, the body 1050 may be metal or may contain rubber. A suitable combination of materials may also be used. Figures 3A and 3B show perspective and front section views of the device 1000 in operation with the cap 1800 removed. The gas outlet 1200 and the body 1050 are coaxial and defined around the central axis BB. In this embodiment, the gas outlet 1200 is constructed separately from the body 1050, and the lower part of the outlet 1200 is configured to connect to the body 1050. Alternatively, the gas outlet 1200 and the body 1050 may be manufactured as a single component. The gas outlet 1200 may comprise a tubular body defining a lumen configured to receive the composition dispersed from the dispersion chamber 1500, as will be described in more detail below. The gas outlet 1200 may be configured to allow the flow of the dispersed composition through it. The lumen of the gas outlet 1200 may extend along a central axis BB. In some embodiments, the lumen of the gas outlet is symmetrical with respect to the central axis BB.

[0052] As shown in Figure 1, the lower part of the outlet 1200 is provided with a first notch 1210 and a second notch 1220. As best illustrated in Figure 3A, the first and second notches 1210, 1220 are continuous with the first and second separated regions 1060, 1070 of the body 1050. The upper part of the gas outlet 1200 is generally conical, which may be desirable for use as a mouthpiece. However, the shape of the gas outlet 1200 can be varied as desired. Advantageously, the gas outlet 1200 allows for flexibility and versatility in use and may be used directly as a mouthpiece or as a connection or fitting for further breathing devices.

[0053] For example, the subject can use the gas outlet 1200 as a mouthpiece and inhale directly through the gas outlet 1200. Alternatively, a suitable respiratory device, such as a mask including an intraoral mask or a mouth-nasal mask, can be connected to the gas outlet 1200.

[0054] As best illustrated in Figures 2B, 4B, and 4C, the composition receptacle 1300 is located within a hollow internal region of the main body 1050. The composition receptacle 1300 of device 1000 is in the form of a well including a wall 1310. The composition receptacle 1300 is adapted to appropriately receive a container, such as a composition capsule 1320, which contains the composition to be administered to a subject using device 1000.

[0055] As shown in Figures 1, 2B, and 3B, the base 1900 of device 1000 comprises a capsule sheet 1920 that receives composition capsules 1320 and forms the bed of composition receptacle 1300. The central axis BB may pass through the center point of the gas outlet 1200 to reach the base 1900.

[0056] As best shown in Figures 2B, 3B, and 4B-4C, the dispersion chamber 1500 is also located within the hollow internal region of the main body 1050 of the device 1000. The dispersion chamber 1500 is in the form of a vortex chamber.

[0057] The dispersion chamber 1500 is adapted to receive the punctured composition capsule 1320 containing the composition for delivery to a target as the punctured composition capsule 1320 translates from the composition receptacle 1300 to the dispersion chamber 1500. The punctured composition capsule 1320 may translate from the composition receptacle 1300 to the dispersion chamber 1500 when the cap body 1810 is moved upward, i.e., away from the base 1900 as described later herein.

[0058] The dispersion chamber 1500 is adapted to facilitate the rotational or swirling motion of the composition capsules 1320 within the dispersion chamber 1500 around a central axis BB, or substantially around the central axis BB. In some embodiments, the dispersion chamber is symmetrical about the central axis BB. The dispersion chamber 1500 may have a circular cross-section whose center coincides with the central axis BB. The rotational or swirling motion of the composition capsules 1320 within the dispersion chamber 1500 facilitates the dispersion of the composition from the composition capsules 1320 into the gas flow between the gas inlets 1100, 1150 and the gas outlet 1200 for delivery to the target airway via the gas outlet 1200. The gas inlets 1100, 1150 may be formed in a portion of the body 1050 that is substantially parallel to the central axis BB. In some embodiments, the central axis BB passes through the center point of the gas outlet 1200 and through substantially the center point or substantially the central region of the dispersion chamber 1500. In some embodiments, the composition receptacle 1300, the dispersion chamber 1500, and the gas outlet 1200 are aligned with the central axis BB.

[0059] As best seen in Figures 4B and 4C, the dispersion chamber 1500 is defined by a wall 1510 having a first opening 1520 and a second opening 1530 within it. The first and second openings 1520, 1530 are continuous with the first and second inlet paths 1540, 1550, respectively, which are at least partially formed by the body 1050. The first and second inlet paths 1540, 1550 extend between the first and second openings 1520, 1530, respectively, and the first and second gas inlets 1100, 1150, respectively, which are also at least partially formed in the body 1050 of the device 1000, thereby allowing gas to enter the device 1000. It will be understood that only one gas inlet, one associated inlet path, and one associated opening may be present, but at least two of each are preferred, and two may be optimal.

[0060] As shown in Figure 4C, the first inlet path 1540 is at least partially defined between the outer first inlet path wall 1542 and the inner first inlet path wall 1544, and the second inlet path 1550 is at least partially defined between the outer second inlet path wall 1552 and the inner second inlet path wall 1554.

[0061] When the outlet 1200 is connected to the main body 1050, the lower part of the outlet 1200 acts as an upper wall or roof for the first and second openings 1520, 1530, the first and second inlet paths 1540, 1550, and the first and second gas inlets 1100, 1150, respectively.

[0062] The wall 1510 of the dispersion chamber 1500 has a distal end adjacent to the composition receptacle 1300 and defining a first plane, and a proximal end closer to the gas outlet 1200 than the distal end and defining a second plane.

[0063] The gas inlets 1100 and 1150 are at least partially formed within the body 1050 of the device 1000, which is substantially adjacent to the dispersion chamber 1500. In this embodiment, the gas inlets 1100 and 1150 are at least partially formed in a region of the body 1050 of the device 1000 that overlaps with a region formed between a first plane and a second plane, which is defined by the distal and proximal ends of the wall 1510 of the dispersion chamber 1500. In this embodiment, the gas inlets 1100 and 1150 are substantially formed in a region of the body 1050 of the device 1000, which is formed between a first plane and a second plane, which is defined by the distal and proximal ends of the wall 1510 of the dispersion chamber 1500.

[0064] The first and second inlet paths 1540 and 1550 extend in a plane substantially perpendicular to the central axis BB of the main body 1050 between the respective first and second gas inlets 1100 and 1150 and the respective first and second openings 1520 and 1530.

[0065] The inlet paths 1540 and 1550 substantially extend between a first plane defined at the distal end of wall 1510 of the dispersion chamber 1500 and a second plane defined at the proximal end of wall 1510 of the dispersion chamber 1500.

[0066] As shown in Figure 4C, the gas inlets 1100 and 1150 define the gas inlet axis DD extending between the gas inlets 1100 and 1150. Each inlet path 1540 and 1550 extends at an angle with respect to the gas inlet axis DD. More specifically, each inlet path 1540 and 1550 extends at an angle of 20 to 70 degrees with respect to the gas inlet axis DD, or at an angle of 30 to 70 degrees with respect to the gas inlet axis DD, or at an angle of 20 to 60 degrees with respect to the gas inlet axis DD, or at an angle of 30 to 60 degrees with respect to the gas inlet axis DD, or at an angle of 20 to 50 degrees with respect to the gas inlet axis DD. A preferred range may be an angle of 30 to 50 degrees with respect to the gas inlet axis DD, such as an angle of 34 to 48 degrees with respect to the gas inlet axis DD.

[0067] The cross-sectional area of ​​each of the first and second inlet paths 1540, 1550 decreases as one moves from the respective first and second gas inlets 1100, 1150 towards the respective first and second openings 1520, 1530. Each inlet path 1540, 1550 has a maximum contraction point 1545, 1555 before their associated openings 1520, 1530 in the wall 1510 of the dispersion chamber 1500. At the maximum contraction points 1545, 1555, the cross-sectional area of ​​each inlet path 1540, 1550 is at its minimum value. In some embodiments, the cross-sectional area of ​​each of the first and second inlet paths 1540, 1550 decreases as one moves from the respective first and second gas inlets 1100, 1150 towards the maximum contraction point 1545, 1555. The maximum contraction points 1545 and 1555 are located closer to the respective openings 1520 and 1530 in the wall 1510 of the dispersion chamber 1500 than to the respective gas inlets 1100 and 1150. The maximum contraction points 1545 and 1555 are located substantially adjacent to, or substantially directly adjacent to, the respective openings 1520 and 1530 in the wall 1510 of the dispersion chamber 1500. In embodiments, the maximum contraction points 1545 and 1555 of each inlet path 1540 and 1550 are located immediately behind (towards the gas inlets 1100 and 1150) or adjacent to the point where the dispersion chamber wall 1510 tapers to the point providing the respective openings 1520 and 1530 in the wall 1510 of the dispersion chamber 1500. The shape of the cross-sectional area of ​​each inlet path 1540 and 1550 is not limited, but in one embodiment of the present disclosure, it may be trapezoidal.

[0068] In some embodiments, at least a portion of the outer first inlet path wall 1542 is tangent to the wall 1510 of the dispersion chamber 1500. In some embodiments, at least a portion of the inner first inlet path wall 1544 is tangent to the wall 1510 of the dispersion chamber 1500. In some embodiments, only one of the outer first inlet path wall 1542 and the inner first inlet path wall 1544 is at least partially tangent to the wall 1510 of the dispersion chamber 1500. For example, at least a portion of the outer first inlet path wall 1542 may be tangent to the wall 1510 of the dispersion chamber 1500, and the inner first inlet path wall 1544 may be connected to the wall 1510 at a relatively steeper non-tangent angle to define the taper or divergence configuration of the first inlet path 1540, as seen along the horizontal plane as shown in Figure 4C. Conversely, the outer first inlet path wall 1542 may be connected to wall 1510 at a relatively steeper non-tangent angle compared to the inner first inlet path wall 1544, which may be tangent to wall 1510 of the dispersion chamber 1500.

[0069] The second inlet path 1550 may have a similar configuration as described in relation to the first inlet path 1540, and at least one of the outer second inlet path wall 1552 and the inner second inlet path wall 1554 is at least partially tangent to the wall 1510 of the dispersion chamber 1500.

[0070] The tapering of the first and / or second inlet paths 1540, 1550 may cause a reduction in the cross-sectional area of ​​the inlet paths 1540, 1550, thereby creating a Venturi effect for the fluid flowing from the wider portion of the inlet paths 1540, 1550 through the tapering into the wider volume of the dispersion chamber 1500. This may generate a higher peak velocity in the dispersion chamber 1500 compared to the case where the first and second inlet paths 1540, 1550 are parallel. The higher peak velocity may be more concentrated toward the outer wall of the dispersion chamber 1500. The higher peak velocity may increase the maximum force applied to the composition particles in the dispersion chamber 1500 for improved deaggregation.

[0071] In the top view shown in Figure 4C, when viewed along the horizontal plane, at least a portion of the outer first inlet path wall 1542 and at least a portion of the inner first inlet path wall 1544 may branch off from each other as they extend from the first opening 1520 toward the first gas inlet 1100. The outer first inlet path wall 1542 and the inner first inlet path wall 1544 may branch in the horizontal plane such that the first inlet path 1540 is widest at the first gas inlet 1100 or in the horizontal plane adjacent to the first gas inlet 1100. The outer first inlet path wall 1542 and the inner first inlet path wall 1544 may converge in the horizontal plane such that the point of maximum contraction 1545 (where the first inlet path 1540 may be narrowest in the horizontal plane) is adjacent to or at the first opening 1520. In some embodiments, the point of maximum contraction 1545 (where the first inlet path 1540 may be narrowest in the horizontal plane) is located between the first gas inlet 1100 and the first opening 1520. The second inlet path 1550 may have a similar configuration as described in relation to the first inlet path 1540, where the point of maximum contraction 1555 in the horizontal plane is located at the second opening 1530, or between the second gas inlet 1150 and the second opening 1530.

[0072] As depicted, device 1000 comprises two primers 1600 on the side of composition receptacle 1300. However, it will be understood that a single primer may also be used.

[0073] As best seen in Figure 2B, the primers 1600 are held in an airtight or substantially airtight manner within the walls 1052, 1054 of the body 1050. Each primer 1600 comprises a button 1610 and a pin 1620. In this embodiment, a spring 1630 is installed in the button 1610 of each primer 1600. However, it will be understood that other suitable elastic buttons, such as deformable buttons, may be used, which can be varied as desired.

[0074] The primer 1600 can create an airtight or substantially airtight seal with the walls 1052, 1054. In some embodiments, the walls 1052, 1054 define respective bores for receiving a pin 1620. The pin 1620 can extend and translate through the bore to puncture the composition capsule 1320. The bore can be sized to closely fit the pin 1620 to minimize or eliminate airflow through the bore. The bore can be sized to closely fit the pin 1620 to avoid or reduce friction with the pin 1620 as it extends and translates through the bore to puncture the composition capsule 1320.

[0075] It will be further understood that devices of this embodiment, such as device 1000, may include a deaglomerator (not shown) adapted to deaggregate a composition for delivery to the target airway. The deaglomerator may be located adjacent to or near the dispersion chamber 1500.

[0076] In one typical embodiment, the deaglomerator is a screen or mesh having a plurality of holes or slots for promoting gas turbulence, or comprising such a screen or mesh. The screen or mesh deaglomerator may be positioned adjacent to or near the dispersion chamber 1500 and at the distal end of the outlet 1200.

[0077] As shown in Figure 2A, device 1000 is shown in a state that may be called “closed,” “delivered,” “loaded,” or “pre-operated.” The cap 1800 is completely submerged on the body 1050 such that the underside of the cap 1800, specifically the cap top 1820, is substantially in contact with the upper surface of the gas outlet 1200. The cap 1800 must be removed from device 1000 before use.

[0078] As best illustrated in Figures 2A and 2B, the cap 1800 comprises a cap body 1810 and a cap top 1820, the cap body 1810 being movable relative to the cap top 1820 as described below. As clearly seen in Figure 2B, a well 1825 is formed in the cap top 1820, and a pair of elongated members 1830 extend from the cap top 1820 to hold the composition capsule 1320 in place. The elongated members 1830 may be in the form of a pair of prongs, as illustrated. However, the embodiments provided herein are not limited to a pair of prongs, and there may be one, three, four, or any other number of prongs, or any other structure that is not in the form of prongs, that perform the function of holding the composition capsule 1320 in place on the capsule sheet 1920 of the base 1900 and within the composition receptacle 1300.

[0079] In this embodiment, the pair of elongated members 1830 extend through a deaglomerator (not shown), so the deaglomerator has two openings formed therein to allow the elongated members 1830 to pass through. The two openings are sized such that the function of the deaglomerator is not substantially affected by their presence when the cap top 1820 is removed and the elongated members 1830 are no longer present.

[0080] The elongated member 1830 extends into the dispersion chamber 1500 to hold the composition capsule 1320 in place when the cap 1800 is fully seated and the composition capsule 1320 is seated within the composition receptacle 1300. This helps prevent displacement or movement of the composition capsule 1320 so that it is in an optimal position relative to the pin 1620 for puncturing the composition capsule 1320 during the initial displacement of the cap body 1810. The composition capsule 1320 is preferably composed of a capsule, such as an HPMC capsule, which can be cut or punctured by the pin 1620.

[0081] As can be seen in the cross-section of Figure 2B, the composition capsule 1320 is seated on the capsule sheet 1920 and within the composition receptacle 1300. The primer 1600 is in a first retracted position, with both the cap body 1810 and the cap top 1820 in place, and the elongated member 1830 of the cap top 1820 holds the composition capsule 1320 in place within the composition receptacle 1300. However, even in the retracted position, the primer 1600 is subjected to some degree of tension, as will be described below.

[0082] The lower part of the wall of the cap body 1810 has a chamfered or beveled portion 1840. The button 1610 of the primer 1600 is in taut contact with the upper region of the chamfered portion 1840 to ensure that the primer 1600 is partially pressed into the body of the device even before use. The contact with the chamfered portion 1840 is such that, during the initial displacement of the cap body 1810 for its removal and use of the device 1000, the chamfered portion 1840 further forces an increase in displacement on the button 1610 beyond the displacement in the stationary or unused state, thereby forcing the pin 1620 to extend further into the composition receptacle 1300 and puncture the composition capsule 1320 located therein. The displacement of the button 1610 can be achieved by pressure applied to the elastic material forming the button 1610. There is no need to operate a separate button or switch to release the composition. Instead, the initial displacement of the cap body 1810 automatically results in the puncture of the composition capsule 1320 and the release of the composition.

[0083] During the initial displacement of the cap body 1810 and the resulting puncture of the composition capsule 1320, the cap top 1820 remains stationary and substantially in contact with the upper surface of the outlet 1200. This ensures that the composition capsule 1320 is held in place within the composition receptacle 1300 by the elongated portion 1830 of the cap top 1820 during puncture, thereby ensuring proper and reproducible punctures between multiple devices.

[0084] After the composition capsule 1320 is punctured, further displacement of the cap body 1810 for its removal engages the cap body 1810 with a portion of the cap top 1820 so that the complete removal of the cap body 1810 also removes the cap top 1820.

[0085] Complete removal of the cap 1800 allows the primer 1600 to retract, resulting in the pin 1620 retracting from the composition receptacle 1300. Complete removal of the cap 1800 also allows the primer 1600 to retract completely beyond the position it was in before the cap removal was initiated, while the primer 1600 is in taut contact with the chamfered portion 1840, thereby causing the primer 1600 to protrude from the body 1810 of the device 1000. Once the primer 1600 is protruding from the body 1050 of the device 1000, it is not possible to simply put the cap 1800 back in place to fully engage with the device 1000 again. This is because the chamfered portion 1840 is in block engagement with the upper surface of the button 1610. The angle of the chamfer in this case acts on the displacement of the button 1610, so the cap 1800 cannot be lowered any further. If a potential user has device 1000 with the cap 1800 removed, they will immediately know that device 1000 has been used, or that the composition capsule 1320 containing the composition has been punctured in another manner and is not suitable for administration. This provides a quick and simple visual cue for the user to know that the device they are carrying or being provided is suitable for their intended purpose. Often, given the critical nature of the final medical use, this is a critical safety feature.

[0086] To further ensure that the cap 1800 cannot be returned to full engagement with the device 1000 after use, a cantilever system (not shown) is provided within the primer 1600 that automatically acts to prevent any further movement of the primer 1600 when the cap 1800 is completely removed. This ensures that the primer 1600 is locked in a fully retracted position and cannot be displaced inward, allowing the cap 1800 to be replaced.

[0087] Complete removal of cap 1800 allows access to gas inlets 1100, 1150 and gas outlet 1200. This can be referred to as the “open,” “ready,” “enabled,” or “operating” state when device 1000 is ready for use, as shown in Figures 3A and 3B.

[0088] During use, the composition capsule 1320 is translated substantially from inside the composition receptacle 1300 into the dispersion chamber 1500 by a gas flow resulting from the negative pressure applied at the gas outlet 1200 by the inhalation of the subject.

[0089] The composition capsule 1320, substantially displaced within the dispersion chamber 1500, is rapidly rotated. During use, the rapid rotation or rotation of the composition capsule 1320 within the dispersion chamber 1500, either against or in close proximity to the chamber wall 1510, disperses the composition from the composition capsule 1320 through the seal or membrane punctured or cut by the action of the primer 1600 during the removal of the cap 1800. The composition is released in this stage due to gas flow, turbulence, and centrifugal force.

[0090] More specifically, during use, the gas flow from the gas inlets 1100 and 1150 toward the gas outlet 1200 enters the dispersion chamber 1500 through the respective inlet paths 1540 and 1550 and the respective openings 1520 and 1530, creating a vortex that rotates the composition capsules 1320 within the dispersion chamber 1500.

[0091] As best illustrated in Figure 4C, the wall 1510 of the dispersion chamber 1500 is continuous with the outer first inlet path wall 1542 and the outer second inlet path wall 1552, which at least partially define the respective first and second inlet paths 1540, 1550. As previously disclosed herein, at least one of the outer first inlet path wall 1542, the outer second inlet path wall 1552, the inner first inlet path wall 1544, and the inner second inlet path wall 1554 may be at least partially tangent to the wall 1510. This configuration forces the gas flow to enter a substantially circular, circulating, or vortex path that is tangent to or substantially continuous with the wall 1510 of the dispersion chamber 1500. This vortex path facilitates the dispersion and / or deagglomeration of the composition into the gas flow.

[0092] In some embodiments, as best shown in Figures 4D and 4E, the body 1050 includes a bump portion 1080. The bump portion 1080 may partially define the inlet paths 1540, 1550, as shown in Figure 4E. The bump portion 1080 may be positioned toward the gas inlets 1100, 1150 such that the inlet paths 1540, 1550 widen toward the openings 1520, 1530 in the wall 1510 of the dispersion chamber 1500.

[0093] The outlet 1200 may partially define the inlet paths 1540, 1550. When the outlet 1200 is connected to the body 1050, as disclosed earlier in this specification, the inlet paths 1540, 1550 may be defined by both the body 1050 and the outlet 1200. The bump portion 1080 may have a ramp or slope that causes a change in the gradient of the inlet paths 1540, 1550 when viewed in a vertical plane as shown in Figure 4E. In some embodiments, the outlet 1200 has a corresponding contour surface that complements the gradient of the bump portion 1080. In this way, the corresponding contour surface of the outlet 1200 and the bump portion 1080 may result in a curved inlet flow path in the inlet paths 1540, 1550 when viewed in a vertical plane as shown in Figure 4E. For example, the inlet passage may have a curved configuration in the vertical plane between the first gas inlet 1100 and the first opening 1520, or between the second gas inlet 1150 and the second opening 1530.

[0094] The corresponding contour surface and bump portion 1080 of outlet 1200 may result in a reduced cross-sectional area of ​​the inlet paths 1540, 1550 between the first gas inlet 1100 and the first opening 1520, or between the second gas inlet 1150 and the second opening 1530. The reduced cross-sectional area of ​​the inlet paths 1540, 1550 in the vertical plane may create a Venturi effect for the fluid flowing from the wider portion of the inlet paths 1540, 1550, over the bump portion 1080, into the wider volume of the inlet paths 1540, 1550 leading into the dispersion chamber 1500. This may increase the peak velocity of the fluid as it enters the dispersion chamber 1500. The increased velocity may improve the de-aggregation of composition particles. The increased velocity may reduce or avoid composition particles accumulating within the device instead of being dispersed for administration to the user.

[0095] In some embodiments, the location of the reduced cross-sectional area of ​​the inlet paths 1540, 1550 in the vertical plane (as shown in Figure 4E) may be the same as the location of the reduced cross-sectional area of ​​the inlet paths 1540, 1550 in the horizontal plane (as shown in Figure 4C). Thus, the point of maximum contraction 1545, 1555 may be the same in both the vertical and horizontal planes. This results in inlet paths 1540, 1550 that produce a Venturi effect at a single location along the inlet paths 1540, 1550.

[0096] In some embodiments, the location of the reduced cross-sectional area of ​​the inlet paths 1540, 1550 in the vertical plane (as shown in Figure 4E) may differ from the location of the reduced cross-sectional area of ​​the inlet paths 1540, 1550 in the horizontal plane (as shown in Figure 4C). Thus, the points of maximum contraction 1545, 1555 may differ in both the vertical and horizontal planes. This may result in inlet paths 1540, 1550 generating a Venturi effect at at least one location along them.

[0097] The gradient of the bump section 1080 and the corresponding contour surface of the outlet 1200 should be carefully considered, as they may affect the quality of the fluid flow through the inlet paths 1540 and 1550. The abrupt downward drop of the bump section 1080 leading to the dispersion chamber 1500 may cause or increase the level of flow separation as the fluid moves toward the dispersion chamber 1500, over the peak 1082 of the bump section 1080 and over the trailing edge 1084 of the bump section 1080. In some embodiments, some flow separation may be acceptable, but it may be desirable to minimize this for better control of the direction and velocity of the fluid flow within the dispersion chamber 1500. A gradual change in the geometric shape of the bump section 1080 may cause a more stable flow over the peak 1082 of the bump section 1080 and over the trailing edge 1084 of the bump section 1080 toward the dispersion chamber 1500, reducing or eliminating flow separation. To maintain the same amount of contraction in the cross-sectional area within the inlet passages 1540 and 1550, the bump portion 1080 may extend along the length of the inlet passages 1540 and 1550. In this way, the inlet passages 1540 and 1550 may gradually contract from the first and second gas inlets 1100 and 1150 toward the peaks 1082 of the bump portion 1080, and then gradually diverge beyond the peaks 1082 of the bump portion 1080 toward the first and second openings 1520 and 1530.

[0098] Furthermore, the gradient of the incline of the bump portion 1080 in the inlet paths 1540, 1550 leading to the dispersion chamber 1500 can provide advantages in terms of air movement into the dispersion chamber 1500 and the subsequent vortex effect generated. This incline is best seen in Figures 4D and 4E. Figure 4E shows the gas inlet 1150 entering the dispersion chamber 1500 and the incline of the gas inlet 1150 in doing so. Figure 4E is an enlarged view of the top of Figure 4D, showing the incline of the gas inlet 1150 into the dispersion chamber 1500 and indicating an incline of 38.5 degrees. Thus, Figure 4E shows the manner in which the relevant angle can be measured. The angle may vary depending on the point from which it is measured, and therefore, for reference, it should be understood that the angle considered herein is measured at its steepest point of entry into the dispersion chamber 1500. In the embodiment, this entry angle of the gas inlet (related to both gas inlets 1100 and 1150) may be between approximately 25 and 60 degrees, or approximately 25 and 50 degrees, or approximately 25 and 45 degrees, or approximately 30 and 60 degrees, or approximately 30 and 50 degrees, or approximately 30 and 45 degrees.

[0099] The tests were conducted using Spraytec® (Malvern Instruments, Worcestershire, UK) to determine the discharge volume (ED) and particulate fraction (FPF) achieved by the device 1000. The system addressed during these tests was the inlet geometry and the resulting device performance when using capsules filled with 25 mg Lactohale 300 batch:37136. The main test results are summarized in Table 1. [Table 1]

[0100] The two calculation results were the percentage of lactose released from the capsule and the percentage of lactose remaining in the device. These were calculated using the following formula:

number

number

[0101] The above tests were also performed on the RS01 inhaler, the industry-standard inhaler for DPI manufactured, owned, and marketed by Berry Global Inc. While there are several variations of the RS01, the tests were performed on the high-resistance RS01 because, due to its limitations, it is less affected by the end-user's lung capacity, allowing end-users to achieve a narrower flow rate range.

[0102] The results showed that device 1000 of the present invention performed better than RS01, achieving a higher percentage of lactose successfully analyzed by Spraytec®, with 27.21% being less than 5 μm. Previous tests using RS01 and 50 mg Lactohale capsules yielded a much lower FPF, averaging only 13.16%. RS01 also had results indicating that the amount of Lactohale remaining in the device was much higher (33.4%) than that seen in the tests of device 1000. This means that device 1000, on average, outputs more lactose less than 5 μm. This indicates that device 1000 offers a significant advantage as a lower flow rate of 57.4 L / min can be used by a wider range of people. The conclusion of this test was that device 1000 performed better than RS01 with relatively lower accumulations in the device. Device 1000 was able to consistently achieve a higher FPF than RS01.

[0103] Further testing between Device 1000 and High-Resistance RS01 was conducted using a Next-Generation Impactor (NGI) test system. Specifically, the NGI test system assessed the aerodynamic particle size distribution (APSD) of epinephrine and lactose formulations for both Device 1000 and High-Resistance RS01 at an intensity of 5.2% (1.3 mg of epinephrine per 25 mg capsule). The results of the NGI tests are shown in the following two tables (Table 2 showing data from High-Resistance RS01 and Table 3 showing data from Device 1000). [Table 2] [Table 3-1] [Table 3-2]

[0104] Figure 5 is a graphical representation of particle delivery using the device and a high-resistance RS01 comparator, and also shows the advantages of device 1000. The particle delivery shown in Figure 5 is obtained based on the average ASPD results of NGI trials as shown in Tables 2 and 3 above. From Figure 5, it is clear that device 1000 delivers a significantly higher percentage of particles to stages 3-5 of the NGI trial system. This indicates greater delivery of appropriately sized particles to the deeper parts of the user's lungs, thereby ensuring faster and more complete therapeutic activity.

[0105] During use, the composition dispersed by the dispersion chamber 1500 may be further dispersed and / or deaggregated by the deaglomerator due to the gas flow between the gas inlets 1100, 1150 and the gas outlet 1200.

[0106] In a typical embodiment where the deaglomerator includes a screen or mesh with multiple holes or slots for promoting gas turbulence, the passage of a composition contained in the gas flow through or through the screen or mesh promotes further dispersion and / or de-aggregation of the composition due to the resulting gas turbulence.

[0107] During use, the composition dispersed by the gas flow between the gas inlets 1100, 1150 and the gas outlet 1200 passes through or through the dispersion chamber 1500, and optionally through the deaglomerator of device 1000, and is delivered to the subject's airway as a result of inhalation by the subject through the gas outlet 1200.

[0108] It will be understood that devices of this disclosure, such as device 1000, can offer several important advantages. In particular, the airflow resistance can be optimally adjusted to specified conditions. Device 1000 is designed to provide high resistance, thereby enabling consistent use across consumers with varying lung capabilities, i.e., suitable for both users with strong lung capabilities and users with impaired lung capabilities. Device 1000 can provide improved delivery efficiency over conventional DPIs such as RS01 DPI.

[0109] Advantageously, embodiments of devices of this embodiment, such as device 1000, can be adjusted or modified to change the dosage in accordance with the specific requirements of the subject.

[0110] For example, the size, shape, and / or number of pins 1620 of primer 1600 can be changed or modified to adjust the rate of composition delivery. It will be readily apparent that a larger number or size of pins 1620 typically allows for a higher rate of release of the composition from dispersion chamber 1500 and subsequent delivery to the target.

[0111] Similarly, in embodiments of devices comprising a deaglomerator, the properties of the deaglomerator (e.g., with respect to screen properties) can be modified or adjusted to control the rate of composition delivery.

[0112] Advantageously, embodiments such as device 1000 are typically highly reliable in use with respect to delivery from a container or capsule.

[0113] Additionally, embodiments such as device 1000, in particular, in which the composition receptacle 1300 is formed to appropriately receive a container or composition capsule 1320, can typically be primed and used when positioned in any orientation, with limited or no change in performance.

[0114] Advantageously, as described above, embodiments such as device 1000 typically feature a substantially sealed gas channel through the body 1050 from inlets 1100, 1150 to outlet 1200. It will be understood that such a sealed channel substantially prevents, or at least limits, undesirable escape or leakage of the composition. The tight seal between the bore and the pin 1620 received therein may aid in improved sealing of the channel to minimize or reduce leakage.

[0115] Furthermore, device 1000 offers a clear advantage in its easy priming for use by simply removing the cap 1800, and since it prevents the replacement of the cap 1800 after use to indicate that the capsule containing the composition has been punctured, device 1000 is no longer suitable for further use.

[0116] The above is a non-limiting list of some typical advantages of exemplary embodiments.

[0117] As will be readily apparent to those skilled in the art, these embodiments allow for the selection of compositions suitable for administration to specific subjects, including specific therapeutic purposes related to particular conditions.

[0118] Generally, the compositions administered as described herein may contain any suitable agents for administration to the airways of a subject, according to the subject's condition and medical requirements. As described above, typically, the compositions are dry powders and may be in the form of one or more pure or substantially pure active ingredients. Alternatively, the compositions may, as is well known in the art, contain one or more pharmaceutically acceptable components in addition to one or more active ingredients, such as fillers, excipients, or diluents.

[0119] As those skilled in the art will understand, the particle size of a dry powder composition administered to the target airway can affect the therapeutic efficacy of the dry powder. Typically, administered particles have a d50, or average mass aerodynamic diameter (MMAD), of less than 6 μm. As those skilled in the art will understand, “d50” or “D50” refers to a value where the particle diameter of 50% by mass of the particle sample is less than that. d50 particle MMADs are preferably about 0.5 to about 20 μm, including about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, and 19 μm, more preferably about 0.5 to 10 μm, and even more preferably 1 to 6 μm, and even more preferably about 2 to about 5 μm, including about 2.5, 3, 3.5, 4, and 4.5 μm. In embodiments where device 1000 includes a deaglomerator, the preceding value will be understood to refer to the particle size after dispersion into the gas flow and / or after passing through the deaglomerator.

[0120] Examples of activators that may be delivered pursuant to this disclosure include steroids such as beta-2-agonists and glucocorticosteroids (preferably anti-inflammatory agents), anticholinergics, leukotriene antagonists, leukotriene synthesis inhibitors, general analgesics such as analgesics and anti-inflammatory agents (including both steroidal and non-steroidal anti-inflammatory agents), cardiovascular agents such as cardiac glycosides, respiratory agents, anti-asthmatics, bronchodilators, anticancer agents, alkaloids (e.g., ergot alkaloids), or triptans that can be used to treat migraines, drugs useful in treating type 1 and type 2 diabetes and related diseases (e.g., sulfonylurea), sleep inducers including sedatives and hypnotics, psychoactive agents, appetite suppressants, antiarthritis agents, antimalarial agents, antiepileptic agents, antithrombotic agents, antihypertensive agents, antiarrhythmic agents, antioxidants, antidepressants, antipsychotics, anxiolytics, and anticonvulsants. Drugs include antiemetics, antiinfectives, antihistamines, antifungals and antivirals, drugs for treating neurological disorders such as Parkinson's disease (dopamine antagonists), drugs for treating alcoholism and other forms of intoxication, drugs such as vasodilators used to treat erectile dysfunction, muscle relaxants, muscle contractors, opioids, stimulants, tranquilizers, antibiotics such as macrolides, aminoglycosides, fluoquinolones and beta-lactams, vaccines, cytokines, growth factors, hormones including contraceptives, sympathomimetic agents, diuretics, lipid regulators, antiandrogens, antiparasitic drugs, anticoagulants, tumor agents, antitumor agents, hypoglycemic agents, nutritional supplements and supplements, growth supplements, anticolitis drugs, vaccines, antibodies, diagnostic agents, and contrast agents and mixtures thereof (e.g., combination therapy for asthma containing both steroids and beta-agonists).

[0121] Activators include, but are not limited to, small molecules (including insoluble small molecules), peptides, polypeptides, proteins, polysaccharides, steroids, nucleotides, oligonucleotides, polynucleotides, fats, and electrolytes, and can be classified into one of several structural classes. Specific examples include the beta-2-agonist salbutamol (e.g., salbutamol sulfate) and salmeterol (e.g., salmeterol xinafoate), the steroid budesonide and fluticasone (e.g., fluticasone propionate), the cardiac glycoside digoxin, the alkaloid antimigraine drug dihydroergotamesylate and other alkaloids ergotamine, the alkaloids bromocriptine, sumatriptan, rizatriptan, naratriptan, flovatriptan, almotriptan, zolmatriptan, morphine and morphine-like fentanyl (e.g., fentanyl citrate), glibenclamide (sulfonylurea), barium, triazolam, alprazolam, midazolam, and crocodile. Examples include benzodiazepines such as lonazepam (typically used, for example, to treat insomnia or panic attacks), the antipsychotic risperidone, apomorphine used to treat erectile dysfunction, the antiinfective amphotericin B, the antibiotics tobramycin, ciprofloxacin, and moxifloxacin, nicotine, testosterone, anticholinergic bronchodilators, ipratropium bromide, the bronchodilator formoterol, monoclonal antibodies and the protein LHRH, insulin, human growth hormone, calcitonin, interferons (e.g., beta- or gamma-interferon), EPO and factor VIII, and, in each case, pharmaceutically acceptable salts, esters, analogs and derivatives thereof (e.g., in prodrug forms).

[0122] Potentially suitable additional activators include asparidinase, amdoxovir (DAPD), antide, becapramin, calcitonin, cyanobilin, denyleukin diphthoxytox, erythropoietin (EPO), EPO agonists, Dormazepam, erythropoiesis-stimulating protein (NESP), coagulation factors such as factor VIIa, factor VIII, factor IX, von Willebrand factor; cerase, cerezyme, alpha-glucosidase, collagen, cyclosporine, alpha-defensin, beta-defensin, exesin-4, granulocyte colony-stimulating factor (GCSF), thrombopoietin (TPO), alpha-1 protein enzyme inhibitors, ercatonin, granulocyte-megaplasmic colony-stimulating factor (GMCSF), fibrinogen, filgracim, growth hormone, growth hormone-releasing hormone (GHRH), GRO-beta , GRO-beta antibody, bone morphogenetic protein-2, bone morphogenetic protein-6, OP-1 and other bone morphogenetic proteins; acid fibroblast growth factor, basic fibroblast growth factor, CD-40 ligand, heparin, human serum albumin, low molecular weight heparin (LMWH), interferon alpha, interferon beta, interferon gamma, interferon omega, interferon tau and other interferons; interleukin and interleukin receptors, interleukin-1 receptor, interleukin-2, interleukin-2 fusion protein, interleukin-1 receptor antagonist, interleukin-3, interleukin-4, interleukin-4 receptor, interleukin-6, interleukin-8, interleukin-12, interleukin-13 receptor, interleukin-17 receptor;Lactoferrin and lactoferrin fragments, luteinizing hormone-releasing hormone (LHRH), insulin, proinsin, insulin analogs, amyrin, C peptide, somatostatin, somatostatin analogs including octreotide, vasopressin, follicular-stimulating hormone (FSH), influenza vaccine, insulin-like growth factor (IGF), insulintropin, macrophage colony-stimulating factor (M-CSF), plasminogen activators such as alteplase, urokinase, reteplase, streptokinase, pamitoprase, lanoteplase, and teneteplase;Nerve growth factor (NGF), osteoprotegerin, platelet-derived growth factor, tissue growth factor, transforming growth factor-1, vascular endothelial growth factor, leukocyte inhibitor, keratinocyte growth factor (KGF), glial growth factor (GGF), T cell receptor, CD molecule / antigen, tumor necrosis factor (TNF), monocyte chemoattractant-1 endothelial growth factor, parathyroid hormone (PTH), glucagon-like peptide, somatropin, thymosin alpha-1, thymosin alpha-1 IIb / II Examples of antiviral agents include, but are not limited to, Ia inhibitors, thymosin beta-10, thymosin beta-9, thymosin beta-4, alpha-1 antitrypsin, phosphodiesterase (PDE) compounds, VLA-4 (latest stage antigen-4), VLA-4 inhibitors, bisphosphonates, respiratory syncytial virus antibodies, cystic fibrous transmembrane regulator (CFTR) genes, deoxyribonuclease (DNase), bactericidal permeability-enhancing proteins (BPIs), and anti-CMV antibodies. Exemplary monoclonal antibodies include etanercept (human 75kD2 bound to the Fc portion of IgG1). Dimeric fusion proteins consisting of the extracellular ligand-binding portion of the TNF receptor), absiximab, afeliomomab, basiliximab, daclizumab, infliximab, ibritumomab tiuxetan, mitumomab, muromonab-CD3, iodine-131 tositumomab conjugate, orizumab, rituximab, and trastuzumab (herceptin), amifostin, amiodarone, aminoglutethimide, amsacrin, A Nagrelide, anastrozole, asparaginase, anthracycline, bexarotene, bicalutamide, bleomycin, buserelin, busulfan, cabergoline, capecitabine, carboplatin, carmustine, chlorambusin, cisplatin, cladribine, clodronate, cyclophosphamide, cyproterone, cytarabine, camptothecin, 13-cisretinoic acid, all transretinoic acids;Dacarbazine, Dactinomycin, Daunorubicin, Dexamethasone, Diclofenac, Diethylstilbestrol, Docetaxel, Doxorubicin, Epirubicin, Estramustine, Etoposide, Exemestane, Fexofenadine, Fludarabine, Fludrocortisone, Fluorouracil, Fluoxymesterone, Flutamide, Gemcitabine, Epinephrine, L-Dopa, Hydroxyurea, Idarubicin, Ifosfamide, Imatinib, Irinotecan, It Laconazole, goserelin, letrozole, leucovorin, rebamizole, lomustine, mechloretamine, medroxyprogesterone, megestrol, melphalan, mercaptopurine, methotrexate, metoclopramide, mitomycin, mitotane, mitoxantrone, naloxone, nicotine, niltamide, octreotide, oxaliplatin, pamidronate, pentostatin, pilcamycin, porfimer, prednisone, procarbazine, prochlorpe Radin, ondansetron, larcitrexed, sirolimus, streptozocin, tacrolimus, tamoxifen, temozolomide, teniposide, testosterone, tetrahydrocannabinol, thalidomide, thioguanine, thiotepa, topotecan, tretinoin, barrubicin; vinblastine, vincristine, vindesine, vinorelbine, dolacetone, granisetron; formoterol, fluticasone, leuprolide, midazolam, alprazolam, amphoteric acid Tericin B, podophyllotoxin, nucleoside antivirals, aroylhydrazone, sumatriptan; macrolides, such as erythromycin, oleandomycin, troleondomycin, roxithromycin, clarithromycin, daversin, azithromycin, flurithromycin, zithromycin, josamycin, spiromycin, midecamycin, leucomycin, myokamycin, rokitamycin, anzithromycin, and swinolide A;Fluoroquinolones, such as ciprofloxacin, ofloxacin, levofloxacin, trovafloxacin, allatrofloxacin, moxifloxacin, norfloxacin, enoxacin, grepafloxacin, gatifloxacin, lomefloxacin, sparfloxacin, temafloxacin, pefloxacin, amifloxacin, fleroxacin, tosufloxacin, prulifloxacin, erloxacin, pazufloxacin, clinafloxacin, and sitafloxacin Syn; aminoglycosides, such as gentamicin, netylmycin, paramesin, tobramycin, amikacin, kanamycin, neomycin, and streptomycin, vancomycin, teicoplanin, lamporanin, mideplanin, colistin, daptomycin, gramicidin, colistimeta; polymyxins, such as polymyxin B, capreomycin, bacitracin, penem; penicillin containing peniclinase-sensitive drugs such as penicillin G and penicillin V. Peniclinase-resistant drugs, e.g., methicillin, oxacillin, cloxacillin, dicloxacillin, floxacillin, naphicillin; Gram-negative microbial activators, e.g., ampicillin, amoxicillin, and hetacillin, cillin, and galampicillin; anti-Pseudomonas penicillins, e.g., carbenicillin, ticarcillin, azurocillin, mezurocillin, and piperacillin; cephalosporins, e.g., cefpodoxime, cefprodil, ceftobutene, ceftizoxime, ceftri Axon, cephalothin, cefapillin, cephalexin, cefladrine, cefoxitin, cephamandol, cefazolin, cefaloridine, cefaclorol, cefadroxil, cephaloglysin, cefuroxime, cefolanide, cefotaxime, cefatoridine, cefacetril, cefepime, cefixime, cefonisid, cefoperazone, cefotetan, cefmetazole, ceftazidime, loracalbef, and monobactams such as moxalactam and aztreonam;Furthermore, examples include carbapenems such as imipenem, meropenem, pentamidiniethiweight, albuterol sulfate, lidocaine, metaproterenol sulfate, beclometasonesprepionate, triamcinolone acetamide, budesonide acetonide, fluticasone, ipratropium bromide, flunizolide, cromolyn sodium, and ergotamine tartrate; taxanes such as paclitaxel; SN-38; and tilphostine.

[0123] Other drugs that may be used include: linezolid; treprostinol, optionally in combination with a PDE5 inhibitor; oxytomodulin; and palonosetron, optionally, preferably in combination with a high-potency NK1 antagonist.

[0124] The exemplary activators described above will be understood to include, where applicable, their analogues, agonists, antagonists, inhibitors, isomers, and pharmaceutically acceptable salt forms. With respect to peptides and proteins, this disclosure is intended to include their synthetic, recombinant, natural, glycosylated, unglycosylated, and biologically active fragments and analogues.

[0125] In some typical embodiments, the composition comprises one or more activators selected from adrenaline (epinephrine), glucose, glucagon, naloxone, insulin, and the like.

[0126] In some typical embodiments, the composition comprises particulate glucose and / or glucagon for the treatment of hypoglycemia, diabetes-induced coma, etc. In embodiments, the dry powder comprises particulate benzodiazepines, phenytoin, or antiseizure agents for the treatment of seizures.

[0127] In some typical embodiments, the composition comprises one or more agents for inducing an immune response, such as one or more vaccines. In embodiments, the dry powder comprises a measles vaccine for inducing an immune response to measles or for immunization against measles. In embodiments, the dry powder comprises a hepatitis B vaccine for inducing an immune response to hepatitis B or for immunization against hepatitis B. In embodiments, the dry powder comprises an influenza vaccine for inducing an immune response to influenza or for immunization against influenza.

[0128] The above description of various embodiments of this disclosure is provided for the benefit of those skilled in the art in the relevant field. It is not intended to be exhaustive or to limit this disclosure to a single disclosed embodiment. As mentioned above, numerous alternatives and variations to this disclosure will be apparent to those skilled in the art of the above teachings. Thus, while several alternative embodiments have been specifically considered, other embodiments will be apparent or relatively easily developed by those skilled in the art. This disclosure is intended to encompass all alternatives, modifications, and variations of this disclosure discussed herein, as well as other embodiments that fall within the spirit and scope of the disclosure described above.

Claims

1. A device for delivering a composition to a target airway, having a body defined around a central axis, Fluids are in communication, A composition receptacle adapted to receive a composition capsule containing the composition, A dispersion chamber defined by at least one wall having two openings inside, located substantially adjacent to the composition receptacle, Equipped with a gas outlet, Each of the two openings is continuous with an inlet path extending between each of the openings and each gas inlet that allows gas to enter the device, and the gas inlets are formed in the body of the device substantially adjacent to the dispersion chamber. A device in which the inlet path extends in a plane substantially perpendicular to the central axis between the gas inlet and the two openings in at least one wall of the dispersion chamber.

2. The device according to claim 1, wherein the at least one wall of the dispersion chamber has a distal end defining a first plane adjacent to the composition receptacle and a proximal end defining a second plane, and each gas inlet is formed in a region of the body of the device that overlaps with a region formed between the first plane and the second plane.

3. The device according to claim 1 or claim 2, wherein the cross-sectional area of ​​each inlet path decreases as it moves from each gas inlet towards each opening.

4. The device according to any one of claims 1 to 3, wherein at least one wall of the dispersion chamber is continuous with a wall that at least partially defines the inlet path.

5. The device according to claim 4, wherein one of the walls of the inlet path is a first inlet path wall that is at least partially tangent to at least one wall of the dispersion chamber.

6. The device according to claim 5, wherein the first inlet path wall is tangent to the at least one wall of the dispersion chamber, and the second inlet path wall that at least partially defines the inlet path is not tangent to the at least one wall of the dispersion chamber.

7. The device according to claim 2, wherein the inlet path substantially extends between the first plane and the second plane.

8. The device according to any one of claims 1 to 7, wherein the gas inlet defines a gas inlet axis extending between both gas inlets, and each inlet path extends at an angle of 20 to 70 degrees with respect to the gas inlet axis.

9. The device according to any one of claims 1 to 8, wherein one or more inlet paths each have a point of maximum contraction in their cross-sectional area in front of their associated openings in the at least one wall.

10. The device according to claim 9, wherein the point of maximum contraction is located closer to each of the openings in the at least one wall of the dispersion chamber than to each of the gas inlets.

11. The device according to claim 10, wherein the point of maximum contraction is located adjacent to the opening in each of the at least one wall of the dispersion chamber.

12. The device according to any one of claims 1 to 11, wherein the angle of the gas inlet when entering the dispersion chamber is approximately 25 degrees to approximately 60 degrees.

13. The device according to any one of claims 1 to 12, wherein the gas outlet is coaxial with the central axis.

14. The device according to any one of claims 1 to 13, further comprising one or more primers, and a cap that engages with and displaces the one or more primers, and is configured to puncture the composition capsule when the cap is removed.

15. The device according to claim 14, wherein each of the one or more primers comprises a cam follower and an associated pin or blade, and the cap comprises one or more cams that engage with and displace each of the primers to puncture the composition capsule when the cap is removed.

16. The device according to claim 15, wherein the associated pin of the primer is received in a bore defined in the body of the device, and the bore is configured to minimize or eliminate airflow through the bore.

17. The device according to any one of claims 1 to 16, further comprising a deaglomerator substantially adjacent to the dispersion chamber and located between the dispersion chamber and the gas outlet.

18. A device for delivering a composition to a target airway, having a body defined around a central axis, Fluids are in communication, A composition receptacle adapted to receive a composition capsule containing the composition, A dispersion chamber defined by at least one wall having two openings inside, located substantially adjacent to the composition receptacle, Equipped with a gas outlet, Each of the two openings is continuous with an inlet path extending between each of the openings and each gas inlet that allows gas to enter the device, and the gas inlets are formed in the body of the device substantially adjacent to the dispersion chamber. A device in which the cross-sectional area of ​​each inlet path decreases as it moves from each gas inlet towards each opening.

19. The device according to claim 18, wherein the at least one wall of the dispersion chamber has a distal end defining a first plane adjacent to the composition receptacle and a proximal end defining a second plane, and the gas inlet is formed in a region of the body of the device that overlaps with a region formed between the first plane and the second plane.

20. The device according to claim 19, wherein the inlet path substantially extends between the first plane and the second plane.

21. The device according to any one of claims 18 to 20, wherein the gas inlet defines a gas inlet axis extending between both gas inlets, and each inlet path extends at an angle of 20 to 70 degrees with respect to the gas inlet axis.

22. The device according to any one of claims 18 to 21, wherein each inlet path has a point of maximum contraction in its cross-sectional area in front of their associated openings in the at least one wall of the dispersion chamber, and the point of maximum contraction is located closer to each of the openings in the at least one wall of the dispersion chamber than to each of the gas inlets.

23. The device according to any one of claims 18 to 22, wherein the angle of the gas inlet when entering the dispersion chamber is about 25 degrees to about 60 degrees.

24. A device for delivering a composition to a target airway, having a body defined around a central axis, Fluids are in communication, A composition receptacle adapted to receive a composition capsule containing the composition, A dispersion chamber defined by at least one wall having two openings inside, located substantially adjacent to the composition receptacle, Equipped with a gas outlet, Each of the two openings is continuous with an inlet path extending between each of the openings and each gas inlet that allows gas to enter the device, and the gas inlets are formed in the body of the device substantially adjacent to the dispersion chamber. A device in which the gas inlet defines a gas inlet axis extending between both gas inlets, and each inlet path extends at an angle of 20 to 70 degrees with respect to the gas inlet axis.

25. The device according to claim 24, wherein the inlet path extends in a plane substantially perpendicular to the central axis between the gas inlet and the two openings in at least one wall of the dispersion chamber.

26. The device according to claim 24 or 25, wherein the cross-sectional area of ​​each inlet path decreases as it moves from each gas inlet towards each opening.

27. The device according to any one of claims 24 to 26, wherein each inlet path has a point of maximum contraction in its cross-sectional area in front of their associated openings in the at least one wall of the dispersion chamber, and the point of maximum contraction is located closer to each of the openings in the at least one wall of the dispersion chamber than to each of the gas inlets.

28. The device according to any one of claims 24 to 27, wherein the at least one wall of the dispersion chamber has a distal end defining a first plane adjacent to the composition receptacle and a proximal end defining a second plane, and is closer to the gas outlet than the distal end, and each gas inlet is formed in a region of the body of the device that overlaps with a region formed between the first plane and the second plane, and the inlet path substantially extends between the first plane and the second plane.

29. A device for delivering a composition to a target airway, having a body defined around a central axis, Fluids are in communication, A composition receptacle adapted to receive a composition capsule containing the composition, A dispersion chamber defined by at least one wall having two openings inside, located substantially adjacent to the composition receptacle, Equipped with a gas outlet, (i) Each of the two openings is continuous with an inlet path extending between each of the openings and each gas inlet that allows gas to enter the device, and the gas inlets are formed in the body of the device substantially adjacent to the dispersion chamber, (ii) The inlet path extends in a plane substantially perpendicular to the central axis between the gas inlet and the two openings in at least one wall of the dispersion chamber, (iii) The cross-sectional area of ​​each inlet path decreases as it moves from each gas inlet towards each opening, (iv) A device in which each inlet path has a point of maximum contraction in its cross-sectional area in front of their associated openings in the at least one wall of the dispersion chamber, and the point of maximum contraction is located closer to each of the openings in the at least one wall of the dispersion chamber than to each of the gas inlets.

30. The device according to claim 29, wherein the point of maximum contraction is located adjacent to the opening in each of the at least one wall of the dispersion chamber.

31. The device according to claim 29 or 30, wherein the at least one wall of the dispersion chamber has a distal end defining a first plane adjacent to the composition receptacle and a proximal end defining a second plane, and is closer to the gas outlet than the distal end, and each gas inlet is formed in a region of the body of the device that overlaps with a region formed between the first plane and the second plane, and the inlet path substantially extends between the first plane and the second plane.

32. The device according to any one of claims 29 to 31, wherein the gas inlet defines a gas inlet axis extending between both gas inlets, and each inlet path extends at an angle of 20 to 70 degrees with respect to the gas inlet axis.

33. The device according to any one of claims 29 to 32, further comprising one or more primers, and a cap that engages with and displaces the one or more primers, and is configured to puncture the composition capsule when the cap is removed.

34. The device according to any one of claims 1 to 33, wherein the main body of the device comprises a bump portion that partially defines at least one of the inlet paths, and the bump portion comprises a ramp that changes the gradient of each of the inlet paths.

35. The device according to claim 34, wherein the inlet path comprises a first inlet passage having a first bump portion and a second inlet passage having a second bump portion, and the first bump portion and the second bump portion are the same.

36. The device according to claim 34 or 35, wherein the bump portion comprises a peak and a trailing edge oriented toward the dispersion chamber, and the transition between the ramp, the peak, and the trailing edge is configured to minimize flow separation of the fluid flowing through one of the inlet channels.

37. The device according to any one of claims 34 to 36, wherein the bump portion is configured to reduce the cross-sectional area of ​​each of the inlet passages.

38. The device according to claim 37, wherein the bump portion is configured to gradually reduce and increase the cross-sectional area of ​​each of the inlet passages between the gas inlet and the opening.

39. The device according to any one of claims 34 to 38, wherein at least one of the inlet passages is tapered between the gas inlet and the opening.

40. The device according to claim 39, wherein the taper causes the inlet passage to contract in a first plane, and the bump portion causes the inlet passage to contract in a second plane, and (i) the first plane and the second plane are not parallel, or (ii) the first plane and the second plane are parallel.

41. The device according to any one of claims 1 to 40, wherein the gas inlet is substantially formed within a region of the body of the device formed between a first plane and a second plane, such that the gas inlet is defined by the distal and proximal ends of the wall of the dispersion chamber.

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