MIXING CHANNEL FOR AN INHALATION DEVICE AND INHALATION DEVICE

Abstract

The invention relates to a mixing channel for an inhalation device, and in particular to a mixing channel with improved injection and mixing properties for injecting and mixing a liquid drug into an air flow streaming in the mixing channel, thereby producing an aerosol to be inhaled by a patient. One aspect of the invention relates to a mixing channel for an inhalation device, comprising an inlet opening, an outlet opening, and an injection zone located between the inlet opening and the outlet opening, wherein the injection zone has a longitudinal center axis, wherein the injection zone comprises (a) a built-in nebulizer, or (b) a detachable nebulizer, or (c) a member adapted to receive a detachable nebulizer, wherein the effective cross sectional area of the mixing channel in a plane perpendicular to the longitudinal center axis is smaller in the injection zone than upstream of the injection zone.

Claims

1-15. (canceled)

16. An inhalation device comprising: a mixing channel having a longitudinal center axis, the mixing channel comprising: a first channel portion, comprising: an upstream end comprising an inlet opening, and a downstream end comprising a transition opening, a second channel portion, comprising: an upstream end comprising the transition opening, and a downstream end comprising an outlet opening, wherein the downstream end of the first channel portion comprises a wall that is orthogonal to the longitudinal center axis of the mixing channel, so that a step is formed between the first channel portion and the second channel portion; and a vibrating mesh nebulizer comprising a perforated membrane, wherein the vibrating mesh nebulizer protrudes into the first channel portion adjacent to the wall from a side of the mixing channel so that the perforated membrane is flush with the upstream end of the second channel portion on the side adjacent to the vibrating mesh nebulizer.

17. The inhalation device of claim 16, wherein the wall obstructs about 50% of a cross-sectional area of the first channel portion.

18. The inhalation device of claim 16, wherein the vibrating mesh nebulizer obstructs about 50% of a cross-sectional area of the first channel portion.

19. The inhalation device of claim 16, wherein there is a step-free transition between the first channel portion and the second channel portion on a side opposite the vibrating mesh nebulizer.

20. The inhalation device of claim 16, wherein the vibrating mesh nebulizer is positioned to emit an aerosol at, or near and towards the longitudinal center axis of the mixing channel at an angle of 90° or an angle from 45° to 135° with respect to the longitudinal center axis of the mixing channel.

21. The inhalation device of claim 16, wherein the vibrating mesh nebulizer further comprises: a main member that is connectable with a liquid drug reservoir; and a ring member made of piezoelectric material, wherein the main member comprises a tubular portion comprising an outer area exhibiting a ring-shaped widening onto which the ring member is attached such that the main member extends through the ring member.

22. The inhalation device of claim 16, wherein an opening angle of the second channel portion immediately downstream of the step is constant.

23. The inhalation device of claim 16, wherein the opening angle of the second channel portion immediately downstream of the step is not more than 8°.

24. The inhalation device of claim 16, wherein the inlet opening of the mixing channel is connectable with an inlet channel of the inhalation device.

25. The inhalation device of claim 16, wherein the vibrating mesh nebulizer protrudes into the first channel portion adjacent to the wall from the side of the mixing channel so that a cross-sectional area of the second channel portion immediately downstream of the nebulizer is smaller than a cross-sectional area of the first channel portion immediately upstream of the nebulizer.

26. An inhalation device comprising: a mixing channel having a longitudinal center axis, the mixing channel comprising: a first channel portion, comprising: an upstream end comprising an inlet opening, and a downstream end comprising a transition opening, a second channel portion, comprising: an upstream end comprising the transition opening, and a downstream end comprising an outlet opening, wherein the downstream end of the first channel portion comprises a wall that is orthogonal to the longitudinal center axis of the mixing channel, so that a step is formed between the first channel portion and the second channel portion; and a vibrating mesh nebulizer comprising a perforated membrane, wherein the vibrating mesh nebulizer protrudes into the first channel portion adjacent to the wall from the side of the mixing channel so that a cross-sectional area of the second channel portion immediately downstream of the nebulizer is smaller than a cross-sectional area of the first channel portion immediately upstream of the nebulizer.

27. The inhalation device of claim 26, wherein the wall obstructs about 50% of the cross-sectional area of the first channel portion.

28. The inhalation device of claim 26, wherein the vibrating mesh nebulizer obstructs about 50% of the cross-sectional area of the first channel portion.

29. The inhalation device of claim 26, wherein there is a step-free transition between the first channel portion and the second channel portion on a side opposite the vibrating mesh nebulizer.

30. The inhalation device of claim 26, wherein the vibrating mesh nebulizer is positioned to emit an aerosol at, or near and towards the longitudinal center axis of the mixing channel at an angle of 90° or an angle from 45° to 135° with respect to the longitudinal center axis of the mixing channel.

31. The inhalation device of claim 26, wherein the vibrating mesh nebulizer further comprises: a main member that is connectable with a liquid drug reservoir; and a ring member made of piezoelectric material, wherein the main member comprises a tubular portion comprising an outer area exhibiting a ring-shaped widening onto which the ring member is attached such that the main member extends through the ring member.

32. The inhalation device of claim 26, wherein an opening angle of the second channel portion immediately downstream of the step is constant.

33. The inhalation device of claim 26, wherein the opening angle of the second channel portion immediately downstream of the step is not more than 8°.

34. The inhalation device of claim 26, wherein the inlet opening of the mixing channel is connectable with an inlet channel of the inhalation device.

Description

LIST OF FIGURES

[0081] FIG. 1A shows a vertical section through the longitudinal center axis of an embodiment of the mixing channel 1 according to the invention.

[0082] FIG. 1B shows a cross section of the first channel portion 2a of mixing channel 1 according to B-B in FIG. 1.

[0083] FIG. 2 shows a bottom view of the mixing channel 1 according to the invention.

[0084] FIG. 3A shows a side view of the mixing channel 1 according to the invention.

[0085] FIG. 3B shows the mixing channel 1 seen from side of the outlet opening 5.

[0086] FIG. 3C shows the mixing channel 1 from the side of the inlet opening 4.

[0087] FIG. 4 shows a top view of the mixing channel 1 according to the invention.

[0088] FIG. 5 shows a vertical section through the longitudinal center axis of another embodiment of the mixing channel 1.

[0089] FIG. 6 shows a perspective view of the mixing channel 1 connected to the mouthpiece 20.

[0090] FIG. 7 shows an inhalation device comprising the mixing channel 1.

[0091] FIG. 8 is an exploded view of the inhalation device shown in FIG. 7.

[0092] FIG. 9 shows an exploded view of a nebulizer configured to be inserted into the through-hole 3a of the mixing channel 1.

[0093] FIG. 10 shows a channel according to the prior art.

[0094] FIG. 11A shows a vertical section through the longitudinal center axis of an embodiment of the mixing channel 1 according to the invention prior to insertion of a nebulizer

[0095] FIG. 11B shows a vertical section through the longitudinal center axis of an embodiment of the mixing channel 1 according to the invention with a nebulizer inserted

[0096] FIG. 11C shows an enlarged cross section of the mixing channel at the transition opening 7 between first channel portion 2a and second channel portion 2b along the line B-B depicted in FIG. 11B

[0097] FIG. 12 shows the angle α between the center axis of the second channel portion and one exemplary tangential plane on the inner surface of the second channel portion, i.e., the line of the tangential plane which is also part of a longitudinal section

[0098] Embodiments of the invention are explained below with the help of FIGS. 1A to 9, FIGS. 11 and 12. FIG. 10 refers to prior art.

[0099] FIG. 1A shows a vertical section through the longitudinal center axis of an embodiment of the mixing channel 1 according to the invention. The mixing channel 1 comprises a first channel portion 2a and a second channel portion 2b. The first channel portion 2a comprises an inlet opening 4 forming an air inlet, and a member adopted to receive a detachable nebulizer, which is realized here by a through-hole 3a. Thereby, the first channel portion 2a is shaped as a cylinder with a longitudinal center axis A. This cylinder is confined at its upstream end by the inlet opening 4, which can be considered as a virtual cut through the cylinder along a cross sectional plane, which is not necessarily orthogonal to the longitudinal center axis A. The through-hole 3a is arranged at the very downstream end of the first channel portion 2a on one side of the circumferential wall of the cylinder. At its downstream end, the first channel portion 2a is partially closed by a wall that is arranged on a cross sectional plane orthogonal to the longitudinal center axis A. Thereby, the wall is arranged so as to cover approximately 50% of the downstream end of the first channel portion 2a on the side of the through-hole 3a. The remaining opening of the downstream end of the first channel portion 2a is formed as an approximate semi-circle, as shown in detail in FIGS. 3B and 3C as well as FIG. 11C (therein, cf. reference numeral 7 labelling the transition opening explained below).

[0100] The downstream opening of the first channel portion 2a is at the same time the upstream opening of the second channel portion 2b; in other words, it forms a transition opening 7 between the first and the second channel portion. Thus, the transition opening 7 between the first channel portion 2a and the second channel portion 2b forms a virtual section or plane distinguishing the first channel portion 2a from the second channel portion 2b. Because of said wall partially closing the downstream end of the first channel portion 2a, a step 18 is formed at the site of the transition between channel portions 2a and 2b. The second channel portion 2b is essentially formed as a truncated cone or tapered elliptical cylinder. Due to the step 18, the second channel portion 2b is not symmetrical or coaxial with respect to the longitudinal center axis A of the first channel portion 2a.

[0101] The second channel portion 2b is formed as follows (cf. FIGS. 1 and 3B together): Taking a sequential series of cross sections of the second channel portion 2b from the upstream to the downstream end (each of the cross sections being orthogonal to the longitudinal center axis A of the first channel portion 2a), the first cross section has a semi-circular shape corresponding to the upstream opening of the second channel portion 2b. Then, the shape of each of the subsequent cross sections extends over the shape of the respective previous cross section. The cross section having the largest size out of that series corresponds to the downstream opening of the second channel portion 2b. The downstream opening of the second channel portion 2b forms at the same time the outlet opening 5 of the mixing channel 1. The outlet opening 5 may be connectable with a mouthpiece for inhalation by a user.

[0102] FIG. 1B shows a cross section of the first channel portion 2a mixing channel 1 along the line B-B depicted in FIG. 1A. The circumferential wall of the first channel portion 2a is essentially formed as a, preferably circular, cylinder. On one side of the cylinder, a through-hole 3a is arranged, which acts as a member 6 adapted to receive a detachable nebulizer.

[0103] FIGS. 2, 3A, and 4 show, respectively, a bottom view, a side view, and a top view of an embodiment of the mixing channel 1 according to the invention. The first channel portion 2a comprises at its upstream end the inlet or rear opening 4. At or near or adjacent to the downstream end of the first channel portion 2a, a through-hole 3a is arranged. Directly behind (with respect to the direction from the upstream to the downstream end) the through-hole 3a, a step 18 is formed by a wall arranged perpendicular to the longitudinal center axis A of the first channel portion 2a, the wall partially closing the downstream end of the first channel portion 2a. Downstream of the first channel portion 2a, the mixing channel 1 comprises the second channel portion 2b formed as a tapered elliptical cylinder with the outlet opening 5 at its downstream end.

[0104] FIG. 3B shows an embodiment of the mixing channel 1 as seen from the side of the outlet or front opening 5, i.e. a front view, wherein the second channel portion 2b formed as a tapered elliptical cylinder. A number of concentric ellipsoidal contour lines 17 visualize the tapered shape of the second channel portion 2b. The approximately semi-circular contour line 7 depicts the transition opening between the first channel portion 2a and the second channel portion 2b. In this context, please be also referred to the description of FIG. 1 given above.

[0105] FIG. 3C shows the same mixing channel 1 as in FIG. 3B now from the side of the inlet opening 4, i.e. a rear view. Seen from this side, the first channel portion 2a appears as a circle. Inside the inlet opening 4, the transition opening 7 between the first channel portion 2a and the second channel portion 2b is visible as a semi-circular shape. The contour of the second channel portion 2b is visible behind the inlet opening 4 as an ellipsoidal profile.

[0106] FIG. 5 shows the view of a vertical section through the longitudinal center axis of another embodiment of the mixing channel 1 according to the invention similar to FIG. 1a, which is connected to a mouthpiece 20. The mouthpiece 20 comprises an inner part 20a and an outer part 20b. The inner part 20a of the mouthpiece 20 is connected to the outlet opening 5 at the downstream end of the second channel portion 2b, for example by means of an air tight press-fit 21. Thereby, the inner part 20a of the mouthpiece 20 acts as or forms an extension of the second channel portion 2b. Furthermore, the connection between the inner part 20a of the mouthpiece 20 and the second channel portion 2b is formed as a continuous or step-free transition. This way, the profile of an air stream propagating through the mixing channel 1 is not disturbed in the area of this connection. When being connected to the mixing channel 1, the outer part 20b of the mouthpiece 20 may cover, for example, approximately two thirds of the second channel portion 2b of the mixing channel 1 on the downstream side.

[0107] FIG. 6 shows a perspective view of the mixing channel 1 connected to the mouthpiece 20. The connection site is located inside the outer circumferential wall of the mouthpiece 20 and therefore not visible. The upstream end of the second channel portion 2b extends out of the mouthpiece 20 and is therefore visible. FIG. 6 gives also a three dimensional view of the first channel portion 2a comprising the inlet opening 4 and the through-hole 3a and connected to the upstream end of second channel portion 2b. Through-hole 3a is surrounded by a sealing lip 12.

[0108] FIG. 7 shows an inhalation device comprising the mixing channel 1 according to the invention. The inhalation device comprises a case or housing 23 and the mouthpiece 20. However, the mixing channel 1 itself is not visible from this perspective, since its upstream part is located inside the inhalation device, and the downstream part is covered by the mouthpiece 20.

[0109] FIG. 8 is an exploded view of the inhalation device shown in FIG. 7. A main body 26 is covered or received in a base piece 27 of a housing. The main body 26 comprises a chamfer 28, into which the mixing channel 1 (preferably) connected to a mouthpiece 20 is placed. Thereby, the mixing channel 1 is placed so into the chamfer 28 that the through-hole 3a is located on the side opposite to the main body 26 or opposite to the base piece 27. Onto the through-hole 3a is placed a reservoir member 25 including a reservoir for a liquid drug formulation (not shown). Furthermore, a nebulizer (not shown in FIG. 8, cf. FIG. 9) may be comprised within the reservoir member 25, optionally in direct contact with the drug reservoir.

[0110] FIG. 9 shows an exploded view of a nebulizer 16 configured to be inserted into the through-hole 3a of the mixing channel 1. The depicted nebulizer 16 may be a built-in nebulizer or a detachable nebulizer. The nebulizer comprises a main member 8 formed as a turned part. The main member 8 comprises a tubular portion comprising an outer area exhibiting a ring-shaped widening 11. A ring member 9 made of piezoelectric material is attached to the ring-shaped widening 11 such that the main member 8 extends through the ring member 9. Further, a perforated membrane 10 is connected into or onto the downstream part, or front part, 15a of the main member 8. The main member 8 is connectable with a drug reservoir (not shown) for a liquid drug at its upstream end 15b. Typically, only the downstream part 15a of the nebulizer 16 is inserted in the through-hole 3a, not the whole nebulizer 16.

[0111] FIG. 10 shows a channel according to the prior art.

[0112] FIG. 11A shows a vertical section through the longitudinal center axis of an embodiment of the mixing channel 1 according to the invention, similar to FIG. 1A, prior to insertion of a nebulizer 16 similar to that of FIG. 9. The mixing channel 1 comprises a first channel portion 2a, or mixing chamber 13, confined by a substantially cylindrical or cylindroidal wall (14), with an inlet opening 4, a member 6 adopted to receive a detachable nebulizer 16 and its through-hole 3a; a second channel portion 2b with outlet opening 5 and a transition opening 7 at the step 18 where the cross sectional diameter of the mixing channel 1 decreases abruptly, such that the cross sectional area is smaller at the step 18 in the injection zone 3 than upstream of the injection zone 3. The nebulizer 16 is to be positioned in such a way that its downstream end 15a with the perforated membrane 10 is inserted through through-hole 3a, while the piezoelectric ring-member 9 and the ring shaped widening 11 (which holds the piezoelectric ring-member 9 in place) remain on the outside of the mixing channel 1. The upstream end 15b of the nebulizer 16 is open and connectable to a liquid reservoir. Optionally, the nebulizer 16 may be fixed within reservoir member 25 (not shown), so that proper insertion of the nebulizer is assured by the correct assembly of reservoir member 25 onto the inhalation device as depicted in FIGS. 7 and 8.

[0113] FIG. 11B shows a vertical section through the longitudinal center axis of an embodiment of the mixing channel 1 according to the invention as depicted in FIG. 11A, now with the nebulizer 16 inserted and positioned such that the downstream part 15a of the nebulizer 16 with the perforated membrane 10 is positioned approximately flush with the upper part of the inner surface of the wall of the mixing channel 1 downstream of the injection zone 3. In other words, the end of the downstream part 15a of the nebulizer 16 is flush with the step 18.

[0114] FIG. 11C shows an enlarged cross section of the mixing channel at the transition opening 7 between first channel portion 2a and second channel portion 2b along the line B-B depicted in FIG. 11B.

[0115] FIG. 12 shows the angle α between the center axis of the second channel portion 2b and an exemplary tangential plane on the inner surface (or, in this case, the line at the intersection of a vertical longitudinal section and the inner surface) of the second channel portion 2b.

EXAMPLE 1

[0116] Five prototype mixing channels (nos. 1 to 5) with different geometries were designed and prepared. The second channel portions were approx. 80 mm long and slightly tapered, i.e. shaped as truncated, roughly circular, cones. The prototypes differed with respect to the diameter of the inlet opening and the opening angle of the cone (which is twice the angle between the center axis of the second channel portion and any tangential plane on the inner surface of the second channel portion). In prototypes nos. 1 to 3, the opening angles increased from a smaller angle at the proximal (or upstream) end to a larger angle at the distal (or downstream) end of the second channel portion. The dimensions of the transition opening at the step between first and second mixing channel portion were selected according to the inlet diameter, in that the radius was not changed but the shape was altered from circular to semi-circular with rounded edges, as depicted in FIG. 11C. The respective parameters are given in table 1.

TABLE-US-00001 TABLE 1 Mixing channel no. 1 2 3 4 5 Inlet diameter (mm) 10 9 8 9 9 Opening angle 5° to 6° 5° to 6° 5° to 6° 5° 6°

[0117] Two aerosol generators (A and B) as described in US 2010/0044460 A1 were used to aerosolise isotonic saline solution (0.9%) in pulses of 5 seconds of aerosolization time followed by pauses of 5 seconds. The experiments were conducted first without any mixing channel, and subsequently with each of the five mixing channels at a flow rate of 15 L/min. In each configuration, the aerosol droplet size distribution was determined using laser diffraction. The volume median diameters (VMD) and the geometric standard deviations (GSD) are given in table 2 for aerosol generator A and in table 3 for aerosol generator B.

TABLE-US-00002 TABLE 2 Mixing channel no. None 1 2 3 4 5 VMD (pulsed mode) 5.3 5.0 5.2 4.9 5.0 5.1 GSD (pulsed mode) 6.4 1.6 1.6 1.6 1.6 1.6

TABLE-US-00003 TABLE 3 Mixing channel no. None 1 2 3 4 5 VMD (pulsed mode) 5.5 4.7 4.8 4.7 4.7 4.7 GSD (pulsed mode) 3.6 1.6 1.6 1.6 1.6 1.6

[0118] In result, a remarkable and—especially in its magnitude completely unexpected—effect of all tested mixing channels was observed in that the geometric standard deviation, i.e. the polydispersity of the aerosol droplets, was dramatically reduced from 6.4 or 3.6 to 1.6, indicating that these aerosol generators, which emit substantially heterogeneous aerosols without any mixing channel can, by means of the mixing channel of the invention, be configured to deliver substantially homogeneous aerosols.

EXAMPLE 2

[0119] Using the same five prototype mixing channels as in example 1 and aerosol generator A, and an additional mixing channel (no. 6, with an inlet diameter of 10 mm and a constant opening angle of 6°), the deposition of the aerosolised isotonic saline solution (0.9%) within the mixing channels at a flow rate of 15 L/min was evaluated. An exactly measured quantity of isotonic saline solution (i.e., NaCl.sub.total) was filled into the reservoir of the aerosol generator and aerosolised while a breathing pump (ASL 5000 by IngMar Medical) simulated 20 breathing manoeuvres. Subsequently, the reservoir and the mixing channel were rinsed with distilled water and their sodium chloride content measured conductometrically. Deposition within the mixing channel (NaCl.sub.deposited) was calculated in percent based on the emitted dose (NaCl.sub.emitted=NaCl.sub.total−NaCl.sub.left in reservoir). The results are given in Table 4.

TABLE-US-00004 TABLE 4 Mixing channel no. 1 2 3 4 5 6 Inlet diameter (mm) 10 9 8 9 9 10 Opening angle 5° to 6° 5° to 6° 5° to 6° 5° 6° 6° Deposition 9.7 16.7 27.2 19.2 10.9 10.3 (% of emitted dose)

[0120] In all cases, an acceptable low degree of deposition in the mixing channel was observed. This is remarkable as the nebulizer itself had not been especially adapted to, or optimised for, the inhalation device or the mixing channel, which is normally required.

[0121] A particularly low aerosol deposition in the device was found for an inlet diameter of 9 or 10 mm and an opening angle of 6°, or from 5° to 6°.

[0122] These experiments demonstrate the effectiveness of the mixing channels in deflecting the vast majority of the aerosol droplets emitted by the nebulizer, such that they can be delivered through the mouthpiece to the user. A relatively small fraction of droplets—probably those having the relatively largest diameter—impacted within the device. Their removal may contribute to the reduction of the geometric standard deviation of the aerosol droplet diameter, as observed in Example 1.

[0123] In addition, computational flow simulations of the prototype mixing channels indicated that the length of the second mixing channel portion of approx. 80 mm is efficient in slowing down the velocity of the aerosol droplets to a value very similar to the velocity upstream of the injection zone and thus suitable for inhalation into the deeper lung areas without impaction in the mouth and/or throat region.

[0124] The computational flow simulations of the prototype mixing channels further indicated that these effects may be achieved by means of the step in the mixing channel (i.e. an abrupt decrease of the effective cross sectional area), e.g. through an abrupt increase in air velocity caused by the step, without interfering with a laminar flow.

[0125] While the invention has been illustrated and described in detail in the drawings and foregoing description, such illustration and description are to be considered illustrative or exemplary and not restrictive. It will be understood that changes and modifications may be made by those of ordinary skill within the scope of the following claims. In particular, the present invention covers further embodiments with any combination of features from different embodiments described above and below.

[0126] Furthermore, in the claims the word “comprising” does not exclude other elements or steps, and the indefinite article “a” or “an” does not exclude a plurality. A single unit may fulfil the functions of several features recited in the claims. The terms “essentially”, “about”, “approximately” and the like in connection with an attribute or a value particularly also define exactly the attribute or exactly the value, respectively. Any reference signs in the claims should not be construed as limiting the scope.