Breathing actuated inhaler

Abstract

A breath-actuated metered dose inhaler includes a housing, a canister, and a trigger mechanism. A trigger mechanism is actuated by suction of air, the trigger mechanism including a diaphragm. The central rigid disc of the diaphragm is provided with interlocking means to securely secure and bond the peripheral flexible polymer ring to the central rigid disc. A mechanical interlock between the central rigid disc and the peripheral flexible polymer ring on the diaphragm prevents peeling of the peripheral flexible polymer ring from the central rigid disc while maintaining a vacuum prior to suction.

Description

Technical Field

[0001] The present invention relates to a breath-actuated metered inhaler. The present invention also provides an improved form of a diaphragm and a valve flap for a trigger mechanism of a breath-actuated metered inhaler. The present invention also provides a method for manufacturing the same. Background Art

[0002] There are various inhalation devices that can spray continuously or release an aerosol drug in a predetermined amount. Examples of such inhalation devices include pressurized metered dose inhalers (pMDIs) and dry powder inhalers (DPIs). Generally, a pMDI consists of three main components; an aerosol canister in which the formulation resides for delivery to the lungs; a metering valve that is disposed in the canister and allows a predetermined amount of the formulation to be dispensed per actuation; and an actuator that holds the canister and allows the patient to operate the device and direct the aerosol into the patient's lungs. The most common in this category are "press-and-breathe" type pMDI inhalation devices, and these devices are actuated by pressure applied by the user's finger, button action, or other related manual techniques. In use, when the patient presses the canister within the actuator, a "puff" or single dose of the stored formulation is metered and delivered.

[0003] A recent development is the so-called "breath-actuated inhaler" that delivers a dose of drug through an interface in response to the user's inhalation. Breath-actuated inhalers are preferred in situations where the coordination between the user's inhalation and manual pressing of the aerosol canister is imperfect. For example, children or elderly patients have difficulty synchronizing the actuation of the MDI with inhalation, or sometimes the patient exhales before inhalation is complete.

[0004] PCT application WO 01 / 93933A2 describes such a breath-actuated metered inhaler. A sufficient amount of preload is applied to an internal aerosol valve to cause dose release, but this is prevented by applying pneumatic resistance. Inhalation causes the release of the pneumatic resistance and allows the preload to actuate the aerosol valve. The pneumatic resistance is established by a negative pressure zone that is partially defined by a diaphragm. The diaphragm includes a central disk made of a first material with relatively high stiffness and a peripheral ring connected by a bend made of a second material with relatively low stiffness. The diaphragm also includes a small valve orifice covered by a valve seal (valve flap). The valve seal (valve flap) seals the valve orifice to create a pressure difference. When the patient inhales through the interface, the valve seal (valve flap) moves out of the sealed position to open the valve orifice, thereby breaking the pressure difference and causing the preload to actuate the aerosol valve.

[0005] US10792447B2 describes a more recent breath-actuated metered inhaler. The patent discloses an improved structure of the valve orifice of an aerodynamic holding unit, which is alleged to reduce the rate of decline of the pressure difference within the aerodynamic holding unit in a preparatory configuration, thereby resulting in a reduced likelihood of accidental actuation, which is beneficial for patient compliance and treatment outcomes.

[0006] Although such a device has the advantage of being able to provide an improved breath actuated device, there is still room for improvement. Naturally, there is a need to develop an effective and durable breath actuated device. The present invention improves the robustness of the device by maintaining the vacuum within the diaphragm when the interface cover is left open for an extended period of time without using an interface cover as discussed herein. The present invention also improves the simplicity of manufacture by using a simplified structure of a central rigid disk while improving the robustness. Summary of the Invention

[0007] In one embodiment, the present invention provides an improved breath actuated inhaler device comprising an actuator housing, a canister, and a mechanical release mechanism for triggering a dose in response to breathing. The mechanical release mechanism is similar to the mechanism of the aerodynamic holding unit disclosed in PCT application WO01 / 93933A2, but includes a structure different therefrom and also provides substantial improvements. The aerodynamic holding unit includes a compression spring (preloaded), a lower lid engaging the canister, a diaphragm connected to the upper surface of the lower lid, and a valve flap for sealing a valve orifice located within the diaphragm. The diaphragm includes a central rigid disk and a peripheral flexible polymer ring.

[0008] In one embodiment, the present invention provides an improved breath actuated inhaler device comprising an actuator housing, a canister, and an aerodynamic holding unit including a compression spring (preloaded), a lower lid engaging the canister, a diaphragm connected to the upper surface of the lower lid, and a valve flap for sealing a valve orifice located within the diaphragm. The diaphragm includes a central rigid disk and a peripheral flexible polymer ring for triggering a dose in response to breathing.

[0009] In one embodiment, the present invention provides an improved breath actuated inhaler device comprising an actuator housing, a canister, and an aerodynamic holding unit for triggering a dose in response to breathing.

[0010] In one embodiment, the present invention provides an improved aerodynamic holding unit wherein the central rigid disk of the diaphragm is provided with an interlocking means to securely fix and bond the peripheral flexible polymer ring.

[0011] In one embodiment, the present invention provides an improved aerodynamic holding unit wherein the central rigid disk of the diaphragm is provided with an interlocking means to securely fix and bond the peripheral flexible polymer ring to the central rigid disk of the diaphragm during injection molding of the diaphragm.

[0012] The interlocking means is one or more grooves or cavities. Preferably, the number of interlocking means is between 1 and 25, more preferably, the number is between 5 - 20. The interlocking means have the same or different geometries and may be positioned equidistantly or non - equidistantly from each other.

[0013] In one embodiment, the central rigid disk and the peripheral flexible polymer ring of the diaphragm are formed by a bi-injection molding process. In the first injection, a central rigid disk with an interlocking device is prepared. In the second injection, the peripheral flexible polymer ring of the diaphragm is prepared. During the second injection molding process, the flexible polymer is allowed to flow through the interlocking device of the central rigid disk to form a continuous and unbroken portion on either side of the central rigid disk of the diaphragm. This allows for mechanical bonding of the peripheral flexible polymer ring to the central rigid disk and simultaneously creates a strong adhesion to the central rigid disk. While maintaining a vacuum prior to inhalation, further mechanical interlocking between the central rigid disk and the peripheral flexible polymer ring on the diaphragm is prevented from peeling away from the central rigid disk.

[0014] In some aspects, materials that can be used to construct the central rigid disk include acrylonitrile-butadiene-styrene (ABS), polypropylene (PP), polyethylene (PE), and polytetrafluoroethylene (PTFE). In some aspects, materials that can be used to construct the flexible polymer ring include thermoplastic polyurethane (TPU), silicone, and thermoplastic polyethylene (TPE).

[0015] The hardness of the central rigid disk 20 is generally between 80 - 140 on the Rockwell R scale, but preferably between 100 - 120 on the Rockwell R scale. The hardness of the flexible polymer ring is generally between 55 - 75 Shore A, but preferably between 60 - 70 Shore A.

[0016] In one embodiment, the present invention provides an improved aerodynamic holding unit with a diaphragm, wherein the central rigid disk of the diaphragm is provided with an interlocking device to firmly fix and bond the peripheral flexible polymer ring to the central rigid disk of the diaphragm during the injection molding of the diaphragm, wherein the central rigid disk and the peripheral flexible polymer ring of the diaphragm are formed by a bi-injection molding process.

[0017] In one embodiment, the present invention provides an improved aerodynamic holding unit with a diaphragm, wherein the central rigid disk of the diaphragm is provided with an interlocking device to firmly fix and bond the peripheral flexible polymer ring to the central rigid disk of the diaphragm during the injection molding of the diaphragm, wherein the central rigid disk and the peripheral flexible polymer ring of the diaphragm are formed by a bi-injection molding process, wherein the central rigid disk is prepared with an interlocking device in the first injection, and the peripheral flexible polymer ring of the diaphragm is prepared in the second injection such that during the second injection, the flexible polymer is allowed to flow through the interlocking device of the central rigid disk to form a continuous and unbroken portion on either side of the central rigid disk of the diaphragm.

[0018] In another aspect of the embodiment, the present invention provides a valve flap for sealing the valve opening of a diaphragm, wherein the valve flap is composed of a rigid member and a soft elastomeric member, and the soft elastomeric member forms an airtight lock with the valve opening of the diaphragm. The hardness of the soft elastomeric member is 10-20 Shore A, preferably 12-16 Shore A.

[0019] In one embodiment, the present invention improves the robustness of the device by maintaining the vacuum within the diaphragm when the interface cover remains open for an extended period of at least about 5 minutes, preferably at least about 10 minutes, more preferably at least about 15 minutes, and even more preferably at least about 25 minutes. While maintaining the vacuum prior to inhalation, mechanical interlocking between the central rigid disk and the peripheral flexible polymer ring on the diaphragm is prevented from peeling away from the central rigid disk. Additionally, the valve flap forms an airtight seal with the valve opening of the diaphragm, thereby preventing leakage. When the interface cover remains open, the device remains in an actuatable state without dispensing a dose for at least about 5 minutes, preferably at least about 10 minutes, more preferably at least about 15 minutes, and even more preferably at least about 25 minutes. The force maintained by the aerodynamic holding unit decreases by less than about 6% within a 5-minute period, preferably less than about 3%, preferably from about 2.7% to about 1%; 1.5% is an example.

[0020] Drawings:

[0021] Figure 1 Shows a partial exploded isometric view of a breath-actuated inhaler device.

[0022] Figure 2 Shows a partial exploded isometric view of a breath-actuated inhaler device, showing an exploded view of the aerodynamic holding unit.

[0023] Figure 3 Shows an isometric view of a diaphragm according to the present invention.

[0024] Figure 4 Shows an isometric view of the central rigid disk of a diaphragm according to the present invention.

[0025] Figure 5 Shows an isometric view of the peripheral flexible polymer ring of a diaphragm according to the present invention.

[0026] Figure 6 Shows an isometric view of a valve flap according to the present invention.

[0027] Detailed description of the present invention:

[0028] The present invention provides an improved form of a diaphragm and a valve flap for a trigger mechanism of a breath-actuated metered-dose inhaler and a method of manufacturing the same.

[0029] Figure 1Shows a partial exploded isometric view of a breath-actuated inhaler device having a top shell 40 and a bottom shell 30, the inhaler device accommodating a canister 31 containing a medicament to be dispensed.

[0030] Figure 2 Shows a breath-actuated inhaler device, an exploded view of an aerodynamic holding unit is shown. The aerodynamic holding unit shows a canister support sleeve 32, a spring 35, a diaphragm 33, a diaphragm retaining ring 34, a valve flap 37, a valve flap spring 36, a valve flap housing 38, a cloth filter 39. The canister support sleeve 32 surrounds and drives the canister 31. When the interface cap 301 is in the closed position, the spring 35 is in the compressed position, as shown in this figure. The diaphragm 33 is held in place on the canister support sleeve 32 by a diaphragm retaining ring 34 that snaps onto the canister support sleeve 32. The spring 35 is a compression spring located between the flange of the valve flap housing 38 and the flat support surface of the diaphragm retaining ring 34. The valve flap housing 38 is provided with features for positioning the valve flap member 37 and the valve flap spring 36. The valve flap spring 36 biases the valve flap member 37 against the open valve orifice 204 of the diaphragm 33( Figure 3 ). The cloth filter 39 is welded to the valve flap housing 38, and the aerodynamic holding unit is located within the top shell 40.

[0031] Figures 3 - 5 Shows an isometric view of a diaphragm 33 according to the present invention, having a central rigid disk 20 and a peripheral flexible polymer ring 10, Figure 4 Shows an isometric view of the central rigid disk 20 of a diaphragm according to the present invention, and Figure 5 Shows an isometric view of the peripheral flexible polymer ring 10 of a diaphragm according to the present invention. The central rigid disk 20 has a circumferential opening 201, a transverse baffle 202, a boss 203, a valve orifice 204, and radial ribs 205. The transverse baffle 202 helps to direct the airflow across the valve flap 37 during inhalation( Figure 2 and Figure 6)。The valve orifice 204 is closed and sealed by the valve flap 37 before inhalation. The boss 203 surrounding the valve orifice 204 provides a guiding channel for air to escape during inhalation. The radial ribs 20 support the boss 203 and facilitate the molding process by providing a connection between the boss 203 and the transverse baffle 202, allowing all the structures of the central rigid disk 20 to be molded in a single injection. The circumferential opening 201 allows the flexible polymer to pass through during the molding process, creating a mechanical bond between the two components. The central rigid disk 20 of the diaphragm and the peripheral flexible polymer ring 10 are formed by a two-shot injection molding process. In the first injection, the central rigid disk 10 is prepared, which has circumferential openings 201 serving as interlocking devices. The number of circumferential openings 201 is between 1 and 25, more preferably between 5 and 20, and has the same or different geometries, and can be positioned equidistantly or non-equidistantly from each other. Materials that can be used to construct the central rigid disk include ABS, PP, PE, PTFE. The hardness of the central rigid disk 20 is generally between 80 - 140 on the Rockwell R scale, but preferably between 100 - 120 on the Rockwell R scale. In the second injection, the peripheral flexible polymer ring 10 of the diaphragm is prepared. During the second injection molding process, the flexible polymer is allowed to flow through the circumferential openings 201 of the central rigid disk 10 to form a continuous and uninterrupted portion on either side of the central rigid disk 20 of the diaphragm. This allows the mechanical bond between the peripheral flexible polymer ring 10 and the central rigid disk 20 and simultaneously creates a strong adhesion to the central rigid disk 20. Further mechanical interlocking between the central rigid disk 20 and the peripheral flexible polymer ring 10 on the diaphragm 33 is prevented from peeling off the central rigid disk 20 while maintaining a vacuum before inhalation, especially in the stretched (compressed) state. The advantage of this special arrangement is that, in addition to the chemical bond generated during the two-shot injection molding process, the mechanical bond provides additional security for the two components, especially while maintaining a vacuum before inhalation, especially in the stretched (stressed) state. Materials that can be used to construct the flexible polymer ring include TPU, silicone, TPE. The hardness of the flexible polymer ring is generally between 55 - 75 Shore A, but preferably between 60 - 70 Shore A.

[0032] Figure 6 An isometric view of the valve flap according to the present invention is shown. The valve flap 37 consists of a rigid component 371 and a soft elastomer 372. During the injection molding process, the valve flap 37 is formed as a two-shot component. When the valve flap spring 36 is biased on the valve flap 37, the soft elastomer 372 engages with the valve orifice 204 of the central rigid disk 20 of the diaphragm ( Figure 3)Form an airtight seal. In use, the patient's airflow biases the valve flap 37 onto the valve flap spring 36, thereby opening the valve port 204 on the rigid member 20 of the diaphragm 33. Materials that can be used to construct the soft elastomer 372 include TPU, TPE, or silicone. The hardness of the soft elastomer 372 is typically between 5 and 20 Shore A hardness, but preferably between 12 and 16 Shore A hardness to allow the elastomer 372 to bend sufficiently over the valve port 204.

[0033] In use, once the interface cover 301 of the bottom case 30 is opened, the spring 35 extends partially and pushes the canister support sleeve 32 through the diaphragm ring 34. This causes the peripheral flexible polymer ring 10 of the diaphragm 33 to extend. The valve port 204 on the central rigid disk 20 of the diaphragm 33 is closed by the valve flap 37 biased by the valve flap spring 36. This prevents the spring 35 from fully extending due to the negative pressure accumulation between the diaphragm 33 and the canister support sleeve 32. The diaphragm 33 of the present invention is advantageous because it helps to maintain the vacuum in this extended (compressed) state for a longer period of time due to the chemical and mechanical bonds generated during the two injection molding processes. This effect is further amplified and / or maintained by the soft elastomer 372 of the valve flap 37 that forms an airtight seal with the valve port 204, thereby preventing vacuum leakage. The present invention improves the robustness of the device by maintaining the vacuum within the diaphragm 30 and the canister support sleeve 32 when the interface cover remains open for an extended period of time of at least about 5 minutes, preferably at least about 10 minutes, more preferably at least about 15 minutes, more preferably at least about 25 minutes. While maintaining the vacuum before inhalation, prevent the mechanical interlock between the central rigid disk and the peripheral flexible polymer ring on the diaphragm from peeling off the rigid disk. When the interface cover remains open, the device remains in an actuatable state without dispensing a dose for at least about 5 minutes, preferably at least about 10 minutes, more preferably at least about 15 minutes, more preferably at least about 25 minutes. The force held by the aerodynamic holding unit drops by less than about 6% within a 5-minute period, preferably less than about 3%, preferably from about 2.7% to about 1%: 1.5% is an example. When the user inhales, air enters the device through the ventilation holes 401 on the top cover 40, and the airflow biases the valve flap 37 against the valve flap spring 36, thereby opening the valve port 204 on the central rigid disk 20 of the diaphragm 33, thus completely releasing the vacuum. This causes the spring 35 to fully extend and actuates the canister 31 to dispense a dose.

[0034] The performance of the aerodynamic holding unit in a breath-actuated inhaler is evaluated by measuring the ability of the aerodynamic holding unit to maintain the pressure differential after actuation over a test period of time, typically 5 minutes. The instrument used is Texture Technologies’ Texture Analyzer TA.XTPlus. The widest force probe is connected to the 50 kg load cell of the texture analyzer. The aerodynamic holding unit is placed under the force probe on the texture analyzer base. The probe is moved downwards at a speed of 0.25 mm / s until the force reading is 90 N. The probe is retracted at a speed of 10 mm / s to 2.6 mm above the current position. As soon as the probe is retracted 2.6 mm, the force is recorded as F1. The force probe is allowed to hold at this position for a period of 5 minutes. After 5 minutes, the force is recorded as F2. The data is used to calculate the change in force (ΔF (F1 - F2)) over a period of time and the percentage change. The results are summarized in Table 1.

[0035] Table 1

[0036]

[0037] As can be seen from the data in Table 1, the aerodynamic holding unit of the breath-actuated inhaler according to the present invention improves the robustness of the device by maintaining the vacuum within the diaphragm when the interface cover is kept open for a long time without being used by the patient, and thus improves patient compliance. Surprisingly, this improvement can be achieved even when a valve seal (flap) surface with an average roughness greater than 0.15 μm is employed, which in the prior art is critical for maintaining aerodynamic forces.

Claims

1. A breath-actuated inhaler device, comprising: an actuator housing; a canister; and an aerodynamic holding unit for triggering a dose in response to a breath; wherein the aerodynamic holding unit includes a compression spring (pre-loaded), a lower lid engaging the canister, a diaphragm attached to the upper surface of the lower lid, and a valve flap for sealing a valve orifice located in the diaphragm, wherein the diaphragm includes a central rigid disk and a peripheral flexible polymer ring for triggering the dose in response to a breath, wherein the central rigid disk of the diaphragm is provided with an interlocking device to firmly fix and bond the peripheral flexible polymer ring to the central rigid disk of the diaphragm.

2. The breath-actuated inhaler device according to claim 1, wherein the valve flap is composed of a soft elastomeric component to form an airtight lock with the valve orifice of the diaphragm.

3. The breath-actuated inhaler device according to claim 1, wherein the central rigid disk and the peripheral flexible polymer ring of the diaphragm are formed by a secondary injection molding process.

4. The breath-actuated inhaler device according to claim 1, wherein the hardness of the flexible polymer ring is between 55 - 75 Shore A.

5. The breath-actuated inhaler device according to claim 2, wherein the hardness of the soft elastomeric component is between 5 - 20 Shore A.

6. The breath-actuated inhaler device according to claim 1, wherein the central rigid disk of the diaphragm is provided with an interlocking device to firmly fix and bond the peripheral flexible polymer ring and the central rigid disk.

7. A breath-actuated inhaler device, comprising: an actuator housing; a canister; and an aerodynamic holding unit for triggering a dose in response to a breath; wherein the aerodynamic holding unit includes a compression spring (pre-loaded), a lower lid engaging the canister, a diaphragm attached to the upper surface of the lower lid, and a valve flap for sealing a valve orifice located in the diaphragm, wherein the valve flap is composed of a soft elastomeric component to form an airtight lock with the valve orifice of the diaphragm.

8. The breath-actuated inhaler device according to claim 7, wherein the hardness of the soft elastomeric component is between 5 - 20 Shore A.

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