Patent Grant
11964097
The present invention relates to an inhaler for delivery of a medicament by inhalation and methods of operation thereof, and in particular to the mechanisms of the inhaler for dispensing a dose of medicament and to the resetting of the mechanisms for dispensing a subsequent dose. The present invention also relates to a method of dispensing medicament from an inhaler, and in particular to a method of dispensing a dose of medicament from the inhaler and resetting the inhaler for dispensing a subsequent dose.
There are many ways to provide a dose of medicament to a patient or other intended recipient of the medicament, particularly when it is desired to provide multiple doses of the medicament, for example as part of a treatment regimen or otherwise. Many medicaments, such as those for treating pulmonary or other conditions, are delivered/dispensed to the recipient by inhalation using a suitable inhaler. One commonly used and effective type of multiple dose inhaler is a pressurised metered dose inhaler (pMDI) in which a canister containing medicament in the inhaler is actuated, e.g. by compression, to deliver/dispense a metered dose of the medicament through a mouthpiece to a user. The inhaler may be configured to deliver/dispense a dose of medicament automatically. For example the inhaler may comprise an actuation mechanism to actuate the canister when triggered. The actuation mechanism may be breath-actuated, i.e. triggered by inhalation of a user through a mouthpiece. This ensures that a dose of medicament is dispensed whilst the user is inhaling, which is particularly advantageous since dispensing of a dose of medicament is co-ordinated with inhalation of the dose and synchronisation of the patient's breath-intake (or inspiration) ensures optimal delivery of aerosol medication to the target region in the respiratory tract, with minimal losses due to deposition in the mouth and pharynx. For multiple dose inhalers, the triggering and dispensing mechanisms must be reset after each actuation to enable a subsequent dose to be dispensed when required.
An example breath-actuated pMDI is described in WO-A-2013/038170. The actuation mechanism of this inhaler is operable to compress a canister containing medicament to deliver a metered dose of the medicament in response to inhalation by a user. The actuation mechanism comprises a spring to compress the canister and a trigger mechanism to prevent the spring compressing the canister until a dose is to be dispensed. When a user inhales through a mouthpiece, the trigger mechanism releases the spring, which then compresses the canister to deliver a dose of medicament through a valve of the canister and into the mouthpiece. A resetting mechanism interacts with a cover or cap for the mouthpiece such that movement of the cover into a closed position resets the spring.
Whilst the inhaler disclosed in this application is effective and reliable at dispensing multiple, consecutive doses to a user, it has been observed that in some circumstances, the consecutive doses dispensed from the inhaler may not have a consistent weight of active ingredient (known as actuation weight). Without intending to be bound by any theory, it is believed that this inconsistency in actuation weight (and thus variation in the delivered dose) may occur from user error, because the user of the inhaler does not reset the dispensing mechanism immediately after dispensing a dose (i.e. does not close the mouthpiece cover straight away). Additionally or alternatively, the canister should be reset with the valve in position beneath the canister, but the user may not always follow this instruction. Either of these problems may lead to the metering chamber of the canister valve being incompletely filed and thus the next dose dispensed from the canister valve may not contain the expected weight of medicament.
Therefore there remains a need for an inhaler for delivery of a medicament by inhalation, and a method of dispensing a medicament from an inhaler, in which the delivered dose upon each actuation is consistent and within acceptable tolerances, compared with other doses dispensed by the inhaler.
In accordance with the present invention, there is provided an inhaler for delivery of a medicament by inhalation and a method of dispensing a medicament from an inhaler, which overcome at least one or more of the drawbacks of the prior art. From a first broad aspect, there is provided an inhaler for delivery of a medicament by inhalation, the inhaler comprising an inhaler body for receiving a canister having a dispensing valve; a drive mechanism comprising a biasing means and a moving component, the drive mechanism for driving the canister, when received in the inhaler body, from a rest position in which the valve is closed to at least an actuating position in which the valve is open, the drive mechanism driving the canister when the biasing means is released from a loaded configuration to move the moving component from a first position to a second position; a resetting mechanism for resetting the drive mechanism by moving the moving component from the second position to the first position and reloading the biasing means to the loaded configuration; and a return mechanism for returning the canister from the actuating position to the rest position; wherein the return mechanism comprises a damping system, the damping system configured to enable the canister to automatically return from the actuating position to the rest position within a predetermined time period measured from the release of the biasing means from the loaded configuration.
The claimed inhaler overcomes at least one of the drawbacks of the prior art. For example, the inhaler automatically returns the canister from the actuating position to the rest position, within a predetermined time period, such that the canister valve is returned to its refill point and refilled for a subsequent dose all within this time, irrespective of whether the user of the inhaler activates the resetting mechanism to restore the inhaler to its pre-fire configuration. This occurs over a period of time sufficient for the valve to dispense the entire current dose as the damping mechanism is configured to prevent the canister return occurring too quickly. Namely the valve is held open for a sufficient time to dispense the dose and the valve is returned at a suitable speed to allow the valve to refill completely, but the valve is not held in an open configuration for any longer than is necessary to perform these actions reliably. Furthermore, the valve is reset to its closed position sufficiently quickly that the user will still be holding the inhaler in an upright position, so the valve will be located beneath the canister.
Whilst the canister reset could be performed as a single step at one speed for the entire time period, optionally the damping system is configured such that the predetermined time period comprises a first time segment and a second time segment, wherein movement of the canister from the actuating position to the rest position is slower during the first time segment than during the second time segment. This arrangement optimises the time during which the valve is held open below its fire point (hereinafter referred to as Time Below Fire (TBF)) and so dispenses the entire dose effectively, but also minimises the time before the canister valve reaches its refill point (hereinafter referred to as Time To Refill (TTR)). As discussed above, all this occurs without the user needing to take any action as it is automatic and controlled by the damping mechanism. In some embodiments, during the first time segment the canister is maintained in the actuating position (i.e. there is no movement) and during the second time segment the canister returns from the actuating position to the rest position.
Whilst the predetermined time period might include other time segments, optionally the damping system is configured such that the second time segment immediately follows the first time segment, so the canister movement transitions immediately from slow return or substantially no movement to fast or faster return without any pause or delay inbetween.
Canisters for use in inhalers according to embodiments of the present invention have generally consistent profiles and configurations but differences between canisters due to tolerances should be expected and also the same canister may perform differently under different conditions. Other issues may be encountered towards the end of life (EOL) of the canister compared with the beginning of life (BOL), such as variability in the return force, which may degrade over time. Therefore the damping system is optionally configured such that the tolerances and variations in performance are accounted for in inhalers of embodiments of the present invention. Optionally the first time segment is in the range of about 0.05 to 2.00 seconds, optionally in the range of about 0.10 to 1.75 seconds, optionally in the range of about 0.20 to 1.50 seconds, optionally in the range of about 0.30 to 1.25 seconds, optionally in the range of about 0.40 to 1.20 seconds. Time segments within one or more of these ranges have been found to be suitable at accounting for variations in performance and also at accounting for tolerances and differences between canisters and batches of canisters etc. Optionally the first time segment is at least about 0.20 seconds, optionally at least about 0.30 seconds, optionally at least about 0.40 seconds. These minimum times have been found to be optimal for ensuring the entire dose in the valve is dispensed each actuation.
Optionally the second time segment is in the range of about 0.10 to 2.00 seconds, optionally in the range of about 0.30 to 1.80 seconds, optionally in the range of about 0.40 to 1.70 seconds, optionally in the range of about 0.60 to 1.60 seconds, optionally in the range of about 0.80 to 1.50 seconds, optionally in the range of about 1.00 to 1.40 seconds. Again, time segments within one or more of these ranges have been found to be suitable at accounting for variations in performance and also at accounting for tolerances and differences between canisters and batches of canisters etc. Optionally the second time segment is less than about 2.0 seconds, optionally less than about 1.75 seconds, optionally less than about 1.50 seconds, optionally less than about 1.25 seconds, optionally about 1.20 seconds. These maximum times have been found to be optimal for ensuring the valve refills quickly and fully. As discussed above, it is thought to be particularly advantageous for the valve to be refilled fully whist the canister is held in a generally upright position, i.e. within a time frame of use by the user where the inhaler has not yet been removed from the user's mouth. Optionally the first time segment combined with the second time segment is a total time of less than about 2.5 seconds, optionally less than about 2.00 seconds, optionally less than about 1.75 seconds, optionally less than about 1.50 seconds. This provides a sufficient time for the valve to dispense and refill but is not so long as to adversely affect the quality of valve refill or to allow the user to significantly reposition the inhaler from the upright position in which it is used.
As discussed above, the inhaler comprises a damping system to provide the damped movement during the predetermined time period. Optionally the damping system comprises a rotary damper. Such dampers are available and perform reliably over multiple uses and are suited for use in embodiments of the present invention. Examples of such devices are rotary dampers as sold by ACE Controls International/Inc. or ACE Stoßdämpfer GmbH, etc.
Optionally the damping system comprises a rod, the rod coupled with a shaft of the rotary damper such that the rod rotates with the shaft, the rod rotation being controlled by the shaft rotation in at least a first direction of rotation. Thus movement of the rod is controlled by the damper. Optionally the rod is moveable relative to the shaft in an axial direction. Optionally the moving component comprises a cam follower and the rod comprises a cam track for receiving the cam follower, the cam track and the cam follower being configured such that the cam follower abuts an edge of the cam track and applies an axial moving force to the rod when the moving component moves from the first position to the second position. Thus a mechanical arrangement is provided in which the rod can move rotationally and/or axially in at least one and optionally two directions. Optionally the cam track and the cam follower are configured such that the axial moving force applied by the cam follower to the edge of the cam track axially moves the rod in a direction away from the shaft and the rod thereby applies a driving force to the canister to drive the canister from the rest position to at least the actuating position. Optionally the cam track comprises at least a first section and a second section, the first section being substantially aligned with the axis of the rod and the second section being curved about a portion of the outer surface of the rod in a direction substantially away from the first section of the track. Thus the two speeds of movement of the rod are provided. The first section of track is configured to allow axial movement of the rod relative to the cam follower and the second section of the track is configured to allow axial and rotational movement of the rod relative to the cam follower. Rotational movement of the rod is damped by the rotational damper and the axial movement of the rod is not damped by the rotational damper so, for example, the combined rotational and axial movement of the rod is controlled and slower and when the cam follower reaches the axial section of the track, more rapid movement of the rod in the axial direction is enabled. Optionally the second section of the track is substantially helical about the portion of the outer surface of the rod. This provides a smooth and controlled movement of the cam follower. Optionally, for balance and improved control, the rod comprises a pair of cam tracks diametrically opposed on the rod outer surface, optionally wherein the second sections of the cam tracks are helical and the helices are either both right-handed or both left-handed.
As discussed above, optionally the cam track is configured such that a first section of the cam track is configured such that the damping system enables the canister to automatically return from the actuating position to the rest position initially at a first speed and is further configured such that the damping system enables the canister to automatically return from the actuating position to the rest position at a second speed at a later time within the predetermined time period. This enables efficient dose dispensing and refill of the canister valve within an appropriate time. In alternative embodiments, as the yoke has not reached its stop position abutting the portions of the cap when the canister has reached its actuating position, the cam track is configured such that the damping system enables the yoke to continue to move and the canister is maintained in its actuating position during yoke movement, and the cam track is further configured such that the damping system enables the canister to automatically return from the actuating position to the rest position at a later time within the predetermined time period, after the yoke movement has ceased. This enables efficient dose dispensing and refill of the canister valve within an appropriate time,
Prior to activation of the inhaler, the inhaler may be held in a closed configuration for many hours and may only be used once or twice a day, for example. Therefore it is helpful in some embodiments to relieve the loading of the biasing means to reduce or avoid stresses on certain components of the inhaler. Optionally the inhaler further comprises a load-relieving mechanism configured to support at least one of the moving component and at least a part of the damping system in a spaced apart position in which the moving component and/or the part of the damping system is not in contact with the canister, when the canister is received in the inhaler body. Thus the stresses that might otherwise be imparted by the loaded biasing means to components of the inhaler are reduced or otherwise alleviated. Optionally the load-relieving mechanism is configured to release the moving component and/or the part of the damping system to thereby bring the moving component and/or the part of the damping system, under the load of the biasing means, into contact with the canister, when the canister is received in the inhaler body. This may be directly or indirectly via another component or mechanism of the inhaler.
Optionally the load-relieving mechanism is configured to release the moving component to thereby bring the rod of the damping system, under the load of the biasing means, into contact with the canister, when the canister is received in the inhaler body, such that the rod is enabled to apply the driving force to the canister to drive the canister from the rest position to at least the actuating position. Thus the rod only contacts the canister when the biasing force is about to be applied to the canister and reduces the likelihood of wear of the rod when the inhaler is not about to be used. Optionally the load-relieving mechanism is configured such that the cam follower does not abut the edge of the cam track when the load-relieving mechanism is supporting the moving component and/or the part of the damping system. Again this alleviates any stresses or wear that might otherwise occur, for example between the cam follower and the edge of the track.
In alternative embodiments of the present invention, the damping system comprises a linear damper. All the above embodiments and optional features are applicable to this alternative embodiment where compatible and appropriate and are not intended to be limited only to the embodiment comprising a rotary damper. In the alternative embodiment, the linear damper comprises a generally cylindrical reservoir containing an incompressible fluid and an elongate piston arranged coaxially through the reservoir and protruding at both a proximal and a distal end from the reservoir, relative to the canister when received in the inhaler body, the piston configured to slide linearly back and forth through the reservoir along the co-axis. The piston performs effectively the same function as the rod of the rotary damper embodiment and the description of features and functions of the rod discussed throughout the specification is also applicable where compatible to the piston.
As discussed above, the piston is configured to slide back and forth through the reservoir, thus the protruding ends move in and out of the reservoir. To seal the piston, particularly as its ends move into and out of the reservoir, optionally the linear damper further comprises a lower seal for sealing the proximal end of the piston relative to the reservoir and an upper seal for sealing the distal end of the piston relative to the reservoir, such that fluid egress from the reservoir is substantially minimised or prevented.
As discussed above in relation to the rotary damper embodiment, optionally the linear (axial) movement of the rod, and in this embodiment, of the piston, can occur at two speeds, one faster than the other. In this embodiment, the damper is optionally configured in this manner. The reservoir of the linear damper comprises a proximal chamber having a first diameter and a distal chamber having a second diameter, the first diameter being less than the second diameter and optionally further comprising an intermediate section between the proximal and distal chambers, the intermediate section having a diameter that increases from a proximal end adjacent the reservoir proximal chamber to a distal end adjacent the reservoir distal chamber. The linear damper optionally further comprises a piston seal inside the reservoir, the piston seal surrounding the piston and affixed thereto and having a diameter such that it seals against the inside of the proximal chamber of the reservoir of the linear damper. As the proximal chamber has a smaller diameter, the piston seal optionally does not contact and/or seal against the larger diameter distal chamber or may contact the walls of the distal chamber but does not completely seal against the walls and therefore allows fluid flow to at least some degree around the outside of the seal as discussed further below.
When the piston seal is located in the proximal chamber and seals against the inside walls of the chamber, fluid flow is restricted or prevented between the proximal and distal chambers by the piston seal. However in order for the piston to be able to move, at least at a slow rate, some fluid flow between the chambers is required. Therefore the piston optionally comprises a fluid flow channel, the fluid flow channel having an inlet beyond the proximal end of the piston seal and an outlet beyond the distal end of the piston seal and configured such that fluid may flow between the proximal chamber and the distal chamber even when the piston seal is positioned so as to fluidly isolate the proximal chamber from the distal chamber. Fluid flow between the chambers is regulated by the configuration of the channel (e.g. its diameter and inlet/outlet sizes), therefore movement of the piston, particularly the rate of movement of the piston, is controlled, at least until the piston seal moves (with movement of the piston in the distal direction) from the proximal chamber and into the distal chamber.
Similar to the rotary damper embodiment, the linear damper is coupled to the moving member such that movement of the moving component from the first position to the second position, when the biasing means is released from the loaded configuration, drives the piston proximally the piston thereby applying a driving force to the canister to drive the canister from the rest position to at least the actuating position. Optionally the channel of the piston is configured such that fluid flow therethrough is restricted to thereby minimise or prevent axial movement of the piston in the distal direction relative to the reservoir until the canister has reached at least the actuating position. Therefore under the significant load when the biasing means is released, fluid flow through the channel is effectively prevented or at least minimised such that the piston is fixed relative to moving member during driving of the canister from the rest position to at least the actuating position (which might occur in, for example, a very short time period such as 10 ms, optionally 8 ms, optionally 6 ms, optionally 5 ms, optionally 4 ms, optionally 3 ms). However, after this initial rapid movement, fluid flow through the channel is possible. Optionally the channel of the piston is configured such that fluid flows therethrough at a restricted rate from the proximal chamber to the distal chamber, thereby enabling the piston to move axially in the distal direction at a controlled rate. Optionally the piston is configured such that a driving force from a return spring of the canister is sufficient to drive the piston axially in the distal direction, optionally wherein the return spring of the canister is further assisted by at least one additional return spring of the inhaler. Canisters for use in such inhalers according to embodiments of the present invention comprise a spring configured to return the valve (which is compressed into the canister to dispense a dose) to its rest position, in which the valve (typically a metering valve with a chamber sized to a desired dose level) is refilled from the main reservoir of the canister ready to dispense the next dose. The force of this spring is typically more than sufficient to return the canister to its rest state and therefore is able to push the canister in the distal direction and to push the piston axially in the distal direction. Fluid flow through the channel controls the rate at which the piston moves and thus the rate at which the canister valve moves to its rest position. Optionally to assist the valve spring of the canister, one or more return springs are provided in the inhaler, that are compressed when the inhaler is fired and unload thereafter to push the canister in the distal direction.
As discussed previously, the linear damper is optionally configured such that axial movement of the piston in the distal direction is for the first time segment at a first speed determined by the piston channel followed in the second time segment at a second speed when the piston seal passes into the distal chamber and thereby fluid flows around the outside of the piston seal. Optionally the piston seal comprises a lip seal comprising concentric rings separated by a thinner section, the lip seal configured to flex radially inwardly or outwardly under fluid pressure to allow or minimise fluid flow around the outside of the piston seal. Therefore as the piston seal moves from the proximal chamber to the distal chamber, the outer ring can flex radially towards the inner ring(s) under fluid pressure to further open the channel around the outside of the seal and conversely as the piston seal moves from the distal chamber to the proximal chamber, the outer ring can flex radially away from the inner ring(s) under fluid pressure (particularly in the gap between the rings) to further improve the seal between the piston seal and the distal chamber walls and to minimise or prevent fluid flow around the outside of the seal.
A further advantage of certain embodiments of the linear damper described herein is the insensitivity of the linear damper to the operating conditions and particularly to the operating temperature. For example, in lower (cold) temperatures, the seal is stiffer, so bypass occurs earlier and this compensates for some of the increased viscosity of the damping fluid due to the cold temperature. Conversely, in higher (hot) temperatures the seal will be more flexible, so bypass occurs later, which compensates for and minimises the effect of the reduced viscosity of the damping fluid.
As discussed above in relation to the rotary damper embodiment, the inhaler of this embodiment optionally further comprises a load-relieving mechanism configured to support at least one of the moving component and at least a part of the damping system in a spaced apart position in which the moving component and/or the part of the damping system is not in contact with the canister, when the canister is received in the inhaler body. Thus the stresses that might otherwise be imparted by the loaded biasing means to components of the inhaler are reduced or otherwise alleviated. Optionally the load-relieving mechanism is configured to release the moving component and/or the part of the damping system to thereby bring the moving component and/or the part of the damping system, under the load of the biasing means, into contact with the canister, when the canister is received in the inhaler body. This may be directly or indirectly via another component or mechanism of the inhaler.
Optionally the load-relieving mechanism is configured to release the moving component to thereby bring the proximal end of the piston of the damping system, under the load of the biasing means, into contact with the canister, when the canister is received in the inhaler body, such that the piston is enabled to apply the driving force to the canister to drive the canister from the rest position to at least the actuating position. Thus the piston only contacts the canister when the biasing force is about to be applied to the canister and reduces the likelihood of wear of the piston when the inhaler is not about to be used.
As discussed above, the reservoir of the damper contains an incompressible fluid. Optionally the incompressible fluid comprises silicone oil, optionally medical grade silicone oil and/or optionally silicone oil with a viscosity of about 5000 cSt, optionally about 4500 cSt, optionally about 4000 cSt, optionally about 3500 cSt, optionally about 3000 cSt, optionally about 2500 cSt, optionally about 2000 cSt, optionally about 1500 cSt, optionally about 1000 cSt, optionally about 750 cSt, optionally about 500 cSt, optionally about 250 cSt, optionally about 200 cSt. The fluid viscosity and other properties are optimised to the specific configuration of the linear damper.
In further alternative embodiments of the present invention, the damping system comprises an alternative linear damper. All the above embodiments and optional features are applicable to this alternative embodiment where compatible and appropriate and are not intended to be limited only to the embodiment comprising a rotary damper or another linear damper. In the alternative embodiment, the linear damper is a hydraulic damper comprising a generally cylindrical reservoir containing an incompressible fluid and an elongate piston arranged coaxially with the reservoir and protruding at proximal end from the reservoir, relative to the canister when received in the inhaler body, the piston configured to slide linearly back and forth into and out of the reservoir along the co-axis. Optionally the linear damper further comprises an elongate piston arranged coaxially with the reservoir and protruding at distal end from the reservoir, the elongate piston comprising a sealing section at a proximal end thereof, wherein the reservoir comprises a distal chamber and a proximal chamber that are fluidly isolated by the sealing section. Optionally the sealing section comprises a channel therethrough configured to allow fluid flow between the distal chamber and the proximal chamber such that movement of the sealing section is enabled and thus movement of the pistons is also enabled.
As is readily appreciable, the linear damper of this embodiment is similar in many aspects to the linear damper of the other embodiment (and has many similar features and functions as the rotary damper embodiment) and therefore all features and functions discussed in relation to the other embodiments are envisaged as part of this embodiment also where compatible.
Furthermore, all embodiments have at least some features in common, for example the biasing means. Optionally the biasing means comprises a spring, the spring optionally having a spring force when compressed in the range of about 45 to 85 N, optionally in the range of about 50 to 80 N, optionally in the range of about 55 to 75 N, optionally in the range of about 55 to 65 N.
Optionally the inhaler further comprises a breath-triggering mechanism configured to hold the biasing means in the loaded configuration and to release the biasing means to move the moving component from the first position to the second position in response to airflow in the inhaler. Optionally the breath-triggering mechanism comprises a vane configured to pivot in response to airflow in the inhaler and a latch configured to release the biasing means when the vane pivots. This embodiment is advantageous as the user of the inhaler need only inhale and the inhaler automatically triggers the dispensing of a dose and then resets the canister, all without further user interaction being required and all within a short period of time, ensuring efficient and reliable performance of the inhaler, particularly on refilling of the valve in preparation for the subsequent dose, as will be described further below.
From a further broad aspect, there is provided a method of dispensing medicament from an inhaler, the method comprising releasing a biasing means of a drive mechanism of the inhaler from a loaded configuration, moving, by the released biasing means, a moving component of the drive mechanism from a first position to a second position to drive a canister, received in a body of the inhaler, from a rest position, in which a valve of the canister is closed, to at least an actuating position, in which the valve is open, automatically returning the canister from the actuating position to the rest position within a predetermined time period measured from the release of the biasing means from the loaded configuration, the automatic return of the canister being regulated by a return mechanism comprising a damping system, and resetting the drive mechanism with a resetting mechanism that moves the moving component from the second position to the first position and reloads the biasing means to the loaded configuration. Optionally the step of automatically returning the canister within the predetermined time period comprises automatically returning the canister during a first time segment during which movement of the canister from the actuating position to the rest position is slower than during a second time segment. Optionally the second time segment immediately follows the first time segment. Optionally the first time segment is in the range of about 0.05 to 2.00 seconds, optionally in the range of about 0.10 to 1.75 seconds, optionally in the range of about 0.20 to 1.50 seconds, optionally in the range of about 0.30 to 1.25 seconds, optionally in the range of about 0.40 to 1.20 seconds. Optionally the first time segment is at least about 0.20 secs, optionally at least about 0.30 seconds, optionally at least about 0.40 seconds. Optionally the second time segment is in the range of about 0.10 to 2.00 seconds, optionally in the range of about 0.30 to 1.80 seconds, optionally in the range of about 0.40 to 1.70 seconds, optionally in the range of about 0.60 to 1.60 seconds, optionally in the range of about 0.80 to 1.50 seconds, optionally in the range of about 1.00 to 1.40 seconds. Optionally the second time segment is less than about 2.0 seconds, optionally less than about 1.75 seconds, optionally less than about 1.50 seconds, optionally less than about 1.25 seconds, optionally about 1.20 seconds. Optionally the first time segment combined with the second time segment is a total time of less than about 2.5 seconds, optionally less than about 2.00 seconds, optionally less than about 1.75 seconds, optionally less than about 1.50 seconds.
Optionally the damping system comprises a rotary damper. Rotary dampers are known in the art and are configured so as to have a torque that must be overcome and by which the rate of rotation of the damper is controlled. Optionally the damping system further comprises a rod, the rod coupled with a shaft of the rotary damper and wherein the rod rotates with the shaft, the rod rotation being controlled by the shaft rotation in at least a first direction of rotation. Optionally the rod moves relative to the shaft in an axial direction. Optionally the moving component comprises a cam follower and the rod comprises a cam track for receiving the cam follower, the cam follower abutting an edge of the cam track and applying an axial moving force to the rod when the moving component moves from the first position to the second position. Optionally the axial moving force applied by the cam follower to the edge of the cam track axially moves the rod in a direction away from the shaft and the rod thereby applies a driving force to the canister to drive the canister from the rest position to at least the actuating position. Optionally the cam track comprises at least a first section and a second section, the first section being substantially aligned with the axis of the rod and the second section being curved about a portion of the outer surface of the rod in a direction substantially away from the first section of the track. Optionally the first section of track allows axial movement of the rod relative to the cam follower and the second section of the track allows axial and rotational movement of the rod relative to the cam follower.
Optionally the rotational damper damps the rotational movement of the rod but not the axial movement of the rod. Optionally the second section of the track is substantially helical about the portion of the outer surface of the rod. Optionally the rod comprises a pair of cam tracks diametrically opposed on the rod outer surface, optionally wherein the second sections of the cam tracks are helical and the helices are either both right handed or both left-handed.
Optionally the canister automatically returns from the actuating position to the rest position initially at a first speed along a first section of the cam track and automatically returns from the actuating position to the rest position at a second speed at a later time along a second section of the cam track within the predetermined time period. Optionally, the first speed is substantially zero, i.e. the canister does not move initially, but returns from the actuating position to the rest position at a later time along a second section of the cam track within the predetermined time period.
Optionally the method further comprises supporting at least one of the moving component and at least a part of the damping system in a spaced apart position by a load relieving mechanism, the moving component and/or the part of the damping system not directly contacting the canister when supported by the load relieving mechanism.
Optionally the method further comprises releasing the moving component and/or the part of the damping system to thereby bring the moving component and/or the part of the damping system, under the load of the biasing means, into contact with the canister. Optionally the load-relieving mechanism releases the moving component to thereby bring the rod of the damping system, under the load of the biasing means, into contact with the canister, enabling the rod to apply the driving force to the canister and driving the canister from the rest position to at least the actuating position. Optionally the cam follower does not abut the edge of the cam track when the load-relieving mechanism supports the moving component and/or the part of the damping system.
Optionally the damping system comprises a linear damper. Optionally the linear damper comprises a generally cylindrical reservoir containing an incompressible fluid and an elongate piston arranged coaxially through the reservoir and protruding at both a proximal and a distal end from the reservoir, relative to the canister when received in the inhaler body, wherein the piston slides linearly back and forth through the reservoir along the co-axis. Optionally the linear damper further comprises a lower seal that seals the proximal end of the piston relative to the reservoir and an upper seal that seals the distal end of the piston relative to the reservoir, such that fluid egress from the reservoir is substantially minimised or prevented. Optionally the reservoir of the linear damper comprises a proximal chamber having a first diameter and a distal chamber having a second diameter, the first diameter being less than the second diameter and optionally further comprising an intermediate section between the proximal and distal chambers, the intermediate section having a diameter that increases from a proximal end adjacent the reservoir proximal chamber to a distal end adjacent the reservoir distal chamber. Optionally the linear damper further comprises a piston seal inside the reservoir, the piston seal surrounding the piston and affixed thereto and having a diameter such that it seals against the inside of the proximal chamber of the reservoir of the linear damper.
Optionally the piston comprises a fluid flow channel, the fluid flow channel having an inlet beyond the proximal end of the piston seal and an outlet beyond the distal end of the piston seal and wherein fluid flows between the proximal chamber and the distal chamber even when the piston seal is positioned so as to fluidly isolate the proximal chamber from the distal chamber. Optionally the step of moving the moving component from the first position to the second position further comprises driving the piston proximally and applying a driving force to the canister to drive the canister from the rest position to at least the actuating position. Optionally the method further comprises the step of restricting the fluid flow through the channel to thereby minimise or prevent axial movement of the piston in the distal direction relative to the reservoir until the canister has reached at least the actuating position. Optionally the channel of the piston is configured such that fluid flows therethrough at a restricted rate from the proximal chamber to the distal chamber, thereby enabling the piston to move axially in the distal direction.
Optionally the method further comprises the step of driving the piston axially in the distal direction with a driving force from a return spring of the canister, optionally further comprising the step of additionally driving the piston axially in the distal direction with a driving force from at least one return spring of the inhaler. Optionally the piston moves axially in the distal direction for the first time segment at a first speed determined by the piston channel followed in the second time segment at a second speed when the piston seal passes into the distal chamber and thereby fluid flows around the outside of the piston seal. Optionally the piston seal comprises a lip seal comprising concentric rings separated by a thinner section, wherein the lip seal flexes radially inwardly or outwardly under fluid pressure and allows or minimises fluid flow around the outside of the piston seal.
Optionally the method further comprises supporting at least one of the moving component and at least a part of the damping system in a spaced apart position by a load relieving mechanism, the moving component and/or the part of the damping system not directly contacting the canister when supported by the load relieving mechanism. Optionally the method further comprises releasing the moving component and/or the part of the damping system to thereby bring the moving component and/or the part of the damping system, under the load of the biasing means, into contact with the canister. Optionally the load-relieving mechanism releases the moving component to thereby bring the proximal end of the piston, under the load of the biasing means, into contact with the canister, enabling the piston to apply the driving force to the canister and driving the canister from the rest position to at least the actuating position.
Optionally the linear damper further comprises a piston seal inside the reservoir, the piston seal surrounding the piston and affixed thereto sealing against the inside of the reservoir of the linear damper. Optionally the piston comprises a fluid flow channel, the fluid flow channel having an inlet beyond the proximal end of the piston seal and an outlet beyond the distal end of the piston seal and wherein fluid flows between a proximal chamber of the reservoir and a distal chamber of the reservoir through the channel, the proximal and distal chambers fluidly isolated by the piston seal. For example, the fluid flow channel may be formed in a solid portion of the piston, some distance removed from the seal area.
Optionally the step of moving the moving component from the first position to the second position drives the piston proximally and the piston applies a driving force to the canister and drives the canister from the rest position to at least the actuating position.
Optionally the method further comprises the step of holding the biasing means in the loaded configuration with a breath-triggering mechanism that releases the biasing means in response to airflow in the inhaler. Optionally the method further comprises the step of pivoting a vane of the breath-triggering mechanism in response to airflow in the inhaler, the pivoting vane releasing a latch of the breath-triggering mechanism to release the biasing means.
Preferred aspects and embodiments of the present invention will now be described, by way of example only, with reference to the accompanying drawings, in which:
Inhalers and methods of operating inhalers in accordance with embodiments of the present invention are illustrated in the figures.
Referring to
Inside the inhaler 10 there is a canister 50 with a reservoir 52 that contains medicament. A valve 54 of the canister 50 has a metering chamber for metering a single dose of the medicament, as is known in the art. To dispense a dose of medicament, the canister 50 is compressed and a stem 53 of the valve 54, which sits in a seat 17 of the mouthpiece 16, is forced into the canister 50, which opens the valve 54 and the pressurised dose of medicament is expelled into the mouthpiece 16 for inhalation by the user. The canister 50 is compressed by a main spring 20 (shown in the exploded view of the inhaler 10 of
Typically the spring 20 has a force in the range of about 45 to 85 N when compressed and therefore drives the yoke 22 rapidly to its fired position when released, for example in just a few milliseconds, such as around 4 ms. As the yoke 22 moves to its fired position, it interacts with a damping system 100 of the inhaler 10, driving a rod 120 of the damping system 100 downwardly as will be described in more detail with reference to
In inhalers 10 known in the art, such as well-known pMDI Inhalers, it is known that a problem may arise if the valve 54 is reset whilst the inhaler is in a position other than being held upright. For example, in the arrangement shown in the figures, the valve 54 remains in its open position until the yoke 22 is pushed back to its first position, which also reloads the spring 20. This is achieved by the user of the inhaler 10 closing the cap 14. The bearing surfaces 15 of the cap 14 are cams that impart an upward force on the feet 23 of the yoke 22 when the cap 14 is rotated by the user to its closed position to cover the mouthpiece 16. A latch mechanism 34 then engages to hold the spring 20 in its compressed state ready for the next actuation. A problem with this arrangement is that the user might forget to close the cap 14 straight after use and it has been observed that in some cases, this can lead to the metering chamber of the valve 54 refilling less effectively. Even if the cap 14 is closed relatively quickly after using the inhaler 10, it is often the case that the user will remove the inhaler 10 from the dispensing position in which the inhaler 10 is generally upright, and close the cap 14 with the inhaler 10 in a different orientation, for example with the mouthpiece 16 facing upwards. It has recently been observed that orientation of the canister 50 when it is moving to its rest position (thereby refilling the valve 54) may also influence how well the valve 54 refills and may affect the quality of the next dose of medicament, since gravity might also affect filling of the valve 54, particularly towards the canister 50 end of life when the fluid level is lower.
Therefore the inhalers 10 according to embodiments of the present invention comprise a mechanism for automating closure of the valve 54 by returning the canister 50 to its rest position soon after the current dose has been dispensed, irrespective of whether the user closes the cap 14 straight after using the inhaler 10. Furthermore, the automated closure of the valve 54 occurs within a predetermined time period and is sufficiently soon after dispensing the dose that it is unlikely, or even not possible, that the user will have reoriented the inhaler 10 from its upright position (i.e. the closure of the valve 54 occurs quickly enough that the user will not have reacted to any significant extent before the valve 54 is closed and so the valve 54 will close whilst the user still has the inhaler 10 in its upright, in use, position). As illustrated in
The damping system 100 further comprises a rod 120. The rod 120 is generally elongate and has an inner bore 122 along its central axis for receiving the shaft 114 of the rotary damper 110 (as seen in
The damping system 100 further comprises a plate 130 and as seen in
Referring to
Operation of the inhaler 10 of this embodiment will now be described, with reference to
When the user wishes to inhale a dose of medicament from the inhaler 10, the first step is to open the cap 14 (although it should be noted that the user may need to shake the inhaler 10 before use, but further discussion of this requirement is not necessary as it is known in the art). Opening the cap 14 rotates the bearing surfaces 15 of the cap 14 and the yoke 22 moves slightly in the proximal direction under the force of the main spring 20, as shown in
The inhaler 10 of these embodiments is a breath-triggered inhaler 10 and, when the user inhales through the mouthpiece 16, the airflow/pressure drop pivots a vane 32 (see
After the inhaler 10 has been fired, as shown in
In the embodiment shown in
Rotation of the rod 120 is controlled by the rotary damper 100 and the shaft 114 rotates at a controlled speed, due to the torque of the damper 100 that must be overcome to rotate the shaft 114 of the damper 100, allowing the rod 120 to move axially along the shaft 114 in the distal direction also at a controlled speed. However once the cam follower tooth 132 reaches the beginning of the lower portion 124 of the cam track, no further rotation of the rod 120 is required to enable the distal, axial rod 120 movement, since the cam track at its lower portion 124 is linear. Thus axial movement of the rod 120 in the distal direction is much quicker in this second segment of the predetermined time period of operation of the inhaler 10 (compared with the first time segment when the cam follower tooth 132 is travelling along the helical portion 126 of the cam track). In effect, the rod 120 bypasses the control of the rotary damper 100 once it reaches the beginning of the lower portion 124 of the cam track. Therefore, as seen in
As shown in
An alternative embodiment of the present invention is shown in
An alternative embodiment of the present invention is shown in
As shown in
Referring to
As shown in
The difference in operation between the two embodiments is illustrated in
As the rod 120 rotates under control of the damping mechanism 100, the cam follower tooth 132 moves along the upper cam track 126 until it reaches the junction with the lower cam track 124. At this point, the rod 120 is released and can move rapidly in the axial direction, allowing the valve stem 53 to be released from the canister 50 and thus moving the canister upwards rapidly, as illustrated by line 501c. In this embodiment, the yoke feet 23 are still not quite in contact with the bearing surfaces 15 and so the yoke 22 moves rapidly downwards to its rest point, as illustrated by line 231c. The force of the return springs is not as great as the force of the drive spring 20, so the lines 501c and 231c are not as close to vertical as lines 501a and 231a.
In contrast, in the embodiment illustrated in
A still further embodiment is illustrated in
Referring to
The reservoir 210 of the damping system 200 is generally cylindrical and has two chambers 212, 214. The upper or distal chamber 214 has an inner diameter that is larger than the inner diameter of the lower or proximal chamber 212. As shown in
As illustrated in
Operation of an inhaler 10 having the linear damping system 200 of this embodiment will now be described, with reference to
As before, when the user wishes to inhale a dose from the inhaler 10, the first step is to open the cap 14, which rotates the bearing surfaces 15 of the cap 14 and the yoke 22 moves slightly in the proximal direction under the force of the main spring 20, as shown in
As discussed above, when the user inhales through the mouthpiece 16 the latch mechanism 34 is released and the main spring 20 unloads, pushing downwardly on the yoke 22. The force of the spring 20 is large and the yoke 22 moves rapidly to a second, fired position, which is shown in
As for the previous embodiment, the initial spacing between the canister base 56 and the yoke collar 24 is maintained, as shown in
However once the piston seal 250 reaches the taper between the two chambers 212, 214, the seal against the inner surface of the reservoir 210 starts to leak and fluid passes around the outside of the piston seal 250. Soon after the piston seal 250 passes into the distal chamber 214 and no longer contacts the inner surface of the reservoir 210 due to the larger diameter of the distal chamber 214. Fluid is now able to flow quite freely between the chambers 212, 214 and the piston 220 moves axially in the distal direction much more quickly in this second segment of the predetermined time period of operation of the inhaler 10 (compared with the first time segment when piston seal 250 sealed against the inner surface of the proximal chamber 212). In effect, the piston 220 reaches a fluid bypass once the piston seal 250 leaves the proximal chamber 212 and enters the distal chamber 214 and little if any damping occurs at this stage and furthermore, as the piston seal 250 is not in contact with the chamber wall, there is no piston seal friction to resist movement either. Therefore, as seen in
The final stage of operation of this embodiment of the invention is again for the drive mechanism of the inhaler 10 to be reset so that the main spring 20 is reloaded ready to dispense a subsequent dose that is now metered into the valve 54 of the canister 50. As discussed above, proximal movement of the yoke 22 under the force of the main spring 20 is halted by the yoke feet 23 contacting the bearing surfaces 15 of the cap 14. Therefore to move the yoke 22 back to its first position, the user simply rotates the cap 14 back to the closed position (in which the cap 14 covers the mouthpiece 16, as shown in
Further alternative embodiments of the present invention are shown in
As discussed above, embodiments of the present invention advantageously provide inhalers 10 which automatically reset after dispensing a dose irrespective of user interaction with the inhalers 10. This is important because effective and reliable dosing from such inhalers 10 is an important requirement of these devices and variation between doses in terms of the amount of medication provided to the user is undesirable. The inhalers 10 of the embodiments of the present invention are very effective in this regard. For example, with reference to
Therefore inhalers in accordance with the embodiments of the present invention address at least one of the drawbacks of the prior art, providing automatic resetting of a canister and its valve to improve performance of the inhaler and its reliability and consistency between doses over the full lifetime of the device.
This application is a U.S. National Stage application of International Application No. PCT/EP2019/055521, filed on Mar. 6, 2019, said International Application No. PCT/EP2019/055521 claims benefit under 35 U.S.C. § 119(e) of the U.S. Provisional Application No. 62/639,704, filed Mar. 7, 2018. Each of the above listed applications is incorporated by reference herein in its entirety for all purposes.
| Filing Document | Filing Date | Country | Kind |
|---|---|---|---|
| PCT/EP2019/055521 | 3/6/2019 | WO |
| Publishing Document | Publishing Date | Country | Kind |
|---|---|---|---|
| WO2019/170718 | 9/12/2019 | WO | A |
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| Number | Date | Country | |
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| 20210008302 A1 | Jan 2021 | US |
| Number | Date | Country | |
|---|---|---|---|
| 62639704 | Mar 2018 | US |
