NZ622662B2

NZ622662B2 - Inhaler

Info

Publication number: NZ622662B2
Application number: NZ622662A
Authority: NZ
Inventors: Simon Christopher Berry; Jonas Christiansen; Svend Erik Elgaard; Esben Johansen; Ller Claus Schmidt M; J Rgen Rasmussen; William Treneman
Original assignee: Astrazeneca Ab
Priority date: 2011-09-14
Filing date: 2012-09-12
Publication date: 2016-02-02

Abstract

inhaler (100) for delivery of a medicament by inhalation is disclosed. The inhaler comprises a dispensing mechanism visible through a magnified window (200) , the dispensing mechanism being configured to dispense a dose of medicament on actuation. The inhaler further comprises a dose counting mechanism comprising a counter and a translating member. The translating member comprises a pawl. The counter comprises a first count wheel, a second count wheel and an intermediate wheel engaged with the second count wheel and in selective engagement with the first count wheel. When the inhaler is fired to dispense a dose of medicament, the dispensing mechanism moves the translating member in a substantially linear direction. The pawl thus rotates the first count wheel, and as the first count wheel rotates, the intermediate wheel is selectively engaged thereby selectively rotating the second count wheel to count the doses of the inhaler. hanism comprising a counter and a translating member. The translating member comprises a pawl. The counter comprises a first count wheel, a second count wheel and an intermediate wheel engaged with the second count wheel and in selective engagement with the first count wheel. When the inhaler is fired to dispense a dose of medicament, the dispensing mechanism moves the translating member in a substantially linear direction. The pawl thus rotates the first count wheel, and as the first count wheel rotates, the intermediate wheel is selectively engaged thereby selectively rotating the second count wheel to count the doses of the inhaler.

Description

/052240 INHALER Technical Field The t invention relates to an inhaler for delivery of a medicament by inhalation and in particular to the mechanisms of the inhaler for dispensing of a dose of medicament and ng the dispensed dose.

Background of the Invention Inhalers are commonly used for ry of a wide range of medicaments. In a dry powder inhaler (DPI) a dose of powdered substance is entrained in an air stream to deliver a dose of medicament through a mouthpiece to a user. In a pressurised metered dose inhaler (pMDI) a canister containing medicament in the r is actuated, e.g. by compression, to deliver a metered dose of the medicament through a mouthpiece to a user.

The inhaler may be conﬁgured to deliver a dose of ment automatically. For example the inhaler may comprise an ion mechanism to e the canister or to deliver the ed substance when red. 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.

A breath-actuated pMDI inhaler is described in W02008/082359. The inhaler actuation mechanism is operable to compress a canister of medicament to deliver a dose of medicament in response to inhalation by a user. The actuation mechanism comprises a loading mechanism to bias compression of the canister. A trigger mechanism holds the loading mechanism against compression of the canister. When a user inhales through a mouthpiece, the trigger mechanism releases the loading mechanism to allow compression of the er to deliver a dose of medicament. A resetting mechanism cts with a mouthpiece cover such that nt of the cover into a closed position resets the actuation mechanism.

The inhaler of W02008/082359 optionally has a registration module responsive to actuation of the inhaler, which can indicate, for example, the number of doses of medicament remaining in the canister. For t safety, the inhaler must not dispense a dose of medicament without counting the dispensed dose, as this may lead to the patient erroneously believing that there are remaining doses in an empty r. The inhaler must also not decrement the count of the dose counter if a dose is not dispensed, since the patient may erroneously believe that no doses remain in the inhaler and a signiﬁcant number of doses may be wasted when the inhaler is disposed of prematurely. Furthermore, the dose counter display must be sufﬁciently clear for a patient to be able to reliably and accurately read the display. For example, if the dose counter displays the number of doses remaining in the inhaler, if there is any ambiguity or lack of clarity with the displayed digits, the t may believe that there are more doses remaining than is actually the case, which is ous for the patient, or may believe that there are fewer doses than actually remain, and may dispose of the inhaler too soon, wasting medicament.

Summary of the Invention In accordance with the present invention, there is provided an inhaler for delivery of a medicament by inhalation which overcomes the drawbacks of the prior art. This is ed by the inhaler as deﬁned in the ndent claims.

From a first broad aspect, there is provided an inhaler for delivery of a medicament by inhalation, the inhaler comprising: a dose ng mechanism comprising a counter and a translating member, the translating member comprising a pawl and the counter sing a first count wheel, a second count wheel and an ediate wheel engaged with the second count wheel and in selective engagement with the first count wheel, a dispensing mechanism conﬁgured, on actuation, to dispense a dose of medicament, wherein: on actuation, the dispensing mechanism moves the translating member in a ntially linear direction, whereby the pawl rotates the first count wheel, and as the first count wheel s, the intermediate wheel is selectively enganged thereby selectively rotating the second count wheel; wherein the dose counting mechanism further comprises a r chassis, the counter chassis being configured to receive and to guide motion of the translating ; wherein the counter chassis further comprises a chassis pawl that is integrally formed with the counter s, the chassis pawl configured to enable the wheels of the dose counting mechanism to rotate in a first, counting direction but to prevent rotation of at least the first count wheel in an opposite, backwards direction. 3A wed by 4) wheel and thus consistent on of the wheel by movement of the pawl in the counting direction.

Embodiments of the present ion are deﬁned in the dependent .

In a particularly preferred embodiment, the ﬁrst count wheel is incremented by 1/10th of a full rotation upon each actuation by the pawl of the translating member (i.e. by about 36°). Preferably in this embodiment the ﬁrst count wheel only engages with the intermediate wheel after one full rotation of the ﬁrst count wheel, thus the ﬁrst count wheel engages with the intermediate wheel after 10 actuations by the pawl, and rotates the second count wheel by an increment of its full rotation. Preferably the second count wheel is incremented by between no more than 1/2 a on (about 180°) and less than 1/40th of a on (about 9°), more preferably by between no more than 1/10th of a rotation (about 36°) and less than 1/20th of a rotation (about 18°), more preferably by between no more than 1/12th of a rotation (about 30°) and less than 1/15th of a rotation (about 24°), more preferably by about 1/12th of a rotation (about 30°).

Preferably in the above embodiments, the ﬁrst count wheel comprises a set of ﬁrst count numbers printed, embossed, or otherwise yed annularly thereon, and preferably the second count wheel comprises a set of second count s printed, embossed or otherwise displayed annularly thereon. In a particularly preferred embodiment, the ﬁrst count wheel ses the numbers 0 to 9 arranged annularly and regularly spaced about a front face f and is incremented by 1/10th of a full rotation (about 36°) upon each actuation by the pawl. Furthermore, in preferred embodiments, the second count wheel comprises the numbers 0 to 12 arranged annularly and regularly spaced about a front face thereof and is ented by 1/12th of a full rotation (about 30°) upon each actuation by the intermediate wheel. The intermediate wheel selectively engages upon each full rotation of the ﬁrst count wheel (i.e. after 10 incremental actuations) and thus rotates the second count wheel by a single 1/12th increment (i.e. about 30°) every time the ﬁrst count wheel has counted 10 dispensed doses. In this way a dose counting mechanism that can decrement a counter from any of 129 to 120 doses through each individual dose count down to zero is provided. Of course, with embodiments for counting 150 doses, the second count wheel comprises the numbers 0 to 15 arranged annularly and regularly spaced about a front face thereof and is incremented by 1/15th of a ﬁlll rotation (about 24°) upon each actuation by the intermediate wheel, for ments for counting 200 doses, the second count wheel comprises the numbers 0 to 20 arranged rly and regularly spaced about a front face thereof and is incremented by 1/20th of a ﬁlll rotation (about 18°) upon each actuation by the intermediate wheel, or any other number of doses from 10 to 400 is envisaged within the scope of the invention, although the number of doses that can be reliably displayed may be constrained by the size of the ents of the counting mechanism or indeed by the size of the inhaler itself Furthermore, the increments by which the wheels are turned do not need to correspond with the numbers displayed on the front face of the count wheels and it is possible, for example, to increment the count wheels in steps smaller than the number of doses to be displayed, particularly if it is desired to have an end of life component, such as a zero dose indicator ﬂag as part of one or both of the count wheels, as discussed below.

The front face (i.e. the displayed face) of the ﬁrst count wheel and/or of the second count wheel preferably comprises not only numerical means to indicate the number of doses (remaining in or dispensed from the inhaler), but also other indicia. In a red embodiment, the counter comprises a low dose indicator, preferably a suitably coloured component so as to be readily visible when displayed, to indicate that the number of doses remaining in the inhaler is fewer than a ermined number. This s the patient to receive a warning that a new inhaler should be obtained so as to be ready to replace the present inhaler when empty. In a preferred ment, the low dose indicator comprises a portion of the front face of the second count wheel, which is preferably coloured yellow or amber. Preferably the coloured n is a background to the final numbers of the second count wheel, for e as a background to the s 2 and l (and zero if a 0 is displayed) to indicate when the remaining doses count is down to 20 or fewer doses.

Preferably the counter further or alternatively comprises a zero dose indicator, preferably a suitably coloured component so as to be readily visible when displayed, to indicate that there are no doses remaining in the inhaler. In red embodiments, the zero dose indicator comprises a red background to the numbers on the front face of one or both of the ﬁrst and second count wheels. However in a particularly preferred embodiment, the zero dose tor comprises a ﬂag portion of the second count wheel, the ﬂag protruding from the second count wheel and pping the ﬁrst count wheel.

Preferably the ﬂag is a distinctive colour, such as red and/or is ctively marked or patterned, such that it is very clear when it is displayed on the inhaler. Thus, when the ediate wheel rotates the second count wheel after the last dose is dispensed, the ﬂag moves into the display area and also covers the display of the ﬁrst count wheel. This is advantageous because, even if the ﬁrst count wheel continues to turn, no dose is visible to the patient and there is no conﬁlsion as to whether any doses remain. In a particularly preferred embodiment, the counting mechanism is conﬁgured such that, once the zero dose indicator has rotated into the display, it is not possible to rotate the second count wheel any ﬁlrther and thus the ﬂag will remain in the y. This is preferably achieved by a suitable toothed arrangement, for example a missing tooth or set of teeth from the second count wheel to prevent further rotation of the ﬂag, or the like. In such an arrangement, if it is desired to indicate 120 doses, the second count wheel should be incremented by less than 1/12th of a full rotation (about 30°) upon actuation by the intermediate wheel, for example by 1/ 13th, 1/ 14th, 1/ 15th (about 28°, 26° or 24° respectively) or even less of ﬁlll rotation, thus providing a region of the front face of the second count wheel on which a ﬂag or other zero dose indication member can be provided separately from the number of doses.

In ance with embodiments of the present invention, the intermediate wheel is selectively engaged with the ﬁrst count wheel and thus is selectively rotated by the ﬁrst count wheel. This may be achieved by any suitable ism. For example at least one of the ﬁrst count wheel and/or the intermediate wheel could be selectively moved, linearly or otherwise, into and out of engagement with the other wheel. Preferably however at least one of the ﬁrst count wheel and/or the intermediate wheel is conﬁgured such that the wheels engage only at one or more predetermined positions during rotation of the ﬁrst count wheel. In a particularly preferred ment, the ﬁrst count wheel comprises a notch or other recess on an outer periphery thereof, for receiving a tooth or other protrusion of the intermediate wheel. Preferably the ﬁrst count wheel comprises a single notch such that only once every ﬁlll on is the intermediate wheel tooth engaged in the notch, as it passes the ediate wheel. Of course, it is envisaged that the ﬁrst count wheel may WO 38170 comprise a plurality of notches, evenly or otherwise spaced apart to engage the intermediate wheel more than once per ﬁlll rotation.

The ediate wheel may be of any suitable conﬁguration. Preferably the intermediate wheel comprises a plurality of evenly spaced teeth about an outer periphery thereof. As the notch (or a notch of a ity of notches) of the ﬁrst count wheel comes into alignment with one of the intermediate wheel teeth, the notch s with the tooth and rotates the intermediate wheel by a predetermined increment which is preferably substantially less than a full on of the ediate wheel. In preferred embodiments the intermediate wheel comprises a le number of teeth for engagement with the notch of the ﬁrst count wheel, for example it is particularly preferred for the intermediate wheel to comprise four evenly spaced teeth. Of course the arrangement of the intermediate wheel and ﬁrst count wheel could be the opposite of the above, i.e. the teeth may be present on the ﬁrst count wheel and the notch form part of the intermediate wheel or the like.

Preferably the intermediate wheel further comprises a second set of evenly spaced teeth, preferably four thereof, interspersed with the teeth for engagement with the ﬁrst count wheel. The second set of evenly spaced teeth are conﬁgured for engagement with notches between teeth of the second count wheel, which is fully engaged with the intermediate wheel and is rotated thereby every time the intermediate wheel is rotated. In preferred embodiments, the second count wheel engages with each and every tooth of the intermediate wheel. Thus the ﬁrst count wheel rotates the intermediate wheel only when the wheels engage, which is preferably every 10th increment of the ﬁrst count wheel, but the intermediate wheel rotates the second count wheel on every ental rotation of the intermediate wheel. In this manner a single digit count can be implemented by the ﬁrst count wheel (which could therefore be referred to as a ‘units’ wheel) and a count every tenth increment of the ﬁrst count wheel can be effected by the second count wheel (which could therefore be referred to as the ‘tens’ wheel).

The interactions and engagement between the wheels of the dose counting mechanism can be achieved in any suitable manner. Preferably the wheels are aligned ve to each other on suitably conﬁgured on axes. In a particularly preferred embodiment, the dose counting mechanism comprises a counter chassis, having a ﬁrst and The counter chassis is configured to receive, and preferably guide motion of, the ating member. For example, protruding tabs on at least one or more preferably two opposed edges of the ating member are received in suitably ured channels of the counter chassis, thus enabling linear movement of the translating member as the tabs run in the channels, but preventing the translating member being pulled away from the counter chassis. Preferably the translating member further comprises a guiding slot, which runs substantially parallel to the direction of linear motion of the ating member when moving in the ng/resetting direction. Preferably the counter s further comprises a guiding protrusion that fits into the guiding slot and allows the translating member to move linearly but prevents movement laterally.

Preferably the guiding sion is integrally formed with a protruding component of the counter chassis, for example the guiding protrusion is preferably and extension of one of the first or second axes of the counter chassis. Thus reliable linear and undeviating motion of the translating member is provided.

The chassis pawl is configured to enable the count wheels to rotate freely in the desired direction but to prevent backwards rotation of at least the first count wheel. This ensures that as the count of the counter is decremented (in ments where the number of remaining doses is displayed by the dose counting mechanism) it is not possible for the wheel to be rotated in the other direction, i.e. for the count to be incremented. This might otherwise occur during resetting of the ng mechanism for the next count, for example as the translating member and integrally formed pawl move back into the initial position (i.e. move in the resetting direction), or may occur accidentally, for example if the r receives an impact from being dropped or the like. In a particularly preferred embodiment, the first count wheel comprises a plurality of counter-rotation teeth, each tooth preferably having a convex back surface. As the ﬁrst count wheel rotates during counting, the pawl is deﬂected along the convex back surface of a counter-rotation tooth and the wheel is able to rotate in a first, forward direction. However the counter-rotation teeth r comprise an angular portion into which the chassis pawl head is received (e. g. snaps into after the pawl elastically returns to its undeﬂected position) after a unit count has been achieved. If there is subsequently any bias to rotate the first count wheel in a second, backward direction, abutment of the pawl head against the inner surface of the angular portion prevents movement of the first count wheel in this direction. In particularly preferred embodiments the angular portion and pawl head are configured such that bias to rotate the first count wheel in the backward direction increases the engagement between the pawl head and the angular portion. For example the pawl head and angular portion are ably configured such that when ng and pushed together, the pawl ﬂexes inwardly towards the r portion.

As discussed above, the second count wheel is arranged to rotate when the ediate wheel, with which it engages, rotates. In preferred embodiments, the second count wheel comprises a plurality of annularly spaced teeth about an outer periphery thereof, with notches between the teeth for ing a tooth of the intermediate wheel, thus effecting ve rotation. In some embodiments the second count wheel has evenly and regularly spaced teeth around the entire outer periphery. However in particularly preferred embodiments there is provided a portion of the outer periphery of the second count wheel in which there are no teeth and corresponding notches or recesses present. In this manner, when the second count wheel has rotated relative to the ediate wheel such that the portion with no teeth aligns with a tooth of the intermediate wheel, the intermediate wheel can no longer effect rotation of the second count wheel (since the rotating teeth of the intermediate wheel have no recesses to engage or teeth to push t). Thus subsequent rotation of the intermediate wheel has no effect at all on the second count wheel and this wheel is effectively permanently immobilised. This is ularly advantageous when the second count wheel has been incremented down to the last count. Thus an end of life indicating mechanism is provided as the user will see that ﬁlrther actuations of the inhaler are not counted by the counter.

In preferred embodiments, the translating member further comprises at least one protrusion, which protrudes from a face of the translating member toward the ﬁrst count wheel and is conﬁgured to engage at least a portion of the ﬁrst count wheel in n conﬁgurations and to prevent over-rotation of the ﬁrst count wheel (and thus prevent overcounting, i.e. the ﬁrst count wheel turning by more than the desired increment). This is particularly advantageous because the forces required to dispense a dose of medicament from the inhaler are relatively large and by associating counting with sing it is possible that such force may affect the counting mechanism. For example, in a preferred embodiment, nt of the dispensing mechanism on actuation is ed by a force of approximately 50 N, from a ssed spring or the like. Preferably a component of the dispensing mechanism that moves as the dose is dispensed pushes, pulls or otherwise actuates the translating member in its linear dispensing direction. The large spring force may cause the tranlating member to be pushed rapidly in the dispensing direction, typically at a velocity of about 4 ms'l. The ﬁrst count wheel, being rotated by the translating pawl moving at such a high ty, could freely spin or at least would likely rotate beyond the d increment, thus overcounting the dispensed dose. Preferably, therefore, the overcount preventing protrusion of the translating member comprises a linear protrusion for engagement with a plurality of spaced ribs protruding from an outer face of the ﬁrst count wheel. As the translating member moves linearly and causes the ﬁrst count wheel to rotate, the ﬁrst overcount preventing protrusion also moves linearly (at the same speed as the pawl) and becomes located between a ﬁrst (leading) rib and a second (following) rib of WO 38170 the ﬁrst count wheel. The ribs and protrusion are conﬁgured such that the protrusion abuts the second wing) rib as the ﬁrst count wheel reaches the end of its desired increment.

The ﬁrst overcount preventing protrusion thus blocks the ﬁrst count wheel from rotating any further and thus prevents the ﬁrst count wheel ng beyond one dose. As the ating member returns to its initial position (i.e. moves ly in the resetting direction), the ﬁrst overcount ting protrusion also moves linearly back to its initial position and is withdrawn from abutment with the rib of the ﬁrst count wheel, thus freeing the count wheel to turn again on the next actuation.

Preferably the translating member further or alternatively comprises a further protrusion which protrudes from the same face of the translating member (toward the ﬁrst count wheel) as the overcount preventing protrusion. The ﬁarther protrusion prevents counting when the counter is in the rest position and this rest count preventing protrusion is conﬁgured to engage at least a portion of the ﬁrst count wheel when the counting mechanism is at rest. The rest count preventing protrusion is preferably conﬁgured to engage the same ribs of the ﬁrst count wheel as the overcount preventing sion, but only when the ating member is in its initial, rest position (i.e. before the translating member has begun its motion in the counting direction, whereas the overcount preventing protrusion engages the ribs of the ﬁrst count wheel after the translating member has completed its motion in the counting ion). The rest count preventing protrusion is preferably also a linear protrusion like the overcount preventing protrusion.

As discussed above, the dose counting mechanism comprises a counter and is preferably conﬁgured to display, inter alia, the number of doses of medicament remaining in the inhaler, or the number of doses of medicament that have been dispensed from the inhaler, etc. In preferred embodiments, the dose counting mechanism is ntially contained within the inhaler such that it is not ible to the patient and cannot be removed from the inhaler. This prevents the dose counting mechanism being removed or otherwise tampered with and ensures that the count or other display of the dose counting mechanism is reliable and is directly associated with the amount of medicament in the inhaler. r it is of course essential that at least the display of the dose ng mechanism is visible to the t. Preferably the dose ng mechanism is contained within the inhaler, preferably behind a front fascia thereof, but the fascia comprises an aperture or window h which the display of the dose counting mechanism is visible.

The aperture is preferably suitably sized and shaped that the display of the dose counting mechanism is clearly visible, but is not so large that the dose counting mechanism can be accessed or removed through the aperture.

Although the display of the dose counting mechanism is visible to the patient through the re in the above embodiments, it is particularly preferred that the patient cannot directly access or touch the display. Furthermore it is also preferable for the display to be covered to prevent ingress of foreign matter such as dirt or the like, which might interfere with operation of the dose counting mechanism and for safety ingress of foreign particles through the aperture and to other inhaler components should also be minimised.

Therefore in particularly preferred embodiments of the t invention, there is provided a cover or window, comprising a substantially transparent material, between the dose counting mechanism and the aperture. The window may comprise means for forming an air and/or moisture tight seal with the aperture, however this is not essential and it is only necessary for the window to provide a barrier to ingress of foreign particles into the dose ng mechanism. The window may be a separately provided component, or it may be integrally formed with the . Preferably, however, the window comprises a component of the dose counting mechanism and more preferably, the window is integrally formed with a component of the dose counting mechanism, preferably with the counter chassis. The counter chassis is thus preferably entirely formed of a suitable transparent plastic, such as an amorphous copolymer like Eastman Tritan TXZOOl. The window may ore comprise the portion of the counter chassis that lines up with the fascia re and may not be a distinct part of the counter chassis. Preferably, however, the window, though integrally formed with the counter chassis, is also a ically configured part of the counter s. In a particularly preferred embodiment, the window is curved and protrudes from the counter chassis and ably is suitably conﬁgured to y the display of the dose counting mechanism. Preferably the window is ﬁthher configured such that, although the display is magniﬁed by the , the display is not signiﬁcantly distorted. Such an arrangement is advantageously provided by a window having a level of magniﬁcation that is greater in one dimension than in a second, substantially perpendicular dimension. For example, if the window is rectangular and is wider (when the inhaler is held upright and in a position in which the display is intended to be read) than it is tall, preferably the cation across the width of the window (i.e. in the x direction) is lower than the magniﬁcation across the height of the window (i.e. in the y direction). In preferred embodiments, the cation in the x direction magniﬁes the size of the display by between about 0 and 30%, preferably between about 5 and 20%, more preferably is about 10%, and the magniﬁcation in the y direction magniﬁes the size of the display by between about 0 and 50%, preferably between about 10 and 30%, more preferably is about 20% and in any event is greater than the magniﬁcation in the x direction. This is preferably the case even for non rectangular (e.g. substantially square) s. In a ularly preferred embodiment, the magniﬁcation in the x direction magniﬁes the size of the y by about 10% and in the y direction by about 20%. Such arrangements provide a window that very effectively allows sufﬁcient light into the display to enable any digits or a, etc., to be clearly visible, and also magniﬁes the digits effectively but without cant distortion f, particularly sideways distortion (i.e. in the x direction which has a lower magniﬁcation). Such a window enhances the readability of the display considerably compared with either a ﬂat window or a window with the same level of magniﬁcation along both axes.

The above dose ng mechanism and window for displaying the display of the counter of the dose counting mechanism provides an inhaler display that is signiﬁcantly improved compared with known inhaler displays. Accordingly, from a further broad aspect of the present invention, there is ed an r for delivery of a medicament by inhalation, the inhaler comprising: a dispensing mechanism conﬁgured, on actuation, to dispense a dose of medicament, 14 (followed by 14A) the window comprises a magnifying outer surface for iying the indicia of the counter, the magnification in a first dimension being greater than the magnification in an second dimension that is substantially perpendicular to the first dimension; wherein the dose counting mechanism comprises a first count wheel, a second count wheel and an intermediate count wheel d with the second count wheel and in selective engagement with the first count wheel; wherein the dose counting mechanism further ses a counter chassis which comprises a chassis pawl that is configured to enable the wheels of the dose counting mechanism to rotate in a first, counting direction but to prevent rotation of at least the first count wheel in an opposite, backwards direction. 14 A wed by 15) In particularly preferred ments, the inhaler r comprises a resetting member conﬁgured for movement between a ﬁrst position and a second position on application of a resetting force, and the sing mechanism sing a loading member. The inhaler preferably ﬁlrther comprises a prevention mechanism comprising at least a ﬁrst engaging member and a second engaging member, the ﬁrst ng member conﬁgured to engage in a mating conﬁguration with the second engaging , wherein when movement of the resetting member in the ﬁrst direction is reversed before the resetting member s the second position, the ﬁrst and second engaging members engage and hold the load of the loading member, thereby preventing actuation of the dispensing mechanism, until the resetting member is moved again in the ﬁrst direction. At least one of the ﬁrst and second engaging members is conﬁgured to resiliently ﬂex, under load, into abutment with a substantially rigid component of the inhaler.

Thus there is provided an improved inhaler for dispensing one or more doses of medicament to a patient, that will not dispense a subsequent dose until the dispensing mechanism of the inhaler is ﬁllly reset. Such an arrangement provides an inhaler capable of dispensing a more le and consistent dose of medicament, as the dispensing mechanism will not ﬁre until ﬁllly reset, which is the optimum initial state for dose dispensing. rmore, if ion of the dispensing ism is prevented until the mechanism is fully reset, activation of the dose counting mechanism is optimised as the dispensing ism is red to adjust the counter of the dose counting mechanism on actuation from a fully reset state. This reduces or eliminates the risk that the dispensing mechanism could ﬁre and dispense a dose from a partially reset conﬁguration whilst not adjusting the counter of the dose counting mechanism. Thus by ensuring the dispensing mechanism is fully reset before enabling a further medicament dose to be sed, activation of the dose counting mechanism should also be reliably performed and the counter should accurately reﬂect the number of actual doses dispensed from (or remaining in) the inhaler.

Preferably the inhaler ﬁlrther comprises a canister containing a medicament, the medicament preferably comprising at least one active pharmaceutical ingredient (API) and preferably also a propellant. In a particularly preferred embodiment, the medicament comprises at least a ﬁrst active ceutical ingredient and a second active pharmaceutical ingredient and a propellant. Preferably the medicament comprises a combination of a ﬁrst active pharmaceutical ingredient and a second active pharmaceutical ingredient of the speciﬁc active ingredients listed in (i) to (xxi) herein below. In other red embodiments, the medicament comprises two or more of the speciﬁc active ingredients listed in (i) to (xxi) herein below. In preferred embodiments, particularly with such combinations of APIs, the medicament also comprises a propellant, preferably HFA 227 (l,l,l,2,3,3,3-heptaﬂuoropropane) or HFA 134a (l,l,l,2,-tetraﬂuoroethane) or any other suitable propellant.

Preferably the loading member ses a mechanism for applying compressive force to another component of the inhaler. In preferred embodiments in which the inhaler comprises a canister containing a medicament, the loading member ably applies a ssive force to the canister. Preferably the compressive force compresses the canister against a retaining member that holds a nozzle of a metering valve of the canister in place (e. g. a nozzle block or a component of a mouthpiece of the inhaler). Compression of the canister opens the metering valve and causes a dose of medicament to be dispensed through the nozzle into the mouthpiece for inhalation by a patient.

In preferred embodiments, the loading member comprises a spring. In a compressed state, the spring stores a force that is at least ent to compress a canister against its valve nozzle and thus to dispense a metered dose of the medicament stored in the canister and preferably is also ent to e the dose counting mechanism.

Typically for a pMDI the force d to the canister by the loading member is in the order of about 50 N. Alternatively the loading member comprises any suitable means for ssing a canister, such as a ssed air mechanism or the like.

Preferably the dispensing mechanism comprises a able locking arrangement for locking the sing mechanism, for example by restraining the load of the loading member, until it is desired to actuate the dispensing mechanism, e.g., by releasing the g member to compress a canister of the inhaler to dispense a dose of medicament.

The releasable locking arrangement may have any suitable conﬁguration for locking the dispensing mechanism that is releasable to enable a dose of medicament to be dispensed.

In particularly preferred embodiments, the releasable locking arrangement comprises a latch mechanism, preferably comprising a drop link for holding a lock member in position, the lock member in turn locking a lever arm in place. The lever arm is biased for rotation by the loading member (e.g. a compressed spring in the loaded conﬁguration) but is held t rotation by the lock . Movement of the drop link releases the lock member which in turn releases the lever arm to , thereby allowing the loading member to unload (e.g. the spring to expand) and to compress a canister to dispense a dose of medicament.

In accordance with embodiments of the present invention, on actuation of the inhaler, the sing mechanism moves the translating member in a substantially linear ion, y the pawl rotates the first count wheel. The dispensing mechanism preferably comprises a component that engages with the translating member, at least in certain configurations, and movement of the ent of the dispensing mechanism during actuation uently moves the translating member. In embodiments comprising a able locking arrangement, the component of the sing mechanism that moves the translating member is preferably an integral part of the lever. Thus a multiﬁanction lever is provided and the counting of a dose is directly related to the mechanism for dispensing a dose of medicament. Preferably the lever comprises an ng protrusion, or more preferably a pair of engaging protrusions that engage with one or more notches on a back face of the translating member. As the lever pivots, the engaging protrusion(s) push downwards on the inner surface(s) of the notch(es) and thereby push the ating member linearly downwards to effect actuation of the counting mechanism.

In embodiments of the invention sing a releasable locking arrangement, the drop link preferably moves in response to actuation by a user of the inhaler. Actuation of the inhaler may be by manual means, for example by means of an actuation member such as a button or lever, or the r may be breath actuated. Particularly preferred inhalers in accordance with the present invention comprise both breath actuation means and manual actuation means so that a patient can choose how to actuate the inhaler (or can, for example, test the inhaler by dispensing a dose to ensure it is properly functioning, or can manually prime the inhaler for example after periods where the inhaler has not been used, or after it has been dropped, etc.). Preferably the manual actuation means acts directly on a the component of the breath ion means that moves in response to patient inhalation (e.g. the manual actuation means acts directly on a vane of the breath actuation means, preferably the manual ion means pushes the vane and simulates patient inhalation).

In a particularly red embodiment of the present invention, the inhaler ses a drop link for holding a lock member in position, the lock member in turn g a lever arm in place as discussed above. The drop link is preferably retained in the locking position by a breath-triggered member, preferably a vane that pivots in response to a pressure drop within the inhaler airﬂow passage, such pressure drop occurring as a patient s through a mouthpiece of the inhaler. Thus the releasable locking arrangement holds the load of a loading member, e.g. a compressed , until a patient inhales through the mouthpiece to cause the releasable locking arrangement to release the load of the spring thereby compressing a canister of the inhaler to dispense a dose of medicament.

Further details of a breath actuated inhaler arrangement are described in W02008/082359 and such an ement is compatible with the inhaler of ments of the t invention.

As discussed above, the inhaler preferably comprises a resetting member. The resetting member resets the inhaler after it has been used, by reloading the loading member of the dispensing mechanism, thus enabling the dispensing mechanism to be actuated again and a further dose to be dispensed.

Preferably the resetting member comprises a manually actuatable component of the r. This enables a user of the r to reset the dispensing mechanism after a dose has been dispensed, arming the inhaler for dispensing further doses as required. In particularly red embodiments, the resetting member comprises a rotatable member of the inhaler, preferably a cap of the inhaler which also s to cover and protect a mouthpiece of the inhaler when in a closed position. Such an arrangement is particularly advantageous because it encourages a patient to close the inhaler cap immediately after use, thus priming the device and resetting it to its preferred rest conﬁguration, as well as protecting the mouthpiece from ingress of dirt or dust, etc. Alternatively or preferably additionally, the cap also prevents actuation of the inhaler when in the closed position, thus preventing accidental actuation of the inhaler. Preferably the cap holds or otherwise prevents movement of certain components of the inhaler and prevents breath and/or manual actuation of the inhaler until it is opened, preferably by abutment with the components.

In particularly preferred embodiments, the resetting member comprises a cap that pivots about an axis between a ﬁrst position and a second position. Pivoting of the cap about its axis is effected by a patient applying a resetting force to rotate the cap. In the ﬁrst position, the cap is rotated away from the mouthpiece leaving it free for a patient to insert into their mouth for inhalation. In a particularly preferred embodiment, the cap is locked into the ﬁrst, open position, for example by a snap ﬁt or friction ﬁt between a portion of the cap and a portion of the inhaler when in the open position. The snap ﬁt or on ﬁt is red to be sufﬁcient to hold the cap in the desired open position, but is also sufﬁciently weak so that it can be y overcome, and the cap displaced, by a typical user of the inhaler.

Applying a resetting force to the resetting member moves the resetting member from a ﬁrst position to a second on. Preferably, in the embodiment where the resetting member ses a cap, in the second position the cap covers, and preferably in co-operation with the inhaler body and other components, ﬁJlly encloses a mouthpiece of the inhaler, y protecting the iece when the inhaler is not in use.

The resetting member is conﬁgured to move in a ﬁrst direction from a ﬁrst position to a second position and to load the loading member as it moves in the ﬁrst direction. Preferably, in the ment where the resetting member comprises a cap, rotation of the cap causes translational movement of a component of the dispensing mechanism, preferably a yoke substantially aligned along a main axis of the inhaler body.

The translation movement of the component, for example the yoke, acts to compress the loading member and thus to load the loading member and reset the sing ism.

In a particularly preferred embodiment, the cap rotates and pushes upwards on a yoke that sses a spring against a top portion of the inhaler, thus loading the dispensing mechanism. Preferably a releasable g arrangement is armed when the 2012/052240 cap has substantially fully rotated (and the yoke has translated the d amount and thus compressed the spring to the d load) to lock the dispensing mechanism until the patient next actuates the inhaler to dispense a dose of medicament. Preferably the cap when in the closed position prevents rd movement of the yoke and thereby helps to prevent the inhaler from being actuated when the cap is closed.

As discussed above, the resetting member of the inhaler is conﬁgured for movement between a ﬁrst position and a second position on ation of a resetting force, the movement from the ﬁrst position to the second position loading the loading member and resetting the dispensing mechanism. In any position between the ﬁrst and second positions, i.e. in an ediate position, the dispensing mechanism may only be partially reset, which may adversely affect the next dispensed dose and/or cause inaccuracies in the dose count of the counter, if the r is actuated from the ediate position. For example, in the ediate position, if the canister is not fully ed from compression by the load of the loading member, the valve of the canister may not reﬁll sufﬁciently or at all and any subsequent dose may be of a lower dose weight than desired.

Still ﬁlrther, in preferred embodiments, for example inhalers comprising a releasable locking arrangement, in the intermediate position the able locking arrangement may not be fully engaged and thus unable to hold the load of the loading member. If the patient releases the resetting member when in the ediate position (i.e. before the dispensing mechanism is fully reset), the releasable locking arrangement may be ineffective and any load applied to the loading member may be released to compress the canister again. This may cause a full or a low dose of medicament to be released, but the dose may not be registered by the dose counting mechanism if the r was not reset beyond a on at which the counting mechanism is reset for further counting. In other words, if the inhaler is only partially reset, it may not be far enough to enable resetting of the dose counting mechanism, thereby allowing a dose (albeit possibly not a ﬁll weight dose) to be dispensed but not counted.

Therefore in preferred embodiments of the present invention, the inhaler comprises a prevention mechanism for preventing actuation of the dispensing mechanism in certain conﬁgurations. In particular, the prevention mechanism prevents actuation of the dispensing ism when the resetting member has been moved from the ﬁrst position but has not ﬁllly reached the second position, i.e. is in an intermediate position therebetween. The prevention mechanism comprises at least a ﬁrst ng member and a second engaging member, the ﬁrst engaging member conﬁgured to engage in a mating conﬁguration with the second engaging member. The engaging members are conﬁgured to mutually engage if, during nt of the resetting member from the ﬁrst position to the second position, movement is ceased and possibly reversed before the resetting member reaches the second on (i.e. if the user stops moving the ing member in the ﬁrst ion before it is ﬁllly reset, and possibly the resetting member begins to move in the opposite, second direction).

The engaging members may engage indirectly with each other, i.e. via an intermediate component, but preferably the ﬁrst engaging member directly engages with the second engaging member. After engagement, the engaging members hold the load of the loading member and at least one of the engaging members is conﬁgured to ﬂex under this load and move into abutment with r, more rigid component of the inhaler. Thus the load that would otherwise be entirely absorbed by the engaging s is at least partially absorbed by the more rigid component of the inhaler against which at least one of the engaging members abuts. This is advantageous because the engaging members must be sufﬁciently ﬂexible to permit engagement and disengagement and are relatively small components in order to ensure the inhaler weight and size is minimised. Absorbing the approximately 50 N force of a spring substantially entirely through the ment members could cause the members to deform or break. Indeed, plastic creep has been observed in members formed of plastics that are typically used for such members. r in the embodiments of the t invention, a signiﬁcant proportion of the load is ed in the compressive contact between at least one of the engaging members and the more rigid inhaler component, which latter component is better suited and conﬁgured to withstand such forces with ntially no detrimental impact on the component.

The engaging members are conﬁgured to engage with each other readily when movement in the ﬁrst direction of the resetting member is reversed. Preferably the ng members are ﬁlrther conﬁgured to disengage with each other readily when movement in the ﬁrst direction of the resetting member is initiated again (for example by the user moving the resetting member ﬁarther onward to the second position to reset the dispensing mechanism and to fully load the loading member). In particularly red ments comprising a releasable locking arrangement, the able locking arrangement is conﬁgured to engage and hold the load of the loading member when the inhaler is ﬁllly reset, i.e. when the resetting member has reached the second position. Prior to the resetting member reaching the second position, the tion mechanism is conﬁgured to age and hold the load of the loading member every time the direction of motion of the resetting member is reversed from the ﬁrst direction, and to again disengage as motion in the ﬁrst direction is d.

The ﬁrst and second engaging members may be of any suitable conﬁguration for mutually engaging and holding a load. Preferably one of the ﬁrst engaging member and the second ng member comprises a female engaging portion and the respective other of the ﬁrst engaging member and the second ng member comprises a male engaging portion. In a preferred embodiment, the female engaging portion comprises a slot, notch or other recess for receiving a male engaging portion comprising a protrusion, hammer head, tooth or the like.

In another preferred embodiment, the ﬁrst engaging member and the second engaging member each comprise a hook portion conﬁgured to engage with the hook portion of the respective other of the ﬁrst engaging member and the second engaging member. Thus when d, the hook portions mutually co-operate to hold at least a proportion of the load of the loading member when under tension (i.e. when loaded).

Other conﬁgurations of the engaging members are possible, for example a hook and eye conﬁguration, a ball and socket ement or the like. Such male/female or hook arrangements are also readily disengagable as required when the load is relieved from the engaging members such that they are no longer pulled against each other, i.e. are no longer held under tension.

The ﬁrst engaging member and the second engaging member are conﬁgured to engage in at least one mating conﬁguration. For example in embodiments where the ﬁrst engaging member comprises a ﬁrst hook portion and the second engaging member comprises a second hook portion the mating conﬁguration comprises engagement of the ﬁrst hook portion with the second hook portion. In some ments however, the ﬁrst engaging member and the second ng member are conﬁgured to engage in a plurality of mating conﬁgurations. For example the ﬁrst engaging member preferably ses at least two hook portions, preferably spaced apart along a length of the ﬁrst engaging member. In this conﬁguration, the ﬁrst hook portion of the ﬁrst engaging member can engage with the second hook portion of the second engaging member at a ﬁrst intermediate position of the resetting member, or the second hook n of the ﬁrst engaging member can engage with the second hook portion of the second engaging member if the ing member is at a second intermediate position (e.g. is further ed towards the second on but still has not reached this end position). Such a ratchet arrangement provides multiple positions of engagement of the engaging members enabling a greater number of intermediate positions of the resetting member to be accounted for if necessary.

Preferably the ﬁrst and second engaging members engage in any suitable manner and in a particularly red embodiment, the ﬁrst and second engaging members ﬂex or snap into engagement.

As discussed above, at least one of the ﬁrst and second engaging s is conﬁgured to resiliently ﬂex, under load, into abutment with a substantially rigid component of the inhaler. In the preferred embodiment where one of the engaging members comprises a hook or hammer head, preferably at least this head portion of the engaging member is deﬂected as the member ﬂexes and abuts another component of the r. In this arrangement, although the head portion is partially under a tensile force across a er dimension, it is through compression of the head portion against the rigid component of the inhaler that much of the force is relieved, and this occurs through a wider dimensioned (and stronger) part of the head. Thus not only is a signiﬁcant proportion of the force relieved from the weaker part of the engaging member, it is also absorbed by another component which can be red to be stronger and more suitable for absorbing forces. Thus material creep, deformation and damage is substantially minimised or prevented and an improved arrangement is provided compared with, for e, the prior art blocking mechanisms discussed above.

The at least one of the ﬁrst and second engaging members that is conﬁgured to resiliently ﬂex, under load, into abutment with a substantially rigid component of the inhaler is also conﬁgured such that, when the load is removed from the engaging member, it ﬂexes back into substantially its al conﬁguration. Namely the engaging member is elastic in this regard and does not cally or ently deform to any signiﬁcant extent.

As discussed above, the ﬁrst and second engaging s engage in a mating conﬁguration and at least one deﬂects into abutment with r component of the inhaler, to hold the load of the loading , when motion of the resetting member is reversed from the ﬁrst direction. Preferably the ﬁrst engaging member is disengaged from the second engaging member in all other conﬁgurations of the inhaler. In particular, when the resetting member is in the ﬁrst position (for example in embodiments where the resetting member comprises a mouthpiece cap, when the cap is open to expose the mouthpiece) and the inhaler has not yet been ﬁred (i.e. the inhaler is in the preﬁre or armed conﬁguration) the ﬁrst engaging member is spaced apart from the second ng member such that they cannot engage. Preferably when the resetting member is in the second position (for example in embodiments where the resetting member comprises a mouthpiece cap, when the cap is closed and covering the mouthpiece) the ﬁrst engaging member is spaced apart from the second engaging member such that they cannot engage.

Preferably when the resetting member is in the intermediate position and is in motion in the ﬁrst direction (i.e. when the patient is in the process of resetting the dispensing mechanism) the ﬁrst engaging member does not engage with the second ng member because they are spaced apart, relatively deﬂected or are otherwise incapable of engagement. This ensures that the engaging members do not engage (and therefore do not hold the load) in any conﬁguration where this would be undesirable, for example when dispensing a dose or when properly resetting the dispensing mechanism. Thus the prevention mechanism does not interrupt proper and d operation of the inhaler but 2012/052240 only engages when undesired operation occurs, such as reverse movement of the resetting member before the inhaler is completely reset.

The engaging s of the prevention mechanism may be brought into mutual engagement and/or separated from mutual engagement by any suitable means. For example the engaging members may be moved in a linear direction towards each other for engagement and away from each other for disengagement, or by translation in any other direction, or by rotation of one or more of the engaging members, etc. Preferably, in conﬁgurations where the ﬁrst engaging member may need to translate, rotate or otherwise move entirely past the second engaging member, at least one of the engaging members is conﬁgured to be able relative to the other, as discussed below.

In preferred embodiments at least one of the engaging members of the prevention mechanism is formed ally with, or is a component of, another component of the inhaler. Preferably the ﬁrst ng member is formed integrally with, or is a ent of a ﬁrst component of the inhaler, and the second engaging member is formed integrally with, or is a component of a second component of the inhaler. In particularly preferred embodiments, the ﬁrst and second components of the inhaler are separately formed ents which move ve to each other as part of at least one ﬁlnction of the inhaler. Furthermore, in preferred embodiments the substantially rigid component of the inhaler into abutment with which at least one of the engaging s moves under load, is also formed integrally with, or is a component of another component of the inhaler. In particularly preferred embodiments, the substantially rigid component and the engaging member which is conﬁgured to abut the substantially rigid component are integrally formed with, or ent parts of, the same component, and ably are both integral components of a chassis of the inhaler as discussed further below.

In particularly preferred embodiments of the invention, sing a releasable locking arrangement as discussed above, the ﬁrst engaging member is preferably formed as an integral part of a lever of the able locking arrangement. Preferably the lever moves, preferably in a pivoting motion, as the load of the loading member is ed to dispense a dose and the integrally formed ﬁrst engaging member also moves as a component part of the lever. Preferably the inhaler further comprises a chassis, the chassis housing many of the components and mechanisms of the inhaler and preferably at least partially deﬁning an airﬂow passage through the inhaler from a mouthpiece. ably the second engaging member is formed as an integral part of the chassis, preferably as an upstanding member that is in the proximity of the lever and the ﬁrst engaging member when the inhaler components are assembled in the chassis. In further embodiments, only one or the other of the engagement members may be integrally formed as a part of another ent of the inhaler, with the other of the engagement members being formed as a separate component. In particularly preferred embodiments, the dose counting mechanism is conﬁgured as a separately provided unit which snap ﬁts into the inhaler chassis in an appropriate position for actuation by the sing mechanism. Whilst the inhaler may be conﬁgured to receive only a single type of counter, in alternative embodiments, the inhaler is conﬁgured to e a plurality of different types of counters. For e, a single inhaler may be capable of receiving a mechanical counter or an electronic counter or even a dummy counter (e.g. a face plate or the like if no counter is required). An inhaler having interchangeable counter mechanisms may be advantageous for users having ent requirements of the device.

In preferred embodiments of the present invention, the prevention mechanism ses at least one ﬁrst engaging member and at least one second engaging member, the engaging members conﬁgured to engage with each other in a mating ration. In preferred embodiments, a plurality of pairs of engaging s is ed, thus providing a robust prevention mechanism with multiple members for mutual engagement.

In a particularly preferred ment, in which the ﬁrst engaging member is a component or an integral part of a lever, there are at least two ﬁrst engaging members, each of which engages in a mating conﬁguration with a respective one of at least two second engaging members, ably that are components or integral parts of a chassis.

The ﬁrst engaging member of the lever and the second engaging member of the chassis in embodiments of the present invention have the following relative positions depending on the ration of the inhaler. When the resetting member is in the second position (e. g. the cap is closed in embodiments having a mouthpiece cap), the ﬁrst engaging member overlaps with, but is preferably displaced away from the second WO 38170 engaging member so that they are not in a mating conﬁguration. To use the inhaler, a patient moves the resetting member s the ﬁrst position (e.g. opens the cap). In preferred embodiments wherein the dispensing mechanism comprises a yoke, the cap is conﬁgured to release the yoke when opened. The yoke moves downwards slightly under the load of the loading member (a compressed spring in red embodiments), until the releasable g mechanism is fully engaged. The rd yoke movement pivots the lever. Thus the ﬁrst engaging member moves towards the second engaging member but ably still does not engage the second engaging member. When the patient inhales, or otherwise actuates the inhaler to dispense a dose of medicament, the releasable locking mechanism releases the dispensing mechanism and the load in the loading member is freed and compresses a canister of the inhaler, preferably via the yoke which is pushed downwards onto the canister base. The yoke rotates the lever and at least the engaging portion of the ﬁrst engaging member must pass beyond the engaging portion of the second engaging member without the two engaging portions mating. In preferred embodiments, at least one of the ﬁrst engaging member and the second engaging member is conﬁgured to be sufﬁciently ﬂexible such that at least the engaging portion of the e engaging member can deﬂect or otherwise ﬂex away from the other engaging member to allow the engaging members to pass without mating. In some embodiments, both engaging s are ﬂexible and may mutually deﬂect each other. In any of these embodiments, the shape of the engaging portion of one or both of the ﬁrst and second engaging members may be conﬁgured to aid deﬂection. For e, in preferred embodiments, at least one of the ng portions comprises a sloped deﬂecting edge to aid deﬂection of the other of the engaging portions. At least one of the engaging portions preferably additionally or atively comprises a ﬂat portion to aid deﬂection and relative travel past of the other of the ng ns. In a preferred ment, the ﬂexible member is biased to pass down one side of the other engaging portion (during ﬁring) and is deﬂected to run up the other side of the other engaging portion upon return.

Thus the prevention mechanism allows (i.e. does not interfere with) operation of the inhaler in the desired manner. Namely the ﬁrst and second engaging members do not engage in the mating conﬁguration during opening of the inhaler cap or during dispensing of a dose of medicament. Rather the ﬁrst and second engaging members are conﬁgured to deﬂect to allow translational movement in a ﬁrst direct, hereinafter referred to as the dispensing ion, during sing of a dose of ment.

After a dose is dispensed, the dispensing mechanism of the inhaler must be fully reset in order to ensure the next dispensed dose is of the correct volume and dose weight and is accurately and reliably counted by the dose counting mechanism. In preferred embodiments, resetting of the dispensing mechanism is achieved by applying a ing force to rotate the mouthpiece cap, thus pushing upwards on the yoke and reloading the spring. When the spring is ﬁally loaded, which is when the cap is ﬁJlly closed (i.e. moved to the second position) the dispensing mechanism is prevented from being actuated, either by the lever of the releasable locking ement being locked or by the closed cap ting downward nt of the yoke, or a combination of these. However when the cap is not fully closed, this is not the case and it is possible the dispensing mechanism could at least partially re-ﬁre. To prevent this, the prevention mechanism is conﬁgured to engage as required in such intermediate positions. Namely, as the cap is initially moved away from the ﬁrst (open) position and the yoke begins to move in the opposite direction to the dispensing direction, hereinafter referred to as the resetting direction, the lever rotates and the ﬁrst engaging member moves towards the second engaging member to a position where it is capable of engagement in a mating conﬁguration therewith. In preferred embodiments, at least one of the ng portions of the ﬁrst or second ng members is conﬁgured to be deﬂected during relative oning of the ng members.

If the cap is not fully closed whilst the engaging members are in this conﬁguration and instead begins to move in the opening direction, then the yoke moves back in the dispensing direction thus rotating the lever and engaging the engaging members in the mating conﬁguration. The mutually engaged engaging members are pulled under the spring load which attempts to pull the engaging members apart and causes the at least one of the ﬁrst and second engaging members that is conﬁgured to resiliently ﬂex under load, to ﬂex and move into the position where it abuts a substantially rigid component of the inhaler. This rigid and strong arrangement is easily e of holding the load of the loading member without cantly ing or otherwise ng the engaging members or g plastic creep of the components even through repeated engagements.

In this manner the engaging members are conﬁgured not to allow movement in the dispensing direction until movement of the ing member is continued and completed, and the ﬁrst engaging member is fully displaced back to the reset position of the lever. In preferred embodiments, the ﬁrst ng member is moved to a non-engaging position relative to the second engaging member by deﬂecting one relative to the other and thus out of the possible mating conﬁguration. At the end of the resetting operation, i.e. when the lever reaches a position in which the releasable locking arrangement will lock the lever in place and/or the when the fully closed cap locks the yoke, the ﬁrst and second engaging members will be at rest and cannot engage Other rations are possible but the basic principle of the interactions between the engagement s remains the same.

Thus a reliable and improved mechanism is provided for ensuring that the dispensing mechanism, which controls dispensing of doses of ment and counting thereof, is fully reset after each dose is sed, thus ensuring reliable dosing and counting of the doses. In the event that the dispensing mechanism is only partially reset, the tion mechanism engages to prevent the sing force of the loading member from dispensing a further, low weight and potentially uncounted dose, until the mechanism is fully reset. The prevention ism allows motion of the component parts of the inhaler during dispensing in the dispensing direction but prevents motion in the dispensing direction once engaged until the engagement is overridden by fully completing the resetting operation. The ﬁrst and second engaging members of the prevention mechanism mutually engage and remain under tension and compression against a rigid component of the inhaler to hold the dispensing mechanism and to prevent further movement in the dispensing direction. Once the tension is released, the ﬁrst and second engaging members may be displaced upon ﬁllly resetting the dispensing mechanism or may re-engage if the dispensing mechanism is still not ﬁllly reset. This is in contrast to the prior art system disclosed in W02004/04l334 for example, which discloses a ng mechanism in a manually actuatable inhaler where the components that block movement are held under a direct compressive force, as shown in ﬁgure 20. The compressive force arrangement may be less reliable and resilient as the components may be difﬁcult to conﬁgure such that they are strong enough to resist material creep and deformation over time and use, but ﬂexible enough to reliably engage and disengage with repeated uses and over a long period of time.

It should be noted that in this application the relative terms such as “upper”, “lower”, “above”, “below”, “upright”, etc., have been used for explanatory purposes to describe the internal relationship between ts of the inhaler, regardless of how the inhaler is oriented in the surrounding environment. rmore references to ctions between components of the inhaler in this application, such as “abutting”, “applying”, “compressing”, etc., are intended to cover direct and indirect interactions (indirect ctions being those with one or more other components between the interacting components and direct interactions being those where the interacting components are in direct contact with no ening components).

The medicament in the r may contain various active ients. The active ingredient may be selected from any therapeutic or diagnostic agent. For example, the active ingredient may be an lergic, a bronchodilator (e.g. a beta2-adrenoceptor agonist or a muscarinic antagonist), a bronchoconstrictor, a pulmonary lung surfactant, an analgesic, an antibiotic, a mast cell inhibitor, an antihistamine, an anti-inﬂammatory, an oplastic, an anaesthetic, an ubercular, an imaging agent, a cardiovascular agent, an enzyme, a steroid, genetic al, a viral , an antisense agent, a n, a peptide, a non-steroidal glucocorticoid Receptor (GR Receptor) agonist, an antioxidant, a chemokine antagonist (e.g. a CCR1 antagonist), a corticosteroid, a CRTh2 antagonist, a DPl antagonist, an Histone Deacetylase Inducer, an IKK2 inhibitor, a COX inhibitor, a lipoxygenase inhibitor, a leukotriene receptor antagonist, an MP0 inhibitor, a p38 inhibitor, a PDE inhibitor, a PPARy agonist, a protease inhibitor, a statin, a thromboxane antagonist, a vasodilator, an ENAC blocker (Epithelial Sodium-channel blocker) and combinations thereof.

Examples of speciﬁc active ingredients that can be incorporated in the inhaler include: (i) antioxidants:- Allopurinol, Erdosteine, Mannitol, N-acetyl cysteine choline ester, N—acetyl cysteine ethyl ester, N—Acetylcysteine, N—Acetylcysteine amide and Niacin; (ii) chemokine antagonists:- BX471 ((2R)[[2-[(aminocarbonyl)amino] chlorophenoxy]acetyl][(4-ﬂuorophenyl)methyl]methylpiperazine monohydrochloride), CCX634, N- {2-[((2S)-3 - {[l-(4-chlorobenzyl)piperidin yl] amino} hydroxymethylpropyl)oxy]hydroxyphenyl} acetamide (see ), and 2- oro {[(2S)(5-chloro- l 'H,3H-spiro[ l - benzofuran-2,4'-piperidin] - l '-yl)hydroxypropyl]oxy} ylamino)carbonyl]phenoxy} methylpropanoic acid (see WO 2008/010765), 656933 (N—(2-bromophenyl)-N'-(4-cyano-lH-l,2,3- benzotriazolyl)urea), 766994 ({[(2R)—4-(3,4- dichlorobenzyl)morpholinyl]methyl} carbonyl] - amino}methyl)benzamide), CCX-282, CCX-915, Cyanovirin N, E-92l, INCB- , INCB-947l, MaraViroc, MLN—3701, 97, T-487 (N-{l-[3-(4- ethoxyphenyl)—4-oxo-3 ,4-dihydropyrido [2,3 -d]pyrimidinyl] ethyl} -N- (pyridin-3 -ylmethyl)[4-(triﬂuoromethoxy)phenyl]acetamide) and VicriViroc (iii) Corticosteroids: metasone dipropionate, Amelometasone, Beclomethasone dipropionate, Budesonide, Butixocort propionate, Ciclesonide, Clobetasol propionate, Desisobutyrylciclesonide, Etiprednol dicloacetate, Fluocinolone acetonide, Fluticasone Furoate, Fluticasone propionate, Loteprednol etabonate (topical) and Mometasone e. (iV) DPl antagonists:- L888839 and MK0525; (V) Histone deacetylase inducers:- ADC4022, Aminophylline, a Methylxanthine or Theophylline; (Vi) IKK2 inhibitors:- 2-{[2-(2-Methylamino-pyrimidinyl)-lH-indole-S- carbonyl]-amino} (phenyl-pyridinyl-amino)-propionic acid; (Vii) COX inhibitors:- Celecoxib, Diclofenac sodium, ac, Ibuprofen, Indomethacin, Meloxicam, Nimesulide, , , 0C2184, OC499, OCD9101, Parecoxib sodium, Piceatannol, Piroxicam, Rofecoxib and Valdecoxib; (viii) Lipoxygenase inhibitors:- Ajulemic acid, elone, Darbufelone mesilate, Dexibuprofen lysine (monohydrate), Etalocib , Licofelone, Linazolast, Lonapalene, Masoprocol, MN-001 ZD- , lin, UCB-35440, Veliﬂapon, 2138, ZD-4007 and Zileuton 1-(1-Benzo[b]thienylethyl) hydroxyurea); (ix) Leukotriene receptor antagonists:- Ablukast, Iralukast (CGP 45715A), Montelukast, Montelukast sodium, Ontazolast, Pranlukast, Pranlukast hydrate (mono Na salt), Verlukast (MK-679) and Zaﬁrlukast; (x) MPO Inhibitors:- Hydroxamic acid derivative (N-(4-chloromethyl-phenyl)- 4-phenyl[[(4-propanylphenyl)sulfonylamino]methyl]piperidine carboxamide), Piceatannol and Resveratrol; (xi) Beta2-adrenoceptor agonists:- metaproterenol, isoproterenol, isoprenaline, albuterol, salbutamol (e.g. as sulphate), erol (e.g. as fumarate), salmeterol (e. g. as xinafoate), terbutaline, orciprenaline, bitolterol (e.g. as te), pirbuterol, indacaterol, salmeterol (e.g. as xinafoate), bambuterol (e. g. as hydrochloride), carmoterol, indacaterol (CAS no 3127533; QAB- 149), formanilide derivatives e.g. 3-(4-{[6-({(2R)—2-[3-(formylamino) hydroxyphenyl]hydroxyethyl} amino)hexyl]oxy} -butyl)- benzenesulfonamide; 3-(4- {[6-( {(2R)hydroxy[4-hydroxy(hydroxy- methyl)phenyl]ethyl} amino)-hexyl]oxy}butyl)benzenesulfonamide; GSK 159797, GSK , GSK 597901, GSK 642444, GSK 678007; and a compound selected from N-[2-(Diethylamino)ethyl]-N—(2-{[2-(4-hydroxy oxo-2,3-dihydro- 1 ,3 thiazolyl)ethyl]amino} ethyl)-3 -[2-(1- naphthyl)ethoxy]propanamide, Diethylamino)ethyl]-N—(2- { [2-(4- hydroxyoxo-2,3-dihydro- 1 ,3 -benzothiazolyl)ethyl]amino} ethyl)-3 - [2-(3 - chlorophenyl)ethoxy]propanamide, 7-[(1R)( {2-[(3- {[2-(2- Chlorophenyl)ethyl]amino l)thio]ethyl} amino)hydroxyethyl] hydroxy-1,3-benzothiazol-2(3H)-one, and N—Cyclohexyl-Ns-[2-(3- ﬂuorophenyl)ethyl]-N—(2- { [2-(4-hydroxyoxo-2,3-dihydro- 1 ,3 -benzothiazol- 7-yl)ethyl]amino}ethyl)-B-alaninamide or a pharmaceutically acceptable salt thereof (e. g. n the counter ion is hydrochloride (for example a drochloride or a dihydrochloride), hydrobromide (for example a monohydrobromide or a dihydrobromide), ﬁlmarate, methanesulphonate, ethanesulphonate, benzenesulphonate, 2,5-dichlorobenzenesulphonate, ptoluenesulphonate , napadisylate (naphthalene- l ulfonate or naphthalene- l - (sulfonic acid)sulfonate), edisylate e-l ,2-disulfonate or ethane-l- (sulfonic acid)sulfonate), D-mandelate, L-mandelate, cinnamate or te.) (xii) Muscarinic antagonists:- Aclidinium bromide, Glycopyrrolate (such as R,R—, R,S-, S,R-, or S,S-glycopyrronium bromide), pium e, Pirenzepine, telenzepine, Tiotropium bromide, 3(R)-l-phenethyl(9H-xanthene yloxy)- l -azoniabicyclo[2.2.2]octane bromide, (3R)[(2S) cyclopentylhydroxythienylacetoxy] - l -(2-phenoxyethyl)- l - azoniabicyclo[2.2.2]actane bromide, a quaternary salt (such as [2-((R)- Cyclohexyl-hydroxy-phenyl-methyl)-oxazolylmethyl]-dimethyl-(3-phenoxy- propyl)-ammonium salt, [2-(4-Chloro-benzyloxy)—ethyl]-[2-((R)-cyclohexyl- hydroxy-phenyl-methyl)-oxazolylmethyl]- dimethyl-ammonium salt and (R) l- [2-(4-Fluoro-phenyl)-ethyl] -3 -((S)phenylpiperidin- l -yl-propionyloxy)- l-azonia-bicyclo[2.2.2]octane salt wherein the counter-ion is, for example, chloride, bromide, e, methanesulfonate, benzenesulfonate (besylate), toluenesulfonate (tosylate), napthalenebissulfonate (napadisylate or hemi- napadisylate), ate, acetate, citrate, lactate, tartrate, mesylate, maleate, ﬁlmarate or succinate) (xiii) p38 Inhibitors:- 681323, 856553, AMG548 2S)amino phenylpropyl]amino]—3-methyl(2-naphthalenyl)(4-pyridinyl)-4(3H)- dinone), Array-797, AZD6703, Doramapimod, KC-706, PH 797804, R1503, SC-80036, SCIO469, 6-chloro[[(2S,5R)[(4-ﬂuorophenyl)methyl]- 2,5-domethyl- l -piperazinyl] carbonyl]-N,N, l -trimethyl-oc-oxo- 1H-indole-3 - acetamide, VX702 and VX745 (5 -(2,6-dichlorophenyl)(phenylthio)-6H- do [l ,6-b]pyridazinone); (xiV) PDE Inhibitors:- 256066, Arofylline chlorophenyl)-3,7-dihydro-l-propyl- lH-Purine-2,6-dione), AWD l2-28l (N—(3,5-dichloropyridinyl)-l-[(4- ﬂuorophenyl)methyl] hydroxy-0L-oxo- l H-indole-3 -acetamide), BAY l 9-8004 (Bayer), CDC-801 (Calgene), Celgene compound ((BR)—B-(3,4- dimcthoxyphcny1)- 1 ,3-dihydr00X0-2H-isoindolcpr0panamidc), Cilomilast (cis—4-cyano[3-(cyclopcntyloxy)—4-rncthoxyphcny1]-cyc10hcxanccarboxy1ic acid), 2-(3 ,5 -dich10r0pyridiny1)(7-rncth0xyspiro[1,3 -bcnz0di0xolc-2,1'- cyclopcntan]y1)cthan0nc (CAS number 1854062)), (2-(3,4- diﬂuorophcnoxy)ﬂuoro-N—[cis—4-[(2-hydroxy methylbcnzoy1)arnino]cyclohcxyl]-)pyridinccarboxarnidc), (2-(3,4- diﬂuorophcnoxy)ﬂuoro-N—[cis—4-[[2-hydroxy (hydroxyrncthyl)bcnzoy1]amino]cyclohcxy1]pyridinccarboxamidc,), CT2820, 16, ast, 1C 485, KP 31334, KW-4490, Lirirnilast ([2-(2,4- dichlorobcnzoy1)[(rncthylsulfonyl)oxy]bcnzoﬁ1rany1])—urca), (N- cyclopropyl- 1 ,4-dihydrooxo[3 -(3 -pyridinylcthyny1)phcny1]-)- 1 ,8- naphthyridinccarb0xarnidc), (N-(3,5-dich10r0pyridiny1) (diﬂuoromcthoxy)[(rncthylsu1fony1)arnino])dibcnz0furancarboxamidc), 6, ORG 20241 (4-(3,4-dimcthoxyphcnyl)-N-hydr0xy-)—2- thiazolccarboximidarnidc), PD189659/PD168787 (Parke-Davis), Pcntoxifyllinc (3 ,7-dihydro-3 ,7-dirncthy1— 1 -(5 -oxohcxy1)—)—1H-purinc-2,6-dionc), compound (5-ﬂu0r0-N—[4-[(2-hydr0xyrncthy1—bcnzoy1)arnino]cyclohcxy1](thian y10xy)pyridinccarboxamidc), nilast (3-(cyc10pcnty10xy)—N—(3,5- dich10r0pyridiny1)rncth0xy-bcnzarnidc), PLX-369 (WO 2006026754), Roﬂurnilast (3-(cyc10propy1rncthoxy)—N—(3 h10r0pyridiny1) (diﬂuororncthoxy)bcnzarnidc), SCH 35 1591 (N—(3,5-dich10ro0Xido pyridiny1)mcthoxy(triﬂuororncthyl)quin01inccarboxarnidc), SchID(TM) CC-10004 (Calgcnc), T-440 (Tanabc), Tctomilast (6-[2-(3,4- dicthoxyphcny1)thiazolyl]pyridinccarboxy1ic acid), Toﬁrnilast (9- cyclopcnty1cthy1-6,9-dihydro(2-thicny1)-5H-pyraz010[3 ,4-c]—1,2,4- triazolo[4,3-a]pyridinc), TPI 1 100, UCB 101333-3 (N,2-dicyc10propy1—6- (hexahydro-1H-achiny1)rncthy1—4-pyrirnidinaminc), V-1 1294A (Napp), VM565 (Vernalis), and Zardavcrinc (diﬂuororncthoxy) methoxyphcny1]-3(2H)-pyridazinonc).

(XV) PDE5 Inhibitors:- Gamma-glutamyl[s-(2-iod0bcnzy1)cystciny1]glycine, Tadalaﬁl, aﬁl, sildcnaﬁl, 4-phcny1—mcthy1aminoch10r0(1- imidaz01y1)-quinaz01inc, 4-phcny1—rncthy1arninoch10r0(3-pyridy1)— quinazoline, 1 ,3 hyl(2-propoxymethanesulphonylamidophenyl)- 1 ,5 - dihydropyrazolo[3,4-d]pyrimidinone and 1-cyclopentylethyl(3-ethoxy- 4-pyridyl)-pyrazolo[3,4-d]pyrimidinone; (xvi) PPARy agonists:- tazone, Pioglitazone hloride, Rosiglitazone Maleate, Rosiglitazone Maleate ((-)-enantiomer, free base), Rosiglitazone maleate/Metformin hydrochloride and Tesaglitizar; (xvii) Protease Inhibitors:- Alphal-antitrypsin proteinase Inhibitor, EPI-HNE4, UT- 77, ZD-0892, DPC-333, Sch-709156 and Doxycycline; (xviii) Statins:- Atorvastatin, Lovastatin, tatin, Rosuvastatin and Simvastatin (xix) Thromboxane Antagonists: Ramatroban and Seratrodast; (xx) lators:- A-306552, entan, Avosentan, EMS-248360, BMS- 346567, BMS-465149, BMS-509701, Bosentan, BSF-302146 (Ambrisentan), Calcitonin Gene-related Peptide, Daglutril, Darusentan, Fandosentan potassium, Fasudil, Iloprost, KC-12615 (Daglutril), KC-12792 2AB (Daglutril) , Liposomal treprostinil, PS-433540, Sitaxsentan sodium, Sodium Ferulate, TBC- 11241 (Sitaxsentan), TBC-3214 (N—(2-acetyl-4,6-dimethylphenyl)[[(4- chloromethylisoxazolyl)amino]sulfonyl]thiophenecarboxamide), TBC- 3711, Trapidil, stinil diethanolamine and Treprostinil sodium; (xxi) ENACs:- Amiloride, Benzamil, Triamterene, 552-02, 84, 69, PSA23682 and AEROOZ.

The inhaler may contain a combination of two or more active ingredients, for example a combination of two or more of the speciﬁc active ingredients listed in (i) to (xxi) herein above.

In one ment the inhaler contains an active ingredient selected from mometasone, ipratropium bromide, tiotropium and salts thereof, salemeterol, ﬂuticasone propionate, beclomethasone dipropionate, reproterol, clenbuterol, roﬂeponide and salts, nedocromil, sodium cromoglycate, ﬂunisolide, budesonide, formoterol fumarate dihydrate, terbutaline, aline sulphate, salbutamol base and sulphate, fenoterol, 3-[2-(4-Hydroxy- 2-oxo-3H-1,3-benzothiazolyl)ethylamino]-N- [2-[2-(4- methylphenyl)ethoxy]ethyl]propane-sulphonamide, hydrochloride, indacaterol, aclidinium e, N-[2-(Diethylamino)ethyl]-N-(2-{[2-(4-hydroxyoxo-2,3-dihydro-1,3- benzothiazolyl)ethyl]amino}ethyl)[2-(1-naphthyl)ethoxy]propanamide or a WO 38170 pharmaceutically acceptable salt thereof (eg. dihydrobromide); N—Cyclohexyl-N3-[2-(3- ﬂuorophenyl)ethyl]—N—(2- { [2-(4-hydroxyoxo-2,3-dihydro- l ,3 -benzothiazol yl)ethyl]amino}ethyl)-B-alaninamide or a pharmaceutically acceptable salt thereof (e.g. di- D-mandelate); a Chloro-benzyloxy)—ethyl]-[2-((R)-cyclohexyl-hydroxy-phenylmethyl )-oxazolylmethyl]- dimethyl-ammonium salt (e.g. hemi-naphthalene-l,5- disulfonate); a (R)- l - [2-(4-Fluoro-phenyl)-ethyl]-3 -((S)phenylpiperidin- l -ylpropionyloxy )-l-azonia-bicyclo[2.2.2]octane salt (eg. bromide or toluenesulfonate); or a combination of any two or more thereof.

Speciﬁc combinations of active ingredients which may be incorporated in the inhaler include:- (a) formoterol (eg. as fumarate) and budesonide; (b) formoterol (e.g. as fumarate) and sone; (c) N—[2-(Diethylamino)ethyl]-N—(2- { [2-(4-hydroxyoxo-2,3-dihydro- l ,3 - benzothiazolyl)ethyl]amino } ethyl)[2-( l -naphthyl)ethoxy]propanamide or a pharmaceutically acceptable salt thereof (e.g. dihydrobromide) and a Chlorobenzyloxy )—ethyl]-[2-((R)-cyclohexyl-hydroxy-phenyl-methyl)-oxazolylmethyl]- yl-ammonium salt (e.g. hemi-naphthalene-l,5-disulfonate); (d) N—[2-(Diethylamino)ethyl]-N—(2- { [2-(4-hydroxyoxo-2,3-dihydro- l ,3 - benzothiazolyl)ethyl]amino } ethyl)[2-( l -naphthyl)ethoxy]propanamide or a pharmaceutically acceptable salt f (e.g. dihydrobromide) and a (R)-l-[2-(4- Fluoro-phenyl)—ethyl] -3 -((S)phenylpiperidin- l -yl-propionyloxy)— l -azoniabicyclo ]octane salt (e.g. bromide or toluenesulfonate); (e) N—Cyclohexyl-Ns-[Z-(3-ﬂuorophenyl)ethyl]-N—(2- { [2-(4-hydroxyoxo-2,3 - dihydro- l ,3-benzothiazolyl)ethyl]amino} ethyl)-B-alaninamide or a pharmaceutically acceptable salt thereof (e.g. di-D-mandelate) and [2-(4-Chlorobenzyloxy l]-[2-((R)-cyclohexyl-hydroxy-phenyl-methyl)-oxazolylmethyl]- dimethyl-ammonium salt (e.g. hemi-naphthalene-l,5-disulfonate); N—Cyclohexyl-N3-[2-(3-ﬂuorophenyl)ethyl]-N—(2- { [2-(4-hydroxyoxo-2,3-dihydro- l ,3 - benzothiazolyl)ethyl]amino}ethyl)-B-alaninamide or a pharmaceutically able salt thereof (e.g. di-D-mandelate) and a (R)-l-[2-(4-Fluoro-phenyl)-ethyl]((S)phenyl piperidin- l -yl-propionyloxy)- l -azonia-bicyclo [2.2 .2]octane salt (e.g. bromide or toluenesulfonate). 2012/052240 Brief Description of the Drawings 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: Figure l is a front side perspective view of an inhaler in accordance with the present invention with the cap closed; Figure 2 is a schematic side view of some internal components of an inhaler in accordance with the present invention with the cap closed; Figure 3 is a schematic side view of the inhaler components of Figure 2 with the cap open and the dispensing mechanism loaded and ready to dispense a dose; Figure 4 is a schematic side view of the inhaler components of Figure 2 with the cap open and the dispensing mechanism unloaded having dispensed a dose; Figure 5 is an exploded schematic view of the ents of the inhaler of Figure l, which has the components shown in Figures 2 to 4; Figure 6 is a schematic side view of the inhaler of Figure 2; Figure 7 is a schematic side view of the inhaler of Figure 3; Figure 8 is a schematic side view of the inhaler of Figure 4; Figure 9 is a perspective front side view of a chassis of an inhaler in accordance with the t invention; Figure 10 is a close up view of the top portion of the chassis of Figure 9, showing a component of the prevention mechanism; Figure 11 is a perspective side view of a lever of a releasable g arrangement of an inhaler in accordance with the present invention; Figure 12 is a perspective front side view of the lever of Figure 11 and a lever lock of the able locking arrangement; Figure 13 is a perspective front side view of the lever of Figure 11 in its operating position in the s of Figure 9; Figure 14 is a perspective rear side view of the inhaler of Figure l with the back housing or cover and n other components removed to show the internal components and the cap in the closed position; 2012/052240 Figure 15 is a perspective rear side view of the r of Figure l with the cap in the open position and the dispensing mechanism loaded and ready to dispense a dose; Figure 16 is a perspective rear side view of the inhaler of Figure l with the cap in the open position and the dispensing mechanism unloaded having sed a dose; Figure 17 is a perspective rear side view of the r of Figure l with the cap in the open position and the dispensing mechanism partially reset, with the reset load being held by the prevention mechanism, Figure 18 schematically shows the various stages of operation and potential misuse of a typical breath actuated inhaler, Figure 19 schematically shows the s stages of operation of a breath actuated inhaler having a tion mechanism in accordance with the present invention, Figure 20 is a perspective view of a prevention mechanism in accordance with the present invention, Figure 21 shows in perspective the wheels of a dose counting mechanism in accordance with the present invention, Figure 22 shows the wheels of Figure 21 located in a counter chassis and having a ating member enclosing them therein, in accordance with the present invention, Figure 23 is a perspective view of the ating member of Figure 23, Figure 24 schematically illustrates the interaction n a dispensing mechanism and a dose counting mechanism via a translating member, in accordance with the present invention, and Figure 25 is a perspective view of a front fascia for an inhaler in accordance with the present invention.

Detailed Description of Preferred Embodiments Referring now to Figure l, a breath actuated inhaler (BAI) 100, in accordance with embodiments of the present ion, is shown. The inhaler 100 comprises a housing or back cover 10, a mouthpiece cover or cap 2 and a front fascia 30 (shown in detail in Figure ) having an aperture 32 through which is visible a counter 201 of a counting mechanism 200. A magnifying protective cover (not shown) ﬁlls the aperture 32 and shields the counting mechanism 200 from ingress of dirt and other rable particulates, whilst enhancing the visibility and brightness of the counter digits. The fascia 30 preferably has a line of weakness (not shown) such that, if it is attempted to forcibly remove the fascia 30 and access the internal ents, the line of weakness shows as a ation or change in the plastic (e.g. colour change or other visible weakness) in the outer surface of the fascia 30, indicating that the inhaler 100 has been ed with and should not be used.

Figure 2 shows some of the internal components of the inhaler 100, as the back cover 10 and front fascia 30 has been removed. Figure 6 also illustrates the components of Figure 2 but in ctive view. In these figures, the inhaler 100 is in the neutral or rest position with the cap 2 closed and covering the mouthpiece 60, which is the preferred state of the inhaler 100 when it is not in use. A canister of medicament 20 (which typically holds a suspension or solution of one or more active pharmaceutical ingredients in a propellant under pressure) is housed in the inhaler 100. Such ers 20 are well known in the art.

A yoke 4 is shown in its uppermost position and a coiled spring 6 is shown in a loaded state, thus g an actuation or dispensing force. Most of the mechanical ents of the inhaler, except the yoke 4, are unloaded and there is no compression of the canister 20. The yoke 4 is ted by the cap 2, specifically by a cam surface 3 of a cam 110 of the cap 2. Thus in the neutral position, the loaded spring force (typically of about 50 N) is held by the yoke 4, which is typically formed of a material that is resistant to ﬂexing and buckling (such as polyoxymethylene, e. g. Ultraform® N 2720 (M60)). A lever 50 and a lever lock 53, both parts of a releasable locking arrangement, are each in their locked ons, although may not be under tension. A further component of the releasable locking arrangement is a drop link 55, which is shown in its latched position whereby it rests upon a pivot shaft 58 of a breath-actuated element, vane 57, thus able to hold the lever lock 53 in its locked position. A return spring 210 abuts the inner surface of the back cover 10 when the inhaler 100 is assembled, to bias the releasable locking arrangement into the locked position so that it will lock when under tension or load.

A manual firing button 48 is provided and enables the user to deliver a dose of medicament as an ncy function if, for any reason, the usual dispensing mechanism 2012/052240 fails, or if the user otherwise cannot breath actuate the dispensing mechanism to deliver a dose of medicament, for example, during a chronic asthma attack. atively the button 48 can be used to test and/or prime the inhaler 100, or simply as an alternative ﬁring mechanism if desired.

Most of the mechanical components of the r 100 are retained in a chassis 40, which is not shown in Figure 2 but is shown in later ﬁgures (such as Figure 9). Most of the components of the dispensing mechanism are d on, engaged with, or supported by the chassis 40.

Figure 3 illustrates the inhaler 100 when it is ready to be used/ﬁred. Figure 7 also illustrates the components of Figure 3 but in perspective view. The cap 2 is opened to uncover a mouthpiece 60. As the cap 2 pivots on opening, the yoke 4 moves downwardly under the force of the spring 6 to engage the base of the canister 20. However compression of the canister 20 to deliver a dose of medicament is substantially prevented by the able locking arrangement which becomes engaged as the yoke moves and holds the load of the spring 6, the lever lock 53 holding the lever 50. In this primed or dispensing state, the inhaler 100 is loaded, ready to ﬁre and deliver a dose of medicament.

Inhalation by the user at the mouthpiece 60 causes air to ﬂow through the air ﬂow path deﬁned inside inhaler 100. Due to the pressure drop created by the air ﬂow (or use of the ﬁring button 48 if manual actuation occurs), the vane 57 pivots and es the drop link 55. The vane 57 is red to be of a suitable size and shape such that it is able to move under a relatively low pressure drop, and the inhalation channel is conﬁgured to be curved at least where it corresponds with the a bottom edge of the vane 57, such that the gap between the edge of the vane 57 and the channel remains substantially the same as the vane 57 rotates under inhalation. Movement of the drop link 55 allows the lever lock 53 to release the lever 50, which is biased into its released position by the load of the spring 6 acting on the yoke 4 which pushes on the yoke protrusions 82 of the lever 50. The lever 50 in its unlocked state allows the coiled spring 6 to unload and to compress the canister 20 to deliver a dose of medicament. The dispensing mechanism also triggers an adjustment of the counter 201 of the ng mechanism 200 via a translating member 250 as discussed below and shown in Figure 24.

Figure 4 illustrates the components of the inhaler 100 after a dose of ment has been dispensed. Figure 8 also illustrates the components of Figure 4 but in perspective view. In order to be able to dispense a ﬁarther dose of medicament, the inhaler 100 must be ﬁllly reset from the Figure 4 conﬁguration to the dispensing state shown in Figure 3. Fully resetting the inhaler 100 allows the metering valve 21 (see Figure 5) of the canister 20 to reﬁll with medicament. It also causes the lever 50 to return to a position where it can be locked by the lever lock 53, which is pushed back into its locking position by the spring 210. The drop link 55 is also pushed back into place by the spring, thus readying the releasable locking arrangement to again lock the dispensing mechanism and t actuation until the r is ﬁred.

Resetting of the r 100 is achieved by closing the cap 2 so that the cam surface 3 pushes the yoke 4 upwards, which in turn pivots the lever 50, etc., and s the inhaler 100 to the state shown in Figure 3. Further details of the resetting mechanism are discussed below, in particular in relation to the prevention mechanism to prevent the inhaler 100 being only partially reset.

Figure 5 is an exploded view of a typical inhaler 100, such as one in accordance with embodiments of the present invention. The component parts are shown in the unassembled state. The ng mechanism 200 is shown separately but is insertable into the chassis 40 such that at least the display of the counter 201 of the counting mechanism 200 is visible through an aperture 32 in the fascia 30. A magnifying window formed ally with the chassis of the ng ism 200 aligns with the aperture 32 as discussed in more detail below.

Figures 9 and 10 show a chassis 40 in accordance with embodiments of the present invention. The chassis 40 comprises an injection moulded ymethylene copolymer, such as Hostaform MTl2U03, although other le materials and/or manufacturing techniques can be used to form a chassis 40 suitable for use in embodiments of the present invention. The chassis 40 is a primary structural component of the exempliﬁed inhalers 100 and deﬁnes many of the pivot points of the inhaler mechanisms and also deﬁnes the position ofmany the other components of the inhaler lOO.

In the embodiment shown in s 9 and 10, the chassis 40 also deﬁnes one of the components of a prevention mechanism 70. As most clearly shown in Figure 10, the chassis comprises an integrally formed second ng member 74. The second engaging member 74 projects generally upwards when the chassis 40 is d in the inhaler 100 and the inhaler 100 is held in an upright on. The second engaging member 74 is sufﬁciently ﬂexible such that it can be deﬂected out of the plane of the chassis side (i.e. in direction A as shown in Figure 20 and also in a direction substantially directly opposite to A). At the upper end of the second engaging member 74 there is provided an engaging portion 75, which is a hooked-shaped portion having a protruding tooth or hammer head.

The tooth is conﬁgured for engagement in a mating ration with an engaging portion 73 of a ﬁrst engaging member 72, which is shown in Figures ll to 13. The tooth 75 is angled to aid in locating and retaining the tooth 75 in the engaging portion 73 of the ﬁrst engaging member 72. The second engaging member 74 is also ently ﬂexible such that it can be deﬂected generally towards the chassis (i.e. in direction B as shown in Figure 20) such that the tooth 75 is brought into abutment with the chassis 40. As well as being sufﬁciently ﬂexible to be able in this ways described above, the second engaging member 74 is also ently resilient such that it will reliably return to its initial position once the deﬂecting force(s) is removed. gh only one second engaging member 74 is visible on the chassis 40 of s 9 and 10, there is provided a further second engaging member 74 of the same conﬁguration but on the opposite side of the chassis 40, which is not visible in these ﬁgures.

Figure ll shows a lever 50 for the inhalers 100 shown in the ﬁgures. The lever 50 is a generally symmetrical component that is held in a pivotable conﬁguration by the chassis 40. Chassis protrusions 80 (only one of which is shown in Figure ll) are provided for engagement with the chassis 40 when the inhaler 100 is led (as shown in Figure 13). In use, e. g., when dispensing a dose of medicament, the lever 50 pivots about these chassis protrusions 80. The lever 50 also comprises two yoke protrusions 82 (only one of which is shown in Figure ll) which engage with the yoke 4 when the inhaler 100 is assembled such that movement of the yoke 4 (e.g. under the force of the spring 6 or when resetting the inhaler 100 using the cap 2) is translated to the lever 50 and pivots the lever 50 about the s protrusions 80.

Lever 50 further comprises a pair of counter protrusions 92 for engaging and actuating the counting mechanism 200 via a translating member 250 as discussed below.

The counter protrusions 92 are curved such that, if the lever 50 rotates too far, the counter protrusions can disengage from the ating member 250 of the counting mechanism 200 to avoid overcounting or damage that may be caused to the translating member 250 by over rotation of the lever 50. Lever 50 also comprises an ng protrusion 52 that is conﬁgured to rest against a portion of a lever lock 53 when the inhaler 100 is in its rest state (as shown in Figures 2, 6 and 12).

Lever 50 further comprises a pair of ﬁrst ng members 72 that protrude from the lever 50, each having a respective engaging portion 73 (only one shown in Figure ll) generally at an end thereof. The ng portions 73 are shaped to receive a tooth of the respective engaging portions 75 of the second engaging members 74 of the chassis 40.

When the engaging portions 75 of the second engaging s are received in the engaging portions 73 of the ﬁrst ng members 72 any tensile force pulls the engaging members 72, 74 ﬁlrther into a mating conﬁguration and ts the ng members 72, 74 being pulled apart. This arrangement locks the lever 50 against rotation about the chassis protrusions 80 even if the yoke 4 acts on the lever 50 via the yoke sions 82 and attempts to move it.

Operation of the inhaler 100 will now be described with a focus on the role of the prevention mechanism 70. Figures 14 to 17 show the inhaler 100 at different stages of operation. In Figure 14, the inhaler 100 is in the neutral or rest state, which is the preferred state for storing the inhaler 100 between uses. The prevention mechanism 70 comprises a pair of ﬁrst engaging members 72 integrally formed with the lever 50 (of which only one is shown in Figure 14) and a pair of ﬁrst engaging members 74 integrally formed with the chassis 40 (of which only one is shown in Figure 14 and for clarity, the rest of the chassis 40 has been removed, including the portions against which the engaging ns 75 of the second engaging s 74 abut when the engaging portions are engaged in the mating conﬁguration and are under load). In the rest state, the engaging portion 75 of the second engaging member 74 sits above and separate from the engaging portion 73 of the ﬁrst engaging member 72. Furthermore the engaging portion 75 is not in contact with the substantially rigid component of the inhaler 100, which in the shown inhaler is another part of the chassis 40.

When a patient wishes to inhale a dose of medicament, the ﬁrst operation step is to open the mouthpiece cap 2 to expose the mouthpiece 60, as shown in Figure 15. The cap 2 is pivotally mounted on the chassis 40 and has a cam 110 at the pivot point. Pivotal movement of the cap 2 from the second or closed position to the ﬁrst or open position allows the yoke 4 to move downwards, under the force applied by the coiled spring 6. As the yoke 4 moves downwards the load of the ssed spring 6 transfers from the yoke 4 (which rests on the cam surface 3, when the cap 2 is ﬁJlly closed), to being held by the releasable locking arrangement, as the cap 2 is opened. Speciﬁcally as the cap 2 opens, the lever 50 rotates and the lever abutting protrusion 52 contacts with, and is locked by, the lever lock 53 which is held by the drop link 55 that rests on the pivot shaft 58 of the vane 57 to hold the load of the spring 6. This can be seen in Figure 15, as when the cap 2 is ﬁJlly opened, there is space between the foot of the yoke 4 and the cam surface 3 of the cap 2. Although, as the load is transferred to the releasable locking arrangement the lever 50 pivots slightly about the chassis protrusions 80 as the yoke 4 moves downwards, any such nt of the lever 50 will be l and will not engage or otherwise affect the prevention mechanism 70, as can be seen in the close-up view of Figure 15.

After opening the cap 2 of the inhaler 100, thus priming it such that a dose is ready to be dispensed (known as the preﬁre point or condition), the patient inhales through the iece 60. The pressure drop in the airﬂow passage through the inhaler 100 es the releasable locking mechanism. Speciﬁcally the pressure drop causes the vane 57 to pivot about its axis 58 generally towards the mouthpiece 60, which allows the drop link 55 to disengage from the top surface of the vane, thus allowing the lever lock 53 to be pushed away by the lever ng protrusion 52, which frees the lever 50 to pivot on the chassis protrusions 80 under the force of the expanding spring 6 (which acts on the yoke 4 which in turn acts on the lever 50 via the yoke protrusions 82). The rd movement of the yoke 4 under the full force of the compressed spring 6 sses the valve stem 24 of the er 20 against a nozzle block 62 of the inhaler 100 (in this embodiment, the nozzle block 62 is an integral part of the mouthpiece 60 but it could be a separately provided component or formed with another component of the inhaler 100). Compression of the valve stem 24 activates the metering valve and ses a dose of ment under pressure into the tion airﬂow and through the mouthpiece 60 to be inhaled by the patient.

Figure 16 shows the inhaler 100 after this sequence has occurred, i.e. in the ﬁred or dispensed state, where a dose of medicament has been sed and the inhaler 100 has not been reset. The yoke 4 has been deployed under the load of the spring 6 and has moved downward back toward t with the cam surface 3 of the cap. The lever 50 has pivoted relative to the chassis 40 such that the counter engaging portion 92 has moved downwards and actuated the counting mechanism 200 and the ﬁrst engaging member 72 has moved upwards. In Figure 16, the vane 57 has returned to its rest position because the patient has stopped inhaling. However the other components of the releasable locking arrangement cannot return to the rest or neutral position as the abutting sion 52 of the lever 50 is still pushing upwards on the lever lock 53 due to the on of the lever 50.

As mentioned above, as the lever 50 pivoted about the chassis protrusions 80, the end of the lever 50 having the ﬁrst ng member 72 (or members as can be seen in the Figure 16 close up) moved upwards. As can be seen in Figure 16, in the dispensed state, the engaging portion 73 of the ﬁrst engaging member 72 has travelled such a distance that it has travelled past the engaging portion 75 of the second engaging member 74 and has d above and spaced away therefrom. Clearly it is undesirable for the engaging portions 73, 75 of the engaging members 72, 74 to engage in a mating conﬁguration during dispensing of a dose of medicament. Therefore the engaging portions 73, 75 are conﬁgured such that if the ﬁrst ng member portion 73 moves upwards from a position below the second engaging member portion 75, then as the engaging portions 73, 75 come into contact, one or both of the engaging portions 73, 75 is ed by the other of the engaging portions 73, 75 such that they pass each other without engaging in the mating conﬁguration. In the present embodiment, the engaging portions 75 of the second engaging members 74 (i.e. those formed on the chassis 40) are deﬂected inwardly (i.e. are squeezed ly towards each other) by the more rigid engaging ns 73 of the ﬁrst engaging members 72 (i.e. those formed on the lever 50).

After inhaling a dose of medicament, the patient is encouraged to reset the inhaler 100 by the conﬁguration of the device, since it is not possible to dispense further doses until it has been fully reset. This not only ensures that the r 100 is returned to its preferred rest state (in which it is conﬁgured to hold the load of the spring 6 through the yoke 4, which is a relatively strong component of the r 100 and is designed to hold such a load reliably and without damage thereto) but also that the mouthpiece 60 is covered straight after use, thus preventing or sing ingress of dirt and other undesired particles or contaminants into the inhaler 100. To reset the inhaler 100, the patient only needs to pivot the cap 2 back from the ﬁrst (open) position to the second (closed) position.

The cam 110 of the cap 2 is engaged with the yoke 4 and as the cap 2 rotates, the cam surface 3, which is helically shaped, helps push the yoke 4 upwards, thus reloading the spring 6 and moving the other components, particularly those of the releasable locking arrangement, back into the rest state.

However, it is possible that the patient might not fully reset the inhaler lOO, i.e. may not move the cap 2 all the way from the ﬁrst, open position to the second, closed position. This may be because, for example, the patient is distracted during the resetting motion and es the cap 2, or the patient may lose their grip on the cap 2, or it may be that the patient plays with the cap 2 and repeatedly move it partially in and out of the open position, without ever fully g the cap 2. This is undesirable as it might lead to the inhaler 100 not ﬁJlly ﬁanctioning when the next dose is dispensed, for example because the ng valve does not ﬁllly reﬁll, or insufﬁcient load is stored in the spring 6 to ﬁllly activate the valve. Still ﬁlrther, the r 100 may not be reset to the point at which the counting mechanism 200 is reset, which means that any dose dispensed subsequently, even if not a ﬁlll dose, will not be counted and the counter 201 may ore inaccurately reﬂect the number of doses of the inhaler 100.

The prevention mechanism 70 is conﬁgured to solve all the above problems. If the cap 2 is not fully moved from the open position to the closed position, i.e. if the patient stops rotating the cap 2 when it is in some intermediate position and the spring force would therefore bias the yoke 4 to rotate the cap 2 back into the open position, the prevention mechanism 70 engages to hold the load of the spring 6 until the cap 2 completes its movement to the fully closed position, in which the inhaler 100 is ﬁllly reset. Thus the yoke 4 is not biased by the spring 6 as the prevention mechanism prevents such biasing.

As can be seen in Figure 17, the engaging portions 73, 75 are conﬁgured such that if the second engaging member portion 75 moves upwards from a position below the ﬁrst engaging member portion 73, then as the engaging portions 73, 75 come into contact they are capable of engaging in the mating ration, should rotation of the cap 2 to the closing position cease. In the t embodiment, in order to optimise the mating engagement, ng portions 73, 75 are red such that as they initially come into contact, one or both of the engaging portions 73, 75 is deﬂected by the other of the engaging portions 73, 75 such that the deﬂected engaging n(s) snap into the mating conﬁguration. In the present embodiment, the ng portions 75 of the second engaging members 74 (i.e. those formed on the chassis 40) are again deﬂected, but this time outwardly (i.e. are deﬂected slightly away from each other) by the more rigid engaging portions 73 of the ﬁrst engaging members 72 (i.e. those formed on the lever 50).

Once the engaging portions 75 have passed beyond a certain point, they deﬂect back inwards (as the material from which they are formed is relatively resilient) and snap or slot into the engaging portions 73 of the ﬁrst engaging s 72, which are sized and shaped to snugly receive the teeth of the engaging portions 75 of the second engaging members 74. This conﬁguration can be seen in Figure 17. Once engaged in the mating conﬁguration, should the cap 2 cease to move and/or move in the opposite direction (i.e. move back towards the ﬁrst, open position) the load of the spring 6 is held (Via the lever 50) by the ﬁrst engaging members 72 which are pulled in their engaged state against the second engaging members 74. As the second engaging members 74 are ﬂexible, the engaging portions 75 f are deﬂected under this tension generally in direction B (as shown in Figure 20) and abut a more rigid part of the chassis 40. The tensile load placed on the ng members 72, 74 in this manner does not disengage the mated engaging portions 73, 75, but rather they are driven together in the mating conﬁguration and by Virtue of the abutment with the chassis 40, the force of the spring 6 is readily withstood by a mixture of tension between the ﬁrst and second engaging members 72, 74 and compression of the engaging portions 75 of the second engaging members 74 against the more rigid portion of the chassis 40. Thus the ﬁrst and second engaging members 72, 74 are strong and reliable and will not suffer signiﬁcant material creep nor permanent damage or deﬂection.

When the cap 2 s its motion towards the second, closed position however, the force through the second engaging members 74 is relieved and they return to their rest position (i.e. no longer abut the chassis 40) and the ng members 72, 74 are effectively pushed together or compressed by the resumed movement of the lever 50. The engaging members 72, 74 are conﬁgured such that a ssive force or motion readily disengages the mated engaging portions 73, 75 (in this ment, by the more rigid engaging portions 73 of the lever 50 again deﬂecting the chassis engaging ns 75 outwardly). The cap 2 can then progress to the ﬁllly closed state and the inhaler 100 will be fully reset thus providing an inhaler 100 that will reliably dispense and count any ﬁarther doses of medicament.

Although the above disclosed embodiments of the present invention have ﬁrst and second engaging members 72, 74 integrally formed with the lever 50 and the chassis 40 respectively, this is an exemplary arrangement and is not limiting to the scope of the present invention. ative arrangements are envisaged, for example one or both of the engaging members 72, 74 may be separately formed components and/or one or both of the engaging members 72, 74 may be integrally formed with one or more other components of the inhaler 100. The more rigid component of the inhaler 100 t which the ﬁrst and/or second engaging members 72, 74 abuts may be a component of the chassis 40 as discussed above, but may alternatively or additionally be any other suitable component.

Figures 18 and 19 tically rate the above operation of an r 100 in accordance with the present invention, with nce to the various trigger points in the operating cycle. Under normal use, starting from the inhaler 100 rest or neutral position (cap closed), the cap 2 must be opened which, as shown under normal operation (closest to the left axis in both ) moves the inhaler 100 in the dispensing direction through the following steps, in order: (i) the yoke 4 contacts the canister 20 (assuming it does not rest in a ted state); (ii) the mechanism reaches the preﬁre point, where the inhaler 100 is primed and ready to ﬁre (but is prevented from doing so by the releasable locking ement. Thereafter, when the inhaler 100 is actuated/ﬁred, the inhaler 100 operates in a dispensing direction through the second part of the cycle in which: (iii) the mechanism compresses the canister past the valve ﬁring point (ﬁre point), at which a dose of medicament is dispensed; (iv) the mechanism passes the ng point at which the counting mechanism 200 is actuated and a dose is counted by the r 201; and ﬁnally (v) the mechanism reaches the end of stroke (ﬁnal rest/dispensed) position. Steps (iii) and (iv) typically occur in the above order although step (iv) can occur before step (iii). In inhalers in which a dose is automatically d as the inhaler ﬁres, it is essential that every dose is counted and that the r never counts when a dose is not sed. To achieve this, ideally the ﬁre point and counting point should be as close together as possible to minimise the potential for one to be reached without then reaching the other (i.e. steps (iii) and (iv) occur as close together as possible, no matter in which order they occur). Furthermore, to ensure a ﬁlll dose of medicament is always sed, such an inhaler must be fully reset, at least past the preﬁre point and preferably past the BAI reset point before a subsequent dose is dispensed. Resetting occurs when the inhaler 100 moves in the resetting direction through the following steps, in order: (i) the mechanism passes the valve 21 reset point (i.e. the reﬁll point, which is the position that, when the r 100 is reset by rotation of the cap 2 in the resetting direction, the mechanism must reach for the valve 21 of the canister 20 to begin to reﬁll; (ii) the mechanism passes the counter 201 reset point (i.e. the position that, when the r 100 is reset by on of the cap 2 in the resetting direction, the mechanism must reach to be ready to subsequently count another dispensed dose); (iii) the mechanism passes the inhaler 100 reset point (i.e. the BAI reset which is the position that, when the inhaler 100 is being reset by rotation of the cap 2 in the resetting direction, the mechanism must reach to be fully reset and ready to subsequently actuate/reﬁre).

As shown in Figure 18, if the device is not fully reset (i.e. does not reach the BAI reset due to, e.g., incomplete cap closure (such as interrupted cap closure or cap tampering)), it is still possible for the inhaler to dispense at least a partial further dose that may be counted as a whole dose. In the upted cap closure example, the cap 2 ceases movement when the inhaler 100 has passed the reﬁll point, so the valve 21 begins to ﬁll with medicament, but before the counter reset point is reached. Therefore if the inhaler 100 reﬁres, er dose has ﬁlled the valve 21 is released (at the ﬁre , but is not counted (although the inhaler 100 passes back h the count point, the counter has not been reset so no count occurs). Thus the inhaler 100 undercounts. In the cap tampering example, the inhaler 100 passes beyond the counter reset point, but does not reach the BAI reset. In the dispensing direction, cap 2 movement is reversed after the ﬁre point but before the counting point (even though they are close together), so a dose is dispensed but not counted as the count point is not reached. Thus the inhaler 100 undercounts. The inhalers of Figure 18 are not in accordance with the present invention as there is no mechanism to prevent actuation (or at least tion of the inhaler 100 reaching the ﬁre/count point) when the inhaler has not been fully reset.

Figure 19, however, shows operation of an inhaler 100 in accordance with the present invention, having a prevention ism as previously described. As is shown in the ﬁgure, normal operation does not differ from the Figure 18 examples. However, when cap 2 closure is interrupted or the cap 2 is tampered with before the inhaler 100 is reset to at least the BAI reset point, the prevention mechanism engages and prevents movement in the dispensing mechanism beyond a blocked point (shown as the horizontal red line). The blocked point is before the inhaler 100 can reach the ﬁre or ng point. Thus the dispensing mechanism does not dispense nor the r count as the inhaler 100 cannot reach the ﬁre point or ng point, until the cap 2 is closed and the inhaler 100 reset at least to the BAI reset point.

Figures 21 to 23 show the main components of the dose counting mechanism 200.

In Figure 21, the ﬁrst count wheel 220, the second count wheel 230 and the intermediate wheel 240 are shown. Both a front face 222 and a back surface 224 of the ﬁrst count wheel 220 are shown in Figures 21(c) and 21 (d) respectively. Front face 222 of the ﬁrst count wheel 220 has numbers printed annularly thereon (not shown) from 0 to 9 which, when the ﬁrst count wheel 220 is aligned on the ﬁrst axis 260 of a counter s 202 (see Figure 22) are concentric with, and aligned inside of, annularly printed numbers 1 to 12 (not shown) on a front face 232 of the second count wheel 230. The ﬁrst (or units) count wheel 220 has rly spaced teeth 226 arranged on the back surface 224, which are conﬁgured such that the notches therebetween receive a pawl 252 of the translating member 250. nt of the translating member 250 in the counting direction C (Figure 22) thus engages between the teeth 226 and rotates the unit count wheel 220 such that the number shown in the display window 280 of the dose counting mechanism 200 is decremented (for example from 9 to 8). However further rotation of the units count wheel 220 (e.g. such that digit 8 passes the window 280) is prevented by an overcount ting protrusion 253 of the translating member 250. This overcount preventing sion 253 is a linear protrusion which protrudes from the face of the translating member 250 towards the back surface 224 of the units count wheel 220. The overcount preventing sion 253 is shaped and positioned on the translating member 250 such that it is capable of abuting one of a plurality of spaced apart ribs 228 arranged annularly around the outer part of the units count wheel 220 back surface 224. The overcount preventing sion 253 slides into a position where it becomes located between a ﬁrst (leading) rib 228 and a second (following) rib 228 of the units count wheel 220 as the translating member 250 moves linearly in the counting direction C (at the same speed as the pawl 252 of the translating member 25 0). The ribs 228 and the overcount preventing protrusion 253 are conﬁgured such that the protrusion 253 abuts the second (following) rib 228 as the units count wheel 220 reaches the end of its desired ent. The overcount preventing protrusion 253 thus blocks the units count wheel 220 from rotating any ﬁarther. As the translating member 250 returns to its initial position (i.e. moves linearly in a direction te the counting direction C), the unt preventing protrusion 253 also moves linearly back to its initial position and is withdrawn from abutment with the rib 228 of the units count wheel 220, thus freeing the wheel 220 to turn again on the next actuation.

The translating member 250 further comprises a rest count preventing protrusion (not shown) which also protrudes from the same face of the ating member 250 as the overcount preventing protrusion 253. The rest count preventing protrusion prevents rotation of the units count wheel 220 when the counting mechanism 200 is in the rest on by engaging one of the plurality of ribs 228 of the units count wheel 220. Thus the rest count preventing protrusion and the overcount preventing protrusion 253 are somewhat complementary. The rest count preventing protrusion is also a linear protrusion and is similar in conﬁguration to the overcount preventing sion 253.

The units count wheel 220 further comprises a pincer 221 which is conﬁgured to engage with the intermediate wheel 240 once per full rotation of the units count wheel 220 (i.e. after the units count wheel 220 has displayed digits 9 through to 0 in the display window 280). The pincer 22l rotates into position and engages with a long tooth 242 of the intermediate wheel 240. As the units count wheel 220 continues to rotate, the intermediate wheel 240 rotates as well, about axis 270 of the counter s 202 on which it is rotatably located. As the pincer 22l rotates still ﬁlrther, it disengages with the long tooth 242 of the intermediate wheel 240 and the intermediate wheel stops rotating until the pincer has rotated another full rotation and reengages therewith.

Rotation of the intermediate wheel 240 effects rotation of the second (or tens) count wheel 230, as the intermediate wheel 240 is engaged with the tens count wheel 230 Via the interaction of tens count wheel teeth 234 and intermediate count wheel long teeth 242 and also short teeth 244. The interaction and relative positions of the wheels 220, 230 and 240 can be seen in Figure 22. Thus tens count wheel 230 is selectively rotated one increment for every ten ents of the units count wheel 220, Via intermediate wheel 240, and the counter display counts down the digits from 120, which can be seen by a patient through the display window 280 which is d in the aperture 32 of the front fascia 30 (see Figure 25). As the count of the display ches and reaches zero, a ﬂag 236, which protrudes inwardly from the tens count wheel 230, is brought into registration and occludes the display window 280. The ﬂag is coloured red 236 and tes to the patient that the inhaler has no doses of medicament remaining. Although the units wheel 220 may continue to rotate, the digits yed thereon cannot be seen through the ﬂag 236 and there is no conﬁlsion for the patient since it remains clear that no doses are remaining. To prevent the ﬂag 236 rotating away from the display window 280, the tens count wheel 230 is red such that a set of the teeth 234 are g ﬁom the wheel 230 at a position 233 that coincides with the ﬂag 236 ing the window 280.

Therefore, even if the intermediate wheel 240 rotates, there are no teeth 234 of the tens count wheel 230 to engage with the teeth 242, 244 of the intermediate wheel 240 and the ﬂag 236 will remain in the window 280.

Figure 23 shows the ating member 250 of the dose ng mechanism 200.

A slot 254 is ed for receiving a protrusion (not shown) from the ﬁrst axis 260 on which the tens and units count wheels 220, 230 are located. The slot 254 guides the translating member 250 as it moves in the counting direction C and back in the opposite direction and ensures reliable linear motion thereof. The linear movement of the translating member 250 is also aided by pairs of tabs 258 on either lateral edge thereof, which are received in channels 204 of the counter chassis 202. The tabs 258 hold the translating member 250 securely in place in the counter chassis 202 and abutting the relevant parts of the dose counting mechanism 200, whilst allowing the translating member 250 to move in the counting direction (and the opposite direction to reset the r) by sliding in the channels 204.

The translating member 250 further comprises notches 256 for receiving a component of the inhaler sing mechanism, in this embodiment the protrusions 92 of the lever 50 as shown in Figure 24. As the lever 50 rotates during dispensing of a dose of medicament, the protrusions 92 engage and push the translating member 250 downwards via notches 256, thus ing the dose counting ism 200 and counting a dose.

The protrusions 92 and notches 256 are suitably conﬁgured such that they will engage and disengage at appropriate points in the sing/counting cycle and will not force the dose counting mechanism 200 to overcount. In particular, the s 256 and protrusions 92 are curved to enable disengagement if needed as the dose counting mechanism 200 is reset.

Figure 25 shows a front fascia 30 of the inhaler 100 of the present embodiment.

An aperture 32 is located where the fascia 30 covers the dose counting mechanism 200 so that the display window 280 is visible. Although not shown, the window 280 comprises a transparent c (amorphous copolymer like Eastman Tritan TX2001) component of the counter chassis 202 and is curved on its outer face in both the x direction and the y direction and protrudes from the counter chassis 202 into the aperture 32. The window 280 has a level of magniﬁcation that is greater in the y ion (i.e. across the height of the window 280) than it is in the x direction (.e. across the width of the window 280). Thus although the display is magniﬁed by the window 280, the display is not signiﬁcantly distorted, particularly in the width dimension which is advantageous for reading digits.

The window 280 of the t embodiment has a magniﬁcation in the x direction that magniﬁes the size of the display by about 10%, and a magniﬁcation in the y direction that magniﬁes the size of the display by about 20%.

Claims

What we claim is:

1. An inhaler for ry of a medicament by inhalation, the r comprising: a dose counting ism comprising a r and a translating , the translating member comprising a pawl and the counter comprising a first count wheel, a second count wheel and an intermediate wheel engaged with the second count wheel and in selective engagement with the first count wheel, a dispensing mechanism configured, on actuation, to dispense a dose of medicament, wherein: on actuation, the dispensing mechanism moves the translating member in a substantially linear direction, whereby the pawl rotates the first count wheel, and as the first count wheel rotates, the intermediate wheel is selectively engaged thereby selectively rotating the second count wheel; wherein the dose counting ism further comprises a counter chassis, the counter chassis being configured to receive and to guide motion of the translating member; wherein the counter chassis further comprises a chassis pawl that is integrally formed with the r chassis, the chassis pawl configured to enable the wheels of the dose counting mechanism to rotate in a first, counting direction but to prevent rotation of at least the first count wheel in an opposite, backwards direction.

2. An r for delivery of a medicament by inhalation, the inhaler comprising: a dispensing mechanism configured, on actuation, to dispense a dose of medicament, a dose counting mechanism sing a r for displaying indicia relating to the number of doses of medicament of the inhaler, and a window substantially aligned with the counter such that the indicia are viewable therethrough, wherein the window ses a magnifying outer surface for magnifying the indicia of the counter, the magnification in a first dimension being greater than the magnification in a second dimension that is substantially dicular to the first dimension; n the dose counting mechanism comprises a first count wheel, a second count wheel and an intermediate count wheel engaged with the second count wheel and in selective engagement with the first count wheel; wherein the dose counting mechanism further comprises a counter chassis which comprises a chassis pawl that is configured to enable the wheels of the dose counting mechanism to rotate in a first, counting direction but to prevent rotation of at least the first count wheel in an opposite, backwards direction.

3. The inhaler of claim 2, wherein the dose counting mechanism and the window are enclosed substantially within a housing of the inhaler behind a front fascia thereof, wherein the fascia comprises an aperture through which the window is visible.

4. The inhaler of claim 2 or 3, wherein the window is integrally formed with the counter chassis of the dose counting mechanism.

5. The inhaler of claim 2, 3 or 4, wherein the magnifying outer surface comprises a curved e, the curvature of the surface in the first dimension being greater than the curvature of the surface in the second ion.

6. The inhaler of any one of claims 2 to 5, wherein the magnification across a width of the window is lower than the magnification across a height of the window.

7. The inhaler of claim 6, wherein the ication across the width of the window ies the size of the display by between about 0 and 30%, and the magnification across the height of the window magnifies the size of the display by between about 0 and 50 %.

8. The inhaler of any one of claims 2 to 7, n: the dose counting mechanism r ses a translating , the translating member comprising a pawl, on actuation, the dispensing mechanism moves the ating member in a substantially linear direction, whereby the pawl rotates the first count wheel, and as the first count wheel rotates, the intermediate wheel is selectively engaged thereby selectively rotating the second count wheel.

9. The inhaler of claim 1 or 8, wherein the pawl rotates the first count wheel by about 36° upon each actuation.

10. The inhaler of any one of claims 1, 8 or 9, wherein the first count wheel engages the intermediate wheel only once for each full rotation through 360° of the first count wheel.

11. The inhaler of any one of claims 1 or 8 to 10, wherein the intermediate wheel rotates the second count wheel by between about 9° and 180° on each actuation.