Patent Description:
For some medical conditions, it can be desirable to administer medicament to a subject via the airways. Inhalers, such as dry powder inhalers, can be used for this purpose, as can insufflators.

Existing inhalers typically have poor reliability and/or repeatability in regard to delivered dose, with dosage generally affected by variation in subject inhalation. This typically restricts the use of inhalers to applications wherein variation in dosage is tolerable, e.g. where effects of substantial under and/or over -dosing are not life-threatening. <CIT> describes a pharmaceutical container, which has a holing slot concaved from a bottom portion of a container. <CIT> describes an inhalation device for a powdered medicament contained initially in a container. <CIT> describes an inhalation device for powdered medicaments. <CIT> describes an inhaler device for facilitating the inhalation of a medicament from a pierceable medicament capsule. <CIT> describes inhaler devices.

More specifically, the document <CIT> discloses an inhalation device comprising a hollow mouthpiece portion having an open end into which is located a body portion, the mouthpiece and body portions being longitudinally relatively moveable with respect to one-another; the body portion having an internal chamber therein adapted to receive a medicament container and having a container piercing cavity in communication with the chamber; the mouthpiece portion having an outlet communicating with the chamber and both portions being provided with co-operating passages in tangential communication with the chamber whereby air can be drawn through the device via the outlet so as to cause a swirling air flow through the chamber; the body portion being provided with a spring biassed piercing needle adapted to be reciprocated transversely into the cavity so as to pierce a container when in the cavity and with a lever arm pivotable about a fulcrum acting on a member so as to reciprocate it into the cavity to eject a container from the cavity into the chamber; the mouthpiece member having a projection adapted to engage in sequence the needle and the lever arm upon insertion of the base member into the mouthpiece member so as to cause actuation thereof.

The document <CIT> discloses an inhalation device for powdered medicaments contained initially in a container, which device comprises first and second housing members attachable one to the other by relative longitudinal movement therebetween to form a body defining an air flow path from an air flow inlet provided therein to an air outlet provided therein, means for locating the container in the air flow path in a position to be opened, appropriate opening means for the container provided on one of said housing members, a cam surface provided on the other of said housing members and adapted to act on the opening means, said opening means being normally in a non-container opening position but movable successively into and out of a container opening position by the action of the cam surface thereon occasioned by the longitudinal movement between the housing members, the cam surface including a step or steps to prevent reverse movement thereof when the opening means is in the non-container opening position after passing through the container opening position.

The document <CIT> discloses an inhaler device for facilitating inhalation of a medicament from a pierceable medicament capsule, the inhaler device comprising: a body having a chamber for receiving the pierceable medicament capsule; piercing means for piercing the medicament capsule received in the chamber; an actuator rotatably mounted to the body; an actuating member moveable relative to the body so as to rotate the actuator; a cam track member connected to the piercing means and comprising a plurality of cam track parts along which the actuator slides; wherein a first movement of the actuating member relative to the body slides the actuator along and in abutment with a first one of the cam track parts so as to press against the cam track member and thereby drive the piercing means towards an extended position; and wherein a second movement of the actuating member relative to the body slides the actuator along and in abutment with a second one of the cam track parts so as to press against the cam track member and thereby drive the piercing means towards a retracted position.

Accordingly, new strategies for respiratory administration of medicament would be desirable. It would be particularly desirable to develop new respiratory delivery devices offering improved versatility or flexibility in use.

More specifically, the present invention provides a device for delivery of a composition to an airway of a subject as defined in claim <NUM>.

Reference will now be made to various embodiments or aspects of the present disclosure.

In a first aspect, a device for delivery of a composition to an airway of a subject is provided, the device comprising:.

Each primer suitably comprises a cam follower activated by a cam on the cap to move a pin or blade to pierce or cut the composition capsule.

The cam follower is preferably elastically deformable.

Preferably the cam followers of the one or more primers prevent the cap from being replaced once removed.

In one form, the cap comprises a cap top movable relative to the cap with one or more elongate members extending from the cap top and adapted to hold the composition capsule in place.

The dispersion chamber is suitably adapted to receive the composition for delivery to the subject and to disperse the composition into gas flow between the gas inlet and the gas outlet, for delivery to the airway of the subject.

Preferably the dispersion chamber is adapted to promote movement of the composition capsule within the dispersion chamber. Suitably the movement is rotational movement or spinning of the composition capsule.

The dispersion chamber may be continuous with one or more chamber ports through which gas flows between the gas inlet and the gas outlet.

The dispersion chamber may comprise one or more protrusions projecting from a surface thereof. The protrusions or projections facilitate dispersion of the composition. The one or more protrusions comprise one or more of elongate protrusions, radially oriented bumps or protuberances on a surface of the dispersion chamber. Preferably, there is provided at least two protrusions, bumps or protuberances. The protrusions, radially oriented bumps or protuberances may project from a wall or ceiling of the dispersion or vortex chamber. Suitably, the composition capsule is displaced by the one or more protrusions, bumps or protuberances during its rotational movement to assist dispersion of the composition. Typically, the height of the radially oriented bumps or protuberances, beyond the surface from which they project, is between about <NUM> and about <NUM>, inclusive of <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, and <NUM>.

Suitably the dispersion chamber is a vortex chamber with gas flow through the one or more chamber ports facilitating production of a vortex within the vortex chamber.

The device preferably further comprises a deagglomerator located substantially adjacent to the dispersion chamber and in fluid communication with the gas inlet, gas outlet, composition receptacle and dispersion chamber.

The deagglomerator may comprise a screen or mesh. Suitably, the screen or mesh comprises a plurality of holes or slots to promote gas turbulence. The deagglomerator further functions to filter the composition to remove debris from the composition capsule including fragments thereof.

In one form the deagglomerator may comprise one or more flexible members. Suitably, the flexible members are adapted to vibrate in response to gas flow between the gas inlet and the gas outlet.

The gas inlet may be in the form of a base having one or more holes for ingress of gas and a capsule seat adapted to locate the composition capsule in the composition receptacle. The holes may be sealed by removable plugs. Suitably, the plugs must be removed before the cap can be removed.

In one form, the composition capsule is held in place for piercing by the one or more primers between the capsule seat formed in the base comprising the gas inlet and the one or more elongate members extending from the cap top of the cap.

The gas outlet is suitably sized and shaped as a mouthpiece.

Suitably, gas flow between the gas inlet and the gas outlet facilitates delivery of the composition to the airway of the subject, via the gas outlet.

The device is preferably sealed, or substantially sealed to the entry and/or exit of gas except by the gas inlet and the gas outlet.

In another aspect there is provided a method of administering a composition to the airway of a subject using the device described above when loaded with a composition capsule substantially inside the composition receptacle, including the steps of:.

Suitably inhalation through the gas outlet by a subject causes gas flow from the gas inlet that moves the composition capsule from the composition receptacle to the dispersion chamber.

Preferably the cap cannot be replaced once removed.

In a further aspect there is provided a method of treating or preventing a condition in a subject by administering an effective amount of composition to the airway of a subject using the device described herein, including the steps of:.

In this specification, the terms "comprises", "comprising", "includes", "including", or similar terms are intended to mean a non-exclusive inclusion, such that a method, system or apparatus that comprises a list of elements does not include those elements solely, but may well include other elements not listed.

It will be appreciated that the indefinite articles "a" and "an" are not to be read as singular indefinite articles or as otherwise excluding more than one or more than a single subject to which the indefinite article refers. For example, "a" gas inlet includes one gas inlet, one or more gas inlets or a plurality of gas inlets.

Respiratory delivery of therapeutic agents can be suitable for a range of applications. These include applications wherein the subject is typically conscious and responsive, such as administration of powdered vaccines, antibiotics, and insulin; and applications wherein the subject may be unconscious, such as administration of powdered adrenaline for the treatment of critical illnesses such as anaphylaxis or cardiac arrest.

The current invention is at least partly predicated on the realisation that there is a need for a device that offers flexibility for respiratory delivery of therapeutic agents. In particular, devices facilitating both respiratory delivery of compositions under negative pressure, similar as for 'inhaler' -type devices, and respiratory delivery of therapeutic agents under positive pressure, similar as for `insufflator' -type devices would be desirable, although without limitation thereto.

Without limitation, compositions for delivery referred to herein will typically be in the form of a dry powder. As used herein, and as will be understood by the skilled person, "dry powder" refers generally to a form of particulate medication for respiratory delivery, that is typically delivered, or suitable for delivery, in the absence of propellant.

The composition (e.g. dry powder or particulate medicament) as described herein will suitably comprise at least one "active ingredient", i.e. a component with biological activity. The dry powder or particulate medicament may be in the form of one or more pure, or substantially pure, active ingredients. Alternatively, the dry powder or particulate medicament may include one or more pharmaceutically acceptable components in addition to one or more active ingredients, e.g. fillers, excipients, or diluents, as are well known in the art. For a non-limiting overview of dry powder formulations, the skilled person is directed to<NPL>. It will be appreciated that an active agent and/or a composition containing an active agent may be alternatively referred to as a "drug".

One aspect of the disclosure provides a device for administering a composition to an airway of a subject. <FIG> set forth a typical embodiment of a device of this aspect, device <NUM>.

Looking at <FIG>, device <NUM> comprises body <NUM>; gas inlet <NUM>; gas outlet <NUM>; composition receptacle <NUM>; actuator <NUM>; dispersion chamber <NUM>; and primers <NUM>.

As best seen in <FIG> and <FIG>, body <NUM> comprises walls <NUM> surrounding a hollow inner region. Body <NUM> is formed from plastic; however, this may be varied as desired. For example, body <NUM> may be metallic, or comprise rubber. Combinations of suitable materials can also be used.

Gas inlet <NUM> and gas outlet <NUM> may be continuous with wall <NUM> of body <NUM> although they may be separately constructed.

Gas inlet <NUM> is adapted for use as a fitting for connecting respiratory equipment, or as a mouthpiece. Similarly, gas outlet <NUM> is adapted for use as a fitting for connecting respiratory equipment, or as a mouthpiece.

As depicted, gas inlet <NUM> and gas outlet <NUM> are conical in shape, which can be desirable for use of as a connection and/or mouthpiece. However, the shape of gas inlet <NUM> and/or gas outlet <NUM> can be varied as desired.

As best seen in <FIG>, <FIG>, composition receptacle <NUM> is located within body <NUM>. Composition receptacle <NUM> of device <NUM> is in the form of a well, comprising walls <NUM>. Composition receptacle <NUM> is adapted to fittingly receive a container, such as a capsule, comprising a composition (not shown) to be administered to a subject using delivery device <NUM>.

As best seen in <FIG>, actuator <NUM> is located within body <NUM>. Actuator <NUM> of device <NUM> is in the form of a piston, comprising inlet end <NUM> and outlet end <NUM>. Piston <NUM> is translatable from a first configuration or position substantially outside of composition receptacle <NUM>, as shown in <FIG> and <FIG>, to a second configuration or position substantially inside composition receptacle <NUM> as shown in <FIG>, wherein piston <NUM> is located adjacent or near to dispersion chamber <NUM>. In particular, the outlet end <NUM> of piston <NUM> will, in the second configuration, sit closer to the dispersion chamber <NUM> than it does in the first configuration.

Dispersion chamber <NUM> of device <NUM> is in the form of a vortex chamber. As best seen in <FIG>, <FIG>, vortex chamber <NUM> comprises chamber wall <NUM>; chamber channels <NUM>; and associated chamber ports <NUM> which allow the flow of gas from the gas inlet <NUM> to the gas outlet <NUM>, and to create and sustain a vortex. In embodiments, vortex chamber <NUM> may comprise at least a partial ceiling.

Vortex chamber <NUM> is adapted to receive a container comprising the composition for delivery, upon translation of the container from composition receptacle <NUM> to vortex chamber <NUM>. Vortex chamber <NUM> is adapted to allow rotation of the container when located therein, against chamber wall <NUM>.

In embodiments, vortex chamber <NUM> may comprise one or more protrusions (seen best in <FIG>) adapted to facilitate dispersion of a composition for delivery from a container comprising the composition. In embodiments, vortex chamber <NUM> comprises one or more protrusions, radially oriented bumps or protuberances on chamber wall <NUM> or the chamber ceiling (<FIG>). Typically, the height of the protrusions, raised portions or radially oriented bumps is between about <NUM> and about <NUM>, inclusive of <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, and <NUM>.

As depicted, device <NUM> comprises two primers <NUM>, flanking composition receptacle <NUM>. It will be appreciated, however, that a single primer can also be used.

As best seen in <FIG>, <FIG>, primers <NUM> are held within walls <NUM> of body <NUM>. Primers <NUM> comprise button <NUM>; and pin <NUM>. Buttons <NUM> of primers <NUM> of device <NUM> may be resilient buttons such as, for example, deformable buttons or spring-loaded buttons, however this can be varied as desired.

It will be appreciated that device <NUM> is sealed, or substantially sealed, to the entry or exit (e.g. by way of leakage or escape) of gas except by gas inlet <NUM> and gas outlet <NUM>. As hereinabove described, gas inlet <NUM> and gas outlet <NUM> are of or continuous with body <NUM> of device <NUM>. Additionally, primers <NUM> are positioned within walls <NUM> of body <NUM> in an airtight, or substantially airtight manner.

It will be further understood that devices of this aspect, such as device <NUM>, may comprise a deagglomerator <NUM> adapted to deagglomerate the composition for delivery to the airway of a subject using the delivery device.

In embodiments of device <NUM> comprising a deagglomerator <NUM>, typically the deagglomerator <NUM> is located adjacent or near to dispersion chamber <NUM> as is best seen in <FIG>.

In one typical embodiment, the deagglomerator is or comprises a screen or mesh comprising a plurality of holes or slots to promote gas turbulence.

In one typical embodiment, the deagglomerator is or comprises one or more flexible members adapted to vibrate in response to gas flow.

Device <NUM> is adapted, in use, to entrain a composition in gas flow between gas inlet <NUM> and gas outlet <NUM>, and deliver the composition entrained in the gas flow to the airway of a subject, via outlet <NUM>.

In use, a container or capsule (not shown) is placed substantially within composition receptacle <NUM>. Typically, the capsule is fittingly held within composition receptacle <NUM>. The container or capsule will suitably comprise a seal or membrane or the like, such as a foil seal or plastic shell, that can be cut or pierced by primers <NUM>. An upper surface of the piston <NUM> may form the base or floor of the composition receptacle <NUM>.

In use, primer <NUM> is pressed, which forces pins <NUM> of primer <NUM> against a container or capsule placed within composition receptacle <NUM>, piercing or cutting a seal or membrane of the container or capsule.

In use, piston <NUM> is translated, by gas flow, from the first configuration, as shown in <FIG>, wherein composition receptacle <NUM> is open and accommodates the container or capsule, and inlet end <NUM> of piston <NUM> prevents or at least substantially constrains gas flow from gas inlet <NUM> to gas outlet <NUM>; to the second configuration, as shown in <FIG>, wherein outlet end <NUM> of piston <NUM> displaces the container or capsule from composition receptacle <NUM>, and gas flow from gas inlet <NUM> to gas outlet <NUM> is facilitated or substantially unconstrained by the movement of inlet end <NUM> of piston <NUM>.

References herein to "substantially unconstrained", in relation to the movement of piston <NUM> during gas flow, should be understood as being substantially unconstrained flow of gas in relation to the first configuration or position of the piston <NUM>. That is, in the second configuration or position the gas flow will be understood to be constrained to some degree by the paths and channels through which it must flow but the degree of constraint will be significantly less than that experienced when the piston <NUM> is in the first configuration or position. In embodiments, "substantially unconstrained" may be read as "facilitated", "open", "free" or "clear" flow of gas relative to that when the piston <NUM> is in the first configuration or position.

In use, piston <NUM> may be translated from the first configuration to the second configuration by each, individually, of application of negative pressure on piston <NUM> through gas outlet <NUM>, and application of positive pressure through gas inlet <NUM>.

In one typical scenario, in use, negative pressure is applied to piston outlet end <NUM> of piston <NUM> by inhalation of a subject through gas outlet <NUM>, which translates piston <NUM> from the first configuration to the second configuration.

In one typical scenario, in use, positive pressure is applied to inlet end <NUM> of piston <NUM> by exhalation of a user into gas inlet <NUM>, which translated piston <NUM> from the first configuration to the second configuration.

In one typical scenario, in use, positive pressure is applied to inlet end <NUM> of piston <NUM> from a pressurised gas source, such as a gas canister, connected to gas inlet <NUM>, which translates piston <NUM> from the first configuration to the second configuration.

In use, when piston <NUM> is translated to the second configuration, displacement of the container or capsule from composition receptacle <NUM> forces the container or capsule substantially inside vortex chamber <NUM>.

In use, when the container or capsule is located substantially inside vortex chamber <NUM>, flow of gas between gas inlet <NUM> and gas outlet <NUM> facilitates dispersion of the composition from the container or capsule.

More particularly, in use, flow of gas between gas inlet <NUM> and gas outlet <NUM> enters vortex chamber <NUM> through chamber channels <NUM> (which are themselves continuous with chamber ports <NUM> as best seen in <FIG>), creating a vortex and causing the container or capsule to rotate within vortex chamber <NUM>. In embodiments, the chamber channels <NUM> facilitate entry of gas flow into the vortex chamber <NUM> such that the gas flow path is tangential to or substantially continuous with a wall of the vortex chamber <NUM>.

In use, rotation of the container or capsule within vortex chamber <NUM> against or near to chamber wall <NUM> disperses the composition from the container or capsule through the seal or membrane pierced or cut by actioning primer <NUM> which, in the embodiments of <FIG>, <FIG>, will activate pins <NUM>. The protrusions on the chamber wall assist in disrupting the spinning motion of the container due to contact therewith at speed and so assist in promoting the release of composition.

In embodiments of devices of this aspect, such as device <NUM>, further comprising a deagglomerator <NUM>, in use, composition dispersed by vortex chamber <NUM> is further dispersed and/or deagglomerated by the deagglomerator by flow of gas between gas inlet <NUM> and gas outlet <NUM>.

In typical embodiments wherein the deagglomerator <NUM> comprises a screen or mesh, as seen in <FIG>, comprising a plurality of holes or slots to promote gas turbulence, passage of the composition entrained in gas flow through or past the screen or mesh facilitates further dispersion and/or deagglomeration of the composition by resulting gas turbulence.

In typical embodiments wherein the deagglomerator comprises one or more flexible members adapted to vibrate in response to gas flow, passage of the composition entrained in gas flow through or past the flexible members facilitates further dispersion and/or deagglomeration of the composition by resulting vibration of the flexible member.

In use, composition dispersed by gas flow between gas inlet <NUM> and gas outlet <NUM> through or past vortex chamber <NUM> and, optionally, a deagglomerator of the device, is delivered entrained in the gas flow to the subject's airway.

In one typical scenario, in use, flow of gas between gas inlet <NUM> and gas outlet <NUM> past or through vortex chamber <NUM> and, optionally, a deagglomerator of the device, to deliver the composition entrained in the gas flow to the subject's airway, results from inhalation by the subject through gas outlet <NUM>.

In one typical scenario, in use, flow of gas between gas inlet <NUM> and gas outlet <NUM>, past or through vortex chamber <NUM> and, optionally, a deagglomerator of the device, to deliver the composition entrained in the gas flow to the subject's airway, results from exhalation by a user of device <NUM> into inlet <NUM>.

In one typical scenario, in use, flow of gas between gas inlet <NUM> and gas outlet <NUM>, past or through vortex chamber <NUM> and, optionally, a deagglomerator of the device, to deliver the composition entrained in the gas flow to the subject's airway, results from direction of gas from a pressurised gas source, such as a gas canister, into gas inlet <NUM>.

<FIG> through to <NUM> demonstrate a preferred embodiment of device <NUM> referred to in these figures as device <NUM>. It will be appreciated that like parts have like numbering between <FIG> and <FIG> and so, for example, actuator or piston <NUM> in <FIG> is actuator or piston <NUM> in <FIG>; gas inlet <NUM> is gas inlet <NUM> etc. All of the comments made for device <NUM> are applicable, mutatis mutandis, to device <NUM> and are considered to be repeated here in full in relation to device <NUM>.

<FIG> shows the components of device <NUM> and the manner in which they are interconnected with actuator or piston <NUM> being seated on an inner surface, particularly a lip or flange thereof, of gas inlet <NUM>; body <NUM> connecting with gas inlet <NUM> to form a gastight connection; primers <NUM> being accommodated within the walls of body <NUM> with pins <NUM> extending towards the composition receptacle <NUM>; gas outlet <NUM> connecting to body <NUM> to form a gastight connection; and, differing to device <NUM>, a cap <NUM> to be located over gas outlet <NUM>.

<FIG> show in more detail the construction and location of the various components of <FIG>. It can be seen that the cap <NUM> has a well <NUM> formed within an upper surface <NUM> thereof. From the underside of the cap <NUM>, beneath the region of the well <NUM>, there is a downwardly extending elongate member <NUM>. In the embodiment shown, elongate member <NUM> takes the form of prongs or a fork but it will be appreciated a number of other forms could be envisaged which provide for the same outcome. Airflow cannot pass through well <NUM> and so the cap <NUM> must be removed from device <NUM> prior to use.

<FIG> is a cross sectional view of device <NUM> when the cap <NUM> is fully seated or engaged with the gas outlet <NUM>. In this position an under surface of cap <NUM> is substantially in abutment with an upper surface of the gas outlet <NUM>. Prongs <NUM> are seen to extend, in this embodiment, through deagglomerator or screen <NUM> (best seen in <FIG>) and so deagglomerator <NUM> has two openings formed therein to allow prongs <NUM> to pass through. The openings are of a size such that the functionality of deagglomerator <NUM> is substantially not affected by their presence when the cap <NUM> is removed and the prongs <NUM> are no longer present. The prongs <NUM>, when the cap <NUM> is fully seated, extend into the dispersion chamber or vortex chamber <NUM> such that, when a container of composition is seated within the composition receptacle <NUM>, they act to hold the container in place. This serves to prevent displacement or movement of the container such that it is in an optimal position with respect to the pins <NUM> for piercing the container upon removal of the cap.

It can be seen that a lower portion of the walls of the cap <NUM> have a chamfered or bevelled portion <NUM> which, in the embodiment shown, may be referred to as cam(s) <NUM>. The buttons, or cam followers, <NUM> of primers <NUM> are in contact with an upper region of chamfered portions/cam <NUM> such that, upon displacing the cap <NUM> for removal thereof and use of the device, the chamfer forces an increasing amount of displacement upon the buttons/cam followers <NUM> thereby forcing the pins <NUM> to extend further into the composition receptacle <NUM> and pierce the container of composition which will be located therein. The displacement may be by the pressure exerted on the resilient material forming the buttons/cam followers <NUM>. This is a distinct advantage of the present disclosure in that no separate buttons or switches have to be actioned to release the composition. Instead, removal of the cap <NUM> automatically results in piercing of the container and release of the composition. Further, the piercing happens only as prongs <NUM> are simultaneously being raised and so optimal placement of the container is guaranteed as inward movement of the pins <NUM> occurs.

The result of this removal of the cap <NUM> can be seen in the change from <FIG> where the cap <NUM> has been raised to the point of maximum displacement of the primers <NUM> and so the pins <NUM> extend the maximum distance into the composition receptacle <NUM>. It can also be seen that prongs <NUM> are raised and have substantially left the vortex chamber <NUM>.

<FIG> shows complete removal of the cap <NUM> and so the prongs <NUM> are also gone and the openings <NUM> in the deagglomerator <NUM> can be seen. <FIG> also provides a better view of a single protrusion <NUM> extending from the vortex chamber <NUM> ceiling immediately adjacent the edges of the deagglomerator <NUM> which is formed therein. Preferably, there are at least two protrusions <NUM> on the vortex chamber <NUM> ceiling. It has been found that two such protrusions <NUM> which are located at approximately <NUM> degrees to one another provides for optimal disruption of the motion of the spinning container during use and so optimal release of the composition. That is, if one protrusions <NUM> is taken to be positioned at <NUM> o' clock, then one other is preferably placed at <NUM> o' clock or <NUM> o' clock with respect to the first. The protrusions <NUM>, in the embodiment shown, are elongate protrusions <NUM>.

In <FIG>, complete removal of the cap <NUM> has also allowed for the primers <NUM> to adopt their original positioning and so the pins <NUM> have retreated from the composition receptacle <NUM>. Importantly, it will be appreciated from <FIG> and <FIG> that once the cap <NUM> is removed and primers <NUM> revert to their original position, it is not possible to once again simply place the cap <NUM> back in full engagement with the device <NUM>. This is because the chamfered portions/cams <NUM> will come into a blocking engagement with an upper surface of the buttons/cam followers <NUM>. The angle of the chamfer this time works against the displacement of the buttons/cam followers <NUM> and so the cap <NUM> cannot be lowered any further. This is an advantage of the present device <NUM> as it effectively becomes a single use device. If a potential user has a device <NUM> with the cap <NUM> removed they will immediately know that the device <NUM> has been used or the container of composition has otherwise been pierced and is not appropriate for administration. This provides a quick and simple visual queue for a user to know that the device <NUM> they are carrying or are provided with is fit for purpose. Given the critical nature of the end medical use in many instances, this is an important safety feature.

It will be appreciated that the piston <NUM> in <FIG> remains unmoved and so no gas is free to flow through the device <NUM>. However, <FIG> can be thought of as a resting or non-use position while <FIG> shows a primed position with the container of composition being pierced and <FIG> shows a ready to use position whereby the container has been pierced, the cap <NUM> has been removed and the device <NUM> is ready for a positive or negative pressure to be applied to move piston <NUM> from the first configuration to the second configuration, as previously discussed, to enable gas flow from the gas inlet <NUM> through to the gas outlet <NUM> at which point it will have entrained composition.

<FIG> is provided to better demonstrate the gas flow pathway itself. It can be seen that the piston <NUM> will normally be seated within the gas inlet <NUM> with its inlet end <NUM> seated, preferably in a sealing engagement, upon a lip or flange and the container of composition sitting on the upper surface <NUM>. When the piston <NUM> is actuated and moves upwards to displace the container of composition, it will be appreciated that air can then flow past the lip or flange. At this point, the gas flow can continue through chamber ports <NUM> which pass through the body <NUM> and are continuous with the interior of the gas inlet <NUM> and also the vortex chamber <NUM>. It will be appreciated there may be only one chamber port <NUM> but at least two are optimal.

<FIG> shows that an upper end of the chamber ports <NUM> are continuous with chamber channels <NUM> which substantially conform to the walls of the body <NUM> such that the entering gas flow is forced into a substantially circular, circulating or vortex pathway. The effect of this is that the container of composition, which has been displaced into the vortex chamber <NUM> by movement of the piston or actuator <NUM>, is caused to spin rapidly. The composition will be released at this stage due to the gas flow and turbulence however, it has been found that release is greatly improved by the presence of the one or more protrusions <NUM> into which the container will continually bump or knock thereby causing spilling of composition from the container. The gas flow with entrained composition then passes through deagglomerator <NUM> and into the gas outlet <NUM> in the manner previously described for device <NUM>.

Device <NUM> may be used and connected to equipment or otherwise exactly in the manner described for device <NUM>.

Therefore, in certain embodiments, there is provided a device for administering a composition to an airway of a subject, the device comprising:.

It will be appreciated that devices of this aspect, such as device <NUM> and device <NUM>, can have several important advantages.

Advantageously, embodiments such as device <NUM> and device <NUM> allow for operation under both positive and negative gas flow conditions. Accordingly, device <NUM> and device <NUM> can be used both as an inhaler device, e.g. for self-administration of a composition to the subject by inhalation through gas outlet <NUM>/<NUM>; and as an insufflator device, e.g. for administration of a composition to the subject by the application of positive pressure gas into gas inlet <NUM>/<NUM> to an unconscious or unresponsive patient.

Advantageously, gas inlet <NUM>/<NUM> and gas outlet <NUM>/<NUM> allow for flexibility and versatility in use, with the potential to be used directly as a mouthpiece, or to be used as a connection or fitting for further respiratory equipment.

By way of example, when device <NUM> and device <NUM> are used as an inhaler device, the subject can use gas outlet <NUM>/<NUM> as a mouthpiece, and inhale directly through gas outlet <NUM>/<NUM>. Alternatively, gas outlet <NUM>/<NUM> can be used to connect suitable respiratory equipment, such as a mask, inclusive of intraoral masks, oronasal masks, and the like, and advanced airway equipment, such as endotracheal tubes, a supraglottic airways, laryngeal airways, and the like, such as when device <NUM> and device <NUM> are used as insufflator device.

By way of further example, device <NUM> or device <NUM>, via gas inlet <NUM>/<NUM>, can be used to connect suitable respiratory equipment, such as a ventilator, a compressed gas supply, a manual resuscitator, and automatic resuscitator, and a demand valve resuscitator, and the like, such as when device <NUM> or device <NUM> is used as an insufflator device. Alternatively, gas inlet <NUM>/<NUM> can be used directly as a mouthpiece for exhalation into device <NUM>/<NUM> by a user or caregiver.

<FIG> demonstrate a further preferred embodiment configured for single-sided operation, that is to say, activation by negative pressure only. This embodiment (which falls under the scope of the appended claims) is referred to as device <NUM>. Like parts have like numbering to the parts of device <NUM> and device <NUM>. Thus, for example, gas outlet <NUM> in <FIG> is the same as gas outlet <NUM> in <FIG> and gas outlet <NUM> in <FIG>.

Looking at <FIG>, device <NUM> comprises body <NUM>; gas outlet <NUM>; primers <NUM>; and cap <NUM>. Unlike devices <NUM> and <NUM>, the gas inlet and actuator are replaced by a base <NUM>. Turning to <FIG>, the structure previously described is evident with composition receptacle <NUM>; vortex chamber <NUM>; but with a composition capsule <NUM> shown loaded in the composition receptacle <NUM>.

<FIG> shows an exploded view of device <NUM>. For simplicity, only those elements that are different from device <NUM> and device <NUM> are described in detail. All other comments made for device <NUM> and device <NUM> apply to device <NUM>, mutatis mutandis. Instead of a gas inlet the device comprises a base <NUM>. The base <NUM> includes holes <NUM> which allow gas (air) to flow into the device in operation. As made clear below, air flows through the holes <NUM>, composition receptacle <NUM>, the vortex chamber <NUM> and out the gas outlet <NUM>, when a user inhales.

Looking at the base <NUM>, apart from holes <NUM> it can be seen that there is a capsule seat <NUM> that receives a composition capsule <NUM>, as depicted in <FIG>.

Looking at cap <NUM>, it will be seen that there is a cap top <NUM>, which is movable relative to the cap <NUM> as explained below. A well <NUM> is formed in the cap top <NUM> and a pair of elongate members <NUM> extend from the cap top <NUM> to hold the composition capsule <NUM> in place, as seen clearly in <FIG>. The elongate members <NUM> may be in the form of a pair of prongs, as shown. However, the invention is not limited to a pair of prongs but there could be <NUM>, <NUM>, <NUM> or some other number of prongs, or some other structure not in the form of prongs that serves the function of holding the composition capsule <NUM> in place in the capsule seat <NUM>.

The structure of device <NUM> and the differences from device <NUM> and <NUM> can best be exemplified by explaining the operation by reference to <FIG>. Looking at <FIG> there is shown device <NUM> in what may be called a 'closed', 'delivered', 'loaded' or pre-activation state. The cap <NUM> is fully down on the body <NUM>. In one form, the holes <NUM> may be closed by plugs or seals (not shown) that are connected to the cap <NUM> to act as a restraint. The plugs must be removed before the cap <NUM> can be lifted from the body <NUM>.

As can be seen in the cross-section of <FIG>, the composition capsule <NUM> is seated in the capsule set <NUM>, primers <NUM> are retracted and cap top <NUM> is in place with elongate members <NUM> holding composition capsule <NUM> in place.

Activation of device <NUM> for use occurs by removing cap <NUM>. This occurs in a number of steps. As shown in <FIG>, initially, the cams <NUM> impinge upon the cam followers <NUM>, causing compression of the primer <NUM> until the pins <NUM> puncture the composition capsule <NUM>. The cap top <NUM> remains in place with the elongate members <NUM> holding the composition capsule <NUM> against the capsule seat <NUM>. It will be appreciated that this arrangement has the advantage that the composition capsule <NUM> is held in place no matter the orientation of the device <NUM>, thus ensuring piercing of the composition capsule <NUM> by the pins <NUM>.

As shown in <FIG>, the cap <NUM> is continued to be removed from the body <NUM> so that immediately after the composition capsule <NUM> is pierced the pressure on the elastically deformable primers <NUM> is released and the pins <NUM> retract. The cap top <NUM> now moves with the cap <NUM> and is removed, thus permitting access to gas outlet <NUM>. This may be called the 'open', 'ready' or 'activated' state as the device <NUM> is ready for use as shown in <FIG>.

As depicted by arrows <NUM>, inhalation by a user causes a flow of air through the holes <NUM>, through the composition receptacle <NUM> which lifts the composition capsule <NUM> into the vortex chamber <NUM> where the composition is dispersed in the manner previously described, and hence through the gas outlet <NUM> with composition entrained for delivery to the user.

A particular advantage of this embodiment of the invention is that, as shown in <FIG>, the cap <NUM> cannot be replaced on the body <NUM> because the primers <NUM> are in the way. It should be clear that the automatic puncturing of the composition capsule <NUM> is not only applicable only to the embodiment of <FIG>. The embodiment of <FIG> can be configured in the same way, in which case the outlet end <NUM> of the piston <NUM> becomes the capsule seat and the cap <NUM> is formed in two parts instead of one.

It will be readily appreciated, in view of the above, that devices of this aspect, such as devices <NUM>, <NUM> or <NUM> can offer advantageous flexibility and/or versatility in use. For example, devices <NUM>, <NUM> or <NUM> can be used as an inhaler device for self-administration of the composition by the subject. Device <NUM> or device <NUM> can also be used in resuscitation scenarios, where the composition is administered in conjunction with artificial breaths from a caregiver. Device <NUM> or device <NUM> can also be used in hospital scenarios, where the composition is administered by insufflation using a respiratory mask or advanced airway arrangement.

Advantageously, embodiments of devices of this aspect, such as devices <NUM>, <NUM> or <NUM> can be adjusted or modified to alter dosage in accordance with the subject's particular requirements.

For example, the size and/or number of pins <NUM>/<NUM>/<NUM> and/or blades of primer <NUM>/<NUM>/<NUM> can be altered or modified to adjust the rate of delivery of the composition. It will be readily appreciated that a greater number or size of pins or blades will typically allow for a higher rate of release of the composition from dispersion chamber <NUM>/<NUM>/<NUM>, and subsequent delivery to the subject.

By way of further example, the number, position, and/or height of protrusions <NUM>/<NUM>/<NUM>, such as elongate protrusions, radially oriented bumps or protuberances, within dispersion chamber <NUM>/<NUM>/<NUM>, such as on wall <NUM>/<NUM>/<NUM> or ceiling of vortex chamber <NUM>/<NUM>, can be altered or modified to adjust the rate of delivery of the composition. It will be readily appreciated that, at least wherein the arrangement of protrusions does not substantially inhibit or constrain rotation of a container or capsule within dispersion chamber <NUM>/<NUM>/<NUM>, increasing number and/or height of the protrusions will typically increase release of the composition from dispersion chamber <NUM>/<NUM>/<NUM>, and subsequent delivery to the subject.

Similarly, in embodiments of the device comprising a deagglomerator <NUM>/<NUM>, characteristics of the deagglomerator (e.g. in respect of the flexible member or screen properties) can be modified or adjusted to adjust the rate of composition delivery.

Advantageously, embodiments such as device <NUM> or device <NUM> are typically reliable in use in respect of delivery from containers or capsules.

For example, the arrangement wherein configuration of actuator <NUM>/<NUM> between the first configuration and the second configuration both (a) moves the container or capsule from composition receptacle <NUM>/<NUM> to dispersion chamber <NUM>/<NUM>; and (b) is facilitated and maintained by gas flow between the gas inlet <NUM>/<NUM> and the gas outlet <NUM>/<NUM>, can be effective for preventing or at least avoiding unwanted displacement or lack of displacement, e.g. 'sticking', of the container or capsule.

Additionally, embodiments such as devices <NUM>, <NUM> or <NUM> particularly wherein composition receptacle <NUM>/<NUM>/<NUM> is formed to fittingly receive the container or capsule, can typically be primed and used when positioned in any orientation, with limited or no change in performance.

Advantageously, as hereinabove described, embodiments such as devices <NUM>, <NUM>, <NUM> typically feature a substantially sealed or airtight gas flow path through body <NUM>/<NUM>/<NUM> from inlet <NUM>/<NUM>/<NUM> to outlet <NUM>/<NUM>/<NUM>. It will be appreciated that such a sealed flow path substantially prevents, or at least constrains, unwanted escape or leakage of the composition.

Advantageously, embodiments such as devices <NUM>, <NUM> or <NUM> particularly embodiments comprising a dosage tracker, allow estimation of the dose of the composition delivered to the subject. It will be appreciated that this can assist in dosage reliability and can decrease the likelihood of under or over dosing, and/or warn a user if under or overdosing occurs.

Further, device <NUM>/<NUM> provides distinct advantages in easy priming of the device <NUM>/<NUM> for use simply by removal of the cap <NUM>/<NUM>.

The above is a non-limiting listing of some typical advantages of exemplary embodiments.

A further aspect of this disclosure provides a method of administering a composition to the airway of a subject using a device of the previous aspect, such as device <NUM>/<NUM>/<NUM>.

A related aspect provides a method of treating or preventing a condition in a subject by administering an effective amount of composition to the airway of a subject using a device of the previous aspect, such as device <NUM>/<NUM>/<NUM>. Typically, the subject according to these aspect is a human subject.

As will be readily appreciated by the skilled person, according to these aspects, a suitable composition can be selected for administration to a particular subject, including for a particular therapeutic purpose in relation to a particular condition.

Generally, compositions administered as described herein may include any suitable medicament for administering to the subject's airway, in accordance with the subject's condition and medical requirements. As hereinabove described, typically the composition will be a dry powder, and may be in the form of one or more pure, or substantially pure, active ingredients. The composition may alternatively include one or more pharmaceutically acceptable components in addition to one or more active ingredients, e.g. fillers, excipients, or diluents, as are well known in the art.

As will be appreciated by the skilled person, the size of particles of a dry powder composition administered to a subject's airways can affect the therapeutic efficacy of the dry powder. Typically, the administered microparticles will have a d50 or Mean Mass Aerodynamic Diameter (MMAD) less than <NUM>. As will be understood by the skilled person "d50" or "D50" refers to the value that the particle diameter of <NUM>% by mass of a particulate sample is less than. The d50 particle MMAD is preferably between about <NUM> and about <NUM>, including about: <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, and <NUM>, more preferably between about <NUM> and <NUM>, and even more preferably between <NUM> and <NUM>, including about: <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM> and <NUM>. It will be appreciated that, in embodiments wherein device <NUM> comprises deagglomerator <NUM>, the preceding values refer to particle size after dispersion into the flow of gas and/or after passing through the deagglomerator <NUM>.

Examples of active agents which may be delivered according to the present disclosure include beta-<NUM>-agonists, steroids such as glucocorticosteroids (preferably anti-inflammatories), anti-cholinergics, leukotriene antagonists, leukotriene synthesis inhibitors, pain relief drugs generally, such as analgesics and anti-inflammatories (including both steroidal and non-steroidal anti-inflammatories), cardiovascular agents such as cardiac glycosides, respiratory drugs, anti-asthma agents, bronchodilators, anticancer agents, alkaloids (e.g. ergot alkaloids) or triptans such as can be used in the treatment of migraine, drugs (for instance sulphonylureas) useful in the treatment of diabetes type I and II and related disorders, sleep inducing drugs including sedatives and hypnotics, psychic energizers, appetite suppressants, anti-arthritics, anti-malarials, anti-epileptics, anti-thrombotics, antihypertensives, anti-arrhythmics, anti-oxidants, anti-depressants, antipsychotics, auxiolytics, anti-convulsants, anti-emetics, anti-infectives, antihistamines, anti-fungal and anti-viral agents, drugs for the treatment of neurological disorders such as Parkinson's disease (dopamine antagonists), drugs for the treatment of alcoholism and other forms of addiction, drugs such as vasodilators for use in the treatment of erectile dysfunction, muscle relaxants, muscle contractants, opioids, stimulants, tranquilizers, antibiotics such as macrolides, aminoglycosides, fluoroquinolones and beta-lactams, vaccines, cytokines, growth factors, hormonal agents including contraceptives, sympathomimetics, diuretics, lipid regulating agents, antiandrogenic agents, antiparasitics, anticoagulants, neoplastics, antineoplastics, hypoglycemics, nutritional agents and supplements, growth supplements, antienteritis agents, vaccines, antibodies, diagnostic agents, and contrasting agents and mixtures of the above (for example the asthma combination treatment containing both steroid and beta-agonist).

The active agent may fall into one of a number of structural classes, including but not limited to small molecules (including insoluble small molecules), peptides, polypeptides, proteins, polysaccharides, steroids, nucleotides, oligonucleotides, polynucleotides, fats, electrolytes, and the like. Specific examples include the beta-<NUM>-agonists salbutamol (e.g. salbutamol sulphate) and salmeterol (e.g. salmeterolxinafoate), the steroids budesonide and fluticasone (e.g. fluticasone propionate), the cardiac glycoside digoxin, the alkaloid anti-migraine drug dihydroergotaminemesylate and other alkaloid ergotamines, the alkaloid bromocriptine used in the treatment of Parkinson's disease, sumatriptan, rizatriptan, naratriptan, frovatriptan, almotriptan, zolmatriptan, morphine and the morphine analogue fentanyl (e.g. fentanyl citrate), glibenclamide (a sulphonyl urea), benzodiazepines such as vallium, triazolam, alprazolam, midazolam and clonazepam (typically used as hypnotics, for example to treat insomnia or panic attacks), the anti-psychotic agent risperidone, apomorphine for use in the treatment of erectile dysfunction, the anti-infective amphotericin B, the antibiotics tobramycin, ciprofloxacin and moxifloxacin, nicotine, testosterone, the anti-cholenergic bronchodilator ipratropium bromide, the bronchodilatorformoterol, monoclonal antibodies and the proteins LHRH, insulin, human growth hormone, calcitonin, interferon (e.g. beta- or gamma-interferon), EPO and Factor VIII, as well as in each case pharmaceutically acceptable salts, esters, analogues and derivatives (for instance prodrug forms) thereof.

Additional examples of potentially suitable active agents include but are not limited to aspariginase, amdoxovir (DAPD), antide, becaplermin, calcitonins, cyanovirin, denileukindiftitox, erythropoietin (EPO), EPO agonists, domase alpha, erythropoiesis stimulating protein (NESP), coagulation factors such as Factor VIIa, Factor VIII, Factor IX, von Willebrand factor; ceredase, cerezyme, alpha-glucosidase, collagen, cyclosporin, alpha defensins, beta defensins, exedin-<NUM>, granulocyte colony stimulating factor (GCSF), thrombopoietin (TPO), alpha-<NUM> proteinase inhibitor, elcatonin, granulocyte macrophage colony stimulating factor (GMCSF), fibrinogen, filgrastim, growth hormones, growth hormone releasing hormone (GHRH), GRO-beta, GRO-beta antibody, bone morphogenic proteins such as bone morphogenic protein-<NUM>, bone morphogenic protein-<NUM>, OP-<NUM>; acidic fibroblast growth factor, basic fibroblast growth factor, CD-<NUM> ligand, heparin, human serum albumin, low molecular weight heparin (LMWH), interferons such as interferon alpha, interferon beta, interferon gamma, interferon omega, interferon tau; interleukins and interleukin receptors such as interleukin-<NUM> receptor, interleukin-<NUM>, interluekin-<NUM> fusion proteins, interleukin-<NUM> receptor antagonist, interleukin-<NUM>, interleukin-<NUM>, interleukin-<NUM> receptor, interleukin-<NUM>, interleukin-<NUM>, interleukin-<NUM>, interleukin-<NUM> receptor, interleukin-<NUM> receptor; lactoferrin and lactoferrin fragments, luteinizing hormone releasing hormone (LHRH), insulin, pro-insulin, insulin analogues, amylin, C-peptide, somatostatin, somatostatin analogs including octreotide, vasopressin, follicle stimulating hormone (FSH), influenza vaccine, insulin-like growth factor (IGF), insulintropin, macrophage colony stimulating factor (M-CSF), plasminogen activators such as alteplase, urokinase, reteplase, streptokinase, pamiteplase, lanoteplase, and teneteplase; nerve growth factor (NGF), osteoprotegerin, platelet-derived growth factor, tissue growth factors, transforming growth factor-<NUM>, vascular endothelial growth factor, leukemia inhibiting factor, keratinocyte growth factor (KGF), glial growth factor (GGF), T Cell receptors, CD molecules/antigens, tumor necrosis factor (TNF), monocyte chemoattractant protein-<NUM> endothelial growth factors, parathyroid hormone (PTH), glucagon-like peptide, somatotropin, thymosin alpha <NUM>, thymosin alpha <NUM> IIb/IIIa inhibitor, thymosin beta <NUM>, thymosin beta <NUM>, thymosin beta <NUM>, alpha-<NUM> antitrypsin, phosphodiesterase (PDE) compounds, VLA-<NUM> (very late antigen-<NUM>), VLA-<NUM> inhibitors, bisphosponates, respiratory syncytial virus antibody, cystic fibrosis transmembrane regulator (CFTR) gene, deoxyreibonuclease (Dnase), bactericidal/permeability increasing protein (BPI), and anti-CMV antibody. Exemplary monoclonal antibodies include etanercept (a dimeric fusion protein consisting of the extracellular ligand-binding portion of the human <NUM> kD TNF receptor linked to the Fc portion of IgG1), abciximab, afeliomomab, basiliximab, daclizumab, infliximab, ibritumomabtiuexetan, mitumomab, muromonab-CD3, iodine <NUM> tositumomab conjugate, olizumab, rituximab, and trastuzumab (herceptin), amifostine, amiodarone, aminoglutethimide, amsacrine, anagrelide, anastrozole, asparaginase, anthracyclines, bexarotene, bicalutamide, bleomycin, buserelin, busulfan, cabergoline, capecitabine, carboplatin, carmustine, chlorambucin, cisplatin, cladribine, clodronate, cyclophosphamide, cyproterone, cytarabine, camptothecins, <NUM>-cis retinoic acid, all transretinoic acid; dacarbazine, dactinomycin, daunorubicin, dexamethasone, diclofenac, diethylstilbestrol, docetaxel, doxorubicin, epirubicin, estramustine, etoposide, exemestane, fexofenadine, fludarabine, fludrocortisone, fluorouracil, fluoxymesterone, flutamide, gemcitabine, epinephrine, L-Dopa, hydroxyurea, idarubicin, ifosfamide, imatinib, irinotecan, itraconazole, goserelin, letrozole, leucovorin, levamisole, lomustine, mechlorethamine, medroxyprogesterone, megestrol, melphalan, mercaptopurine, methotrexate, metoclopramide, mitomycin, mitotane, mitoxantrone, naloxone, nicotine, nilutamide, octreotide, oxaliplatin, pamidronate, pentostatin, pilcamycin, porfimer, prednisone, procarbazine, prochlorperazine, ondansetron, raltitrexed, sirolimus, streptozocin, tacrolimus, tamoxifen, temozolomide, teniposide, testosterone, tetrahydrocannabinol, thalidomide, thioguanine, thiotepa, topotecan, tretinoin, valrubicin, vinblastine; vincristine, vindesine, vinorelbine, dolasetron, granisetron; formoterol, fluticasone, leuprolide, midazolam, alprazolam, amphotericin B, podophylotoxins, nucleoside antivirals, aroyl hydrazones, sumatriptan; macrolides such as erythromycin, oleandomycin, troleandomycin, roxithromycin, clarithromycin, davercin, azithromycin, flurithromycin, dirithromycin, josamycin, spiromycin, midecamycin, leucomycin, miocamycin, rokitamycin, andazithromycin, and swinolide A; fluoroquinolones such as ciprofloxacin, ofloxacin, levofloxacin, trovafloxacin, alatrofloxacin, moxifloxicin, norfloxacin, enoxacin, grepafloxacin, gatifloxacin, lomefloxacin, sparfloxacin, temafloxacin, pefloxacin, amifloxacin, fleroxacin, tosufloxacin, prulifloxacin, irloxacin, pazufloxacin, clinafloxacin, and sitafloxacin; aminoglycosides such as gentamicin, netilmicin, paramecin, tobramycin, amikacin, kanamycin, neomycin, and streptomycin, vancomycin, teicoplanin, rampolanin, mideplanin, colistin, daptomycin, gramicidin, colistimethate; polymixins such as polymixin B, capreomycin, bacitracin, penems; penicillins including penicllinase-sensitive agents like penicillin G, penicillin V; penicllinase-resistant agents like methicillin, oxacillin, cloxacillin, dicloxacillin, floxacillin, nafcillin; gram negative microorganism active agents like ampicillin, amoxicillin, and hetacillin, cillin, and galampicillin; antipseudomonal penicillins like carbenicillin, ticarcillin, azlocillin, mezlocillin, and piperacillin; cephalosporins like cefpodoxime, cefprozil, ceftbuten, ceftizoxime, ceftriaxone, cephalothin, cephapirin, cephalexin, cephradrine, cefoxitin, cefamandole, cefazolin, cephaloridine, cefaclor, cefadroxil, cephaloglycin, cefuroxime, ceforanide, cefotaxime, cefatrizine, cephacetrile, cefepime, cefixime, cefonicid, cefoperazone, cefotetan, cefmetazole, ceftazidime, loracarbef, and moxalactam, monobactams like aztreonam; and carbapenems such as imipenem, meropenem, pentamidineisethiouate, albuterolsulfate; lidocaine, metaproterenolsulfate, beclomethasonediprepionate, triamcinolone acetamide, budesonide acetonide, fluticasone, ipratropium bromide, flunisolide, cromolyn sodium, and ergotamine tartrate; taxanes such as paclitaxel; SN-<NUM>; tyrphostines.

Other agents that may be used include: Linezolid; Treprostinol optionally in combination with a PDE5 Inhibitor; Oxyntomodulin; and Palonosetron optionally in combination with a, preferably high potency, NK1 antagonist.

It will be understood that the above exemplary active agents encompass, as applicable, analogues, agonists, antagonists, inhibitors, isomers, and pharmaceutically acceptable salt forms thereof. In regard to peptides and proteins, the present disclosure is intended to encompass synthetic, recombinant, native, glycosylated, non-glycosylated, and biologically active fragments and analogues thereof.

In some typical embodiments, the composition includes one or more active agents selected from adrenaline, glucose, glucagon, naloxone, insulin or the like.

In some typical embodiments, the composition includes microparticles, nanoparticles, microcapsules, nanocapsules, microspheres, and/or nanospheres of adrenaline and/or atropine for the treatment of cardiac failure, cardiac dysfunction, cardiac arrest, anaphylaxis, drug overdose or the like.

In some typical embodiments the composition includes particulate glucose and/or glucagon for the treatment of hypoglycaemia, diabetes induced coma or the like. In embodiments, the dry powder includes particulate benzodiazepine, phenytoin or anti-seizure medications for the treatment of seizure.

In some typical embodiments, the composition includes one or more agents for inducing an immune response, such as one or more vaccines. In embodiments, the dry powder includes a measles vaccine, for inducing an immune response to, or immunising against, measles. In embodiments, the dry powder includes a Hepatitis B vaccine, for inducing an immune response to, or immunising against, Hepatitis B. In embodiments, the dry powder includes an influenza vaccine, for inducing an immune response to, or immunising against, influenza.

Claim 1:
A device (<NUM>) for delivery of a composition to an airway of a subject, the device (<NUM>) comprising:
in fluid communication:
a gas inlet (<NUM>);
a gas outlet (<NUM>);
a composition receptacle (<NUM>) in which a composition capsule (<NUM>) containing the composition is received; and
a dispersion chamber (<NUM>); one or more primers (<NUM>) each comprising a pin or blade (<NUM>); and
a cap (<NUM>) configured to be located over the gas outlet (<NUM>),
wherein each primer (<NUM>) comprises a cam follower (<NUM>) that is activated by a cam (<NUM>) on the cap (<NUM>) to move the pin or blade (<NUM>) to pierce or cut the composition capsule (<NUM>) to release the composition upon removal of the cap (<NUM>), and
wherein the composition capsule (<NUM>) is held in place for piercing or cutting by the one or more primers (<NUM>) between a capsule seat (<NUM>) formed in a base (<NUM>) of the device (<NUM>) and one or more elongate members (<NUM>) which extend from a cap top (<NUM>) of the cap (<NUM>).