Atomising device

Abstract: A metered dose inhaler comprises a piston (3) which is mounted in a cavity (2) within a body (1), and is urged by a pre-loaded spring (6) into a reduced cross-section pressure chamber (4). The piston (3) may be loaded by means of an actuating rod (31) having a handle (32), and may be latched in a loaded position by a latching means (33). A liquid drug (e.g. in aqueous solution) is contained in a collapsible bag (10). Metered quantities of the drug are successively presented in the pressure chamber (4), and then subjected to a sudden and great increase in pressure, to eject the liquid drug through an atomising head (22), to reduce it to a fine atomised spray of small mean particle size - for example, less than 30 micrometres. Non-return valves (13 and 23) control the flow of liquid through the device. The sudden pressure pulse is caused by releasing the spring loaded piston (3), upon depressing an actuating button (35) connected to the latching means (33).

Description: The present invention relates to atomising devices and methods, and, in its preferred forms, aims to protide self contained hand held devices for dispensing droplets of a mean size less than about 10 to 12 micrometres without the use of pressurised gas or liquefied propellants, and methods for administering fluid droplets to a locus. In an attempt to overcome the problems associated with CFC propellants, there have been many proposals to adapt the mechanical pump type dispensers used to spray furniture polishes, hair lacquers and the like. In such devices a manually operated piston and cylinder or flexing diaphragm type of pump is operated by depressing an axial plunger or via a trigger type mechanism to force a fluid composition through a mechanical break up device, for example a swirl chamber and fine bore nozzle orifice, to form a spray of droplets without the use of a propellant gas or airstream. In general, the droplets formed are of a comparatively large size, typically 30 to 200 micrometres diameter; and the volume of the spray discharged at each operation of the pump is of little concern to the user. Furthermore, it has not hitherto been considered possible to achieve the required very small droplet size consistently. A conventional hand operated pump type sprayer is typically operated by the user manually depressing the free end of the pump housing or plunger or a trigger mechanism so as to discharge fluid held in the pump, for example from the cylinder of the pump as the piston of the pump is driven up the cylinder, see for example US Patents Nos 3,838,686, 4,693,675 and 4,694,977. However, not only is the pressure generated by the pump comparatively low, but the pressure generated will depend upon the speed at which the pump is operated and the strength of the user. As a result, the droplet size in the spray varies from operation to operation, even with the same person operating the pump. It has been proposed to provide a spring against which the pump mechanism acts as fluid is drawn into the pump on the sucking stroke of the pump, for example into the cylinder as the piston is retracted in a piston/cylinder type of pump, see for example US Patents Nos 3,471,065, 3,790,034, 3,797,748, 4,260,082, 4,183,449 and 4,345,718. The spring then provides a consistent driving force when released to drive the fluid out of the pump. In these proposals, the pump is designed so that fluid cannot escape from the cylinder until a release or outlet valve is operated. Therefore, the fluid is held within the pump under the pressure exerted by the compressed spring. When the valve is operated, the fluid is discharged from the pump under the action of the spring. Although this achieves a greater uniformity of the pressure at which the fluid is discharged, the fluid may be held under pressure within the pump before the outlet valve is operated. This can result in a number of problems. For example, the pump mechanism and outlet valve must be designed to resist the substantial pressures generated by the compressed spring, otherwise leakage may occur or the pump cylinder walls may rupture. Furthermore, where the pressure is retained for any length of time, some weepage of the fluid past the seals in the pump mechanism, for example past the seals between the piston and the cylinder wall, will occur, resulting in a loss of fluid and pressure from the cylinder. This will affect the volume of fluid dispensed and the droplet size in the spray which is eventually produced when the outlet valve is actuated. A further problem arises in that the user may not operate the pump mechanism for its full stroke. This will not only affect the volume of fluid dispensed, but will also affect the peak pressure achieved and hence the droplet size, since the spring will not be fully compressed. In an alternative form of device proposed in US Patent No 4,892,232, the fluid is held under pressure in a main container and a predetermined quantity is transferred to a distendable rubber or similar sleeve carried by the valve actuator stem of the outlet valve to the container. The stem is provided with suitable porting so that the sleeve is connected to the remainder of the container when the stem is in the raised position. Fluid will thus flow under pressure from the container into the annular space between the sleeve and the stem wall to expand the sleeve radially. When the valve stem is depressed, the porting to the remainder of the container is closed and a port is opened allowing the fluid to escape from the annular space to a nozzle orifice as the sleeve is stretched axially and collapsed radially. Again, this device suffers from the problems of variable dose and variable droplet size due to variations in the speed and force used by the user in the depression of the valve stem and the extent to which the valve stem is moved. Patent Specification US-A-4 391 620 discloses a device for intermittently applying lubrication to molten glass, comprising a high-pressure pump driven by a solenoid to force a metered amount of a lubricant through atomising means to produce a cone of atomised lubricant. We have devised a form of atomizer device which reduces the above problems and does not use a liquefied propellant or gas stream to discharge the contents of the device. According to the invention there is provided a device for dispensing a metered amount of a fluid as a spray of droplets by discharging the metered amount of the fluid under pressure through an atomising means, wherein the device comprises: a chamber for containing the metered amount of a fluid; a spring for retaining a predetermined amount of energy and applying it via a piston to the metered amount of fluid in the chamber so as to subject the metered amount of fluid to a predetermined increase in pressure from a lower pressure to a higher pressure of 5 x 10 6 Pa (50 bar) or more so as to permit discharge of said metered amount of fluid from said chamber at said higher pressure; and atomising means for atomising the fluid discharged from said chamber. In a preferred embodiment of the device of the invention the user imparts energy to the spring which is retained in the "loaded" state until required to act upon a measured dose of the fluid via the piston to discharge it through the atomising means. The fluid need not be held under pressure in the device, thus reducing some of the problems associated with earlier proposals. Since the "loading" of the spring can be interlinked with the measurement of the dose of fluid, the operation of a latch or other means for retaining of the spring in its "loaded" state can be used to ensure that the correct dose of fluid is achieved. In a preferred embodiment, the metering chamber is provided with an inlet connection to supply liquid to said chamber, and an outlet connection to receive pressurised liquid from said chamber, and the atomising means is provided at or adjacent said outlet. The device of the invention may further comprise one or more control means for controlling fluid flow between said metering chamber, said inlet and said outlet. Preferably, the spring is adapted to be actuated by a user of the device, preferably to store energy imparted thereto by the user during operation of the device, and has a releasing or actuator means for releasing the predetermined amount of energy from the spring in the form of one or more pressure pulses. The device preferably also comprises loading means for loading the spring; retaining means, for example a latch or other detent means, for retaining the spring in a loaded state; and release means for releasing the retaining means, thereby to release the spring so as to cause the fluid to be discharged through the atomising means as a spray of droplets. Preferably, the device of the invention comprises a piston-in-cylinder type pump mechanism, at least part of the bore of the cylinder acting as the metering chamber adapted to receive a predetermined quantity of fluid from a reservoir, preferably corresponding to the swept volume of the metering chamber, upon actuation of the pump on its suction stroke. The piston acts as an interface means to transmit the energy pulse(s) to the fluid in the chamber. It is also preferred that the operation of the pump be interlinked with the retaining of the energy storage means in the loaded state so that the user is required to operate the pump to its full or a predetermined extent in order to cause the retaining mechanism to engage. However, it will be appreciated that the retaining of the energy storage means may be transient and that the operation of the device may pass through the fully loaded state directly to the discharge cycle at which the energy in the storage means is released to discharge the fluid in the metering chamber of the pump through the atomising means to form the desired spray. Preferably the spring is a compression spring which is located Substantially co-axially below the piston of a piston-in-cylinder type of pump so that operation of the pump on its suction stroke causes the spring to be compressed and thus store energy for the discharge stroke of the pump. If desired, more than one spring may be used. It is particularly preferred that the spring be at least partially pre-compressed so that the force applied by the spring as it expands does not vary greatly. The design and construction of the sprang can be selected in known manner to achieve the pressure required in the metering chamber during expansion of the spring on the discharge stroke of the pump. The device of the invention is preferably in the form of a unit containing the operating mechanism of the device, i.e. the atomising means, the spring and the fluid metering chamber; which unit can be mounted upon or can contain a removable reservoir for the fluid to be dispensed. Typically, the fluid will be contained in a collapsible container removably connected to the inlet to the metering chamber or pump cylinder. Where large volumes of fluid are to be discharged, the reservoir can take the form of a discardable can, tube or the like onto the outlet of which the operative mechanism unit of the device of the invention is a screw, push or other fit. Part of the container can be used to provide part of the operative mechanism of the device of the invention. For example, the outlet tube of the container can be used to provide the piston of the piston-in-cylinder pump. In order to achieve the high pressures required to form very fine droplets, for example less than 10 micrometres mean diameter, it will usually be necessary to provide some form of mechanical advantage in the energy loading mechanism and/or in the discharge mechanism of the pump. Thus, it will usually be desired to provide a lever or cam mechanism to aid compression of the spring; and/or to step or otherwise reduce the diameter of the pressure chamber or the outlet from the pump cylinder so as to achieve an hydraulic pressure advantage at the inlet to the atomising means. Typically, the lever mechanism will be associated with a trigger type mechanism which the user operates single handedly with the spray outlet adjacent to and directed towards the locus to which the spray is to be applied. If desired, the spray outlet can incorporate a shroud or mouthpiece to aid directionality of the spray. As indicated above, the device preferably incorporates a latch or other retaining mechanism for retaining the spring in the compressed or energy loaded state prior to initiation of the discharge cycle of the device. Such a retaining means can be a simple mechanical detent or latch which physically engages the spring or the pump mechanism and prevents release of the compression in the spring until some further operation is initiated. However, the retaining means may be provided by a stepped cam or over centre type of mechanism which bears against the spring so as to hold the spring transitorily in the desired state of compression during the loading cycle, but which automatically releases the spring with continued operation of the device to discharge the fluid. The invention can be applied to spraying of a wide range of materials in solution, emulsion, dispersion or suspension form to produce droplets with sizes of up to 200 micrometres or more. For convenience, the invention will be described hereinafter in terms of dispensing a spray of an aqueous solution of a medicament for inhalation into the lungs of a patient via the mouth. For such use, the droplet size is desirably less than 10 micrometres, typically 2 to 6 micrometres. Such small droplet sizes can be achieved by atomising the fluid using a wide range of atomising devices, for example ultra sonic blades, impingement of two jets of fluid or impaction of a jet or spray onto a baffle or the like. However, we prefer to form the spray by passing the fluid at high pressure through a small nozzle orifice, preferably in association with a swirl chamber or other device for causing a significant secondary flow in the fluid transverse to the main flow at the nozzle orifice. The optimum pressure and nozzle orifice shape and size can be determined for any given case using techniques known in the art. Thus, where very high pressures can be generated in the pump cylinder or other metering chamber, for example 3 x 10 7 P to 5 x 10 7 P (300 to 500) bar, comparatively large nozzle orifice diameters can be used, for example up to 100 micrometres, typically greater than 30 to 50 micrometres. However, we prefer to operate the device of the invention with pressures of from 5 x 10 6 P to 4 x 10 7 P (50 to 400 bar), preferably 10 7 P to 3.5 x 10 7 P (100 to 350 bar); and with nozzle orifice diameters of from 1 to 12 micrometres, notably 2 to 6 micrometres. If desired, the device of the invention can incorporate means to vary the pressure generated, for example by adjusting the extent of compression of the spring, and/or the diameter of the nozzle orifice. The pressure noted herein are the absolute pressures achieved in the metering chamber; and the nozzle orifice diameters are the effective hydraulic diameters. Preferably, the atomising means comprises an outlet orifice mounted in or on a body, and the device of the invention further comprises a member which is moveable with respect to said body to initiate operation of said atomising means, the arrangement being such that such movement of said member does not cause movement of said orifice. It is thus possible for a user to operate the device without moving an outlet nozzle containing the orifice, which is of benefit when applying a medicament through the mouth or nose. It is also preferred that, where the device of the invention is to be used as a Metered Dose Inhaler (MDI) for the application of a medicament to the lungs, the device is provided with a shroud or mouthpiece surrounding the atomising means so as to assist in containing and direction of the spray into the nose or mouth. The shroud or mouthpiece may also assist the user in inhaling the spray. The device of the invention preferably incorporates one or more valve means or other control means for regulating the flow into and out of the pump cylinder or other metering chamber. Thus, it will usually be necessary to provide a non-return valve on the inlet and outlet to the cylinder so that fluid flows into the cylinder only during the suction stroke of the pump; and fluid flows to the atomising means only when the pressure is applied to the fluid in the pump cylinder. In order to reduce the risk of premature escape of fluid from the device, it may be preferred that the outlet be provided with a pressure release valve, typically set to open when a pressure in excess of 50 bar is achieved in the metering chamber. Alternatively, the flow to and from the metering chamber can be controlled by a rotary or other valve mechanism which is interlinked with the operation of a trigger or a lever mechanism which are respectively used to operate the device and to load the spring. Thus, a lever and trigger mechanism can be pivotally mounted on a shaft which incorporates a rotary valve so that as the mechanism is progressively depressed it not only operates the pump to suck fluid into the pump cylinder through the valve, but also compresses the spring to store energy, and which rotates the valve so that the connection between the cylinder and the reservoir is shut off and the connection to the nozzle outlet opened prior to release of the spring, for example as a cam carried on the shaft goes over centre. It is also preferred that the device of the invention incorporate one or more separation members upstream of the nozzle orifice to reduce the risk of blockage of the fine nozzle orifice by particulate material in aqueous or other solutions of medicaments to be applied to the lungs. Thus, a fine mesh filter, a ceramic or fritted disc or the like can be incorporated into a nozzle chamber or in the outlet to the metering chamber. Typically, the filter will have an effective aperture or mesh size which is about half the nozzle orifice diameter. The preferred devices of the invention are operated by charging the metering chamber with the required quantity of fluid; loading the energy storage means with the required amount of energy (where this has not already been done as when a bulb of pressurised gas is used to drive a piston of a pump); and then releasing the energy to apply one or more pressure pulses to the fluid in the metering chamber so as to eject it through the atomising means to form the desired spray of fluid. Other preferred features of the invention are set out in the dependent claims. For a better understanding of the invention, and to show how the same may be carried into effect, it will now be described, by way of illustration only, with reference to the accompanying diagrammatic drawings, in which: Figure 1 is a sectional view of a Metered Dose Inhaler (MDI) according to the invention, with the fluid to be dispensed carried in a collapsible bag removably mounted in the device; Figure 2 is a view similar to Figure 1, but with a product to be dispensed in a pressurised container; Figure 3 is a sectional view of part of an alternative Metered Dose Inhaler, in which a product to be dispensed is contained in a collapsible tube having a nozzle which serves as a piston; Figure 4 is a view similar to Figure 3, showing an alternative pressurising arrangement; Figure 5 is an enlarged detail view of one example of an atomising orifice assembly: Figure 6 is an enlarged detail view of one example of a mechanical break-up orifice; Figure 7 illustrates, diagrammatically, an alternative atomising means; and Figure 8 illustrates, diagrammatically, another alternative atomising means. In the Figures, like reference numerals denote like or corresponding parts. The MDI shown in Figure 1 comprises a body in which there is defined a cylinder 2 of circular cross-section, in which a piston 3 is mounted for reciprocating movement. The cylinder 2 communicates with a metering chamber 4 of reduced cross-section. The piston 3 has a reduced diameter portion 5 which sealingly engages within the metering chamber 4, by means of a plastics [e.g. PTFE or Nylon] sealing cap or ring provided on the piston portion 5. The seal may be formed integrally with the reduced diameter portion 5 of the piston - for example, as a cap, rib or bead. A pre-loaded compression spring 6 is located in the cylinder 2, between the enlarged head of the piston 3 and an opposite end wall of the cylinder 2. An operating rod 31 is connected to the piston 3, and passes through the spring 6 and through a passageway 34 in the body 1, to protrude from the body 1. At or adjacent an and of the rod 31 there is provided a handle means 32 for moving the rod 31 and the piston 3. If desired, the end of rod 31 can be connected to a mechanism such as a lever mechanism incorporating a mechanical advantage so that the user can readily operate the device against the compressive force of spring 6. A latching means 33 provided on the body 1 engages with the rod 31, to latch the rod 31 in a loaded position, as illustrated in Figure 1. An actuating or trigger button 35 is provided, for releasing the latching means 33 . Also defined within the body 1 is a cavity 15 in which there is located a collapsible bag 10 containing the product to be dispensed [e.g. a liquid drug]. A door 16 on the side of the body 1 may be opened, in order to exchange the collapsible bag 10. By means of a connector 12, the interior of the bag 10 communicates with an inlet passage 11 which, in turn, communicates with the chamber 4 via a non-return valve 13. Also connected to the chamber 4 is an outlet passage 21 which extends from the chamber 4 to an atomising head 22, via a non-return valve 23 and a pressure release valve 25. Optionally, the body 1 is provided with a mouthpiece 40, which affords an atomization chamber around the atomising head 22. In use of the MDI of Figure 1, when the piston 3 is in the loaded position as illustrated in Figure 1, the metering chamber 4 is full of liquid which has been supplied from the bag 10, via the passage 11 and non-return valve 13. The compression spring 6, as mentioned above, is already pre-loaded when fitted in the cylinder 2. The loading of the spring is increased further by withdrawing the rod 31 and thereby the piston 3 to the loaded position that is illustrated in Figure 1. The rod 31 is latched in its loaded position as illustrated in Figure 1, by the latching means 33. Upon depressing the actuating button 35, the latching means 33 is released, thereby allowing the piston 3 to move suddenly forward under the force of the compression spring 6, to impart a sudden pressure pulse to the liquid in the chamber 4. The pressure of the liquid in the chamber 4 therefore quickly builds up to exceed the limit value of the pressure release valve 25, and the liquid is then ejected under high pressure through the outlet passage 21 to the atomising head 22, via the one-way valve 23. During the forward travel of the piston 3, the non-return valve 13 prevents liquid from being returned to the bag 10, via the inlet passage 11. As the liquid is ejected through the atomising head 22, it is atomised into a fine spray, which can then be inhaled. The optional mouthpiece 40 provides an atomization chamber within which the fine spray is enclosed, and facilitates the inhalation of the spray. To reload the MDI, the rod 31 is pulled back by means of the handle 32 against the resilient bias of the spring 6 and, at the end of its travel, the latching means 33 automatically latches the rod 31 into a latched end position. During this travel of the piston 3, liquid is sucked out of the collapsible bag 10 into the pressure chamber 4, via the inlet passage 11 and one-way valve 13. At this time, the one-way valve 23 prevents air being sucked into the pressure chamber 4 via the outlet passage 21. Due to the latching of rod 31, the liquid in pressure chamber 4 is held at ambient pressure and there is little or no risk of loss of fluid from the chamber. The operation of latching means 33 provides the user with a clear indication when piston 3 has completed the desired travel within cylinder 2 and that the required dose of liquid has been taken up. If the user fails to withdraw rod 31 to a sufficient extent, the latching means 33 will not engage and the user will detect the spring bias from spring 6 and will know to withdraw rod 31 further. The latching means 33 thus provides both the means for holding liquid in chamber 4 under ambient pressure and a means for alerting the user to incomplete operation of the device, hence reducing the risk of variable operation of the device. Thus, the MDI is again in a loaded position, as illustrated in Figure 1, ready for firing. It will be appreciated that, in use of the MDI illustrated in Figure 1, a metered dose of liquid product is pressurised and atomised in a highly accurate and repeatable manner. When the rod 31 and piston 3 are withdrawn to their loaded position, an exact metered quantity of liquid product is drawn into the pressure chamber 4. Upon releasing the latching means 33, the piston 3 is urged forwardly to impart a predetermined amount of energy to the liquid, and thereby increase its pressure by a predetermined amount. Thus, as the pressurized liquid is then ejected through the atomising head 22 of predetermined atomising characteristics, the liquid is atomised to a fine spray of predetermined mean particle size without the use of liquefied propellant or other gases. In order to atomise the liquid to a very fine spray - for example, having a mean particle size in the range 1 to 12 micrometres - a very high pressure has to be applied to the liquid in the chamber 4. By way of example, the capacity of the chamber 4 may be 20 microlitres; the diameter of the small end 5 of the piston 3 may be 2 mm; the diameter of the cylinder 2 may be 15 mm; the force of the spring 6 may be 100 Newtons; and the atomising head 22 may have an exit orifice of a diameter of 3 to 15 micrometres. In such an arrangement, a pressure of the order of 4 x 10 7 P (400 bar) may be generated in the liquid in the chamber 4. The cavity 15 may be open to atmosphere and at atmospheric pressure. In an alternative embodiment, the cavity 15 may be pressurised above atmospheric pressure, which helps to force the contents of the collapsible bag 10 into the chamber 4, without the need to create sub-atmospheric pressures in the chamber 4. This can help to avoid the formation of gas bubbles in liquid sucked into the chamber 4. The pressure release valve 25 is optional; it may be omitted if desired. The pressure release valve 25 and non-return valve 23 may also be combined as a single unit (not shown). It will be appreciated that the illustration of Figure 1 is essentially diagrammatic in nature. A practical embodiment may be of different construction; for example, a lever or other gearing mechanism may be employed to assist loading of the piston 3 against the force of the spring 6. In one example, the MDI may be provided with a cover which, when opened, automatically loads the piston 3 and latches the latching means 33, so that the MDI is then ready for firing. The MDI would be fired by actuating the button 35, when the cover was open. In an alternative arrangement, the piston 3 may be loaded against the spring 6 and the latching means 33 latched, whilst a cover of the MDI is being closed. Thus, the device would be pre-loaded and may be fired straight away, upon opening the cover. In another variation, opening of a cover of the device may automatically load the piston 3 against the force of the spring 6, latch the latching means 33, and then automatically release the latching means 33 at the end of the action of the opening of the cover so that the latching is only transient. The MDI of Figure 1 is preferably of small, pocket size. Since, in contrast to known MDIs, it does not have to provide an appreciable volume to contain a liquified gas propellent under pressure it can readily be made of small dimensions. Despite this, the product container, in the form of the collapsible bag 10, can contain much more medicament than conventional MDIs. For example, whereas conventional MDIs might be limited to 200 to 400 doses, an MDI constructed along the lines illustrated in Figure 1 may readily contain 1,000 or more doses, in the collapsible bag 10. As will be appreciated, the contents of the bag 10 are protected from contamination by the atmosphere and the operation of the device of the invention is by way of atomization of the fluid in chamber 4 without the use of an air blast, i.e. the device of the invention operates as an airless sprayer. When the bag 10 is empty, it may simply be removed from the cavity 15 and replaced with a fresh bag. Preferably, the bag 10 includes a seal to prevent the escape of product from the bag 10, unless the bag 10 is connected to a connector such as 12. In alternative embodiments, part of the piston and/or valve arrangement may be made disposable, together with the product container such as the collapsible bag 10. It is to be appreciated that, in use of the illustrated MDI, there is nothing [short of catastrophic failure of the apparatus] to stop the discharge of the contents of the chamber 4 as an atomised spray, once the actuating button 35 has been depressed to release the latching means 33 and thereby release the spring 6. Thus, the amount of energy applied by the spring 6 to the metered quantity of liquid in the pressure chamber 4 is absolutely predetermined, so that the increase in pressure to which the metered quantity of liquid is subjected is likewise absolutely predetermined. This objective is to be realised in all other illustrated embodiments of the invention described below. Another feature of the MDI of Figure 1 is that the metered quantity of liquid in the chamber 4 is subjected to an increase in pressure only when the actuating button 35 has been depressed to release the latching means 33 and thereby release the spring 6. This has the advantage that no seals or other means are required to constrain highly pressurised liquid prior to the atomization stroke. The increase in pressure applied by spring 6 and piston 3 to the metered quantity of liquid in the chamber 4 causes the pressurised liquid to pass through the atomising head 22, to be atomised thereby. This objective is to be realised in all other illustrated embodiments on the invention described below. Another important advantage of the MDI of Figure 1 is that, upon depressing the actuating button 35 to release the latching means 33 and spring 6, the atomising head 22 does not move within the body 1 - only the button 35 moves. This facilitates accurate direction of the atomised spray, and contrasts with a conventional vertical-axis finger pump arrangement, in which the atomising nozzle itself is depressed to initiate atomization. This would be inconvenient in a medical inhaler, since it would be difficult to direct the spray accurately. Again, this objective is to be realised in all other illustrated embodiments of the invention described below. The MDI illustrated in Figure 2 is generally similar to that of Figure 1. However, in Figure 2, the pressure release valve 25 is not provided. Also, the product container comprises a long tube 16 in which liquid product 17 is stored under pressure, which is created by a reservoir of gas 18 stored behind the liquid 17. As the piston 3 is pulled back to a loaded position, liquid product 17 is forced into the chamber 4 via the inlet passage 11 and non-return valve 13, under the pressure of the gas 18. As the liquid product 17 is used, the gas 18 expands into the tube 16, pushing the liquid product 17 ahead and losing some pressure. The initial pressure of the gas 18 should be sufficient to maintain a pressure above atmospheric, until all of the liquid product 17 is used up. The pressure tube 16 may be made as a replaceable item, for exchange in the MDI when the liquid product 17 is used up. Alternatively, the whole MDI may be manufactured quite cheaply of principally plastics parts, such that it may be a throw-away item. If the tube 16 is at least partly visible from the outside of the MDI, a visual check may be provided, as to the level of product remaining. In the embodiments of Figures 1 and 2, the spray action is initiated by actuating the button 35. In an alternative arrangement, the latching mechanism 33 may be released automatically in response to a user inhaling adjacent the atomising head 22. For example, a mouthpiece such as 40 may be connected to a vane that is caused to move by pressure difference across it when a user inhales, and thereby release the latching mechanism 33 to initiate the spray. Such automatic actuating mechanisms are known in themselves, in existing MDIs. In the embodiments of Figures 1 and 2, the stroke of the piston 3 is fixed. If desired, means may be provided for varying the stroke of the piston. Preferably, such means is calibrated, so that a user may optionally adjust the MDI to dispense differing quantities of spray. However, it will be appreciated that, in every case, once the adjustment means has been set to a particular value, the MDI will then provide a metered dose of spray in a highly repeatable manner, just as if the stroke of the piston were fixed. It will be appreciated that the devices of Figures 1 and 2 have been described above in terms of a device in which the cylinder of the pump mechanism is static and the piston moves axially therein. However, it is possible to carry the cylinder upon the rod 31 and to have the piston fixed. In the embodiment illustrated in Figure 3, a liquid product 50 is contained within a collapsible tube 51 which is formed integrally with an extended nozzle 52 which serves s a piston. The nozzle/piston 52 is located for reciprocating movement within a cylinder 53. At the end of the nozzle/piston 52 there is incorporated a simple non-return valve 54. A metering chamber 55 is defined at the end of the cylinder 53, and communicates via a simple non-return valve 56 with an atomising head 57. The cylinder 53, non-return valve 56 and atomising head 57 are all contained within a casing 58, which is formed with annular ribs 59, which serve to locate the casing 58 in a first main body part 60. The top of the product tube 51 is formed with an annular rib 61, which serves to locate the tube 51 in a second main body part 62. Resilient bias means is provided for urging the two main body parts 60 and 62 towards one another. A latching means is provided for latching the two main body parts 60, 62 at a predetermined distance apart, in a loaded condition, and actuating means is provided for releasing the latching means. In the interests of clarity, the resilient bias means, latching means and actuating means have not been shown in Figure 3, but, of course, examples of these have already been shown in Figures 1 and 2. The embodiment of Figure 3 operates as follows: as illustrated in Figure 3, the MDI is in an unloaded or "fired" condition. By means of a suitable loading mechanism, such as a lever mechanism, the main body parts 60 and 62 are moved away from one another, to cause the nozzle/piston 52 to withdraw relative to the cylinder 53. The depressurisation in the chamber 55 thereby causes the liquid product 50 to be sucked out of the tube 51, via the non-return valve 54, to fill the chamber 55. During this action, the non-return valve 56 serves to prevent air from entering the chamber 55 from the atomising assembly 57. At the end of the loading stroke, the latching means operates to hold the main body parts 60, 62 apart at predetermined relative positions. Upon releasing the latching means by the actuating means, the nozzle/piston 52 is suddenly urged under the action of the resilient bias means into the cylinder 53, to apply sudden pressure to the liquid product 50 in the chamber 55, in a manner generally similar to that in the embodiments of Figures 1 and 2. The pressurised liquid product is then ejected under pressure into the atomising assembly 57, via the non-return valve 56, and is then atomised into a fine spray by the atomising assembly 57. The MDI is then reloaded by the loading mechanism to move apart again the two main body parts 60, 62, against the force of the resilient bias means. Thus, it will be appreciated that the embodiment of Figure 3 operates in a generally similar manner to the embodiments of Figures 1 and 2. However, in Figure 3, the product 50 is provided in a particularly convenient manner in the product tube 51 which, together with the nozzle/piston 52 and the built in simple non-return valve 54, may be exchanged as a complete throw-away unit. It will be appreciated that the product tube 51 and its integral nozzle 52 and non-return valve 54 may readily be manufactured in a relatively economical manner out of plastics materials. The user is protected from contact with the liquid product 50, except when the MDI is properly actuated. Features of the embodiments of Figures 1 and 2, including variations as discussed above, may be provided, where appropriate, in combination with features of the embodiment of Figure 3. In the embodiment of Figure 3, either of the parts 60, 62 may be fixed in relation to a main body of the MDI, the other of the parts 60, 62 then being moveable with respect to the fixed part. Alternatively, both parts 60, 62 may be moveable with respect to a main body of the MDI. In the embodiment of Figure 4, liquid product 70 is contained within a collapsible tube 71. A nozzle 72 of the tube 71 connects with an inlet passage 73 which contains a non-return valve 74. The non-return valve 74 communicates with a flexible tube 75, which may flex between a "full" position [illustrated in solid lines] and an "empty" position 75a [illustrated in broken lines]. The flexible tube 75 communicates with another non-return valve 76 which, in turn, communicates with an atomising head (not shown]. The flexible tube 75 is contained within a pressure chamber 77 which is filled with a secondary liquid 78. The secondary liquid 78 communicates with a pressure pulse generator [not shown] via a passage 79. The embodiment of Figure 4 operates as follows: when a flexible tube 75 is in its "full" position, it is full of liquid product 70 sucked from the collapsible tube 71. Upon applying a pressure pulse to the secondary liquid 78, the pressure in the pressure chamber 77 suddenly increases, and this causes the flexible tube 75 to be urged into its "empty" position 75a, during which action the liquid product within the tube 75 is expelled out of the non-return valve 76 to the atomising head [not shown] under high pressure, such that the atomising head atomises the liquid product into a fine spray, generally as in the preceding embodiment. At the end of the pressure pulse, the flexible tube 75 resumes its initial "full" position and, during this action, liquid product 70 is sucked up from the collapsible tube 71, via the non-return valve 74, into the space within the flexible tube 75. The flexible tube 75 may return to its "full" position under its own natural resilience. Alternatively or additionally, it may be assisted in this by the application of a negative or reduced pressure pulse to the secondary liquid 78 in the pressure chamber 77. It is important that the pressure pulses are of a predetermined amplitude and duration to ensure that a metered dose of liquid is repeatedly sucked into the flexible tube 75 and subsequently expelled therefrom under a predetermined pressure increase, to produce a repeatable spray through the atomising head. The pressure pulse generator includes a piston and cylinder arrangement, together with latching and actuation means, of a type generally Similar to that illustrated in Figures 1 and 2. Typically, the pressure pulses may be of substantially square wave form. However, if desired, the pressure pulses may be of any predetermined shape - for example, if a time-varying spray spectrum were deliberately chosen. The important factor is that whatever the shape of the pulses, they are accurately repeatable. This may apply to all embodiments. Figure 5 shows, in enlarged detail, one example of an atomising head assembly 80. An inlet passage 81 formed in a body 82 leads to an inlet chamber 83. Interposed between successive sections of the inlet chamber 83 is a filter 84. The final section of the inlet chamber 83 leads to swirl chamber 85 which, in turn, leads to a nozzle 86. The purpose of the filter 84 is to prevent particles from blocking the final orifice. For example, the filter 84 may be made of stainless steel mesh, having a mesh size in the range 1 to 10 micrometres - preferably, 3 micrometres. Figure 6 shows one example of an atomising orifice 90, which is formed in a plate 91 which may be positioned, for example, downstream of the atomising nozzle 86 in the assembly of Figure 5, as shown by chain-dot lines in that Figure. As illustrated in Figure 6, the final exit orifice 90 has a diameter of 6 micrometres, and an overall length of 30 micrometres, to include an inwardly tapering throat 92 at an angle of 30° to normal and an outwardly flared mouth 93. The orifice plate 91 has a thickness of the order of 1 mm, and a tapering inlet passage has a length of about 1 mm, tapering at an angle of 20° from an initial entry orifice size of 70 micrometres. We have found that, surprisingly, using a final atomising orifice of the order of 6 micrometres, together with a high pressure applied to the liquid to be atomised [by means of the energy store such as the compression spring 6, etc], can lead to a very effective and uniform mean particle size of the eventual spray. Tests with an exit orifice of the order of 6 micrometres, as illustrated in Figure 6, together with a liquid pressure of the order of 3 x 10 7 P (300 bars), has produced a uniform spray of mean particle size of the order 5-8 micrometres. Preferably, the diameter of the exit orifice 90 is less than 100 micrometres. The preferred range for its diameter is 1 - 20 micrometres and the most preferred range is 3 - 10 micrometres. The exit orifice 90 may be formed by piercing the plate 91 - for example, by means of a tungsten carbide needle [e.g. similar to those used in forming spinarettes in the textile industry] or by any other suitable method. Although it is preferred to use a small bore nozzle orifice to achieve atomization of the fluid, it is possible to use alternative atomising means. For example, as shown in Figure 7, a liquid jet 102 may be produced through an exit orifice 104 to impinge at high velocity upon an object such as a metal ball 106, which then causes the liquid to atomise. Another alternative arrangement is shown in Figure 8, where two liquid jets 110 at high velocity and pressure are caused to meet, such that the liquid becomes atomised at their meeting point. Initial experiments with MDIs having constructions along the lines of at least some of the embodiments illustrated herein have proved to be surprisingly effective, readily providing repeatable spray doses of drugs having a mean particle size less than 30 micrometres and typically of the order of 3-10 micrometres. Mean particle sizes in the range 2 - 8 micrometres or less than 5 micrometres may be preferred. A particularly important aspect of such embodiments of the invention is that the drug can be used immediately in its water soluble form. Many drugs used at present have two formulations - one for use in an MDI, and the other for use in nebulizers usually used in hospitals. The latter formulation is almost always an aqueous solution of the drug, so such formulations are immediately available for use with embodiments of the present invention. By enabling application of drugs in aqueous solution with MDIs embodying the invention, new drug development may be accelerated. This is because much of the present long term testing is to ensure that the propellant (typically CFC) does not degrade or affect the drug and its effect and, of course, as described, no additional propellant agent is required. Many of the drugs presently administered by MDIs are concerned with bronchodilators and similar drugs for treating asthma, allergies and congestive disorders. However, it is becoming increasingly important to be able to treat other conditions (such as pneumonocystes carinii) by inhalation therapy. The reason for this is that drugs taken via the stomach are often destroyed by stomach secretions, or that which does get into the blood stream is taken out by the liver ("first pass metabolism"). In other cases, side effects can be severe. Some of these new drugs are difficult to micronise and, until now, they have been administered only be nebulization in hospitals , because a portable delivery method has not previously been available. Hospital nebulizers typically comprise gas blast devices in which small quantities of liquid product are added to large quantities of gas blasted under high pressure. Large gas cylinders are required for such apparatus, which is therefore distinctly non-portable. (Certainly in the sense of a pocket-sized device, or the like). Embodiments of the present invention may readily apply such drugs and are readily portable devices, and an important advantage is that such embodiments may be used immediately to administer drugs that are already tested and available for nebulizer application. Another particularly useful advantage of the illustrated embodiments is that they may be used quite satisfactorily in any orientation. In contrast to this, existing sprayers, both the propellant type (eg CFC) and pump action type will work only in one (usually upright) orientation. It will be appreciated that patients cannot always be relied upon to be in an upright position. As suggested above in the foregoing description, embodiments of the present invention may include product containers or reservoirs which are at least partially transparent, so that the level of the contents may be visually checked. A further advantage of illustrated embodiments of the invention is that they may be constructed quite satisfactorily without the use of any elastomeric sealing members. This is in contrast to all known MDIs of which we are aware, which use resilient sealing members which may possibly degrade in contact with products to be dispensed, and/or in which compounds extractable from the elastomers (eg rubbers) may leach into the products to be dispensed. One reason why preferred embodiments of the invention can function well without the need for elastomeric seals is that the products are not stored under high pressure. High pressure exists only for a very short time, during the atomization cycle, Therefore, in the embodiments of Figures 1 and 2, for example, only a sealing cap or ring on the piston end portion 5 is required and, as mentioned above, this can be of PTFE or Nylon. In fact, it is both possible and desirable to manufacture the embodiments of Figures 1 and 2 entirely from stainless steel and approved plastics materials (eg polypropylene, PTFE, Nylon) which are entirely safe and non-reactive with the products to be dispensed. If there is need for a seal at the connectors 12, this can be provided by a sealing ring or gasket of approved plastics (eg PTFE). Alternatively or additionally, the connectors such as 12 may include parts which screwthreadly engage, and at least one of which is of an approved plastic. In the embodiment of Figure 4, it is possible if desired, to employ elastomeric seals in the pressure pulse generator (not shown). This is because the product 70 is completely isolated from such seals by the flexible tube 75 and secondary liquid 78. The flexible tube 75 is of an approved plastics (eg polypropylene, PTFE, Nylon). In the embodiment of Figures 1 and 2, a mechanical piston, urged by a strong spring, is used to create a pressure pulse which is applied to the liquid in the pressure chamber 4. Although the above described embodiments of the invention utilize a liquid product which may typically comprise an aqueous solution of a drug, alternative fluid products may be used, For example, a fluid which is a suspension, emulsion or solution in water, alcohol or other liquid may be used. As mentioned above, the illustrated embodiments of the invention may emit a spray at much less velocity than conventional MDIs. For example in a conventional CFC repellant MDI, the cloud or bolus of spray that is emitted may travel at a speed of the order of 30 metres per second. Preferred embodiments of the present invention may release an equivalent amount of spray at a quarter of this speed. In fact it is possible to design embodiments of the present invention to match the optimum inhalation rate of the user at a figure of the order of 60 litres per minute. The illustrated embodiments of the invention include means for metering a quantity of fluid to be atomised. In alternative embodiments atomising devices may be provided with pre-metered quantities of fluid to be atomised. For example a strip of foil or plastics material (or other material) may contain individual pre-metered doses of liquid product and the strip could be punctured locally prior to or as part of a pressurising operation, following which the liquid is atomised to a fine spray. To this end, the strip may be pre-weakened at predetermined locations, to promote correct rupturing of the strip material when required. Alternatively pre-metered doses of liquid product may be contained in individual capsules which are fed successively to a pressure chamber or other pressurizing location where the capsules are then ruptured. The strip material or capsules may be designed to rupture at a predetermined pressure applied by the atomising device, such that a pressure release effect is created in the liquid product upon rupture.

Claims: A device for dispensing a metered amount of a fluid as a spray of droplets by discharging the metered amount of the fluid under pressure through an atomising means (22; 57; 80), wherein the device comprises: a chamber (4; 55; 75) for containing the metered amount of a fluid; a spring (6) for retaining a predetermined amount of energy and applying it via a piston (3, 52) to the metered amount of fluid in the chamber (4; 55; 75) so as to subject the metered amount of fluid to a predetermined increase in pressure from a lower pressure to a higher pressure of 5 x 10 6 Pa (50 bar) or more so as to permit discharge of said metered amount of fluid from said chamber (4; 55; 75) at said higher pressure; and atomising means (22; 57; 80) for atomising the fluid discharged from said chamber (4; 55; 75). A device as claimed in claim 1, wherein said higher pressure is 10 7 Pa (100 bar) or more. A device as claimed in claim 1 or claim 2, wherein said atomising means (80) comprises an outlet aperture (90; 104) having an hydraulic diameter in the range 1 to 100 micrometres. A device as claimed in claim 3, wherein the outlet aperture (90; 104) has an hydraulic diameter in the range 1 to 50 micrometres. A device as claimed in any preceding claim, wherein application of said predetermined amount of energy to the fluid initiates discharge of the fluid from said chamber (4; 55; 75). A device as claimed in any preceding claim, wherein a means (33) is provided to retain said spring (6) in a state retaining said predetermined amount of energy, and the actuation means (35) is provided for releasing said predetermined amount of energy from said spring (6). A device as claimed in claim 1, wherein the piston (3, 52) acted on by said spring (6) is part of a pump mechanism (3, 4, 13, 23; 52, 55, 54, 56) and said chamber (4; 55) is provided as the cylinder space in the pump mechanism beyond the pump piston (3; 52). A device as claimed in claim 7, wherein the pump mechanism (3, 4, 13, 23) is provided with a mechanism (33) whereby the pump can be held in the cocked state prior to release of the energy from the spring (6). A device as claimed in any preceding claim, wherein the piston (52) is hollow and provides a channel for fluid to enter the chamber (55). A device as claimed in claim 9, wherein the channel is provided with a non-return inlet valve means (54) for the chamber (55). A device as claimed in claim 9 or claim 10, wherein the piston (52) extends from a fluid reservoir (51). A device as claimed in any one of claims 1 to 10, including a fluid reservoir (10; 16; 51) from which said chamber (4; 55) can be charged with fluid. A device as claimed in claim 11 or claim 12, wherein the reservoir (10; 51) is replaceable. A device as claimed in anyone of claims 11, 12 or 13, wherein the reservoir (10; 51) is collapsible. A device as claimed in any preceding claim, wherein said chamber is a variable volume chamber (4; 55; 75) with non-return inlet valve means (13; 54; 74) and a non-return outlet valve means (23; 56; 76) to permit repeated charge of fluid into said chamber (4; 55; 75) and discharge of fluid from said chamber (4; 55; 75). A device as claimed in any preceding claim, wherein said atomising means (22; 57; 80) comprises an outlet aperture (104) arranged to form a jet of the fluid (102) and an impingement body (106) which is located in the line of trajectory of the jet of fluid (102) and which is arranged to cause break up of the jet of fluid (102) into a spray of droplets. A device as claimed in any one of claims 1-15, wherein said atomising means (22; 57; 80) forms a spray of droplets by providing jets of the fluid (110) which impinge upon one another. A method of discharging a metered amount of fluid as a spray of droplets in which there is employed a device as claimed in claim 1 or any claim dependent thereon. A method as claimed in claim 18, wherein the droplets have a mean size in the range of 1 to 12 micrometres.

Inventors: DUNNE STEPHEN TERENCE, WESTON TERENCE EDWARD, DUNNE, STEPHEN TERENCE, WESTON, TERENCE EDWARD
Applicants: BOEHRINGER INGELHEIM INT, BOEHRINGER INGELHEIM INTERNATIONAL GMBH
Application year: 1991
Main classification: B05B11
IPC codes: A61M15, B05B15, B05B11, B05B1, B05B9, G01F11, A61M11