Apparatus for administering pharmaceutical suspensions - Patent application

Abstract

The present invention relates to a dose delivery device (1, 100, 200, 300, 400) comprising a variable volume reservoir (10, 110, 210, 310, 410) holding a medicinal suspension and comprising an outlet (12, 112, 212, 312, 412), a dose preparation system comprising a dose ejection mechanism adapted for activation to eject a volume of the medicinal suspension through the outlet (12, 112, 5 212, 312, 412), and a preparation member (30, 130, 230, 330, 430) operable to enable administration of said volume of medicinal suspension to a subject prior to activation of the dose ejection mechanism, wherein the dose preparation system comprises a variable volume reservoir (10, 110, 210, 310, 10 the agitation member (40, 140, 240, 340, 440) capable of relative agitation motion with respect to the preparation member (30, 130, 230, 330, 430), the relative agitation motion causing resuspension agitation of the medicinal suspension, the agitation member (40, 140, 240, 340, 440) being operably coupled to the preparation member (30, 130, 230, 330, 430) and configured to undergo said relative agitation motion in response to operation of the preparation member (30, 130, 230, 330, 430).

Description

[Technical field]

[0001] The present invention relates generally to medical devices, and more specifically to a delivery device for administration of medicinal suspensions. [Background technology]

[0002] Pharmaceutical suspensions are widely used for different routes of administration and can be broadly classified as injectable suspensions, oral suspensions, and topical suspensions.

[0003] In an ideal pharmaceutical suspension, the insoluble drug particles are uniformly dispersed in three dimensions throughout the carrier medium and remain so over time. Thus, two equally sized volumetric doses from an ideal pharmaceutical suspension will contain the same amount of drug and provide the same clinical benefit to the recipient.

[0004] However, in practice, pharmaceutical suspensions are physically unstable. In the absence of agitation, dispersed drug particles will settle under the influence of gravity and form a sediment layer at the bottom of the container. This will cause local variations in drug concentration and therefore non-uniform dosing if unmitigated. In particular, a significant risk of underdosing is introduced.

[0005] US Patent No. 5,399,633 discloses a compressible container for storing and dispensing pharmaceutical suspensions, which allows for easy resuspension of particles that have settled out of the liquid during storage. By squeezing the container between two or more fingers, the user can force the liquid through an orifice and into a spherical container portion that allows for the formation of a vortex, which is sufficient to resuspend the settled particles.

[0006] Following proper resuspension of the drug particles, any metered dose should contain the intended amount of drug, thereby eliminating the risk of not receiving the correct dose. However, with containers of the type described in U.S. Pat. No. 5,999,633, the user must remember to manipulate the prescribed liquid before administering the dose. Failure to do so will result in uncertainty regarding the amount of drug actually dispensed. Furthermore, elderly people and other people with reduced mobility and finger strength may find the container difficult to handle, and as a result, these people are at higher risk of not receiving the correct treatment. [Prior art documents] [Patent documents]

[0007] [Patent Document 1] U.S. Patent No. 8,882,736 (Norton Healthcare Limited) Summary of the Invention

[0008] It is an object of the present invention to eliminate or reduce at least one disadvantage of the prior art, or to provide a useful alternative to the prior art solutions.

[0009] In particular, it is an object of the present invention to provide a solution for administering pharmaceutical suspensions, in which the risk of the user not receiving the intended dose of drug is minimized or eliminated.

[0010] It is a further object of the present invention to provide an apparatus or system for administering pharmaceutical suspensions which is safe, easy to handle and yet reliable with regard to delivery of the intended dose of drug.

[0011] In the present disclosure, aspects and embodiments will be described that address one or more of the above objectives and / or that address objectives that are apparent from the following passage.

[0012] In a solution embodying the principles of the present invention, a dose delivery device comprises a variable volume reservoir holding a medicinal suspension and having an outlet, a dose ejection mechanism adapted for activation to eject a volume of the medicinal suspension through the outlet, and a dose preparation system operable to enable administration of said volume of medicinal suspension to a subject prior to activation of the dose ejection mechanism, wherein operation of the dose preparation system causes agitation of the medicinal suspension.

[0013] Thereby, it is not possible to carry out dose administration using the dose delivery device without the pharmaceutical suspension being first agitated, thus automatically ensuring resuspension before the volume of pharmaceutical suspension enters the subject's body.

[0014] In one aspect, the present invention therefore provides a dose delivery device comprising a variable volume reservoir holding a medicinal suspension and comprising an outlet, a dose discharge mechanism adapted for activation to discharge a volume of the medicinal suspension through the outlet, and a dose preparation system comprising a preparation member operable to enable administration of said volume of the medicinal suspension to a subject prior to activation of the dose discharge mechanism. The dose preparation system further comprises a stirring member capable of agitating relative movement with respect to the variable volume reservoir, the agitating relative movement causing re-suspension agitation of the medicinal suspension. The agitating member is operably coupled to the preparation member and configured to undergo said relative agitation movement in response to operation of the preparation member.

[0015] Thereby, when the user operates the preparation member in preparation for a dose administration event, the medicament suspension is automatically agitated and thus ready for proper and reliable administration. Since the operation of the preparation member is necessary to enable administration of said volume of medicament suspension to the subject, the dose delivery device provides an assurance that the medicament particles have been resuspended when the dose ejection mechanism is activated, and thus the user does not have to remember to perform a specific manual resuspension act. Moreover, as will be apparent from the following, the operation of the preparation member is ergonomically very simple and effortless, and may also enable use by people with reduced strength and dexterity.

[0016] The stirring member may be movable relative to the variable volume reservoir between a first position and a second position and may be configured to move between the first position and the second position, e.g., from the first position to the second position, in response to operation of the preparation member. The first position may be a first predetermined position. Similarly, the second position may be a second predetermined position.

[0017] In an exemplary embodiment of the invention, the dose ejection mechanism is operably coupled to the preparation member and configured to automatically activate in response to operation of the preparation member when or after the stirring member reaches the second position. For example, the preparation member may include a shield member carrying a magnet and proximally displaceable relative to the variable volume reservoir from an outlet covering position to an outlet exposed position, the stirring member may include a magnetic element within the variable volume reservoir, the magnetic element being movable from a distal position to a proximal position within the variable volume reservoir in response to the shield member moving from the outlet covering position to the outlet exposed position, and the dose ejection mechanism may be spring powered and configured to release in response to the shield member reaching the outlet exposed position.

[0018] The stirring member may be movable relative to the variable volume reservoir along a reference axis, e.g., perpendicular to and / or about the reference axis, at an angle, i.e., the movement may be translational, rotational, or a combination of translational and rotational, e.g., helical, relative to the reference axis. Alternatively, the stirring member may be movable relative to the variable volume reservoir along a first reference axis and about a second reference axis. The first and second reference axes may be orthogonal. In either case, the first and second positions may be respective axial, lateral, and / or angular positions relative to the variable volume reservoir.

[0019] For example, the stirring member may be configured to extend along a reference axis and undergo relative stirring motion by translating along the reference axis and / or rotating about the reference axis relative to the variable volume reservoir between a first position and a second position in response to operation of the preparation member.

[0020] The configuration of the agitating member may be selected by the manufacturer to create a desired turbulence in the medicinal suspension during agitation relative motion with respect to the variable volume reservoir.

[0021] The preparation member may be operable to allow ejection of a volume of medicinal suspension through the outlet before activation of the dose ejection mechanism. In other words, the dose ejection mechanism may be prevented from ejecting a volume of medicinal suspension through the outlet before operation of the preparation member. In such a case, the dose delivery device may further comprise a releasable lock switchable from an initial state in which activation of the dose ejection mechanism is prevented to a released state in which activation of the dose ejection mechanism is enabled, the releasable lock being operably coupled to the preparation member and configured to switch from the initial state to the released state in response to operation of the preparation member. Thus, operation of the preparation member may include removal of a physical obstruction to movement of one or more parts of the dose ejection mechanism.

[0022] Such an arrangement would prevent the user from activating the dose ejection mechanism without prior manipulation of the preparation member, thereby eliminating the risk of the user unintentionally activating the dose ejection mechanism and the resulting disposal of medicament into the environment, for example simply as a result of the dose delivery device being carried roughly in a pouch or bag.

[0023] The releasable locking body may form part of the stirring member, thereby reducing the number of different components in the dose delivery device.

[0024] The dose delivery device may further comprise a housing containing at least a part of the dose ejection mechanism and defining a reference axis.

[0025] The variable volume reservoir may be any type of variable volume container suitable for holding a pharmaceutical suspension, such as, for example, a syringe with a staked needle, a cartridge-type container including a generally cylindrical body sealed proximally by a slidable rubber stopper and with a narrowing distal outlet portion that may be sealed by a pierceable septum, or a pouch-type container with a deformable body with an integrated outlet portion.

[0026] In an exemplary embodiment of the invention, the variable volume reservoir is a deformable reservoir, such as a flexible foil reservoir, and the stirring member includes a deformation element adapted to deform the flexible foil reservoir, thereby causing resuspension stirring of the medicinal suspension. Thereby, resuspension can be achieved without the presence of foreign bodies in the medicinal suspension. The deformation element can be adapted to sweep and squeeze the outer surface of the flexible foil reservoir to cause resuspension stirring of the medicinal suspension, which provides a mechanically simple and ergonomic structure. Alternatively, the deformation element can be adapted to squeeze different areas of the outer surface in a predetermined or random sequence, for example without sweeping, or to rub the outer surface with a rotational motion. In either case, the impact on the outer surface causes compression of the flexible foil reservoir, which in turn causes turbulence in the medicinal suspension.

[0027] As used herein, the term "flexible foil reservoir", or simply "foil reservoir", refers to a container that can be deformed by a deformation element to obtain a resuspension agitation, i.e., a container having one or more flexible surface portions. Thus, a "foil reservoir" may be fully flexible in the sense that all of its portions are deformable, e.g., like a pouch, or only some of its portions may be partially flexible, e.g., like a foil sheet welded or otherwise sealably attached to a rigid base member. It may be equipped with an integrated exit element, such as a syringe needle, or may be adapted to receive a separate exit element.

[0028] The preparation member may include a cap removably attached to the housing for covering the outlet, and the deformation element may be attached to or form part of the cap, and the cap may be adapted to be removed by relative axial movement with respect to the housing and the flexible foil reservoir, the deformation element thereby sweeping and squeezing the outer surface of the flexible foil reservoir. This provides a simple and easy to use dose preparation system having a minimum number of components.

[0029] The stirring member may further comprise a second deformation element and a third deformation element disposed axially spaced from each other and from the deformation element, at least two of the deformation elements intersecting the reference axis at different angles The deformation elements intersecting the reference axis at different angles will undergo different relative movements with respect to the outer surface of the flexible foil reservoir, which will promote turbulence created in the medicinal suspension.

[0030] Alternatively, the preparation member may include a pull tab removably attached to the housing, and the deformation element may be attached to or form part of the pull tab, and the pull tab may be adapted to be removed by relative lateral movement with respect to the housing and the flexible foil reservoir, whereby the deformation element sweeps and squeezes the outer surface of the flexible foil reservoir.

[0031] The stirring member may further include a second deformation element disposed laterally spaced from the deformation element, and the two deformation elements may intersect the reference axis at different angles to promote turbulence created in the medicinal suspension.

[0032] The dose delivery device may further comprise a cap removably attached to the housing for covering the outlet, and the stirring member and the cap may comprise mutually interacting contact members configured to prevent removal of the cap when the pull tab is attached to the housing, such that removal of the pull tab, which causes automatic resuspension, is required to expose the outlet and thereby enable administration of the dose to a user.

[0033] The dose ejection mechanism may comprise an actuator and a compression member adapted to fold the flexible foil reservoir in response to axial displacement of the actuator from a first axial position to a second axial position, the agitation member being configured to block movement of the actuator from the first axial position towards the second axial position when the pull tab is attached to the housing. This constitutes an example of the releasable lock mentioned above, in this case forming part of the agitation member, where removal of the pull tab switches the releasable lock from an initial state to a released state, thereby allowing actuation of the actuator.

[0034] In other exemplary embodiments of the invention, in which the variable volume reservoir may be a deformable reservoir or a non-flexible reservoir, the stirring member is configured to be immersed in the medicinal suspension and move within the variable volume reservoir, thereby causing resuspension stirring of the medicinal suspension.

[0035] In some such embodiments, the variable volume reservoir is a non-flexible reservoir, the stirring member is configured to promote turbulent flow within the non-flexible reservoir, and the preparation member is integrally or mechanically connected to the stirring member.

[0036] For example, the non-flexible reservoir may comprise an elastomeric piston having a central bore, and the dose ejection mechanism may comprise a piston rod structure for actuating the piston, the piston rod structure comprising: a) a shaft having a forward shaft portion configured to extend through the central bore in an airtight connection, and b) a drive tube abutting a proximal surface of the piston, the shaft adapted to undergo an initial proximal movement relative to the piston and the drive tube and a subsequent joint distal movement with the piston and the drive tube from a pre-use position to a dose-ready position in which the drive tube engages the shaft. In that case, the preparation member may constitute an enlarged proximal end portion of the shaft configured for user manipulation, and the agitation member may constitute an enlarged distal end portion of the shaft configured to promote vortex movement of the medicament suspension during the initial proximal movement.

[0037] Thus, the dose preparation system may form part of the dose ejection mechanism such that the preparation member, stirring member, and shaft may be either one single component or two or three mechanically coupled components, minimizing the number of parts required for automatic resuspension of the medicinal suspension.

[0038] The non-flexible reservoir may be a syringe with a syringe barrel and a staked needle, thereby eliminating the need for preparatory needle handling actions.

[0039] In other such embodiments, the stirring member is or comprises a magnetic element and the preparation member is or comprises a magnet that can influence the position of the magnetic element within the variable volume reservoir. This allows for the development of solutions where resuspension stirring of the pharmaceutical suspension is performed automatically by one or more actions performed by the user as part of the regular use of the device, i.e. no dedicated additional operation of the device is introduced to obtain resuspension.

[0040] For example, the outlet may comprise an injection needle having a needle end portion configured for insertion into the skin, the preparation member may include a needle shield carrying a magnet and displaceable proximally relative to the variable volume reservoir from a first shielded position in which the needle end portion is covered to a second shielded position in which the needle end portion is exposed, and the stirring member which is or includes a magnetic element may be movable from a distal position to a proximal position within the variable volume reservoir in response to the needle shield moving from the first shielded position to the second shielded position.

[0041] The proximal displacement of the needle shield required to expose the needle end portion and enable its insertion into the user's skin therefore causes the stirring member within the variable volume reservoir to follow the proximal movement of the carried magnet, thereby ensuring resuspension stirring of the medicinal suspension by creating turbulence in the medicinal suspension.

[0042] In an auto-injector version of the dose delivery device, the dose ejection mechanism may be spring powered and configured for release and automatic dose ejection in response to the needle shield reaching the second shield position. Thus, the very same movement that causes resuspension of the medicinal suspension also causes automatic ejection of the medicinal suspension shortly thereafter. This provides an easy to handle dose delivery device in which a dose may be administered by simply placing the needle shield at a desired location on the skin surface and pressing the variable volume reservoir towards the skin.

[0043] Alternatively, the preparation member may include an outlet protective cap that must be removed from the variable volume reservoir to allow dose discharge to the skin. The cap may carry a magnet and may be removable by distal movement relative to the variable volume reservoir, and the stirring member, which is or comprises a magnetic element, may be movable from a proximal to a distal position within the variable volume reservoir in response to the cap being removed.

[0044] Thus, distal displacement of the cap, which is necessary to expose the outlet, causes the stirring member within the variable volume reservoir to follow the distal movement of the carried magnet, thereby ensuring resuspension stirring of the medicinal suspension by creating turbulence in the medicinal suspension. After removal of the cap, the dose delivery device may be ready for dose administration.

[0045] The stirring member may be shaped to optimize the conditions for generating turbulence in the pharmaceutical suspension. In particular, when the variable volume reservoir is a non-flexible reservoir, the stirring member may have an external dimension that substantially corresponds to the internal dimension of the non-flexible reservoir. For example, when the non-flexible reservoir includes a cylindrical reservoir body having an internal reservoir diameter, the stirring member may comprise an annular stirring member body having an external stirring member diameter slightly smaller than the internal reservoir diameter. In that case, the outer surface portion of the stirring member body may be provided with one or more grooves to allow the passage of the pharmaceutical suspension along the stirring member body. One or more of the grooves may extend axially or may be inclined with respect to the longitudinal axis defined by the reservoir body, the latter inducing a vortex motion of the liquid immediately following the stirring member.

[0046] The agitator body may further define a central bore having an inner agitator diameter to allow for liquid passage therethrough, i.e., reducing drag.

[0047] The stirring member body may be formed of a magnetic material, or may include a magnetic core surrounded by a non-magnetic shell of, for example, plastic.

[0048] In a variation of the above, the dose preparation system may comprise a first preparation member in the form of an outlet protection cap carrying a first magnet capable of influencing the position of a magnetic element within the variable volume reservoir, and a second preparation member in the form of a needle shield carrying a second magnet capable of influencing the position of a magnetic element within the variable volume reservoir. With an appropriate ratio of the individual magnet strengths, a first resuspension agitation of the medicinal suspension may be achieved during removal of the outlet protection cap, and a second resuspension agitation of the medicinal suspension may be achieved thereafter during proximal displacement of the needle shield.

[0049] As used herein, the term "pharmaceutical suspension" refers to any dosage form containing therapeutically active solid particles dispersed in a liquid medium, where the solid particles are large enough for settling. The term applies to such dosage forms even when the particles are in a settled state. Also, when a first specified feature and a second specified feature are said to be "operably linked", this means that the two features are connected in a manner that performs a specified function, and a change in the state, position, and / or orientation of one feature affects the state, position, and / or orientation of the other. The term encompasses features that are integrally connected, abutting, assembled, or configured to interact at a distance, i.e., the features may be different but integral parts of one single piece, or they may be separate pieces that are mechanically connected or otherwise affect each other without contact, such as by magnetization.

[0050] For the avoidance of any doubt, in this context, the term "injection device" refers to an apparatus suitable for injecting a fluid medium into the body of a subject, for example with the aid of an attachable needle device, and the term "medicament" refers to a medium used in the treatment, prevention, or diagnosis of a condition, i.e. including a medium that has a therapeutic or metabolic effect in the body. Furthermore, the terms "distal" and "proximal" refer to a position on or a direction along a drug delivery device, drug reservoir, or needle unit, with "distal" referring to the drug exit end and "proximal" referring to the end opposite to the drug exit end.

[0051] Reference herein to a particular aspect or embodiment (e.g., "one aspect," "first aspect," "one embodiment," "exemplary embodiment," or the like) indicates that the particular feature, structure, or characteristic described in connection with each aspect or embodiment is included or inherent in at least that aspect or embodiment of the invention, but not necessarily in or inherent in all aspects or embodiments of the invention. However, it is emphasized that any combination of the various features, structures, and / or characteristics described in connection with the invention is encompassed by the invention, unless expressly stated herein or clearly contradicted by context.

[0052] The use of any and all examples or exemplary language (such as, for example, etc.) in the text is intended merely to better clarify the invention and does not limit the scope of the invention unless otherwise claimed. Moreover, no language or phraseology in the specification should be construed as indicating any non-claimed element as essential to the practice of the invention.

[0053] In the following the invention will be further explained with reference to the drawings. [Brief description of the drawings]

[0054] [Figure 1]FIG. 1 is an exploded view of a dose delivery device according to a first exemplary embodiment of the present invention. [Diagram 2] FIG. 2 is a perspective view of the dose delivery device in a pre-use state. [Diagram 3-4] 3 and 4 are perspective and longitudinal cross-sectional views, respectively, of a dose delivery device during initial uncapping. [Diagram 5] FIG. 5 is a schematic diagram of the resuspension principle used in the dose delivery device. [Figure 6-11] Figures 6 to 11 show different views of the dose delivery device in various operational states during dose preparation and dose administration. [Figure 12] FIG. 12 is an exploded view of a dose delivery device according to a second exemplary embodiment of the present invention. [Figure 13] FIG. 13 is a perspective view of the dose delivery device in a pre-use state. [Figure 14-19] Figures 14 to 19 show different views of the dose delivery device of Figure 13 in various operational states during dose preparation and dose administration. [Figure 20] FIG. 20 is a longitudinal cross-sectional view of a dose delivery device according to a third exemplary embodiment of the present invention. [Figure 21-22] Figures 21 and 22 show longitudinal cross-sections of the dose delivery device of Figure 20 after dose preparation and dose administration, respectively. [Diagram 23] FIG. 23 is an exploded view of a dose delivery device according to a fourth exemplary embodiment of the present invention. [Figure 24-27] 24 to 27 show different views detailing various components of the dose delivery device of FIG. [Figure 28-37] Figures 28 to 37 show different views of the dose delivery device of Figure 23 in various operational states during dose preparation and dose administration, with portions of the device cut away for clarity. [Figure 38-39] 38 and 39 are respective exploded assembly views of subassemblies of a dose delivery device according to a fifth exemplary embodiment of the present invention. [Diagram 40] FIG. 39 is a longitudinal cross-sectional view of the subassembly of FIG. 38. [Figure 41-46] 41-46 show various views of the individual components of the subassembly. [Figure 47] FIG. 47 is a perspective view of a subassembly prior to final assembly of the dose delivery device, with various parts cut away or made transparent for clarity. [Figure 48-60] Figures 48 to 60 show different views of the dose delivery device in various operational states during dose preparation and dose administration. [Figure 61-64] 61-64 are close-up views of the dose release mechanism. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0055] In the drawings, like structures are primarily identified with like reference numbers.

[0056] When / if relative expressions such as "up" and "down", "left" and "right", "horizontal" and "vertical", "clockwise" and "counterclockwise" are used below, they refer to the attached figures and do not necessarily refer to actual usage situations. The figures shown are schematic representations, so that the configuration of different structures, as well as their relative dimensions, are intended to serve illustrative purposes only.

[0057] Figure 1 is an exploded view of a dose delivery device 1 according to a first exemplary embodiment of the present invention. The dose delivery device 1 comprises a rigid base member 4 disposed within a housing 2, 3 defined by a top shell 2 and a bottom shell 3. A flexible foil reservoir 10 having an integrated injection needle 12 and carrier plate 14 is fixed to a front portion 7 of the base member 4, just proximal to a lateral end plate 6. The foil reservoir 10 holds a volume of a medicinal suspension. A pair of axially extending rails 5 are disposed along either side of the base member 4.

[0058] The dose delivery device 1 further comprises a cap 30 to which an axially extending rib structure 40 is attached. The rib structure 40 comprises two parallel side members 41 and three ribs 44a, 44b, 44c. The distal rib 44a connects the side members 41 at a first inclined angle, the central rib 44b connects the side members 41 at a second inclined angle and the proximal rib 44c connects the side members 41 at a third inclined angle identical to the first inclined angle. Each of the side members 41 has a thin proximal section 42 carrying a V-shaped hook 43.

[0059] The dose delivery device 1 also comprises a dose discharge member 20 having an elongated body 21 with a proximal push button 22 and a distal recess 29 adapted to receive a two-part rubber squeezer 27, 28. A colour marking 21c is located on the upper surface of the elongated body 21 just distal to the protruding guide member 21p, and two lateral protrusions 23, 24 are arranged in axial extension of each other on either side of the elongated body 21 (only one pair is visible). One of the lateral protrusions 23 has an oblique leading surface 25 and the other lateral protrusion 24 has an oblique trailing surface 26, leaving a V-shaped recess between the two lateral protrusions 23, 24. The protruding guide member 21c is adapted to provide linear advancement of the dose ejection member 20 into the housing 2, 3 and the colour markings 21c are arranged to be visible to a user through the window 2w in the upper shell 2 when the dose ejection member 20 is fully advanced into the housing 2, 3, thereby visually signalling that the dose administration action has been properly performed.

[0060] 2 is a perspective view of the dose delivery device 1 in a pre-use state, with the top shell 2 removed for clarity. In this state, the cap 30 is fully fitted onto the housings 2, 3, thus covering and protecting the injection needle 12. As can be seen, the side member 41 is fixedly attached to the inner end wall 31 of the cap 30, for example by gluing or welding, with the distal rib 44a being positioned proximal to the foil reservoir 10. It can also be seen that the rib structure 40 and the dose ejection member 20 are connected in that the hooks 43 (only one of which is visible) are trapped between the respective lateral projections 23, 24 and the rail 5.

[0061] The following figures show the dose delivery device 1 in various operating states. To prepare for administration of a volume of medicinal suspension contained in the foil reservoir 10, the cap 30 must first be withdrawn from the housing 2, 3 in the direction of the arrow as shown in Fig. 3. This leads to the ribs 44a, 44b, 44c continuously sweeping the foil reservoir 10, thereby inducing a resuspension stirring movement of the medicinal suspension, and to the dose ejection member 20 being withdrawn into the housing 2, 3 due to the engagement between the hook 43 and the lateral projections 23, 24. During distal displacement of the cap 30, the oblique trailing surface 26 exerts a reaction force on the hook 43, which reaction force has a small non-axial component pointing radially outwards. However, as long as the hook 43 moves along the rail 5, the hook 43 is prevented from disengaging from the recess between the two lateral projections 23, 24. In FIG. 3, the distal rib 44a sweeps completely across the foil reservoir 10, and the central rib 44b is approximately halfway.

[0062] Figure 4 is a longitudinal cross-sectional view of the dose delivery device 1 in the state shown in Figure 3 and shows two parts of the rubber squeezers 27, 28 arranged on each side of the base member 4. When the dose ejection member 20 is pulled distally by movement of the cap 30, the two parts of the rubber squeezers 27, 28 slide along the base member 4 and approach the foil reservoir 10.

[0063] Figure 5 is a schematic illustration of the resuspension principle employed by the dose delivery device 1. The use of a flexible reservoir allows the resuspension of drug particles in a liquid by applying pressure to the foil and varying the location of the applied pressure to mechanically induce a turbulent movement of the liquid. Turbulent movement is preferred for two reasons: firstly, it ensures much better mixing and therefore a more uniform concentration, and secondly, it involves higher velocities and thinner boundary layers, causing the liquid to agitate the particles closer to the surface than laminar flow.

[0064] High velocity turbulent flow is induced in the foil reservoir 10 by applying pressure to an area and moving the area relative to the foil while continuously applying this pressure. When pressure is applied to an area, liquid is displaced from that area and moves to other locations within the foil reservoir 10. Figure 5 illustrates the principle of what happens as a central rib 44b moves axially over the foil reservoir 10, although for simplicity the central rib 44b is depicted here as having an axis of extension perpendicular to the axis of motion.

[0065] In any interaction position, the central rib 44b creates a depression in the liquid-filled foil reservoir 10. When the central rib 44b is in the first intermediate position p i,1 to the second intermediate position p i,2 When the central rib 44b moves with a velocity v to the rib apex, a volume V of liquid, shown by the light grey colouring in Figure 5, will be displaced and forced to move under the rib apex by the pressure buildup in front of the central rib 44b. This volume V can only pass through a small area V under the rib apex, shown by the darker grey colouring in Figure 5, which in this example is approximately 1 / 4 of the volume V. As a result, the average velocity of the liquid passing under the rib apex is approximately 4v.

[0066] Due to the boundary conditions, the velocity profile of the liquid is parabolic with zero velocity at the interface with the rigid carrier plate 14 and a maximum velocity significantly higher than four times the velocity of the central rib 44b, so that even moderate rib velocities will generate a high velocity turbulent flow of liquid passing under the rib apex. This high velocity flow will enter the liquid residing behind the central rib 44b and cause turbulence in this volume as well.

[0067] Thus, as the cap 30 is removed from the housing 2, 3, the three ribs 44a, 44b, 44c sweep successively across the foil reservoir 10, causing vigorous agitation of the medicament suspension, resulting in automatic resuspension.

[0068] In FIG. 6, the cap 30 has been pulled distally to the point where the central rib 44b has completely swept the foil reservoir 10 and the proximal rib 44c has just begun its interaction with the foil. Meanwhile, the thin proximal section 42 of the side member 41 has moved out of contact with the rail 5. At this point, the rail 5 no longer prevents lateral movement of the thin proximal section 42, and thus continued pulling of the cap 30 leads to the thin proximal section 42 bending outward in response to the respective non-axial reaction force components from the oblique trailing surface 26. This is illustrated in FIG. 7. As a result, the hooks 43 disengage from the respective recesses between the lateral projections 23, 24 and the cap 30, and thus disengage from the dose ejection member 20, as can be seen in FIG. 8. During the last part of the removal movement of the cap 30, the dose ejection member 20 consequently remains stationary as the proximal rib 44c sweeps the foil reservoir 10.

[0069] Figures 9a and 9b show the remaining parts of the dose delivery device 1 after removal of the cap 30. From figure 9b it can be seen that the rubber squeezers 27, 28 are located at the transition section 8 where the thickness of the base member 4 gradually increases. This gradual increase in thickness provides increased resistance to distal movement of the rubber squeezers 27, 28 along the base member 4 and thus contributes to an easier removal of the cap 30 from the dose ejection member 20, since the force required to pull the dose ejection member 20 is even greater than the force that can be transmitted at the interface between the laterally released hooks 43 and the recess between the lateral projections 23, 24.

[0070] However, the transition portion 8 is easy for the rubber squeezers 27, 28 to pass through when being pushed by the elongate body 21. Thus, when the user subsequently inserts the injection needle 12 into the skin and presses the push button 22 down towards the housing 2, 3 to effect a dose administration, the rubber squeezers 27, 28 easily overcome the increased thickness of the base member 4 and advance towards the foil reservoir 10 without requiring significant effort.

[0071] The increased thickness of the base member 4 at the front portion 7 leads to a slight elastic deformation of the rubber squeezers 27, 28 upon passing the transition portion 8, which in turn leads to the rubber squeezers 27, 28 exerting a greater compressive force on the front portion 7 and ultimately on the foil reservoir 10 as the dose discharge member 20 is pushed further into the housing 2, 3. Thus, as the dose discharge member 20 advances distally into the housing 2, 3 illustrated by the different views of Figures 10 and 11, the foil reservoir 10 is tightly compressed and increasingly collapses, thereby forcing the medicinal suspension through the injection needle 12 and into the user's body.

[0072] Figure 12 is an exploded view of a dose delivery device 100 according to a second exemplary embodiment of the present invention. The dose delivery device 100, which can be seen as a compact variation of the dose delivery device 1 described above, comprises a rigid base member 104 disposed within a housing 102, 103 defined by a top shell 102 and a bottom shell 103. A flexible foil reservoir 110 having an integrated injection needle 112 and a carrier plate 114 is fixed to a front portion 107 of the base member 104, just proximal to a lateral end plate 106. The foil reservoir 110 holds a volume of a medicinal suspension. A pair of axially extending rails 105 are disposed along either side of the base member 104.

[0073] The dose delivery device 100 further comprises a pull tab 130 to which a laterally extending rib structure 140 is attached. The rib structure 140 comprises two parallel side members 141 adapted to extend through the opening 109 in the top shell 102 and two ribs 144a, 144b. The front rib 144a connects the side members 141 at a first inclination angle and the rear rib 144b connects the side members 141 at a second inclination angle different from the first inclination angle.

[0074] The dose delivery device 100 also comprises a removable cap 150 and a dose ejection member 120 having an axially extending body 121 with a proximal push button 122 and a distal recess 129 adapted to receive a two-part rubber squeezer 127, 128. Lateral projections 123 are disposed on either side of the elongated body 121 (only one is visible). Each of the lateral projections 123 has an oblique leading surface 125. The cap 150 comprises a pair of axially extending parallel arms 151 each terminating in an enlarged end section 152 having an oblique proximal surface 154 and a straight distal surface 153.

[0075] 13 is a perspective view of the dose delivery device 100 in a pre-use state, with the top shell 102 removed for clarity. In this state, the cap 150 is fully seated on the housings 102, 103, thus covering and protecting the injection needle 112. The arm 151 extends over the rib structure 140, and the straight distal face 153 of the enlarged end section 152 abuts against the proximal side 143 of one of the side members 141, such that axial movement of the cap 150 relative to the housings 102, 103 is prevented. Furthermore, the beveled leading face 125 of the lateral projection 123 abuts against the beveled proximal face 154 of the enlarged end section 152, and thus the pre-use state of the dose delivery device 100 is effectively a locked state, in which the presence of the rib structure 140 prevents both removal of the cap 150 and activation of the dose ejection member 120.

[0076] The following figures show the dose delivery device 100 in various operational states. To prepare for administration of a volume of medicinal suspension contained in the foil reservoir 110, the pull tab 130 must first be pulled out of the housings 2, 3 in the direction of the arrows as shown in Figures 14 and 15. This causes the ribs 144a, 144b to continuously sweep the foil reservoir 110, thereby inducing a resuspension stirring movement of the medicinal suspension in a similar manner as described above in relation to the first exemplary embodiment of the invention.

[0077] Once the pull tab 130 has been fully removed, such that the proximal side 143 no longer impedes movement of the enlarged end section 152, the cap 130 can be removed from the housings 102, 103 by relative axial movement in the direction of the arrows shown in Figure 16. This exposes the injection needle 112 and the dose delivery device 100 is thus ready for dose administration with a suitably resuspended medicament.

[0078] Figures 17a and 17b illustrate the dose delivery device 100 in a ready state, and from Figure 17b it can be seen that the rubber squeezers 127, 128 are initially positioned at the transition section 108 of the gradually increasing thickness of the base member 104. Thereby, as in the case of the previously described exemplary embodiment of the invention, when the user inserts the injection needle 112 into the skin and presses the push button 122 towards the housing 102, 103 to perform a dose administration, the rubber squeezers 127, 128 will elastically deform slightly upon passing the transition section 108 as the dose discharge member 120 is pressed into the housing 102, 103, thus exerting an increased compressive force on the front section 107 and the foil reservoir 110.

[0079] Thus, as the dose ejection member 120 advances distally into the housings 102, 103 illustrated by the different views of Figures 18 and 19, the foil reservoir 110 is tightly compressed and increasingly collapses, thereby forcing the medicinal suspension through the injection needle 112 and into the user's body.

[0080] 20 is a longitudinal cross-sectional view of a dose delivery device 200 according to a third exemplary embodiment of the present invention. The dose delivery device 200 comprises a housing 202 that accommodates a syringe barrel 210. The syringe barrel 210 has a proximal collar 213 in locking engagement with a proximal housing end 203 and a distal outlet end portion 211 to which an injection needle 212 is fixedly attached. The injection needle 212 is in a pre-use state of the dose delivery device 200 covered by a removable protective cap 219.

[0081] A sealed rubber piston 218 separates the interior of the syringe barrel 210 into two chambers: a wet chamber 215, which is pre-filled with a pharmaceutical suspension, and a dry chamber which houses a piston drive tube 220. The piston drive tube 220 has an axially rigid drive tube body 221 having a distal body end 228 that abuts the proximal end face of the piston 218. The proximal end section of the drive tube body 221 tapers toward the center of the syringe barrel 210 and terminates in a proximal body end 222.

[0082] The piston 218 has a central bore through which a central shaft 232 extends in a liquid-tight manner. The central shaft 232 has a radially enlarged shaft section 231 in the dry chamber and a distal mix head 240 in the wet chamber 215. The enlarged shaft section 231 terminates proximally in a user-operable pull-push knob 230, outside the housing 202 and distal to the transition section 236. The radial dimension of the enlarged shaft section 231 is greater than the radial extent of the proximal body end 222 in the relaxed state of the drive-tube body 221. This means that the proximal body end 222 is biased radially inwards in the pre-use state of the dose delivery device 200.

[0083] The mixing head 240 has a radial dimension that is slightly smaller than the inner diameter of the syringe barrel 210. In the pre-use state shown in FIG. 20, the central shaft 232 extends almost completely into the wet chamber 215, and the mixing head 240 is positioned near the outlet end portion 211. Accordingly, the pull-push knob 230 is positioned near the proximal housing end 203. The central shaft 232, including the enlarged shaft section 231, the mixing head 240, and the pull-push knob 230, are provided as one unitary component.

[0084] In operation, after removal of the protective cap 219 from the outlet end portion 211, the user pulls back on the central shaft 232 by operation of the pull-push knob 230 until the mix head 240 reaches the piston 218, as shown in FIG. 21. Proximal movement of the mix head 240 relative to the syringe barrel 210 causes an agitating movement (not visible) of the pharmaceutical suspension around the mix head 240 that is sufficient to resuspend any settled drug particles. As the mix head 240 reaches the piston 218, the transition section 236 passes the proximal body end 222 which consequently snaps into a smaller diameter position, thereby axially locking the piston 218 and piston drive tube 220 between the mix head 240 and the transition section 236.

[0085] To administer the resuspended medicinal suspension, the user now pushes the pull-push knob 230 distally toward the proximal housing end 203, which causes the transition section 236 to apply an axial driving force to the proximal body end 222, which is transmitted to the piston 218 via the axially rigid drive tube body 221. As the piston 218 advances through the syringe barrel 210, a volume of medicinal suspension is expelled through the injection needle 212. In FIG. 22, the pull-push knob 230 has been fully depressed and the piston 218 has reached its final end-of-dosage position within the syringe barrel 210.

[0086] 23 is an exploded view of a dose delivery device 300 according to a fourth exemplary embodiment of the present invention. The dose delivery device 300 is based on a cartridge type reservoir and comprises a cartridge assembly 301c and a housing assembly 301h. The cartridge assembly 301c comprises a cartridge 310 having a distal outlet end portion 311 and a pair of diametrically opposed proximal cartridge flanges 316. The cartridge 310 holds a volume of medicinal suspension and is sealed proximally by a slidable piston 318 and distally by a pierceable septum 313 bonded to the outlet end portion 311 in which the injection needle 312 is also disposed. A disk 317 is fixedly mounted on the injection needle 312 at a position that defines the possible depth of insertion of the injection needle 312 in the skin.

[0087] The cartridge assembly 301c further comprises a needle cap 330 having a hollow needle cap body 331 adapted to accommodate the injection needle 312 and the cartridge 310. At its proximal end, the hollow needle cap body 331 comprises a pair of diametrically opposed needle cap flanges 332 connected by a semicircular overhang 333 adapted to cover and hold a semicircular magnet 334. The magnet 334 is adapted to attract a magnetic mixer element 340 disposed within the interior 315 (see Figures 24a and 24b) of the cartridge 310. Each needle cap flange 332 has an abutment surface 332s and comprises a notch 335 on an inner surface portion for rotationally sliding reception of one of the cartridge flanges 316.

[0088] The housing assembly 301h comprises a three-part outer housing consisting of a central housing part 302, a proximal housing part 303, and a distal housing part 304. As such, the outer housing is divided to allow for positioning of the internal components. Each housing part has a means for fixed attachment to at least one of the other housing parts. Specifically, the proximal housing part 303 has a number of distally extending snap arms 303m, each of which is adapted to engage one of a number of corresponding receiving recesses 302f in the central housing part 302, which in turn has a number of distally extending snap arms 302m, each of which is adapted to engage one of a number of corresponding receiving recesses 304f in the distal housing part 304. The distal housing part 304 further has a distal rim 304r that projects radially inward.

[0089] The outer housing houses the locking ring 350, the stator 360, the piston rod 320, the drive spring 370, and the distal spring base 371. The piston rod 320 has an elongated piston rod body 321, a distal piston rod foot 328 adapted to interact with the piston 318, a central plate 322 for supporting the distal spring base 371, and a proximal stud 323 for interaction with an internal portion of the proximal housing part 303. Just distal to the central plate 322, the piston rod 320 comprises a hanger profile having an axially extending arm 326. A push button 380 extends proximally from the proximal housing part 303. The push button 380 has a lateral end surface 382 adapted to interact with a finger, and an axially protruding stem 383, and is biased proximally by a button spring 385.

[0090] 24a and 24b are perspective and longitudinal cross-sectional views, respectively, of cartridge assembly 301c in a pre-use state, showing cartridge 310 inside hollow needle cap body 331. In the pre-use state, cartridge flange 316 is received in notch 335, thereby axially fixing cartridge 310 relative to needle cap 330. The position of magnet 334 in overhang 333 causes magnetic mixer element 340 to maintain a proximal end position within cartridge 310 next to piston 318.

[0091] 25a and 25b are perspective and longitudinal cross-sectional views, respectively, of a magnetic mixer element 340 having a ring-shaped plastic body 341 of an outer diameter substantially corresponding to the inner diameter of the cartridge 310, with a central through bore 345 and an iron core 346. A plurality of grooves 344 are formed on the outer surface of the plastic body 341. Each groove 344 extends between a proximal mixer end surface 342 and a distal mixer end surface 343 and is inclined with respect to the longitudinal axis defined by the cartridge 310 and the injection needle 312.

[0092] 26a and 26b are different perspective views of locking ring 350. Locking ring 350 comprises a cylindrical locking ring body 351 having an inner surface 352 in which two longitudinal tracks 353 are provided for sliding receipt of respective needle cap flanges 332. At a proximal end portion, locking ring 350 has a pair of diametrically opposed internal shelves 356 (only one is visible) and a pair of diametrically opposed flats 354 with diametrically opposed bores 355 configured to receive respective arms 326 for rotationally interlocking the hanger profile and locking ring 350. The interior of locking ring 350 also comprises vertical reaction surfaces 357 (only one is visible) for interaction with respective abutment surfaces 332s.

[0093] 27a and 27b are side and perspective views, respectively, of a stator 360 comprising a stator base 363 supporting two proximally extending curved struts 361, each having a key 362 projecting radially outwardly along its entire length. The stator 360 further comprises a distal locking geometry 364 having two openings 365 (only one is visible) for receipt and rotational fixation of a respective cartridge flange 316. Two diametrically opposed curved slots 366 are provided in the stator base 363, which allow passage of the respective arms 326, and thus, together with the circumferential spacing between the curved struts 361, for a given angular movement of the hanger profile relative to the stator 360.

[0094] In the following, the operation of the dose delivery device 300 will be described with reference to Figures 28 to 37.

[0095] FIG. 28 is a perspective view of the dose delivery device 300 showing the cartridge assembly 301c ready for insertion into the housing assembly 301h. A portion of the housing assembly 301h has been removed to allow inspection of the internal components. It can be seen that the locking ring 350 and the stator 360 are axially fixed relative to the outer housing between the distal rim 304r and the proximal spring base 305. The stator 360 is further rotationally fixed relative to the outer housing due to the key 362 being rotationally locked into the proximal spring base 305. Additionally, the proximal stud 323 engages a pair of flexible fingers 303h that hold the piston rod 320 in place against the biasing force from the pre-tensioned drive spring 370.

[0096] Figure 29 shows the dose delivery device 300 after the initial step of linear insertion of the cartridge assembly 301c into the housing assembly 301h. During insertion, the needle cap flanges 332 slide within their respective longitudinal tracks 353 until they abut an axial stop in the locking ring 350 (not shown). When this occurs, the cartridge flanges 316 enter their respective openings 365 in the stator 360. In this view, the stator 360 is shown in full, and part of the internal configuration of the locking ring 350 is made visible, in particular to allow identification of one of the shelves 356.

[0097] After performing the translational relative motion between the cartridge assembly 301c and the housing assembly 301h, the user now rotates the needle cap body 331 in the direction of the arrow seen in FIG. 30. This causes the abutment surfaces 332s to interact with the respective reaction surfaces 357, resulting in the locking ring 350 rotating in conjunction with the needle cap body 331. The cartridge 310 remains stationary relative to the outer housing, as the stator 360 is rotationally fixed within the outer housing and the cartridge flange 316 is positioned within the opening 365. The rotation of the locking ring 350 causes an angular displacement of the shelf 356 and the hanger profile due to the arms 326 being received within the bore 355.

[0098] During rotation, the arm 326 travels through the curved slot 366, and thus the circumferential extent of the curved slot 366 defines the possible angular displacement of the needle cap body 331 relative to the outer housing. At the point where the needle cap body 331 contacts the rotational stop, the ledge 356 has moved to a position just below the cartridge flange 316, and thus the locking ring 350 supports and prevents axial movement of the cartridge 310. This can be seen in FIG.

[0099] With the cartridge 310 now in place and secured relative to the outer housing, the user pulls the needle cap body 331 away from the housing assembly 301h in the direction of the arrow shown in FIG. 32. This introduces axial movement of the overhang 333 relative to the cartridge 310, which pulls the magnetic mixer element 340 distally due to the magnet 334 held within the overhang 333. The magnetic mixer element 340 consequently moves downward within the interior 315 of the cartridge 310, which forces the liquid within the forward portion of the interior 315 through the body 341, partially through the bore 345 and partially through the angled groove 344, creating a high velocity vortex motion of the liquid immediately following the body 341, as shown by flow line F in FIGS. 32 and 33.

[0100] Thus, when the needle cap body 331 is fully withdrawn from the distal housing part 304, the magnetic mixer element 340 resides in the outlet end portion 311 and the medicinal suspension is in resuspended form and ready for dose administration. In Figure 34, the exposed injection needle 312 has been inserted through the skin barrier (not shown) and the outlet end portion 311 has been pressed down against the disk 317, causing the rear portion of the injection needle 312 to slide into the interior 315 of the cartridge 310, causing penetration of the septum 313 (not shown).

[0101] To effect a dose administration, the user now presses push button 380 in the direction of the arrow shown in Figure 35. Downward movement of push button 380 eventually engages stem 383, causing flexible fingers 303h to deflect radially and thus disengage from stud 323.

[0102] 36, this releases the distal spring base 371 and thereby the drive spring 370 which extends and urges the piston rod 320 downwardly. The piston rod foot 328 consequently advances the piston 318 distally within the interior 315 of the cartridge 310 such that the resuspended medicinal suspension is expelled through the bore 345 and the injection needle 312 and into the skin.

[0103] In FIG. 37, the piston 318 abuts against the magnetic mixer element 340 and the cartridge 310 is (substantially) empty. Thus, the user can remove the used cartridge 310 from the locking ring 350 by retracting the injection needle 312 from the skin, reinserting the needle cap body 331 linearly into the housing assembly 301h, rotating the needle cap body 331 against the direction of rotation during installation of the cartridge 310, and pulling the needle cap body 331 with the cartridge 310 therein away from the distal housing part 304. During the proximal movement of the needle cap body 331 relative to the outer housing, the cartridge flange 332 abuts against the arm 326, lifting the piston rod 320 upward until the stud 323 abuts and snaps behind the flexible finger 303h, thereby restoring the drive spring 370. The housing assembly 301h is then ready for use with a new cartridge assembly.

[0104] Figure 38 is an exploded view of a cartridge assembly 401c forming part of a dose delivery device 400 (see Figure 47) according to a fifth exemplary embodiment of the invention. The cartridge assembly 401c comprises a cartridge 410 extending along a reference axis and having a distal outlet portion 411. The cartridge 410 holds a volume of medicinal suspension (not shown) and a magnetic mixer element 440 similar to the magnetic mixer element 340 described above in relation to the fourth exemplary embodiment of the invention.

[0105] The cartridge 410 is sealed proximally by a slidable piston 418 and distally by a pierceable septum 413 disposed around the rear portion of the needle 412 and fixed to the outlet portion 411. The pierceable septum 413 may, for example, comprise an elastic needle coating applied directly to the needle 412 such that an initial bond between the elastic needle coating and the needle 412 is provided, the initial bond being irreversibly breakable by relative axial displacement between the two. A disk 417 is fixedly mounted on the needle 412 at a position that defines the possible depth of insertion of the needle 412 in the skin. At its proximal end, the cartridge 410 comprises a flange 416.

[0106] The cartridge assembly 401c further comprises a three-piece inner housing comprised of a central inner housing part 492, a proximal inner housing part 493 that is snap-fitted onto a proximal end portion of the central inner housing part 492, and a distal inner housing part 494 that is snap-fitted onto a distal end portion of the central inner housing part 492. The proximal inner housing part 493 has a pair of radially opposed proximal projections 493p (only one is visible in FIG. 38), while the central inner housing part 492 has a pair of radially opposed central projections 492p. The distal inner housing part 494 has a receiving section 494r at its distal end configured to receive and retain the flange 416, whereby the cartridge 410 is axially secured relative to the inner housing.

[0107] The inner housing is configured to house the rotor 495, a piston rod 420 adapted to drive the piston 418, and a drive spring 470 capable of storing energy and releasing the stored energy to actuate the piston rod 420.

[0108] The cartridge 410 and inner housing are disposed within a shield member 430, which includes a tubular shield body 431, a distal needle shield portion 436, and a pair of proximally extending arms 432. The shield body 431 has two diametrically opposed internal tracks 431t (one visible in FIG. 50) along an inner surface portion configured to slidably engage a central protrusion 492p on a central inner housing component 492. The distal needle shield portion 436 has a lateral end wall 437 having an opening 439 in which a penetrable shield seal 438 is disposed. The shield member 430 is biased by a shield spring 435 and carries a semicircular magnet 434 held in a magnet holder 433 disposed at the distal end of the shield body 431.

[0109] 39 is an exploded view of a housing assembly 401h of the dose delivery device 400. The housing assembly 401h comprises a main housing part 402 and an upper housing part 403 snap-fitted thereto, a tubular base member 450 with a pair of diametrically opposed internal bayonet tracks 459 (only one is visible) at its distal end portion, a locking member 460, a locking spring 465, a dose release button 480 whose proximal portion extends through a proximal opening in the upper housing part 403, and a button spring 485. The base member 450 is received by and axially and rotationally fixed to the main housing part 402.

[0110] 40 is a longitudinal cross-sectional view of the cartridge assembly 401c showing the relative positions of the components in the pre-use state and further detailing the structural features of some of these components. As can be seen, each of the proximally extending arms 432 of the shield member 430 includes an inclined proximal end 432i. Additionally, the piston rod 420 has a distal piston rod foot 428 adapted to abut against a proximal surface of the piston 418 and act as a distal base of the drive spring 470, and a pair of radial projections 425 that abut against a proximal side of a central barrier 492c inside the central inner housing part 492 in the pre-use state. The distal side of the central barrier 492c acts as a proximal base of the drive spring 470, which is therefore pre-tensioned and safely raised, since in this state of the cartridge assembly 401c the piston rod 428 cannot move distally relative to the inner housing. Note that the magnetic mixer element 440 is initially positioned distally within the cartridge interior 415 and is partially surrounded by the semicircular magnet 434 of the magnet holder 433 .

[0111] FIG. 41 is a perspective view of a piston rod 420, which comprises a cylindrical main piston rod body 421, a proximal end piece 423 having a rectangular cross section, as well as a piston rod foot 428 and a radial projection 425.

[0112] FIG. 42a is a longitudinal cross-sectional view of a central inner housing part 492 with a cylindrical wall 492w, a pair of proximal snap arms 492s for interlocking engagement with a proximal inner housing part 493, and a pair of distal recesses 492i for interlocking engagement with a distal inner housing part 494. A central barrier 492c has a through keyhole 492k and is connected to the cylindrical wall 492w by an annular bridge section 492b. The keyhole 492k has a similar cross-section to the main piston rod body 421 with the radial projection 425, but has a slightly larger configuration, such that the central barrier 492c allows the passage of the radial projection 425 only at certain angular orientations of the piston rod 420 relative to the central inner housing part 492. The configuration of the keyhole 492k can be seen in FIG. 42b, which is a top view of the central inner housing part 492.

[0113] FIG. 43 is a perspective view of a rotor 495 having a cylindrical outer wall 496, shown as transparent for clarity and to visualize the internal contour (illustrated in dotted lines). The rotor 495 is formed with an internal tower 497 adapted to accommodate a proximal portion of the piston rod 420. The tower 497 thus defines a narrow space substantially similarly shaped as the proximal portion of the piston rod 420. In particular, the tower 497 comprises a proximal portion having an opening 499 that is rectangular in cross section, which mates with the proximal end piece 423 to provide a rotationally interlocked but axially free connection between the piston rod 420 and the rotor 495. A pair of helical ramps 498 are formed between the outer wall 496 and the tower 497. The ramps 498 extend approximately half a turn and are offset from each other by 180°.

[0114] 44 is a perspective view of a dose release button 480 comprising a cylindrical body 483 having two legs 484, each having an angled distal end surface 484i, a proximal collar portion 481, and a slightly concave upper surface 482. The collar portion 481 comprises three circumferentially equidistantly spaced carvings 489 (only one is visible) configured to slidingly engage a mating protrusion on the inner surface of the upper housing part 403 to rotationally lock the dose release button 480 relative to the upper housing part 403 and main housing part 402.

[0115] FIG. 45 is a perspective view of base member 450 comprising a base member body 451 having a through bore 455, a base member flange 452 with four circumferentially spaced knots 453 configured for engagement with protrusions on the inner surface of main housing component 402, a stud 456 defining an initial angular position of locking member 460 relative to base member 450, and two diametrically opposed slots 454 configured to permit sliding reception of proximally extending arm 432, base member 450, and shield member 430 thereby being rotationally interlocked but allowed to undergo relative axial movement.

[0116] 46a and 46b are perspective and top views, respectively, of locking member 460, including locking member body 461 and proximal locking member flange 462. Locking member flange 462 has two diametrically opposed radial projections 463, each having an angled edge portion 464 configured for connection with one of angled proximal ends 432i of proximally extending arms 432, and a distal surface portion 466 for abutment with base member flange 452.

[0117] The distal end of the locking member body 461 includes two inwardly projecting ledges 468 spaced apart to define diametrically opposed gaps 469 therebetween. The gaps 469 allow passage of the legs 484 when the locking member 460 and dose release button 480 are in a particular relative angular position.

[0118] In housing assembly 401h, locking member body 461 extends through bore 455 with a distal surface portion 466 resting on the proximal face of base member flange 452. Locking member 460 is thus axially constrained within main housing component 402, but can rotate relative thereto. Locking spring 465 is a torsion spring that biases one of radial projections 463 into abutment with stud 456.

[0119] In the following, the assembly and use of the dose delivery device 400 will be described with reference to Figures 47 to 64.

[0120] Figure 47 is a perspective view of the dose delivery device 400 prior to attachment of the cartridge assembly 401c to the housing assembly 401h. For clarity, a portion of the main housing part 402 has been cut away and a portion of the base member body 451 and the entire shield member 430 are shown as transparent.

[0121] To assemble the dose delivery device 400, the cartridge assembly 401c is first linearly moved in a proximal direction, as indicated by the arrow in Fig. 48, until the proximal protrusion 493p reaches the end of the entrance section of the bayonet track 459. The shield member 430 is then rotated counterclockwise relative to the main housing part 402, allowing the proximal protrusion 493p to move to the end of the bayonet track 459, thereby axially locking the inner housing and cartridge 410 relative to the base member 450 and main housing part 402. This is shown in Fig. 49.

[0122] 50, further counterclockwise rotation of the shield member 430 relative to the main housing part 402 causes a relative angular displacement between the shield body 431 and the inner housing as the proximal inner housing part 493 is prevented from further counterclockwise rotation relative to the base member 450 due to the position of the proximal protrusion 493p at the end of the bayonet track 459. As a result, the central protrusion 492p forces the respective circumferential track portions of the inner track 431t to move into alignment with the connected axial track portions, thereby allowing the shield member 430 to be axially displaced relative to the inner housing. The dose delivery device 400 is now in an unlocked state ready for an injection event.

[0123] Figures 51 to 54 show the dose delivery device 400 in a further exploded version in which some elements have been removed and some have been made transparent (some outlines are shown in dotted lines) to allow visualising what is happening inside the cartridge 410. The state of the dose delivery device 400 shown in Figure 51 therefore corresponds to the state shown in Figure 50. So, in the unlocked state of the dose delivery device 400, the magnetic mixer element 440 is positioned axially opposite the piston 418 in the distal part of the cartridge 410 and the disk 417 is axially spaced apart from the outlet portion 411.

[0124] To insert the injection needle 412, the user places the lateral end wall 437 at a desired location on the skin and pushes the main housing part 402 towards the body. As shown in FIG. 52, this causes the forward tip 412t of the injection needle 412 to pierce the shield seal 438 as the shield member 430 is consequently displaced proximally relative to the main housing part 402. Also, due to the proximal displacement of the shield member 430 relative to the main housing part 402, the magnet 434 moves proximally relative to the cartridge 410, thereby forcing the magnetic mixer element 440 to slide upward within the cartridge interior 415, subsequently generating a vortex motion of the medicinal suspension, as shown by flow line F.

[0125] As the main housing part 402 gradually approaches the user's body, thereby forcing the shield member 430 further proximally into the main housing part 402, the injection needle 412 is inserted deeper into the skin until the lateral end wall 437 having the shield seal 438 reaches the disc 417, as shown in FIG. 53, and the magnetic mixer element 440 moves further upward within the cartridge interior 415, stirring more of the medicinal suspension.

[0126] When the lateral end wall 437 reaches the disc 417, further movement of the main housing part 402 towards the body causes a relative convergent movement between the cartridge 410 and the disc 417 as the outlet portion 411 is forced into contact with the disc 417. During this convergent movement, the initial bond between the pierceable septum 413, which is fixed to the outlet portion 411, and the needle 412 to which the disc 417 is fixedly attached, breaks and the rear tip 412r of the needle 412 consequently penetrates the pierceable septum 413 as the needle 412 slides a small distance into the cartridge interior 415. This can be seen from figure 54.

[0127] Now, the shield member 430 is pressed completely down into the main housing part 402 and the magnetic mixer element 440 travels throughout the cartridge interior 415 and reaches the piston 418, thereby ensuring complete resuspension of the medicinal suspension and establishing fluid communication between the cartridge interior 415, which partially resides in the user's body, and the injection needle 412.

[0128] The state changes of the dose delivery device 400 described in relation to Figures 51 to 54 also include the movement of several other notable components. Figures 55 and 56 show the dose delivery device 400 with an opaque inner housing to allow for the description of what is happening in the outer layers of the cartridge 410. The state of the dose delivery device 400 shown in Figure 55 corresponds to the state shown in Figure 52 and the state of the dose delivery device 400 shown in Figure 56 corresponds to the state shown in Figure 54.

[0129] Thus, in FIG. 55, shield member 430 has been moved slightly proximally relative to main housing part 402, allowing forward tip 412t to penetrate shield seal 438 (not visible in FIG. 55). Disk 417 is still axially spaced from outlet portion 411 at this point. Axial movement of shield member 430 is possible because central projection 492p is guided within the axial track portion of internal track 431t. Thus, as shield body 431 translates proximally relative to base member 450, proximally extending arms 432 extend through slots 454 in base member flange 452. Proximal to base member flange 452, angled proximal end 432i interacts with radial protrusion 463, and as proximally extending arm 432 continues proximal movement, this interaction leads to angled edge portion 464 sliding along angled proximal end 432i, thereby leading to rotation of locking member 460 about the central axis of main housing part 402. Rotation of locking member 460 continues until central protrusions 492p reach the respective ends of the axial track portions of internal track 431t, as seen in FIG. 56. This is the point at which shield member 430 is fully pressed into main housing part 402.

[0130] Figures 57 and 58 show a dose delivery device 400 without an inner housing and with a transparent outer wall 496 of the rotor 495 and a transparent locking member 460 to allow for illustration of movement of components in further layers of the structure. The state of the dose delivery device 400 shown in Figure 57 corresponds to the state shown in Figures 52 and 55, and the state of the dose delivery device 400 shown in Figure 58 corresponds to the state shown in Figures 54 and 56.

[0131] Figure 57 shows that the leg 484 is initially seated on the ledge 468 of the locking member 460, thereby preventing the dose release button 480 from distal movement relative to the main housing part 402. However, the above described proximal displacement of the shield member 430 leading to rotation of the locking member 460 eventually causes the locking member 460 to occupy an angular position relative to the dose release button 480 in which the gap 469 is aligned with the leg 484. In this particular relative angular position, shown in Figure 58, the dose release button 480 is no longer prevented from distal movement relative to the main housing part 402 and therefore activation of the injection mechanism is now permitted.

[0132] Once the injection needle 412 is safely inserted into the skin, the user presses the top surface 482 down towards the upper housing part 403 to perform the injection. As shown in FIG. 59, this initially causes the angled distal end surface 484i of the leg 484 to move through the gap 469 into sliding abutment with the helical ramp 498. As the dose release button 480 is pressed further into the main housing part 402, the leg 484 moves along the ramp 498, causing the rotor 495 to rotate about its central axis. It is therefore clear from FIG. 60 that the rotor 495 rotates clockwise about its central axis (when viewed from a proximal perspective).

[0133] Because of the mating connection between the opening 499 and the proximal end piece 423, rotation of the rotor 495 causes a similar rotation of the piston rod 420. Figures 61-63 show the resulting angular displacement of the piston rod 420 as the leg 484 moves down the ramp 498 (illustrated in dotted lines). Initially (Figure 61), the main piston rod body 421 is oriented so that the radial projection 425 rests on the central barrier 492c and secures the piston rod 420, and finally (Figure 63), the main piston rod body 421 is rotated 90° clockwise relative to the central inner housing part 492, resulting in the radial projection 425 being properly aligned with the keyhole 492k.

[0134] When the radial projection 425 and keyhole 492k are so aligned, the drive spring 470 is allowed to extend and the energy released by the extension of the drive spring 470 will urge the piston rod 420 downward through the tower 497, thereby forcing the piston 418 and magnetic mixing element 440 distally within the cartridge interior 415 towards the outlet portion 411 and expelling a predetermined dose of resuspended medicinal suspension through the injection needle 412. This is shown in FIG.

Claims

1. A dose delivery device (1, 100, 200, 300, 400) comprising: a variable volume reservoir (10, 110, 210, 310, 410) holding a pharmaceutical suspension and provided with an outlet (12, 112, 212, 312, 412); a dose-dispensing mechanism adapted for actuation to dispense a volume of said medicament suspension through said outlet (12, 112, 212, 312, 412); a dose preparation system comprising a preparation member (30, 130, 230, 330, 430) operable to allow administration of said volume of said medicinal suspension to a subject prior to activation of said dose discharge mechanism; the dose preparation system further comprising an agitating member (40, 140, 240, 340, 440) capable of agitating relative movement with respect to the variable volume reservoir (10, 110, 210, 310, 410), the agitating relative movement causing resuspension agitation of the medicament suspension; A dose delivery device, wherein the stirring member (40, 140, 240, 340, 440) is operably coupled to the preparation member (30, 130, 230, 330, 430) and is configured to undergo the stirring relative motion in response to operation of the preparation member (30, 130, 230, 330, 430).

2. 2. The dose delivery device of claim 1, wherein the agitating relative movement comprises movement of the agitating member (40, 140, 240, 340, 440) relative to the variable volume reservoir (10, 110, 210, 310, 410) from a first predetermined position to a second predetermined position.

3. 3. The dose delivery device of claim 1 or 2, further comprising a releasable locking body (143, 460) switchable from an initial state in which activation of the dose discharge mechanism is prevented to a release state in which activation of the dose discharge mechanism is enabled, the releasable locking body (143, 460) being operably coupled to the preparation member (130, 430) and configured to switch from the initial state to the release state in response to the operation of the preparation member (130, 430).

4. said variable volume reservoir (10, 110) being a flexible foil reservoir; 2. The dose delivery device of claim 1, wherein the stirring member (40, 140) comprises a deformation element (44a, 144a) adapted to deform the flexible foil reservoir, thereby causing the re-suspension stirring of the medicinal suspension.

5. 5. The dose delivery device according to claim 4, wherein the deformation element (44a, 144a) is adapted to deform the flexible foil reservoir by sweeping and squeezing the outer surface of the flexible foil reservoir.

6. a housing (2, 3) containing at least a portion of said dose discharge mechanism and defining a reference axis; the preparation member (30) includes a cap removably attached to the housing (2, 3) to cover the outlet (12); the deformation element (44a) is attached to or forms part of the cap; and 6. The dose delivery device of claim 5, wherein the cap is adapted to be removed by relative axial movement with respect to the housing (2, 3) and the flexible foil reservoir, the deformation element (44a) thereby sweeping and squeezing the outer surface of the flexible foil reservoir.

7. the stirring member (40) further comprises a second deformation element (44b) and a third deformation element (44c) disposed axially spaced apart from each other and from the deformation element (44a); and 7. The dose delivery device according to claim 6, wherein at least two of the deformation elements (44a, 44b, 44c) intersect the reference axis at different angles.

8. a housing (102, 103) containing at least a portion of said dose discharge mechanism and defining a reference axis; the preparation member (130) comprises a pull tab removably attached to the housing (102, 103); said deformation element (144a) being attached to or forming part of said pull tab; 6. The dose delivery device of claim 5, wherein the pull tab is adapted to be removed by relative lateral movement with respect to the housing (102, 103) and the flexible foil reservoir, whereby the deformation element (144a) sweeps and squeezes the outer surface of the flexible foil reservoir.

9. the agitating member (140) further comprises a second deformation element (144b) disposed laterally spaced from the deformation element (144a); 9. The dose delivery device according to claim 8, wherein the two deformation elements (144a, 144b) intersect the reference axis at different angles.

10. a cap (150) removably attached to the housing (102, 103) to cover the outlet (112); 10. The dose delivery device of claim 8 or 9, wherein the stirring member (140) and the cap (150) are provided with mutually interacting contact members (143, 152) configured to prevent removal of the cap (150) when the pull tab is attached to the housing (102, 103).

11. the dose-dispensing mechanism comprises an actuator (120) and compression members (127, 128) adapted to fold the flexible foil reservoir in response to axial displacement of the actuator (120) relative to the housing (102, 103) from a first axial position to a second axial position, 10. The dose delivery device of claim 8 or 9, wherein the stirring member (140) is configured to prevent movement of the actuator (120) from the first axial position towards the second axial position when the pull tab is attached to the housing (102, 103).

12. 2. The dose delivery device of claim 1, wherein the stirring member (340, 440) is immersed in the pharmaceutical suspension and is or comprises a magnetic element, and the preparation member (330, 430) is or comprises a magnet capable of influencing the position of the magnetic element.

13. the preparation member (330) comprises an outlet protective cap carrying the magnet and removable by distal movement relative to the variable volume reservoir (310); and 13. The dose delivery device of claim 12, wherein the stirring member (340), which is or comprises the magnetic element, is adapted to move from a proximal position to a distal position within the variable volume reservoir (310) in response to the cap being removed.

14. the outlet (412) comprises an injection needle having a needle tip portion (412t) configured for insertion into the skin; the preparation member (430) comprises a needle shield carrying the magnet and displaceable proximally relative to the variable volume reservoir (410) from a first shielded position in which the needle end portion (412t) is covered to a second shielded position in which the needle end portion (412t) is exposed; 13. The dose delivery device of claim 12, wherein the stirring member (440) being or comprising the magnetic element is adapted to move from a distal position to a proximal position within the variable volume reservoir (410) in response to the needle shield moving from the first shielding position to the second shielding position.

15. 15. The dose delivery device of claim 13 or 14, wherein the stirring member (340, 440) is configured to promote turbulence in the medicament suspension during movement between the proximal and distal positions.

Images