CN117897191A - Device for administering a pharmaceutical suspension - Google Patents

Abstract

The present invention provides a dose delivery device (1, 100, 200, 300, 400) comprising: a variable volume reservoir (10, 110, 210, 310, 410) containing a drug suspension and comprising an outlet (12, 112, 212, 312, 412), a dose expelling mechanism adapted to be activated to expel a volume of the drug suspension through the outlet (12, 112, 212, 312, 412), and a dose preparing system comprising a preparing member (30, 130, 230, 330, 430) operable prior to activating the dose expelling mechanism to enable administration of the volume of the drug suspension to a subject, wherein the dose preparing system further comprises an agitating member (40, 140, 240, 340, 440) capable of an agitating relative motion with respect to the variable volume reservoir (10, 110, 210, 310, 410) that causes a re-suspension agitation of the drug suspension, and wherein the agitating member (40, 140, 240, 340, 440) is operatively coupled with the preparing member (30, 130, 230, 330, 430) and configured to undergo the agitating relative motion in response to the preparing member (30, 130, 330, 430).

Description

Device for administering a pharmaceutical suspension

Technical Field

The present invention relates generally to medical devices, and more particularly to delivery devices for administering drug suspensions.

Background

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

In an ideal drug suspension, the insoluble drug particles are uniformly dispersed in three dimensions throughout the carrier medium and remain in this state over time. Thus, every two volumetric doses of the same size from an ideal drug suspension will contain the same amount of drug and will have the same clinical effect on the recipient.

However, in practice, the drug suspension is physically unstable. Without agitation, the dispersed drug particles will settle under the influence of gravity and form a sediment layer at the bottom of the container. This results in local variations in drug concentration and, therefore, if not improved, non-uniformity of administration. In particular, there is a significant risk of under-dosing.

US 8,882,736 (Norton Healthcare Limited) discloses a compressible container for storing and dispensing a pharmaceutical suspension, which allows easy re-suspension 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 the aperture and into the spherical container portion, which allows a vortex to be formed that is sufficient to re-suspend the settled particles.

After the drug particles are properly resuspended, any metered dose should contain the desired amount of drug, thereby eliminating the risk of not receiving the correct dose. However, using a container of the type described in US 8,882,736, the user must remember to manipulate the liquid as prescribed prior to dose administration. If this is not done, uncertainty will be brought about in the amount of medicament actually dispensed. In addition, elderly and other persons with reduced motor skills and finger strength may find the container difficult to handle and therefore there is a greater risk that these persons will not be properly treated.

Disclosure of Invention

It is an object of the present invention to obviate or mitigate at least one disadvantage of the prior art, or to provide a useful alternative to the prior art solutions.

In particular, it is an object of the present invention to provide a solution for administering a suspension of a drug, by which the risk that the user does not receive the intended dose of the drug is minimized or eliminated.

It is a further object of the present invention to provide a device or system for administering a drug suspension which is safe and easy to handle, and which is furthermore reliable in expelling a desired dose of drug.

In the disclosure of the present invention, aspects and embodiments will be described which achieve one or more of the above objects and/or which will become apparent from the following.

In a solution embodying the principles of the present invention, a dose delivery device comprises a variable volume reservoir containing a drug suspension and comprising an outlet, a dose expelling mechanism adapted to be activated to expel a volume of the drug suspension through the outlet, and a dose preparation system operable prior to activating the dose expelling mechanism to enable administration of the volume of the drug suspension to a subject, and operation of the dose preparation system causes agitation of the drug suspension.

It is therefore not possible to dose administer the drug suspension with the dose delivery device without the drug suspension first being agitated, and thus automatically ensure re-suspension before the volume of the drug suspension enters the subject's body.

In one aspect, the present invention accordingly provides a dose delivery device comprising a variable volume reservoir containing a drug suspension and comprising an outlet, a dose expelling mechanism adapted to be activated to expel a volume of the drug suspension through the outlet, and a dose preparation system comprising a preparation member, the dose preparation system being operable prior to activating the dose expelling mechanism to enable administration of the volume of the drug suspension to a subject. The dose preparation system further comprises an agitation member capable of an agitation relative motion with respect to the variable volume reservoir, the agitation relative motion causing a resuspension agitation of the drug suspension. The stirring member is operatively coupled with the preparing member and configured to undergo the stirring relative motion in response to operation of the preparing member.

Thus, when the user operates the preparation member to prepare for a dosing event, the drug suspension becomes automatically agitated and thus ready for proper and reliable administration. Since the operation of the preparation means is necessary for being able to administer a volume of the drug suspension to a subject, the dose delivery device provides a guarantee that the drug particles have been resuspended once the dose expelling mechanism is activated, so that the user does not need to remember to perform a specific manual resuspension operation. Furthermore, as will be apparent from the following, the operation of the preparation means may be very simple and effortless ergonomically, allowing for reduced strength and dexterity to be used by persons as well.

The agitation 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 location may be a first predetermined location. Similarly, the second position may be a second predetermined position.

In an exemplary embodiment of the invention, the dose expelling mechanism is operatively coupled with the priming member and configured to be automatically activated in response to operation of the priming member when or after the agitation member reaches the second position. For example, the preparation member may comprise a shield member carrying a magnet and being proximally displaceable relative to the variable volume reservoir from an outlet covered position to an outlet exposed position, the agitation member may comprise a magnetic element in the variable volume reservoir, the magnetic element being movable in the variable volume reservoir from a distal position to a proximal position in response to movement of the shield member from the outlet covered position to the outlet exposed position, and the dose expelling mechanism may be spring powered and configured to release in response to the shield member reaching the outlet exposed position.

The agitation member may be movable relative to the variable volume reservoir along, at an angle to (e.g. perpendicular to) and/or about a reference axis, i.e. the movement may be a translational movement, a rotational movement, or a combination of translational and rotational movements, e.g. a helical movement, relative to the reference axis. Alternatively, the agitation 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 perpendicular. In any case, the first and second positions may be respective axial, lateral, and/or angular positions relative to the variable volume reservoir.

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

The configuration of the agitation member may be selected by the manufacturer to create a desired turbulence within the drug suspension during the agitation relative motion with respect to the variable volume reservoir.

The preparation member may be operable prior to activating the dose expelling mechanism to enable expelling a volume of the drug suspension through the outlet. In other words, the dose expelling mechanism may be prevented from expelling a volume of the drug suspension through the outlet before the preparation member is operated. In such a case, the dose delivery device may further comprise a releasable lock switchable from an initial state preventing activation of the dose expelling mechanism to a release state allowing activation of the dose expelling mechanism, wherein the releasable lock is operatively coupled with the priming member and configured to switch from the initial state to the release state in response to operation of the priming member. Thus, the operation of the priming member may comprise removing a physical barrier to movement of one or more parts of the dose expelling mechanism.

Such an arrangement will prevent the user from activating the dose expelling mechanism without prior manipulation of the preparation member, thereby eliminating the risk of the user accidentally activating the dose expelling mechanism (e.g. simply as a result of loosely placing the dose delivery device in a purse or bag, and resulting wastage of medication to the surrounding environment).

The releasable lock may form part of the agitation member, thereby reducing the number of different parts in the dose delivery device.

The dose delivery device may further comprise a housing containing at least a portion of the dose expelling mechanism and defining a reference axis.

The variable volume reservoir may be any type of variable volume container suitable for containing a drug suspension, such as a syringe with a staked needle, a cartridge-type container comprising a generally cylindrical body sealed proximally by a slidable rubber stopper and having a necked distal outlet portion sealable by a pierceable septum, or a bag-type container comprising a deformable body having an integrated outlet portion.

In an exemplary embodiment of the invention, the variable volume reservoir is a deformable reservoir, such as a flexible foil reservoir, and the agitation means comprises a deforming element adapted to deform the flexible foil reservoir, thereby causing a re-suspension agitation of the drug suspension. Whereby the re-suspension can be accomplished without the presence of foreign bodies in the drug suspension. The deformation element may be adapted to sweep and press the outer surface of the flexible foil reservoir to cause re-suspension agitation of the drug suspension, which provides a mechanically simple and ergonomic configuration. Alternatively, the deformation elements may be adapted to press against different areas of the outer surface in a non-swept, predetermined or random sequence, or to rub the outer surface in a rotational motion, for example. In any case, the impact on the outer surface will result in compression of the flexible foil reservoir, which in turn will cause disturbance of the drug suspension.

As used herein, the term "flexible foil reservoir" or simply "foil reservoir" means a container, i.e. a container having one or more flexible surface portions, capable of being deformed by a deforming element to obtain a re-suspension agitation. Thus, if each of its parts is deformable, the "foil reservoir" may be entirely flexible, e.g. like a bag, or if only certain parts thereof are deformable, it may be partly flexible, e.g. like a foil welded or otherwise sealingly attached to a rigid base member. It may comprise an integrated outlet element, such as an injection needle, or it may be adapted to receive a separate outlet element.

The preparation member may comprise a cap removably attached to the housing to cover the outlet, 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 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 with a minimum number of parts.

The agitating member may further comprise second and third deforming elements axially spaced apart from each other and from the deforming elements, and at least two of the deforming elements intersect the reference axis at different angles. The deforming elements intersecting the reference axis at different angles will experience different relative movements with respect to the outer surface of the flexible foil reservoir and this will promote turbulence created in the drug suspension.

Alternatively, the preparation member may comprise a pull tab removably attached to the housing, 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 flexible foil reservoir, the deformation element thereby sweeping and squeezing the outer surface of the flexible foil reservoir.

The agitating member may further comprise a second deforming element arranged laterally spaced apart from the deforming element, and the two deforming elements may intersect the reference axis at different angles, thereby promoting turbulence generated in the drug suspension.

The dose delivery device may further comprise a cap removably attached to the housing to cover the outlet, and the agitation member and the cap may comprise interacting contact members configured to prevent removal of the cap when the pull tab is attached to the housing. Thus, the pull tab needs to be removed, resulting in an automatic re-suspension to expose the outlet, enabling the administration of a dose to the user.

The dose expelling mechanism may comprise an actuator and a compression member adapted to collapse the flexible foil reservoir in response to an axial displacement of the actuator from a first axial position to a second axial position, and the agitation member may be configured to prevent movement of the actuator from the first axial position to the second axial position when the pull tab is attached to the housing. This constitutes an example of the releasable lock described above, in which case the removal of the pull tab forms part of the agitating member, wherein the releasable lock is switched from the initial state to the release state, thereby enabling activation of the actuator.

In other exemplary embodiments of the invention wherein the variable volume reservoir may be a deformable reservoir or a non-flexible reservoir, the agitation member is immersed in the drug suspension and configured to travel within the variable volume reservoir, thereby causing re-suspension agitation of the drug suspension.

In some such embodiments, the variable volume reservoir is a non-flexible reservoir, the agitating member is configured to promote turbulence in the non-flexible reservoir, and the preparing member is integrally or mechanically connected to the agitating member.

For example, the inflexible reservoir may comprise an elastomeric piston having a central bore, and the dose expelling mechanism may comprise a piston rod structure for actuating the piston, wherein the piston rod structure comprises a) a shaft having a front shaft portion configured to extend in a tight connection through the central bore, and b) a drive tube abutting a proximal surface of the piston, and wherein the shaft is adapted to undergo an initial proximal movement relative to the piston and drive tube from a pre-use position to a dose ready position in which the drive tube engages the shaft and subsequently moves distally with the piston and drive tube. In this case, the preparation member may constitute an enlarged proximal end portion of the shaft, which proximal end portion is arranged for user operation, and the stirring member may constitute an enlarged distal end portion of the shaft, which distal end portion is configured to promote a swirling motion of the drug suspension during the initial proximal movement.

Thus, the dose preparing system may form part of the dose expelling mechanism, as the preparing member, agitating member and shaft may be one integral part or two or three mechanically coupled parts, thereby minimizing the number of parts required for automatic re-suspension of the drug suspension.

The non-flexible reservoir may be a syringe having a syringe barrel and a staked needle, thereby eliminating the need for a ready needle handling action.

In other such embodiments, the agitating member is or includes a magnetic element and the preparing member is or includes a magnet capable of affecting the position of the magnetic element in the variable volume reservoir. This enables the development of solutions in which the resuspension agitation of the drug suspension is automated by one or more actions performed by the user as part of the regular use of the device, i.e. obtaining the resuspension without the need for special additional operations to be introduced into the device.

For example, the outlet may comprise an injection needle having a needle end portion configured to be inserted into the skin, the preparation member may comprise a needle shield carrying a magnet and being displaceable proximally relative to the variable volume reservoir from a first shield position in which the needle end portion is covered to a second shield position in which the needle end portion is exposed, and the agitating member, which is or includes a magnetic element, may be moved proximally in the variable volume reservoir from a distal position in response to movement of the needle shield from the first shield position to the second shield position.

Thus, the proximal displacement of the needle shield necessary to expose the needle end portion and allow its insertion into the skin of the user ensures a re-suspension agitation of the drug suspension by causing the agitation member inside the variable volume reservoir to follow the proximal movement of the carried magnet and thereby create turbulence in the drug suspension.

In an auto-injector form of the dose delivery device, the dose expelling mechanism may be spring powered and configured to release and automatically expel a dose in response to the needle shield reaching the second shield position. Thus, the exact same movement that results in the resuspension of the drug suspension also results in the automatic draining of the drug suspension immediately thereafter. This provides an easy to handle dose delivery device from which a dose can be administered by simply placing the needle shield at a desired location on the skin surface and pressing the variable volume reservoir against the skin.

Alternatively, the preparation member may comprise an outlet protection cap which has to be removed from the variable volume reservoir in order to enable the dose to be expelled into the skin. The cap may carry a magnet and may be removable by distal movement relative to the variable volume reservoir, and the agitating member, which is or includes a magnetic element, may be movable in the variable volume reservoir from a proximal position to a distal position in response to the cap being removed.

Thus, the distal displacement of the cap necessary to expose the outlet ensures a re-suspension agitation of the drug suspension by causing the agitation member inside the variable volume reservoir to follow the distal movement of the carried magnet and thereby create turbulence in the drug suspension. After removal of the cap, the dose delivery device may be ready for dose administration.

The agitation member may be shaped to optimize the conditions that create turbulence in the drug suspension. In particular, if the variable volume reservoir is a non-flexible reservoir, the agitating member may have an outer dimension substantially corresponding to an inner dimension of the non-flexible reservoir. For example, if the inflexible reservoir comprises an annular cylindrical reservoir body having a reservoir inner diameter, the agitating member may comprise an annular agitating member body having an agitating member outer diameter slightly smaller than the reservoir inner diameter. In this case, the outer surface portion of the stirring member body may be provided with one or more channels to allow the passage of the drug suspension along the stirring member body. The one or more channels may extend axially or may be inclined relative to a longitudinal axis defined by the reservoir body, the latter inducing a swirling motion of the liquid in the wake of the agitating member.

The stirring member body can further define a central aperture having a stirring member inner diameter that allows liquid to pass therethrough, i.e., reduces resistance.

The stirring member body can be formed of a magnetic material. Alternatively, the stirring member body can comprise a magnetic core covered by a non-magnetic housing (e.g., of plastic).

In a variant of the above, the dose preparing system may comprise a first preparing member in the form of an outlet protection cap carrying a first magnet capable of affecting the position of the magnetic element in the variable volume reservoir and a second preparing member in the form of a needle shield carrying a second magnet capable of affecting the position of the magnetic element in the variable volume reservoir. With an appropriate proportion of the respective magnet strengths, a first resuspension agitation of the drug suspension may be accomplished during removal of the outlet protective cap, and a second resuspension agitation of the drug suspension may then be accomplished during proximal displacement of the needle shield.

As used herein, the term "pharmaceutical suspension" refers to any dosage form containing therapeutically active solid particles dispersed in a liquid medium, wherein the solid particles are large enough to settle. The term applies to such dosage forms even in the state where the particles have settled. In addition, when a first named feature and a second named feature are referred to as being "operably coupled," it means that the two are connected in a manner that performs the specified function, and that a change in the state, position, and/or orientation of one of the features affects the state, position, and/or orientation of the other feature. The term encompasses features that are integrally connected, abutted, assembled or configured to interact at a distance, i.e., the features may be different, but they are integral parts of one piece, or they may be separate components that are mechanically connected or otherwise (e.g., contactlessly, such as by magnetism) influence each other.

For the avoidance of any doubt, in the context the term "injection device" means a device suitable for injecting a fluid medium into a subject, for example by means of an attachable needle device, and the term "medicament" means a medium used in the treatment, prevention or diagnosis of a condition, i.e. including a medium having a therapeutic or metabolic effect in the body. Furthermore, the terms "distal" and "proximal" refer to positions at or along the drug delivery device, the drug reservoir or the needle unit, wherein "distal" refers to the drug outlet end and "proximal" refers to the end opposite the drug outlet end.

In this specification, reference to an aspect or an embodiment (e.g., "an aspect," "a first aspect," "an embodiment," "an example embodiment," etc.) means that a particular feature, structure, or characteristic described in connection with the corresponding aspect or embodiment is included in or inherent to at least this aspect or embodiment of the invention, but is not necessarily included in or inherent to 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 this invention is encompassed by the invention unless otherwise indicated herein or clearly contradicted by context.

The use of any and all examples, or exemplary language (e.g., such as, etc.) herein is intended merely to illuminate the invention and does not pose a limitation on the scope of the invention unless otherwise claimed. Also, no language or phrase in the specification should be construed as indicating any non-claimed element as essential to the practice of the invention.

Drawings

The invention will be further described with reference to the accompanying drawings, in which

Figure 1 is an exploded view of a dose delivery device according to a first exemplary embodiment of the present invention,

figure 2 is a perspective view of the dose delivery device in a pre-use state,

figures 3 and 4 are respective perspective and longitudinal sectional views of the dose delivery device during initial cap removal,

figure 5 is a schematic view of the re-suspension principle employed in a dose delivery device,

figures 6-11 are different views of the dose delivery device in various operational states during dose preparation and dose administration,

figure 12 is an exploded view of a dose delivery device according to a second exemplary embodiment of the present invention,

figure 13 is a perspective view of the dose delivery device in a pre-use state,

figures 14-19 are different views of the dose delivery device of figure 13 in various operational states during dose preparation and dose administration,

Figure 20 is a longitudinal cross-sectional view of a dose delivery device according to a third exemplary embodiment of the present invention,

figures 21 and 22 are longitudinal cross-sectional views of the dose delivery device of figure 20 after dose preparation and dose administration respectively,

figure 23 is an exploded view of a dose delivery device according to a fourth exemplary embodiment of the present invention,

figures 24-27 are different views detailing the various components of the dose delivery device of figure 23,

fig. 28-37 are different perspective views of the dose delivery device of fig. 23 in various operational states during dose preparation and dose administration, wherein a portion of the device has been cut away for clarity,

figures 38 and 39 are respective exploded views of a sub-assembly of a dose delivery device according to a fifth exemplary embodiment of the invention,

figure 40 is a longitudinal cross-sectional view of the subassembly of figure 38,

figures 41-46 are various views of various components of the subassembly,

fig. 47 is a perspective view of the subassembly of the dose delivery device prior to final assembly, portions being cut away or rendered transparent for clarity,

fig. 48-60 are different views of the dose delivery device in various operational states during dose preparation and dose administration, and

fig. 61-64 are close-up views of the dose release mechanism.

In the drawings, like structures are denoted mainly by like reference numerals.

Detailed Description

When/if relative expressions such as "upper" and "lower", "left" and "right", "horizontal" and "vertical", "clockwise" and "counterclockwise" are used hereinafter, these terms refer to the drawings and do not necessarily refer to actual use. The drawings shown are schematic representations, so the construction of the different structures and their relative dimensions are intended for illustration purposes only.

Fig. 1 is an exploded view of a dose delivery device 1 according to a first exemplary embodiment of the invention. The dose delivery device 1 comprises a rigid base member 4 arranged in a housing 2, 3 defined by a top housing 2 and a bottom housing 3. A flexible foil reservoir 10 with integrated injection needle 12 and carrier plate 14 is fixed to the front part 7 of the base member 4 just proximal to the transverse end plate 6. The foil reservoir 10 contains a volume of a drug suspension. A pair of axially extending rails 5 are arranged along opposite sides of the base member 4.

The dose delivery device 1 further comprises a cap 30, to which cap 30 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 member 41 at a first inclination angle, the intermediate rib 44b connects the side member 41 at a second inclination angle, and the proximal rib 44c connects the side member 41 at a third inclination angle, which is the same as the first inclination angle. Each side member 41 has a thinned proximal section 42 carrying a v-shaped hook 43.

The dose delivery device 1 further comprises a dose expelling member 20, the dose expelling member 20 having an elongated body 21, the elongated body 21 having a proximal button 22 and a distal recess 29 adapted to accommodate a two-part rubber press 27, 28. The color marking 21c is positioned on the top surface of the elongated body 21, just distal to the protruding guide member 21p, while two lateral protrusions 23, 24 are arranged axially extending to each other on each side of the elongated body 21 (only one pair is visible). One of the lateral protrusions 23 has an inclined leading face 25 and the other lateral protrusion 24 has an inclined trailing face 26, leaving a v-shaped recess between the two lateral protrusions 23, 24. The protruding guiding member 21c is adapted to provide a linear travel of the dose expelling member 20 into the housing 2, 3, whereas the color marking 21c is arranged to become visible to the user through a window 2w in the top housing 2 when the dose expelling member 20 is fully traveled into the housing 2, 3, thereby visually signaling that a dose administration action has been performed correctly.

Fig. 2 is a perspective view of the dose delivery device 1 in a pre-use state, with the top housing 2 removed for clarity. In this state, the cap 30 is completely mounted on the housing 2, 3, thereby covering and protecting the injection needle 12. It can be seen that the side member 41 is fixedly attached to the inner end wall 31 of the cap 30, for example by gluing or welding, and that the distal rib 44a is positioned proximally of the foil reservoir 10. It can also be seen that the rib structure 40 and the dose expelling member 20 are connected, wherein the hooks 43 (only one visible) are confined between the respective lateral protrusions 23, 24 and the track 5.

The following figures show the dose delivery device 1 in various operating states. In order to prepare for administration of a volume of the drug suspension contained in the foil reservoir 10, the cap 30 must first be pulled off the housing 2, 3 in the direction of the arrow shown in fig. 3. This causes the ribs 44a, 44b, 44c to continuously sweep over the foil reservoir 10, thereby causing a re-suspension agitation movement of the drug suspension and causing the dose expelling member 20 to be pulled into the housing 2, 3 due to the engagement between the hooks 43 and the lateral protrusions 23, 24. During distal displacement of cap 30, sloped trailing face 26 applies a reaction force to hook 43 that has a small non-axial component directed radially outward. However, as long as the hook 43 moves along the track 5, the hook 43 is prevented from disengaging from the recess between the two lateral protrusions 23, 24. In fig. 3, the distal rib 44a has been fully swept through the foil reservoir 10 and the intermediate rib 44b has been swept approximately halfway.

Fig. 4 is a longitudinal cross-sectional view of the dose delivery device 1 in the state shown in fig. 3, showing two parts 27, 28 of a rubber press arranged on each side of the base member 4. When the dose expelling member 20 is pulled distally by the movement of the cap 30, the two parts 27, 28 of the rubber press slide along the base member 4 and approach the foil reservoir 10.

Fig. 5 is a schematic view of the re-suspension principle employed by the dose delivery device 1. The use of a flexible reservoir enables the drug particles to be resuspended in the liquid by applying pressure to the foil and changing the location of the applied pressure to mechanically induce turbulent motion of the liquid. Turbulent motion is preferred for two reasons. Firstly, it ensures better mixing and thus a more uniform concentration, and secondly, it involves higher speeds and thinner boundary layers, which result in the liquid stirring up particles closer to the surface than laminar flow.

By applying pressure to the region and moving the region relative to the foil while continuously applying the pressure, high velocity turbulence is induced in the foil reservoir 10. When pressure is applied to a region, liquid is displaced from the region and moves elsewhere within the foil reservoir 10. Fig. 5 illustrates the principle of an event occurring when the intermediate rib 44b moves in an axial direction on the foil reservoir 10, although for simplicity the intermediate rib 44b is depicted here as having an axis of extension perpendicular to the axis of motion.

In any interaction position, the intermediate rib 44b forms an indentation in the liquid-filled foil reservoir 10. When the intermediate rib 44b moves from the first intermediate position p at the velocity v _i,1 To a second intermediate position p _i,2 At this time, the volume V of liquid represented by the light grey coloration in fig. 5 will be displaced and forced to move below the rib apex due to the pressure build up in front of the intermediate rib 44 b. This volume V can only pass through a small region V below the rib apex, which in this example is about 1/4 of the volume V, as indicated by the dark grey coloration in fig. 5. Thus, the average velocity of the liquid passing under the rib apex is about 4v.

Due to the boundary conditions, the velocity profile of the liquid is parabolic, the velocity at the interface with the rigid carrier plate 14 is 0, and the maximum velocity is significantly higher than four times the velocity of the intermediate rib 44 b. Thus, even moderate rib speeds can create high velocity turbulence of the liquid passing under the rib apex. This high velocity flow enters the liquid present behind the intermediate rib 44b and also causes turbulence in this volume.

Thus, when the cap 30 is removed from the housing 2, 3, the drug suspension is vigorously agitated and thus automatically resuspended by the three ribs 44a, 44b, 44c continuously sweeping across the foil reservoir 10.

In fig. 6, cap 30 has been pulled distally to the point where intermediate rib 44b has completely swept past foil reservoir 10 and proximal rib 44c has just begun to interact with the foil. At the same time, the thinned proximal section 42 of the side member 41 has moved out of contact with the rail 5. At this point, the track 5 no longer resists lateral movement of the thinned proximal section 42, and thus continued pulling of the cap 30 causes the thinned proximal section 42 to flex outwardly in response to a corresponding non-axial reaction force component from the angled trailing surface 26. This is shown in fig. 7. As a result, the hooks 43 are disengaged from the corresponding recesses between the lateral protrusions 23, 24, and the cap 30 is thus disengaged from the dose expelling member 20, as seen in fig. 8. During the final part of the removal movement of the cap 30, the dose expelling member 20 thus remains stationary as the proximal rib 44c sweeps over the foil reservoir 10.

Fig. 9a and 9b show the remainder of the dose delivery device 1 after removal of the cap 30. As can be seen in fig. 9b, the rubber presses 27, 28 are located at the transition portion 8 of the base member 4, where the thickness gradually increases. This gradual increase in thickness provides increased resistance to distal movement of the rubber press 27, 28 along the base member 4 and thus facilitates easy disengagement of the cap 30 from the dose expelling member 20, as any force required to pull the dose expelling member 20 further becomes greater than might be transferred in the interface between the lateral free hook 43 and the recess between the lateral protrusions 23, 24.

However, with the rubber presses 27, 28, it is easy to pass the transition portion 8 when pushed by the elongated body 21. Thus, when the user subsequently inserts the injection needle 12 into the skin and depresses the button 22 towards the housing 2, 3 to perform a dose administration, the rubber squeezer 27, 28 easily overcomes the increased thickness of the base member 4 and continues towards the foil reservoir 10 without requiring too much effort.

The increased thickness of the base member 4 at the front portion 7 causes the rubber presses 27, 28 to become slightly elastically deformed when passing the transition portion 8, which in turn causes the rubber presses 27, 28 to apply a larger compressive force towards the front portion 7 and eventually to the foil reservoir 10 when the dose expelling member 20 is pressed further into the housing 2, 3. Thus, as shown in the different views in fig. 10 and 11, when the dose expelling member 20 is advanced distally into the housing 2, 3, the foil reservoir 10 is firmly compressed and gradually collapses, thereby pressing the drug suspension out through the injection needle 12 and into the user's body.

Fig. 12 is an exploded view of a dose delivery device 100 according to a second exemplary embodiment of the invention. The dose delivery device 100, which may be regarded as a compact variant of the dose delivery device 1 described above, comprises a rigid base member 104 arranged in a housing 102, 103 defined by a top housing 102 and a bottom housing 103. A flexible foil reservoir 110 with integrated injection needles 112 and carrier plate 114 is fixed to the front portion 107 of the base member 104, just proximal to the transverse end plate 106. Foil reservoir 110 contains a volume of a drug suspension. A pair of axially extending rails 105 are disposed along opposite sides of the base member 104.

The dose delivery device 100 further comprises a pull tab 130, to which pull tab 130 a laterally extending rib structure 140 is attached. The rib structure 140 comprises two parallel side members 141 and two ribs 144a, 144b, which side members 141 are adapted to extend through the opening 109 in the top shell 102. 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.

The dose delivery device 100 further comprises a removable cap 150 and a dose expelling member 120, the dose expelling member 120 having an axially extending body 121, the axially extending body 21 having a proximal button 122 and a distal recess 129 adapted to accommodate a two part rubber press 127, 128. The lateral protrusions 123 are arranged on each side of the elongated body 121 (only one is visible). Each transverse projection 123 has an inclined leading face 125. The cap 150 includes a pair of axially extending parallel arms 151, each terminating in an enlarged end section 152 having an inclined proximal face 154 and a straight distal face 153.

Fig. 13 is a perspective view of the dose delivery device 100 in a pre-use state, with the top housing 102 removed for clarity. In this state, the cap 150 is completely mounted on the housing 102, 103, thereby covering and protecting the injection needle 112. The arms 151 extend over the rib structure 140 and the straight distal face 153 of the enlarged end region 152 abuts 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 inclined leading surface 125 of the transverse projection 123 abuts the inclined proximal surface 154 of the enlarged end region 152, and the pre-use state of the dose delivery device 100 is thus effectively a locked state, wherein the presence of the rib structure 140 prevents removal of the cap 150 and activation of the dose expelling member 120.

The following figures illustrate the dose delivery device 100 in various operating states. In order to prepare for administration of a volume of the drug suspension contained in the foil reservoir 110, the pull tab 130 must first be pulled out of the housing 2, 3 in the direction of the arrow as shown in fig. 14 and 15. This causes the ribs 144a, 144b to continuously sweep across the foil reservoir 110, thereby causing a re-suspension agitation movement of the drug suspension in a similar manner as described above with respect to the first exemplary embodiment of the present invention.

Once the pull tab 130 is completely removed, and thus the proximal side 143 no longer resists movement of the enlarged end section 152, the cap 130 may be disengaged from the housing 102, 103 by axial relative movement in the direction of the arrow shown in fig. 16. This exposes the injection needle 112 and the dose delivery device 100 is thus ready for dose administration with the drug suitably resuspended.

Fig. 17a and 17b depict the dose delivery device 100 in a ready state, and it can be seen from fig. 17b that the rubber presses 127, 128 are initially located at the transition portion 108 of the base member 104 where the thickness gradually increases. Thus, as in the case of the previous exemplary embodiment of the present invention, when the user inserts the injection needle 112 into the skin and presses the button 122 towards the housing 102, 103 to perform a dose administration, the rubber press 127, 128 becomes slightly elastically deformed when passing the transition portion 108 and thus an increased compressive force is applied to the front portion 107 and the foil reservoir 110 when the dose expelling member 120 is pressed into the housing 102, 103.

Thus, as shown in the different views in fig. 18 and 19, as the dose expelling member 120 is advanced distally into the housing 102, 103, the foil reservoir 110 is firmly compressed and gradually collapses, thereby pressing the drug suspension out through the injection needle 112 and into the user's body.

Fig. 20 is a longitudinal cross-sectional view of a dose delivery device 200 according to a third exemplary embodiment of the invention. The dose delivery device 200 includes a housing 202 containing a syringe barrel 210. The syringe barrel 210 has a proximal collar 213 in locking engagement with the proximal housing end 203 and a distal outlet end portion 211, to which distal outlet end portion 211 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.

The sealing rubber piston 218 divides the interior of the syringe barrel 210 into two parts: a wet chamber 215 pre-filled with a drug suspension and a dry chamber containing a piston drive tube 220. The piston drive tube 220 has an axially rigid drive tube body 221, the drive tube body 221 having a distal body end 228 that abuts a proximal face of the piston 218. The proximal end region of the drive tube body 221 tapers toward the center of the syringe barrel 210 and terminates at a proximal body end 222.

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

The radial dimensions of the mixing head 240 are 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 close to the outlet end portion 211. Accordingly, push-pull handle 230 is positioned proximate proximal housing end 203. The central shaft 232, including the enlarged shaft section 231, the mixing head 240 and the push-pull handle 230, are provided as one integral component.

In operation, after removing the protective cap 219 from the outlet end portion 211, the user pulls back the central shaft 232 by operating the push-pull handle 230 until the mixing head 240 reaches the piston 218, as shown in fig. 21. Proximal movement of the mixing head 240 relative to the syringe barrel 210 causes an agitating movement (not visible) of the drug suspension around the mixing head 240, which is sufficient to re-suspend any deposited drug particles. When the mixing head 240 reaches the piston 218, the transition 236 passes the proximal body end 222, which proximal body end 222 thus snaps into a smaller diameter position, thereby axially locking the piston 218 and the piston drive tube 220 between the mixing head 240 and the transition 236.

To administer the resuspended drug suspension, the user now pushes push-pull handle 230 distally toward proximal housing end 203, which causes transition 236 to apply an axial driving force to proximal body end 222, which is transmitted to piston 218 through axially rigid drive tube body 221. As the plunger 218 travels through the syringe barrel 210, a volume of the drug suspension is expelled through the needle 212. In fig. 22, the push-pull handle 230 has been fully depressed and the plunger 218 has reached its final, end-of-dose position in the syringe barrel 210.

Fig. 23 is an exploded view of a dose delivery device 300 according to a fourth exemplary embodiment of the 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 includes a cartridge 310, the cartridge 310 having a distal outlet end portion 311 and a pair of diametrically opposed proximal cartridge flanges 316. The cartridge 310 contains a volume of a drug suspension and is sealed proximally by a slidable piston 318 and distally by a penetrable septum 313 adhered to an outlet end portion 311, in which outlet end portion 311 an injection needle 312 is also arranged. The disc 317 is fixedly mounted on the injection needle 312 at a position defining the possible depth of insertion of the injection needle 312 into the skin.

The cartridge assembly 301c further comprises a needle cap 330, the needle cap 330 having a hollow needle cap body 331 adapted to accommodate the injection needle 312 and the cartridge 310. The hollow needle cap body 331 is provided at its proximal end with a pair of diametrically opposed needle cap flanges 332, said flanges 332 being connected by a semicircular overhang 333 adapted to cover and retain a semicircular magnet 334. The magnet 334 is adapted to attract a magnetic mixer element 340 arranged in the interior 315 (see fig. 24a and 24 b) of the cartridge 310. Each of the needle cap flanges 332 has an abutment surface 332s and is provided with a notch 335 on an inner surface portion for rotationally slidably receiving one of the cartridge flanges 316.

The housing assembly 301h includes a three-part outer housing comprised of a central housing portion 302, a proximal housing portion 303, and a distal housing portion 304. The outer housing is so divided as to allow positioning of the internal components. Each housing part has means for fixed attachment to at least one other housing part. Specifically, the proximal housing portion 303 has a plurality of distally extending snap arms 303m, each snap arm 303m adapted to engage one of a corresponding number of receiving recesses 302f in the central housing portion 302, and the central housing portion 302 similarly has a plurality of distally extending snap arms 302m, each snap arm 302m adapted to engage one of a corresponding number of receiving recesses 304f in the distal housing portion 304. Distal housing portion 304 further has a radially inwardly projecting distal rim 304r.

The outer housing houses the lock ring 350, the stator 360, the piston rod 320, the drive spring 370, and the distal spring seat 371. The piston rod 320 has an elongated piston rod body 321, a distal piston rod foot 328 adapted to engage the piston 318, a central plate 322 for supporting a distal spring seat 371, and a proximal stud 323 for interacting with an interior portion of the proximal housing portion 303. Just distal to central plate 322, piston rod 320 is provided with a hanger profile having axially extending arms 326. A button 380 extends proximally from the proximal housing portion 303. The button 380 has a lateral end surface 382 adapted to interact with a finger and an axially protruding stem 383 and is biased in a proximal direction by a button spring 385.

Fig. 24a and 24b are respective perspective and longitudinal sectional views of the cartridge assembly 301c in a pre-use state, showing the cartridge 310 inside the hollow needle cap body 331. In the pre-use state, the cartridge flange 316 is received in the slot 335 and the cartridge 310 is thereby axially fixed relative to the needle cap 330. The position of the magnet 334 in the overhang 333 is such that the magnetic mixer element 340 remains in a proximal position within the cartridge 310, close to the piston 318.

Fig. 25a and 25b are respective perspective and longitudinal sectional views of a magnetic mixer element 340, the magnetic mixer element 340 having an annular plastic body 341 with an outer diameter substantially corresponding to the inner diameter of the cartridge 310, having a central through hole 345 and an iron core 346. A plurality of channels 344 are formed on the outer surface of the plastic body 341. Each channel 344 extends between the proximal mixer end surface 342 and the distal mixer end surface 343 and is inclined with respect to a longitudinal axis defined by the cartridge 310 and the injection needle 312.

Fig. 26a and 26b are different perspective views of the locking ring 350. The lock ring 350 includes a cylindrical lock ring body 351 having an inner surface 352 with two longitudinal rails 353 disposed in the inner surface 352 for slidably receiving the respective needle cap flanges 332. In the proximal portion, the locking ring 350 has a pair of diametrically opposed internal shelves 356 (only one visible) and a pair of diametrically opposed platforms 354, the platforms 354 being provided with diametrically opposed holes 355, the holes 355 being configured for receiving the respective arms 326 to rotationally interlock the hanger profile and the locking ring 350. The interior of the locking ring 350 is also provided with vertical reaction surfaces 357 (only one visible) for interaction with the corresponding abutment surfaces 332 s.

Fig. 27a and 27b are side and perspective views, respectively, of a stator 360, the stator 360 including a stator base 363 supporting two proximally extending curved posts 361, each curved post 361 having a key 362 projecting radially outward along its entire length. The stator 360 further includes a distal lock geometry 364 having two openings 365 (only one visible) for receiving and rotationally securing the respective cartridge flange 316. Two diametrically opposed curved slots 366 are provided in the stator base 363 that allow the passage of the respective arms 326 and thus, together with the circumferential spacing between the curved posts 361, allow for a predetermined angular movement of the hanger profile relative to the stator 360.

The operation of the dose delivery device 300 will be described below with reference to fig. 28-37.

Fig. 28 is a perspective view of the dose delivery device 300 showing the cartridge assembly 301c ready for insertion into the housing assembly 301 h. A portion of the housing assembly 301h has been removed to enable inspection of the internal components. It can be seen that the lock ring 350 and the stator 360 are axially fixed relative to the outer housing between the distal rim 304r and the proximal spring seat 305. Since the key 362 is rotationally locked in the proximal spring seat 305, the stator 360 is further rotationally fixed relative to the outer housing. In addition, 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 pretensioned drive spring 370.

Fig. 29 shows the dose delivery device 300 after an initial step of linearly inserting the cartridge assembly 301c into the housing assembly 301 h. During insertion, the needle cap flanges 332 slide in the respective longitudinal tracks 353 until they encounter axial stops (not shown) in the lock ring 350. When this occurs, the cartridge flange 316 has entered the corresponding opening 365 in the stator 360. In this view, the stator 360 is shown in its entirety, and some of the internal construction of the locking ring 350 is visible, particularly to enable identification of one of the shelves 356.

After having performed a translational relative movement 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 surface 332s to interact with the corresponding reaction surface 357 and as a result the lock ring 350 rotates with the needle cap body 331. Since the stator 360 is rotationally fixed in the outer housing and the cartridge flange 316 is positioned in the opening 365, the cartridge 310 remains stationary relative to the outer housing. Rotation of the locking ring 350 causes angular displacement of the shelf 356, as well as the hanger profile, as the arms 326 are received in the holes 355.

During rotation, the arm 326 travels end-to-end in the curved slot 366, and the circumferential extent of the curved slot 366 thus defines a possible angular displacement of the needle cap body 331 relative to the outer housing. By the time the needle cap body 331 encounters the rotational stop, the shelf 356 has moved to a position just below the cartridge flange 316, and the lock ring 350 thus supports and prevents axial movement of the cartridge 310. This can be seen in fig. 31.

The cartridge 310 is now in place and fixed 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 an axial movement of the overhang 333 relative to the cartridge 310, which results in a distal pull on the magnetic mixer element 340, as the magnet 334 remains in the overhang 333. Thus, the magnetic mixer element 340 moves downward in the interior 315 of the cartridge 310, which forces the liquid in the front of the interior 315 partially through the aperture 345 and partially through the inclined channel 344 through the body 341, thereby creating a high-speed swirling motion of the liquid in the wake of the body 341, as shown by flow line F in fig. 32 and 33.

Thus, when the needle cap body 331 has been fully pulled out of the distal housing part 304, the magnetic mixer element 340 stays at the outlet end part 311 and the drug suspension is in resuspended form and ready for dose administration. In fig. 34, the exposed needle 312 has been inserted through the skin barrier (not shown) and the outlet end portion 311 has been pressed down against the disc 317, whereby the rear of the needle 312 has slid into the interior 315 of the cartridge 310, causing penetration of the septum 313 (not visible).

To perform a dose administration, the user now presses button 380 in the direction of the arrow shown in fig. 35. Downward movement of the push button 380 will eventually cause the stem 383 to engage and radially deflect the flexible fingers 303h, which flexible fingers 303h thus disengage from the studs 323.

As seen in fig. 36, this releases the drive spring 370, which drive spring 370 expands and pushes down on the distal spring seat 371, thereby pushing down on the piston rod 320. As a result, the piston rod foot 328 advances the piston 318 distally in the interior 315 of the cartridge 310 and the resuspended drug suspension is thus expelled through the aperture 345 and the injection needle 312 into the skin.

In fig. 37, the piston 318 abuts the magnetic mixer element 340 and the cartridge 310 is (substantially) emptied. Thus, the user may retract the injection needle 312 from the skin, reinsert the needle cap body 331 into the housing assembly 301h linearly, and remove the used cartridge 310 from the lock ring 350 by rotating the needle cap body 331 opposite the direction of rotation during attachment of the cartridge 310 and pulling the needle cap body 331 with the cartridge 310 therein away from the distal housing portion 304. During proximal movement of the needle cap body 331 relative to the outer housing, the cartridge flange 332 abuts the arm 326 and lifts the piston rod 320 upwardly until the stud 323 encounters and snaps behind the flexible finger 303h, whereby the drive spring 370 reconverts into a ready-to-fire state (re-cocked). The housing assembly 301h is thus ready for use with a new cartridge assembly.

Fig. 38 is an exploded view of a cartridge assembly 401c forming part of a dose delivery device 400 (see fig. 47) according to a fifth exemplary embodiment of the invention. Cartridge assembly 401c includes a cartridge 410 extending along a reference axis and having a distal outlet portion 411. The cartridge 410 contains a volume of a drug suspension (not visible) and a magnetic mixer element 440, similar to the magnetic mixer element 340 described above with respect to the fourth exemplary embodiment of the invention.

The cartridge 410 is sealed proximally by a slidable piston 418 and distally by a penetrable septum 413, the penetrable septum 413 being arranged around the rear of the injection needle 412 and fixed to the outlet portion 411. The penetrable septum 413 may, for example, include an elastomeric needle coating applied directly to the needle 412 such that an initial adhesion is provided between the elastomeric needle coating and the needle 412 that is irreversibly broken by a relative axial displacement therebetween. The disc 417 is fixedly mounted on the needle 412 at a position defining the possible depth of insertion of the needle 412 into the skin. The cartridge 410 is provided with a flange 416 at its proximal end.

The cartridge assembly 401c further comprises a three-part inner housing consisting of a central inner housing part 492, a proximal inner housing part 493 snap-fitted to a proximal end part of the central inner housing part 492, and a distal inner housing part 494 snap-fitted to a distal end part of the central inner housing part 492. The proximal inner housing portion 493 has a pair of diametrically opposed proximal projections 493p (only one is visible in fig. 38), while the central inner housing portion 492 has a pair of diametrically opposed central projections 492p. The distal inner housing part 494 has a receiving section 494r at its distal end, which receiving section 494r is configured to receive and retain the flange 416, whereby the cartridge 410 is axially fixed relative to the inner housing.

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.

The cartridge 410 and inner housing are disposed within a shield member 430, the shield member 430 including 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 inner rails 431t (one visible in fig. 50) along the inner surface portion that are configured to slidingly engage the central protrusion 492p on the central inner housing portion 492. The distal needle shield portion 436 has a transverse end wall 437 with an opening 439 in which opening 439 a penetrable shield seal 438 is disposed. The shield member 430 is biased by a shield spring 435 and carries a semicircular magnet 434, which semicircular magnet 434 is held in a magnet holder 433 disposed at the distal end of the shield body 431.

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

Fig. 40 is a longitudinal cross-sectional view of cartridge assembly 401c showing the relative positions of the component parts in a pre-use condition and further detailing the structural features of some of these parts. As can be seen, each proximally extending arm 432 of the shield member 430 is provided with an angled proximal end 432i. In addition, the piston rod 420 has a distal piston rod foot 428 adapted to abut a proximal surface of the piston 418 and act as a distal base for the drive spring 470, and a pair of radial projections 425, said radial projections 425 abutting the proximal side of the central barrier 492c inside the central inner housing portion 492 in a pre-use state. The distal side of the central barrier 492c acts as a proximal seat for the drive spring 470 and thus, in this state of the cartridge assembly 401c, the drive spring 470 is pre-tensioned and safely in a cocked state (cocked) because the piston rod 428 cannot move distally relative to the inner housing. It should be noted that the magnetic mixer element 440 is initially located distally in the cartridge interior 415, partially surrounded by the semicircular magnet 434 in the magnet holder 433.

Fig. 41 is a perspective view of a piston rod 420, which piston rod 420 comprises, in addition to a piston rod foot 428 and a radial projection 425, an annular cylindrical main piston rod body 421 and a proximal end piece 423 having a rectangular cross-section.

Fig. 42a is a longitudinal cross-sectional view of a central inner housing portion 492 comprising a cylindrical wall 492w, a pair of proximal snap arms 492s for interlocking engagement with a proximal inner housing portion 493, and a pair of distal notches 492i for interlocking engagement with a distal inner housing portion 494. The central barrier 492c has a keyhole 492k therethrough and is connected to the cylindrical wall 492w by an annular bridge segment 492 b. The keyhole 492k has a configuration similar to but slightly larger than the cross-section of the main piston rod body 421 with the radial projection 425, and the central barrier 492c thus allows the radial projection 425 to pass only at a specific angular orientation of the piston rod 420 relative to the central inner housing portion 492. The configuration of the keyhole 492k can be seen in fig. 42b, which is a top view of the central inner housing portion 492.

Fig. 43 is a perspective view of a rotor 495 having an annular cylindrical outer wall 496, the outer wall 496 being shown transparent for clarity to visualize the interior profile (depicted in phantom). Rotor 495 is formed with an internal tower 497 adapted to receive a proximal portion of piston rod 420. Thus, the tower 497 defines a narrow space shaped substantially like the proximal portion of the piston rod 420. In particular, tower 497 includes a proximal portion having an opening 499, which opening 499 is rectangular in cross-section and cooperates with proximal member 423 to provide a rotationally interlocking but axially free connection between piston rod 420 and 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 °.

Fig. 44 is a perspective view of a dose release button 480, the dose release button 480 comprising a cylindrical body 483 having two legs 484 (each leg 484 having an inclined distal surface 484 i), a proximal collar portion 481 and a slightly concave top surface 482. The collar portion 481 is provided with three circumferentially equally spaced engraving portions 489 (only one visible), said engraving portions 489 being configured to slidingly engage with mating protrusions on the inner surface of the top housing portion 403 to rotationally lock the dose release button 480 with respect to the top housing portion 403 and the main housing portion 402.

Fig. 45 is a perspective view of a base member 450, the base member 450 including a base member body 451 having a through hole 455, a base member flange 452 (provided with four circumferentially spaced notches 453, the notches 453 being configured to engage with protrusions on an inner surface of the main housing portion 402), a stud 456 defining an initial angular position of the lock member 460 relative to the base member 450, and two diametrically opposed slots 454 configured to allow sliding receipt of the proximally extending arms 432, whereby the base member 450 and the shield member 430 are rotationally interlocked, but allowed to undergo relative axial movement.

Fig. 46a and 46b are perspective and top views, respectively, of a lock member 460, the lock member 460 including a lock member body 461 and a proximal lock member flange 462. The lock member flange 462 has two diametrically opposed radial projections 463, each radial projection 463 having an angled edge portion 464 configured to interact with one of the angled proximal ends 432i of the proximally extending arms 432 and a distal surface portion 466 for abutment with the base member flange 452.

The distal end of the lock member body 461 is provided with two inwardly projecting lugs 468, the lugs 468 being spaced apart to form diametrically opposed gaps 469 therebetween. When the lock member 460 and the dose release button 480 are in a particular relative angular position, the gap 469 allows the legs 484 to pass.

In the housing assembly 401h, the lock member body 461 extends through the aperture 455 and the distal surface portion 466 rests on the proximal face of the base member flange 452. Thus, the lock member 460 is axially constrained within the main housing portion 402, but is able to rotate relative to the main housing portion 402. The lock spring 465 is a torsion spring that biases one of the radial projections 463 into abutment with the stud 456.

The assembly and use of the dose delivery device 400 will be described below with reference to fig. 47-64.

Fig. 47 is a perspective view of the dose delivery device 400 prior to attachment of the cartridge assembly 401c to the housing assembly 401 h. A portion of the main housing portion 402 has been cut away for clarity, and a portion of the base member body 451, as well as the entire shield member 430, is shown as transparent.

To assemble the dose delivery device 400, the cartridge assembly 401c is first moved linearly in the proximal direction as indicated by the arrow in fig. 48 until the proximal protrusion 493p reaches the end of the inlet section of the bayonet track 459. Thereafter, shield member 430 is rotated counter-clockwise relative to main housing portion 402 to allow proximal protrusion 493p to travel to the end of bayonet track 459, thereby axially locking inner housing and cartridge 410 relative to base member 450 and main housing portion 402. This is shown in fig. 49.

As shown in fig. 50, further counterclockwise rotation of shield member 430 relative to main housing portion 402 now causes relative angular displacement between shield body 431 and the inner housing because proximal inner housing portion 493 is prevented from further counterclockwise rotation relative to base member 450 due to the position of proximal protrusion 493p at the end of bayonet track 459. As a result, the central protrusion 492p is forced to travel the corresponding circumferential track portion of the inner track 431t and align with the connected axial track portion such that the shield member 430 is axially displaceable relative to the inner housing. The dose delivery device 400 is now in the unlocked state ready for an injection action.

Fig. 51-54 show a further simplified form of a dose delivery device 400, in which some elements have been removed and some elements become transparent (some contours are shown in dashed lines) to enable visualization of events occurring inside the cartridge 410. Thus, the state of the dose delivery device 400 shown in fig. 51 corresponds to the state shown in fig. 50. Thus, in the unlocked state of the dose delivery device 400, the magnetic mixer element 440 is positioned in the distal portion of the cartridge 410 axially opposite the piston 418, and the disc 417 is axially spaced from the outlet portion 411.

To insert the injection needle 412, the user places the transverse end wall 437 in a desired position on the skin and presses the main housing portion 402 against the body. As shown in fig. 52, when the shield member 430 is thus displaced proximally relative to the main housing portion 402, this causes the forward tip 412t of the needle 412 to pierce the shield seal 438. Moreover, due to the proximal displacement of shield member 430 with respect to main housing portion 402, magnet 434 is moved proximally with respect to cartridge 410, thereby forcing magnetic mixer element 440 to slide upwards in cartridge interior 415, thereby creating a swirling motion of the drug suspension in its wake, as indicated by flow line F.

As the main housing portion 402 gets closer to the user's body and the shield member 430 is thereby pressed further proximally into the main housing portion 402, the injection needle 412 is inserted deeper into the skin until, as shown in fig. 53, the transverse end wall 437 with the shield seal 438 reaches the disc 417 and the magnetic mixer element 440 moves further upwards in the cartridge interior 415, agitating more drug suspension.

When the transverse end wall 437 has reached the disc 417, further movement of the main housing part 402 towards the body causes a relative converging movement between the cartridge 410 and the disc 417 as the outlet part 411 is forced into contact with the disc 417. During this converging movement, the initial adhesion between the penetrable septum 413 fixed to the outlet portion 411 and the injection needle 412 on which the disc 417 is fixedly mounted breaks and the rear tip 412r of the injection needle 412 thus pierces the penetrable septum 413 when the injection needle 412 slides a small distance into the cartridge interior 415. This can be seen in fig. 54.

The shield member 430 is now fully pressed into the main housing portion 402, the magnetic mixer element 440 has traveled the entire cartridge interior 415 and reached the piston 418, thereby ensuring a complete re-suspension of the drug suspension and establishing fluid communication between the cartridge interior 415 and the injection needle 412 partially residing in the user.

The change of state of the dose delivery device 400 described in connection with fig. 51-54 also includes many other notable component movements. Fig. 55 and 56 show a dose delivery device 400 having an opaque inner housing to allow description of events occurring in layers outside of a cartridge 410. The state of the dose delivery device 400 shown in fig. 55 corresponds to the state shown in fig. 52, whereas the state of the dose delivery device 400 shown in fig. 56 corresponds to the state shown in fig. 54.

Thus, in fig. 55, shield member 430 has been moved slightly proximally relative to main housing portion 402, allowing forward tip 412t to pierce shield seal 438 (not visible in fig. 55). At this point, the disc 417 is still axially spaced from the outlet portion 411. Because the central projection 492p is guided in the axial track portion of the inner track 431t, axial movement of the shield member 430 is possible. When the shield body 431 is thus translated proximally relative to the base member 450, the proximally extending arms 432 extend through slots 454 in the base member flange 452. Proximal to the base member flange 452, the ramped proximal end 432i engages the radial protrusion 463 and as the proximally extending arms 432 continue to move proximally, the engagement causes the ramped edge portion 464 to slide along the ramped proximal end 432i, thereby causing the lock member 460 to rotate about the central axis of the main housing portion 402. The lock member 460 continues to rotate until the central projection 492p reaches the corresponding end of the axial rail portion of the inner rail 431t, as seen in fig. 56. This is the point when the shield member 430 is fully pressed into the main housing portion 402.

Fig. 57 and 58 show a dose delivery device 400 without an inner housing but with a transparent outer wall 496 of a rotor 495 and a transparent lock member 460 to allow movement of components in another layer describing the configuration. The state of the dose delivery device 400 shown in fig. 57 corresponds to the state shown in fig. 52 and 55, whereas the state of the dose delivery device 400 shown in fig. 58 corresponds to the state shown in fig. 54 and 56.

Fig. 57 shows that the legs 484 initially rest on the lugs 468 of the lock member 460 and thereby prevent distal movement of the dose release button 480 relative to the main housing portion 402. However, the above-described proximal displacement of shield member 430, which causes rotation of lock member 460, causes lock member 460 to eventually occupy an angular position relative to dose release button 480, where gap 469 is aligned with leg 484. At this particular relative angular position shown in fig. 58, the dose release button 480 is no longer prevented from moving distally relative to the main housing portion 402 and thus the injection mechanism is now enabled to activate.

When the injection needle 412 is safely inserted into the skin, the user presses the top surface 482 towards the top housing portion 403 to perform an injection. As shown in fig. 59, this first causes the sloped distal surface 484i of the leg 484 to move through the gap 469 and into sliding abutment with the helical ramp 498. As the dose release button 480 is pressed further into the main housing portion 402, the legs 484 ride along the ramps 498, causing the rotor 495 to rotate about the central axis. As best seen in fig. 60, rotor 495 is thus rotated clockwise (when viewed from a proximal perspective) about the central axis.

Due to the mating connection between opening 499 and proximal member 423, rotation of rotor 495 results in similar rotation of piston rod 420. Fig. 61-63 illustrate the resulting angular displacement of piston rod 420 as leg 484 travels down ramp 498 (shown in phantom). Initially (fig. 61), the main piston rod body 421 is oriented such that the radial projections 425 rest against the central barrier 492c, thereby securing the piston rod 420, and finally (fig. 63), the main piston rod body 421 is rotated 90 ° clockwise relative to the central inner housing portion 492, thereby causing the radial projections 425 to become properly aligned with the key holes 492 k.

When the radial projections 425 and the key holes 492k are so aligned, the drive spring 470 is allowed to expand and the energy released by the expansion of the drive spring 470 will push the piston rod 420 downward through the tower 497, thereby pushing the piston 418 and the magnetic mixing element 440 distally in the cartridge interior 415 towards the outlet portion 411 to expel a predetermined dose of resuspended drug suspension through the injection needle 412. This is shown in fig. 64.

Claims (15)

1. A dose delivery device (1, 100, 200, 300, 400) comprising:

a variable volume reservoir (10, 110, 210, 310, 410) containing a drug suspension and comprising an outlet (12, 112, 212, 312, 412),

A dose expelling mechanism adapted to be activated to expel a dose of a substance through said outlet (12, 112, 212,

312 412) draining a volume of said drug suspension, and

a dose preparing system comprising a preparing member (30, 130, 230, 330, 430),

the dose preparation system is operable prior to activating said dose expelling mechanism to enable administration of said volume of said pharmaceutical suspension to a subject,

wherein the dose preparation system further comprises an agitation member (40, 140, 240, 340, 440) capable of an agitation relative movement with respect to the variable volume reservoir (10, 110, 210, 310, 410), the agitation relative movement causing a resuspension agitation of the drug suspension, and

wherein the stirring member (40, 140, 240, 340, 440) is operatively coupled with the preparing member (30, 130, 230, 330, 430) and configured to undergo the stirring relative movement in response to operation of the preparing member (30, 130, 230, 330, 430).

2. The dose delivery device of claim 1, wherein the agitation relative movement comprises movement of the agitation 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. The dose delivery device of claim 1 or 2, further comprising a releasable lock (143, 460), the releasable lock (143, 460) being switchable from an initial state preventing activation of the dose expelling mechanism to a release state allowing activation of the dose expelling mechanism, the releasable lock (143, 460) being operatively coupled with the priming member (130, 430) and being configured to switch from the initial state to the release state in response to operation of the priming member (130, 430).

4. A dose delivery device according to any of claims 1-3, wherein the variable volume reservoir (10, 110) is a flexible foil reservoir, and

wherein the agitation member (40, 140) comprises a deforming element (44 a,144 a), the deforming element (44 a,144 a) being adapted to deform the flexible foil reservoir thereby causing a re-suspension agitation of the drug suspension.

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

6. The dose delivery device of claim 5, further comprising a housing (2, 3) containing at least a portion of the dose expelling mechanism and defining a reference axis,

Wherein the preparation member (30) comprises a cap removably attached to the housing (2, 3) to cover the outlet (12),

wherein the deformation element (44 a) is attached to or forms part of the cap, and

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 (44 a) thereby sweeping and squeezing the outer surface of the flexible foil reservoir.

7. The dose delivery device of claim 6, wherein the agitation member (40) further comprises a second deformation element (44 b) and a third deformation element (44 c) arranged axially spaced apart from each other and from the deformation element (44 a), and

wherein at least two of the deformation elements (44 a,44b,44 c) intersect the reference axis at different angles.

8. The dose delivery device of claim 5, further comprising a housing (102, 103) containing at least a portion of the dose expelling mechanism and defining a reference axis,

wherein the preparation member (130) comprises a pull tab removably attached to the housing (102, 103),

wherein the deformation element (144 a) is attached to or forms part of the pull tab, and

Wherein the pull tab is adapted to be removed by a relative lateral movement with respect to the housing (102, 103) and the flexible foil reservoir, whereby the deformation element (144 a) sweeps and presses the outer surface of the flexible foil reservoir.

9. The dose delivery device of claim 8, wherein the agitation member (140) further comprises a second deforming element (144 b) arranged laterally spaced apart from the deforming element (144 a), and

wherein the two deformation elements (144 a,144 b) intersect the reference axis at different angles.

10. The dose delivery device of claim 8 or 9, further comprising a cap (150) removably attached to the housing (102, 103) to cover the outlet (112),

wherein the stirring member (140) and the cap (150) comprise interacting contact members (143, 152), the contact members (143, 152) being configured to prevent removal of the cap (150) when the pull tab is attached to the housing (102, 103).

11. The dose delivery device of any of claims 8-10, wherein the dose expelling mechanism comprises an actuator (120) and a compression member (127, 128), the compression member (127, 128) being adapted to collapse the flexible foil reservoir in response to an axial displacement of the actuator (120) relative to the housing (102, 103) from a first axial position to a second axial position, and

Wherein the stirring member (140) is configured to prevent movement of the actuator (120) from the first axial position to the second axial position when the pull tab is attached to the housing (102, 103).

12. A dose delivery device according to any of claims 1-3, wherein the agitation member (340, 440) is immersed in the drug suspension and is or comprises a magnetic element, and the preparation member (330, 430) is or comprises a magnet capable of affecting the position of the magnetic element.

13. The dose delivery device of claim 12, wherein the preparation member (330) comprises an outlet protection cap carrying the magnet and being removable by distal movement relative to the variable volume reservoir (310), and

wherein the agitating member (340) that is or includes a magnetic element is adapted to move from a proximal position to a distal position in the variable volume reservoir (310) in response to the cap being removed.

14. The dose delivery device of claim 12, wherein the outlet (412) comprises an injection needle having a needle end portion (412 t) configured to be inserted into the skin,

wherein the preparation member (430) comprises a needle shield carrying the magnet and being proximally displaceable relative to the variable volume reservoir (410) from a first shield position in which the needle end portion (412 t) is covered to a second shield position in which the needle end portion (412 t) is exposed, and

Wherein the agitating member (440) that is or includes a magnetic element is adapted to move from a distal position to a proximal position in the variable volume reservoir (410) in response to movement of the needle shield from the first shield position to the second shield position.

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