WO2013153121A2

WO2013153121A2 - Medical injection device with time delay indicator

Info

Publication number: WO2013153121A2
Application number: PCT/EP2013/057501
Authority: WO
Inventors: Christian Peter ENGGARD; Michael Frank PETERSEN; Mads Grønlund ANDERSEN; Ebbe Kiilerich; Sarah Nete BACK
Original assignee: Novo Nordisk A/S
Priority date: 2012-04-10
Filing date: 2013-04-10
Publication date: 2013-10-17
Also published as: WO2013153121A3

Abstract

The present invention relates to an indicating device (100) for use with medical injection devices for administering a drug into the body of a subject user wherein the indicating device is configured for indicating after administration that a dose of the drug actually has been administered and for maintaining this indication until lapse of a pre-defined time interval. The time delay indicator (120) disclosed may be based on a mechanical time delay device and includes a visual indicator that is controlled by the mechanical time delay device for signalling the status of the device during lapse of the pre-defined time interval. The injection device (100) includes a force absorbing structure (110, 111, 130, 140, 150) adapted to absorb activation forces exerted on an activation member (110, 111) and exceeding a pre-defined magnitude from being transferred to the time delay indicator (120).

Description

MEDICAL INJECTION DEVICE WITH TIME DELAY INDICATOR

FIELD OF THE INVENTION

The present invention relates to medical injection devices for administering a drug into the body of a subject user that incorporate an indicating device configured for visually indicating after administration that a dose of the drug actually has been administered and for maintaining this indication until lapse of a pre-defined time interval.

BACKGROUND OF THE INVENTION

Some medication, such as insulin, is typically self-administered using a medical delivery device such as an injection pen. The typical diabetes patient will require injections of insulin several times during the course of a week or a day. However, typical injection devices, such as the one disclosed in WO 2006/076921 , do not address the problem of a user not remembering when the last injection was administered.

Even shortly after administering a dose of insulin, the user now and then will be in doubt as to whether or not an injection has actually been carried out. This could be minutes or even hours after the intended time for performing an administration. Thus, there exist the potential risk that the patient chooses not to take his medication or that he takes it twice.

Some prior art devices, such as the electronic syringe disclosed in WO 97/30742, are provided with an electronic monitoring system adapted to automatically start an electronic timer when a selected dose is injected and to show the progress in time on an electronic display. Such an injection device generally provides a satisfactorily solution to the problem addressed above. However, for simpler devices such as disposable injection devices, i.e. the so-called pre-filled devices, the solution with integrated electronics will in most cases not be economically viable. In addition, such a solution may not be environmentally acceptable due to the potential increase in the disposal of electronic components such as batteries etc. WO 2010/127995 and WO 2010/023303 include disclosure of medical injection devices that incorporate lapsed time indicators of a type that makes them suitable to be used as pre-filled devices. The particular embodiment shown in fig. 2 of WO 2010/023303 relates to a type of lapsed time indicator that makes use of a mechanical time delay device. A spring is tensed as part of the initial injection procedure. The spring is utilized to operate the mechanical time delay device during lapse of the pre-defined time interval. In such a design it is a challenge to ensure optimal operation both during injection and during lapse of the pre-defined time interval to provide time indication signals that fully reflects the history of use of the device.

WO 201 1/123515 discloses a reversible timer system that includes a fluid disposed within a cavity defined by first and second substrates where the fluid spreads from an equilibrium state to an active state upon application of a force to the system and wherein the fluid contracts upon relief of said force. Further related timer devices are disclosed in WO 201 1/050128.

When designing devices utilizing such a timer system it is a challenge to make the system robust and to make it work in a consistent way regardless of the way the device is being operated or handled by the user. Example scenarios include situations where activation of the timer system occurs by applying an excessive force where the applied force exceeds the force that the device is designed to withstand. Further challenges relate to activation of the timer system where forces are applied along directions that are different than the intended one.

BRIEF DESCRIPTION OF THE INVENTION

Having regard to the above-identified prior art, it is an object of the present invention to provide a timer device solution for medical injection devices which provides a time delay indicator having a visual indication output for signalling the occurrence of a performed injection within lapse of a pre-defined time interval, wherein the status indication of the time delay indicator is less ambiguous. A further object is to provide a timer device solution that, no matter how the injection device is handled by the user, consistently and correctly signals the history of use of the injection device. A still further object is to provide a timer device solution that is more robust than prior art solutions. In a first aspect the present invention relates to a medical injection device for dispensing a dose of a drug from a held drug container. The injection device defines: a) a base, b) an activation member which is movable relative to the base in a first direction from a non- activated position to an activated position to activate dose dispensing, c) a delivery mechanism comprising a dispense control member configured for movement relative to the activation member, the dispense control member being operated by the activation member so that when the activation member moves from the non-activated position to the activated position the dispense control member moves relative to the base from a first position to a second position to cause the delivery mechanism to dispense a dose of drug from the container, d) biasing means acting on the dispense control member for urging the dispense control member towards the first position, and e) a time delay indicator that is coupled between the activation member and the dispense control member, the time delay indicator being configured to provide a first visual indication prior to activation of the activation member, to provide a second visual indication in response to activation of the activation member, and to provide a third visual indication after lapse of a pre-defined time interval subsequent to activation of the activation member.

The device is so configured that when the activation member assumes its activated position, the biasing means exerts a predetermined force on the dispense control member.

Hereby it is ensured that a well-defined activation force is applied on the time delay indicator such that the time delay indicator is deployed in correct correspondence with the true state of the device. Also, in this way it is ensured that the time delay indicator is not damaged even if excessive forces are applied onto the activation member. Excessive forces may be redirected into robust parts of the injection device such as redirected into the housing part of the injection device or to components that are axially fixed with respect to the housing. Also by the above provisions it is ensured that the activation of the time delay indicator is accompanied by a correctly activated dose expelling operation whereas when the activation member has only been manipulated to an extent where no dose expelling operation will be initiated, the time delay indicator correctly reflects this condition.

Implementing the time delay indicator in a device in a configuration where forces applied on the time delay indicator are controlled and limited, the risk of having the time delay device emitting a false signal indication will be reduced. Defining threshold forces for minimum force activation as well as maximum force will make the indication provided by the time delay indicator less ambiguous. The dispense control member may be configured to be operated by movements of the activation member via the time delay indicator. Hence, when a user manipulates the activation member by exerting a force resulting in a movement of the activation member the time delay indicator transfers a force to the dispense control member to make the latter move.

The activation member may define a first surface portion so that, when an externally applied force on the activation member acting in the first direction has caused the activation member to assume its activated position, an increase in the externally applied force is redirected to a surface of the base but not redirected to the time delay indicator. Hence, should excessive forces be applied by the user of the device, the housing will take up forces exceeding the force required for correctly operating the time delay indicator.

In some embodiments the activation member is configured for limited travel relative to the base from the non-activated position to the activated position defining an activation member travel length 'B'. When the activation member moves from the non-activated position to the activated position, the time delay indicator is operated by the activation member moving a distance 'At' relative to the dispense control member. When the activation member assumes its non-activated position, the dispense control member is positioned relative to the base with a clearance of magnitude 'Α', where the clearance 'A' is greater or equal to the activation member stroke length 'B' minus the distance 'At', i.e.

A≥ B - At.

In this way it is ensured that the dispense control member will not get into abutment with the base even if excessive forces are applied on the activation member.

In one embodiment the movements of the activation member and the dispense control member may be linear movements that occur along an axis of the device. In embodiments provided as a pen-shaped device for example, the activation member, such as an injection button, may be forced to move along a central longitudinal axis of the device when an external force is applied on the injection button. The time delay indicator transfers at least part of the applied force as a force acting on the dispense control member for effectuating axial movement of the latter. In other embodiments involving rotationally mounted members provided by the activation member and the dispense control member the said movements occur as angular movements where the time delay indicator transfers a torque from the activation member to the dispense control member.

The biasing means may be provided as a spring device comprising a single or a plurality of spring elements, such as one or more compression springs, foam elements, a compressed gas spring or the like. The biasing means may be configured to exert a force on the dispense control member generally along a direction opposite to the first direction.

The biasing means may be pre-tensioned to provide a well-defined limit for activating the time delay indicator, i.e. to make the time delay indicator shift from the first visual indication to the second visual indication, so that the risk of activating the time delay indicator without activating the dose dispensing procedure is minimized.

In some embodiments, the device is configured so that the activation force needed to activate the time delay indicator is selected so that the activation of the time delay indicator does not occur merely by the weight of the device itself. For instance, if the device is arranged to be supported only on the activation member, no false activation of the time delay indicator is likely to occur.

In some embodiments the time delay indicator may comprise a mechanical time delay device which is started upon activation of the device, i.e. initialized by movement of the activation member/ the dispense control member, and which operates until lapse of said pre- defined time interval, the visual states, i.e. the visual indication of the time delay indicator, being controlled by the mechanical time delay device. For certain embodiments described in the context of the present disclosure, initializing a mechanical time delay device upon activation of the dispense control member shall mean the procedure of releasing external pressure from the activation member subsequent to activating the activation member. In other embodiments the initial activation of the activation member, such as by pressing down an injection button, defines the start of the mechanical time delay device.

The second visual indication may be a state that is perceived visually different than the first visual indication so as to be readily differentiated from the first visual indication. Also the third visual indication may be a state that is readily discernable from the second visual indication. In certain embodiments the third visual indication corresponds to the first visual indication. In such embodiments the time delay indicator may define a reversible indicator that may be reactivated a number of times.

Typically, the time delay indicator will be a non-electrical time delay indicator. A nonelectrical time delay indicator may be characterized in that the state change during lapse of the pre-defined time interval does not involve electrical parameters. Rather, the mechanical energy applied when a user exerts a force to activate the activation member is used to bring the time delay indicator from the first visual indication to the second visual indication. The state change from the second visual indication to the third visual indication may take place by means of mechanical energy accumulated during activation of the activation member, i.e. when the time delay indicator is changed from the first indication state to the second visual indication.

In certain embodiments the time delay indicator comprises a fluid type mechanical time delay device comprising at least one fluid reversibly flowable between a first configuration and a second configuration wherein the first configuration defines said first visual indication and the second configuration defines said second visual indication of the time delay indicator.

One embodiment includes a reversible timer system such as described in WO 201 1/123515. The mechanical time delay indicator may comprise a first substrate associated with the activation member and a second substrate associated with the dispense control member, wherein the first substrate and the second substrate are spaced apart to define a cavity, and wherein a first fluid is arranged in the cavity, the first fluid being configured to change from the first configuration and into the second configuration by moving at least a part of the first substrate relative to at least a part of the second substrate.

The first fluid may maintain an equilibrium state when in its first configuration and may be adapted to enter into an activated state when in its second configuration, i.e. when the activation member is in the activated position. When the activation member is moved away from the activated position back towards the inactivated position, the first and the second substrate are allowed to return to an initial state which allows the fluid slowly to flow towards its first configuration, during which time interval the time delay indicator provides a visual indication of the recent performed activation of the device. Each of the first substrate and the second substrate may be arranged transverse to said axis. Also, the first fluid may be located at a central location relative to the axis when the first fluid is in its equilibrium state. The first fluid may be adapted to spread radially outwards relative to the central location when the time delay indicator is in the activated state whereas the first fluid contracts to a central location when the fluid re-enters its equilibrium state. In some embodiments, the fluid type mechanical time delay device comprises one or more additional fluids.

The first and/or the second substrate may be provided as a transparent material offering a view to the fluid, the colour of which may be selected to provide a readily perceivable impression of whether the fluid is in the first configuration or the second configuration.

The activation member and the dispense control member may be configured for exerting a force on the respective ones of the first substrate and the second substrate mainly at a central location relative to the axis whereas peripheral portions of the first and second substrate are unsupported by the activation member and the dispense control member, respectively.

The assembly of the first substrate and the second substrate may be formed as a disc having a circular shape when looked in a direction along an axis transverse to the substrates.

In some embodiments, the first substrate is defined by the activation member such as being formed unitarily therewith, Also the second substrate may be defined by the dispense control member.

In some embodiments, the first substrate and the second substrate may each define peripheral portions. In such embodiments, the activation member and the dispense control member may be so configured that the peripheral portions of the first substrate and the second substrate are substantially unsupported in directions parallel to the axis. In this way it is ensured that activation forces that are not perfectly aligned with the axis will not incorrectly activate the time delay indicator.

In accordance with the first aspect, the time delay indicator as claimed herein may be provided only by a fluid where the activation member and the dispense control member cooperates with the fluid to provide a time delay indicator similar to the two substrate fluid timer device as described above, i.e. the activation member and the dispense control member additionally functions as the two substrates that define the cavity that contain the fluid.

In some embodiments, the base may define a housing which at least partly accommodates the delivery mechanism.

Alternatively, in some embodiments the injection device comprises a housing and wherein the base defines a component that is movable relative the housing but where the position of the base relative to the housing is axially fixed. In one embodiment, the base defines a rotatable dose setting member. Still alternatively, in some embodiments the base defines a component that is arranged to move relative to a housing of the device along a helical path. For example, the device may be so configured that a threaded connection defines the movements of the base relative to the housing. In such an embodiment, when an externally applied force on the activation member acting in the first direction has caused the activation member to assume its activated position, an increase in the externally applied force is redirected via the base and further via the thread to the housing. Forces exceeding the force needed to move the activation member into its activated position will not be exerted onto the time delay indicator.

In the above embodiments, the reference to the activated and non-activated positions of the activation member refers to the position of the activation member relative to the base. In particular embodiments, the pre-defined time interval is longer than 30 minutes, such as longer than 1 hour, such as longer than 2 hours, such as longer than 3 hours, such as longer than 5 hours, such as longer than 12 hours, such as longer than 24 hours, such as longer than 36 hours.

The mechanical time delay device may be configured so as to re-initialize the timing function if a renewed activation of the activation member occurs during lapse of a previously initiated pre-defined time interval.

The medical delivery device may for example be in the form of an injection pen, either of the durable type where a medicine filled reservoir or cartridge is removably attached or of the pre-filled type where a medicine filled reservoir or cartridge is irremovably arranged in the pen. Alternatively, instead of a pen, the medical delivery device may be in the form of a doser. The medical delivery device may be of the manual type, where a user, during injection, supplies the force necessary for expelling medicine from the reservoir. Such device may include an injection button that is so configured that the injection button is forced to continuously move back towards an initial position as a dose expelling operation progresses. Alternatively, the medical delivery device may be of the kind commonly known as a wind-up pen or AutoPen®, where energy accumulated in a spring device is released to expel a dose of the medicine. Such device may be configured e.g. as an injection device where the user, during an initial procedure such as dose setting, supplies the mechanical energy required for the expelling operation, the mechanical energy being stored as potential energy for example in a spring member. Also, the injection device may be of a kind where the mechanical energy required for expelling the total usable content of a container is stored in the device during manufacture thereof. In such devices an injection button may be configured so as to move from a rest position to an activated or pushed in position, where the activated position is maintained as a dose expelling operation progresses.

In certain embodiments, the device is configured to be operable in at least two modes of operation, e.g. a dose setting mode and a dose expelling mode. In the dose setting mode, expelling of a set dose is prevented whereas when the device is in dose expelling mode, altering of an already set dose is prevented. As the biasing means may be configured to exert a biasing force on the dispense control member, the biasing means additionally provides a control function to maintain the device in dose setting mode, except when a user forces the activation member into its activated position.

In a second aspect the present invention relates to a medical injection device for introducing a dose of a drug from a held drug container, the injection device defining: a) a base, b) an activation member movable relative to the base in a first direction along an axis from a non-activated position to an activated position, c) a delivery mechanism comprising a dispense control member and configured for dispensing a dose of drug from the container responsive to activation of the dispense control member, wherein the activation member and the dispense control member are movable relative to each other and wherein an activation force exerted on the activation member is transferred to activate the dispense control member, and d) a time delay indicator coupled between the activation member and the dispense control member, the time delay indicator being adapted to change from a first visual state prior to activation of the dispense control member to a second visual state responsive to activation of the dispense control member, and to change to a third visual state after lapse of a predefined time interval subsequent to activation of the dispense control member.

In such an embodiment the device includes a force absorbing structure adapted to absorb activation forces exerted on the activation member and exceeding a pre-defined magnitude from being transferred to the time delay indicator.

A limiter may be arranged to prevent movement of the activation member in the first direction beyond the activated position. The force absorbing structure may comprise a biasing means such as a spring or like arrangements arranged to act between the dispense control member and the base so that the biasing means exerts a pre-defined force on the dispense control member when the activation member assumes its activated position.

The device according to the second aspect may in particular embodiments comprise any of the features and combination of constructional details discussed above in connection with the discussion of the device according to the first aspect.

In the context of the present invention, the term "medical injection device" shall be understood as any device capable of actively bringing a medicament-containing drug into the body of a user by means of an appropriate delivery mechanism such as by using a canula or by a needle-less jet-stream. A non-exhaustive list of medical injection devices within the context of the present invention comprises pre-filled or durable injectors such as pen-shaped injectors or dosers. The drug may be flowable or solid such as drugs forming medicine pegs for insertion through the derma. Representative medicaments includes pharmaceuticals such as peptides, proteins (e.g. insulin, insulin analogues and C-peptide), and hormones, biologically derived or active agents, hormonal and gene based agents, nutritional formulas and other substances in both solid (dispensed) or liquid form. DETAILED DESCRIPTION OF THE INVENTION

The invention will now be described in further detail with reference to the drawings in which:

Fig. 1 shows a schematic representation of a prior art medical injection device,

Fig. 2 shows a cross section view of a fluid timer device suitable for inclusion in a medical injection system according to the present invention,

Fig. 3a is a cross sectional view of a proximal part of an injection device of a first embodiment according to the invention incorporating a fluid timer device as shown in fig. 2, the device being shown in a state prior to operation with an injection button in a released state,

Fig. 3b is a cross sectional view that corresponds to fig. 3a but in a state where the injection button is activated, and

Fig. 4 is a cross sectional exploded view of selected parts shown in figs. 3a and 3b.

Fig. 1 shows a schematic representation of a prior art medical injection system forming an injection pen 1 comprising a medicament filled cartridge 2 which is accommodated in a distal part of the pen. The proximal part 4 of the device holds a mechanism 7 for setting and injecting specific doses of a medicament from the cartridge 2. The cartridge 2 comprises a passage in a distal neck part which is sealed by a pierceable sealing member 5. Cartridge 2 further comprises a slideably mounted piston 6 which is adapted to slide towards the distal part of the container 2 when a distally directed force is exerted on the piston 6. Typically, medication is delivered through an injection needle 3 which may be releasably secured to the distal part of the injection pen. The injection pen further comprises a dose dial 9 which may be manipulated by the hand of a user for selecting a dosage, the magnitude of which is visible in window 10. The injection pen further comprises an injection button 8 for injecting the dosage as set. In the depicted form, a distally directed force on the button 8 exerted by the hand of the user is transferred by the dosing mechanism 7 of the pen to the piston 6 of cartridge 2. Fig. 1 further shows a cap 1 1 which is adapted to be removably attached to the distal part of the injection pen. In the storage state, when the cap 1 1 is attached to the injection pen 1 , the cap protects the cartridge 2 and the needle 3. Fig. 2 shows a cross-sectional view of a time delay indicator 120 suitable for inclusion in an injection device 1 of the type generally discussed in relation to fig. 1 . The depicted time delay indicator generally corresponds to the timer system disclosed in WO 201 1/123515, this document being incorporated herein by reference in its entirety. In the context of the present application, although exemplified by a fluid type mechanical time delay device, the present invention is not limited to such a timer device but may include other mechanical time delay devices, such as the mechanical time delay device shown in WO 2010/023303 but equally well mechanical timer devices that are based on piezochromatic substances which exhibits a colour change when exerted to pressure or force. Example time delay devices of this type are disclosed in WO 2010/127995. In further embodiments other mechanical time delay devices may be incorporated such as the ones disclosed in WO 201 1/050128. The present invention particularly finds application for time delay indicators where the working principle for activation of the timer relies on the application of mechanical force and wherein the magnitude of the force being applied for activation at least to some extent is decisive for the visual appearance of the time delay device, i.e. where the visual indication of the time delay indicator when being activated may vary in accordance with the magnitude of the applied activation force.

Time delay indicator 120 comprises a first substrate 121 and a second substrate 122 arranged in a parallel configuration with the substrates spaced apart by spacer 123. The inner surfaces of the first substrate 121 and the second substrate 122 define a cavity. A fluid 125 is disposed within the cavity. The first and optionally the second cavity are made of a transparent material. On the side of the first substrate121 facing away from the cavity a mask 124 is located. The colour of the mask 124 and the colour of the fluid 125 are selected so that the fluid 125 is readily discernible from the mask 124.

Fig. 2 shows the time delay indicator 120 with the fluid 125 in an equilibrium state. In this state the fluid 125 is in a configuration where it is hidden from visual inspection beneath the mask 124. When a force is applied to the time delay indicator 120 such as by urging the substrates 121 and 122 relatively towards each other, the fluid 125 enters an activated state where it is spread out so that the fluid is visually observable outside the limits of mask 124. Upon relief of the force from the time delay indicator 120, the fluid slowly flows back into the equilibrium state where the fluid 125 is covered by mask 124. As disclosed in WO 201 1/123515 the time delay indicator 120 may be designed such that the fluid 125 returns to the equilibrium state within a time interval selected within the range 30 seconds to 85 minutes subsequent to the relief of the activation force. However, other reversal times may be selected by selecting other material parameters. The substrates 121 and 122 of time delay indicator 120 may be shaped so that the time delay indicator 120 assumes a rounded design such as an oval or circular shape when looked in a direction along an axis transverse to the substrates 121 and 122.

In accordance with an embodiment of the present invention and as shown in figs. 3a and 3b, the time delay indicator 120 is intended to be an integral part of an injection device 100 such as within the injection pen which is schematically shown in fig. 1. In fig. 3a which shows a cross sectional view of a proximal part of the injection device 100, the time delay indicator 120 forms part of an actuator and release system for the delivery mechanism of an example embodiment of an auto-injector having a spring actuated dose and delivery mechanism. Non-limiting examples of suitable injection device delivery mechanisms are disclosed in WO 2006/076921 .

The injection device 100 of fig. 3a includes a housing (not shown) having a dose setting member 150 rotatably mounted around a central longitudinal axis of the housing so that the dose setting member 150 is mounted in a way which excludes axial movements between the dose setting member 150 and the housing. As is commonly known in the art, the dose setting member 150 may be adapted to be rotated away from an initial rotational position so as to adjust the size of the dose intended to be injected. As known in the art, such rotation may be accompanied by an energy accumulation in a spring (not shown) where the accumulated energy of the spring is subsequently, during an expelling procedure, utilized for driving forward the piston of a held cartridge (not shown) a distance which corresponds to the dose as initially set. Internally, along the central longitudinal axis of the housing of the injection device 100, a dispense control member is axially movable between a non-activated state where dose expelling is prevented and into an activated state where dose expelling is effectuated. For the shown embodiment, in the non-activated state the dispense control member assumes a proximal position (shown in fig. 3a) whereas in the activated state the dispense control member assumes a distal position (as shown in fig. 3b). In the shown embodiment, the dispense control member is defined by a first longitudinal release member 131 which is coupled to a rivet 130 so that the relative axial movement between release member 131 and the rivet 130 are prevented. In the shown embodiment, due to manufacturing reasons, the rivet 130 snaps axially into engagement with the release member 131 . When the release member 131 is moved into its distal position energy accumulated in the spring will be released for driving forward the piston of the cartridge. The delivery mechanism included in the injection device 100 may be of the type which provides the possibility of halting the dispensing operation during expelling of a set dose by releasing the release member 131 so that it assumes its proximal rest position. When desired, an unfinished dispensing operation may be continued by moving the release member 131 into its distal position again.

Between a proximally facing bearing surface of dose setting member 150 and a distally facing support surface of rivet 130 a compression spring 140 is arranged so as to exert a proximally directed force onto rivet 130. This urges rivet 130 into the non-activated state. Rivet 130 is retained in this position by means of axial snap features (non-referenced) on the rivet 130, release member 131 and dose setting member 150 respectively. Compression spring 140 also ensures that the release member 131 is moved into its rest position (the proximal position) whenever the dose expelling procedure is not desired. As such, as is a well-known principle used in injection devices, the spring 140 acts to control a clutch mechanism which controls the expelling of the device, such as to differentiate between a dose setting mode and a dose expelling mode.

An activating member constituting an injection button is formed by a generally cylindrical part 1 1 1 and a top cap part 1 10, the top cap part 1 10 being permanently mounted relative to the cylindrical part 1 1 1 . In the assembled state of the injection device 100 the injection button 1 10/1 1 1 accommodates the rivet 130 in the interior of cylindrical part 1 1 1. Also within injection button 1 10/1 1 1 , sandwiched between the top cap part 1 10 and rivet 130 the previously described time delay indicator 120 is arranged. Fig. 4 provides a cross sectional exploded perspective view of elements 1 10, 1 1 1 , 120 and 130.

The cylindrical part 1 1 1 forms an interior circular ledge (non-referenced) that prevents the cylindrical part 1 1 1 , in the state shown in fig. 3a, from moving axially in the proximal direction relative to the rivet 130. However, the injection button 1 10/1 1 1 is to a limited extent allowed to move axially in the distal direction relative to rivet 130. A distal facing surface of top cap part 1 10 includes a central distally extending protrusion 1 12 arranged to abut the central portion of the first substrate 121 of time delay indicator 120. Likewise, a proximal facing surface of rivet 130 includes a central proximally extending protrusion 132 arranged to abut the central portion of the second substrate 122 of time delay indicator 120. In the shown embodiment, the radial dimension of the protrusions of top cap part 1 10 and rivet 130 may correspond to the mask 124 and thereby to correspond to the extension of the fluid 125 when in the equilibrium state. When the injection button is pressed distally relative to the housing (and the dose setting member 150), due to the limited relative axial movement that is permitted between injection button 1 10/1 1 1 and rivet 130 the protrusions of the top cap part 1 10 and rivet 130 are adapted to exert a force on time delay indicator 120 in order to activate the time delay indicator 120. When comparing figs. 3a and 3b, when the injection button 1 10/1 1 1 is moved from the non-activated state into the activated state, it is clear that the time delay indicator 120 is reduced in its axial extension corresponding to a distance At = t-ι - 1₂.

The cylindrical part 1 1 1 of the injection button includes a distally facing rim part 1 13 which is adapted to abut a surface 153 of the dose setting member 150 when the injection button assumes its activated state. As indicated in fig. 3a, the injection button 1 10/1 1 1 is movable in the axial direction relative to dose setting member 150 for a limited stroke length B.

Also indicated in fig. 3a, when the injection button 1 1 1 assumes its non-activate state, the rivet 130 has an axial clearance relative to the dose setting member 150 of magnitude A.

By ensuring that axial clearance A is at least equal to and preferably greater than the stroke length B minus the above described dimension At it is ensured that extensive forces that potentially may be applied on the injection button is not transferred to the time delay indicator 120. In the activated state of the injection button 1 10/1 1 1 , due to the limited stroke length B, the spring force exerted by compression spring 140 on rivet 130 may be designed to provide a well-defined activation force on the time delay indicator 120. In this way, excessive forces applied onto the injection button 1 10/1 1 1 is redirected towards the dose setting member 150 and hence the housing of the injection device 100.

It is to be noted that the peripheral parts of time delay indicator 120 is generally unsupported in the axial direction. The centrally located protrusions on top cap part 1 10 and rivet 130 ensure that substantially all the force permitted to be transferred onto the time delay indicator 120 is transferred towards the longitudinal release member 131 for activating the dispensing operation of the injection device 100. In this way it is substantially ensured that the activation of the time delay indicator 120 is accompanied by a correctly performed activation of the dispensing operation and hence the expelling of a previously set dose.

Subsequent to the state shown in fig. 3b, when a desired dose has been fully injected injection button 1 10/1 1 1 is released whereby the force exerted onto button is relieved. This activates the transformation of the time delay indicator 120 from the activated state and back into the equilibrium state. Such transformation will typically be selected in the order of 30 minutes to a full hour or even 2 or 3 hours.

In the shown embodiment, the cap part 1 10 is made of a transparent material allowing visual inspection of the first substrate 121 as well as mask 124 of the time delay indicator 120. Hence, by inspecting the proximal part of the injection device 100 a user may retrospectively check whether or not an injection has been performed by injection device 100 within the time-interval defined by time delay indicator 120. As an alternative to a transparent top cap part 1 10, the top cap part may be provided with one or more windows allowing inspection of time delay indicator 120. Some preferred embodiments have been shown and discussed in the foregoing, but it should be stressed that the invention is not limited to these, but may be embodied in other ways within the subject matter defined in the following claims. The figures e.g. discloses medical delivery systems of the present invention in the form of an injection pen, however, this particular delivery device and its shape is in no way limiting for the present invention as defined in the claims. This also applies to time delay indicators being more fully integrated into an injection device than the embodiments shown in this disclosure, e.g. time delay indicators being integrated into a dosing mechanism such as providing an indicator viewable through a window of the housing of the device or alongside a dose amount indicator such as a dose dial scale. Also, actuators for activating an injection other than the push-button type described in the application are within the subject matter defined in the following claims. A non-limiting example being devices having and actuator which is automatically activated subject to insertion of a needle into the skin of a subject user. Furthermore, additional intermediate visual status indications may be provided between the said first, second and third visual indications without departing from the scope of the subject matter defined in the claims.

Claims

1. A medical injection device for dispensing a dose of a drug from a held drug container, the injection device (100) defining:

- a base (150), - an activation member (110,111) which is movable relative to the base (150) in a first direction from a non-activated position to an activated position to activate dose dispensing,

- a delivery mechanism comprising a dispense control member (130,131) configured for movement relative to the activation member (110, 111), the dispense control member (130,131) being operated by the activation member (110,111) so that when the activation member (110,111) moves from the non-activated position to the activated position the dispense control member (130,131) moves relative to the base (150) from a first position to a second position to cause the delivery mechanism to dispense a dose of drug from the container,

- biasing means (140) acting on the dispense control member (130,131) for urging the dispense control member (130,131 ) towards the first position, and

- a time delay indicator (120) coupled between the activation member (110,111) and the dispense control member (130,131), the time delay indicator (120) being configured to provide a first visual indication prior to activation of the activation member (110,111), to provide a second visual indication in response to activation of the activation member (110,111), and to provide a third visual indication after lapse of a pre-defined time interval subsequent to activation of the activation member (110,111), wherein, when the activation member (110,111) assumes its activated position, the biasing means (140) exerts a predetermined force on the dispense control member (130,131).

2. A medical injection device as defined in claim 1, wherein a) the activation member (110,111) is configured for limited travel relative to the base (150) from the non-activated position to the activated position defining an activation member travel length B, wherein b) when the activation member (1 10,1 1 1 ) moves from the non-activated position to the activated position, the time delay indicator (120) is operated by the activation member (1 10,1 1 1 ) moving a distance At relative to the dispense control member (130,131 ), and wherein c) when the activation member (1 10,1 1 1 ) assumes its non-activated position, the dispense control member is positioned relative to the base (150) with a clearance of magnitude A, wherein

A≥ B - At.

3. A medical injection device as defined in any of claims 1 -2, wherein the time delay indicator (120) transfers an activation force exerted on the activation member (1 10,1 1 1 ) to activate the dispense control member (130,131 ) to cause dose dispensing.

4. A medical injection device as defined in any of the claims 1 -3, wherein the time delay indicator (120) comprises a mechanical time delay device (121 ,122,123,125) which is started upon activation of the activation member (1 10,1 1 1 ) and which operates until lapse of said pre-defined time interval, the visual indication of the time delay indicator (120) being controlled by the mechanical time delay device (121 ,122,123,125).

5. A medical injection device as defined in any of the claims 1 -4, wherein the third visual indication corresponds to the first visual indication.

6. A medical injection device as defined in claim 5, wherein the time delay indicator (120) comprises a fluid type mechanical time delay device (121 ,122,123,125) comprising at least one fluid (125) reversibly flowable between a first configuration and a second configuration wherein the first configuration defines said first visual indication and the second configuration defines said second visual indication of the time delay indicator (120).

7. A medical injection device as defined in claim 6, wherein the mechanical time delay device (121 ,122,123,125) comprises a first substrate (121 ) associated with the activation member (1 10,1 1 1 ) and a second substrate (122) associated with the dispense control member (130,131 ), the first substrate (121 ) and the second substrate (122) being spaced apart to define a cavity, and wherein a first fluid (125) is arranged in the cavity, the first fluid (125) being configured to change from the first configuration and into the second configuration by relatively moving at least a part of the first substrate (121 ) relative to at least a part of the second substrate (122).

8. A medical injection device as defined in claim 7, wherein the first fluid (125) maintains an equilibrium state when in its first configuration and enters into an activated state when in its second configuration.

9. A medical injection device as defined in any of the claims 7-8, wherein each of the first substrate (121 ) and the second substrate (122) is arranged transverse to said axis.

10. A medical injection device as defined in claim 9, wherein the first fluid (125) is located at a central location relative to the axis when the first fluid (125) is in its equilibrium state. 1 1. A medical injection device as defined in claim 7-10, wherein the activation member (1 10,

1 1 1 ) and the dispense control member (130,131 ) are configured for exerting a force on the respective ones of the first substrate (121 ) and the second substrate (122) mainly at a central location relative to the axis.

12. A medical injection device as defined in claims 7-1 1 , wherein the first substrate (121 ) and the second substrate (122) each define peripheral portions and wherein the activation member (1 10,1 1 1 ) and the dispense control member (130,131 ) are so configured that the peripheral portions of the first substrate (121 ) and the second substrate (122) are substantially unsupported in directions parallel to the axis.

13. A medical injection device as defined in any of the claims 1 -12, wherein the base (150) defines a housing which at least partly accommodates the delivery mechanism.

14. A medical injection device as defined in any of the claims 1 -12, wherein the injection device (100) comprises a housing and wherein the base (150) defines a component that is movable relative the housing but where the position of the base (150) relative to the housing is axially fixed.

15. A medical injection device as defined in any of the claims 1 -14, wherein the activation member (1 10,1 1 1 ) defines a first surface portion (1 13), when an externally applied force on the activation member (1 10,1 1 1 ) acting in the first direction has caused the activation member (1 10,1 1 1 ) to assume its activated position, an increase in the externally applied force is redirected to a surface (153) of the base (150) but not redirected to the time delay indicator (120).