Injection device for a multi-chamber cartridge or syringe

Abstract

An autoinjector including a main housing, a drive mechanism 202 contained within the main housing and having a plunger 206 moveable along a drive axis, an energy storage element 204 coupled to the dri

Description

Technical field The present invention relates to an injection device for use with a multi-chamber cartridge or syringe and preferably, though not necessarily, to such a device having an orientation detection feature. Background Therapeutic agents are terms used to identify a diverse group of medicines including, but not limited to, vaccines, growth factors, immune modulators, monoclonal antibodies, as well as products derived from human blood and plasma. However, the inherent instability of some therapeutic agents is a limitation that has a direct impact on the drug delivery sector. For example, therapeutic proteins must either be stored under cold chain conditions or formulated to retain their efficacy from the time of manufacture until they are dispensed. Liquid protein drugs require refrigeration until dispensed. Alternatively, proteins can be formulated as powders (lyophilization) which must be reconstituted prior to injection. Lyophilized drugs are sold with reconstitution injector vial systems, or packaged in special injection devices (e.g., pens, two-chamber cartridges, two-part syringes) that allow reconstitution to take place in the device prior to injection. The reconstitution device market is known to be challenging for users; known reconstitution methods can require separate transfer units involving a vial, a syringe, and multiple needles, all of which create a significant number of steps for the user as well as additional safety challenges. Some of these issues have been addressed with use of a multi-chamber cartridge having, for example, two chambers. A two chamber cartridge 100 is illustrated schematically in Figure 1 and comprises a glass or plastics body 101 defining a first proximal chamber 102 containing a dried component 103 and a second distal chamber 104 contains a rehydration liquid 105. The proximal and distal chambers are separated by a first “rubber” bung 106 whilst a second rubber bung 107 stops a distal end of the distal chamber 104. By applying a force to the second bung 107, that bung is moved through the cartridge, in turn moving the liquid rehydration agent and the first rubber bung. A passage 108 is formed on an inner surface of the cartridge and is initially blocked by the first bung. It is however exposed after movement of the first bung 106 by a predetermined amount whereupon the passage 108 provides a fluid path between the proximal and distal chambers. Further force applied to the second bung 107 forces liquid 105 from the distal chamber 104 into the proximal chamber 102 through the exposed passage and into contact with the dried component 103. This rehydrates the dried component readying it for injection via a needle that is attached to a proximal end of the cartridge. Figure 1 illustrates a pen-tip type needle 109 suitable for attachment to the dual chamber cartridge. The needle 109 comprises an insertion end 109a and a piercing end 109b, the piercing end being configured to pierce a septum 110 provided at the proximal end of the cartridge to bring an interior channel of the needle into fluid communication with the proximal chamber. Such known dual chamber cartridges may be used with an injection assistance device such as an autoinjector, where the autoinjector is configured to contain at least a part of the cartridge and comprises a piston rod for driving the distal bung and some drive mechanism that, when activated, applies a driving force to the piston rod. Autoinjectors may rely upon manual needle insertion (into a patient) or may facilitate needle insertion automatically or semi-automatically. Similar, multi-chamber syringes are known, here the syringe differs from the multichamber cartridge in that the former is provided with a plunger whilst the latter relies upon a plunger of an autoinjector to drive the distal bung through the cartridge. There is therefore a desire for a reconstitution device that is simpler and safer to use. Summary According to an aspect of the present invention there is provided an autoinjector including a main housing, a drive mechanism contained within the main housing and having a plunger moveable along a drive axis, an energy storage element coupled to the drive mechanism, a controller configured to cause the energy storage element to provide energy to the drive mechanism to perform a set of one or more predefined operations, an orientation detection mechanism for detecting an orientation of the drive axis relative to a horizontal or vertical axis and for providing to said controller a signal indicative of the orientation; and a feature or features for attaching a cartridge housing to the autoinjector. The set of predefined operations include a movement or movements of the plunger along said drive axis into an attached cartridge housing and / or a rotation of the cartridge housing about said axis, relative to said main housing, and the controller is configured to cause the predefined operation or at least one of the predefined operations only when said signal indicates that the autoinjector is in a predefined orientation or within a range of orientations. The predefined operation may be rotation of an attached cartridge housing about said axis, and said controller is configured to cause the rotation only when said signal indicates that the drive axis is substantially horizontal and / or a movement of the plunger along said drive axis into an attached cartridge housing, and said controller is configured to cause the movement only when said signal indicates that a proximal end of the autoinjector is above a distal end of the autoinjector, and the drive axis is vertical or substantially vertical. The feature or features may be configured to accept a plurality of different cartridge housing formats. Optionally, the drive mechanism may be an electrically powered drive mechanism and said energy storage element is an electrical power source. The electrically powered drive mechanism may be one or more electrical motors The autoinjector may include at least one user actuatable button, wherein said controller is configured to detect user actuation of the button and in response cause a predefined operation or operations subject to said signal indicating that the autoinjector is in a predefined orientation or range of orientations. The autoinjector may be provided with a first electrical motor for moving the plunger along said drive axis into an attached cartridge housing and a second electrical motor for rotating of the cartridge housing about said axis, relative to said main housing. The controller of the autoinjector may include a memory for storing instructions for performing said set of predefined operations and a processor for reading and executing the instructions. Optionally, the controller may also be configured to control parameters of a caused predefined operation according to an orientation of the autoinjector. A parameter may be a speed or direction of a movement. The auto-injector may include a cartridge housing having one or more second features for cooperating with said feature or features of the autoinjector to attach the cartridge housing to the autoinjector, the cartridge housing defining an internal space for receiving a cartridge containing a biological or biological components and further comprising a feature or features for preventing relative rotational movement of the cartridge and the cartridge housing. Brief Description of the Drawings Figure 1 illustrates schematically a multi-chamber cartridge of known construction; and Figure 2 illustrates a partial cross-section of an autoinjector containing a multi-chamber cartridge. Detailed Description In the following discussion the terms “proximal” and “distal” are used to refer respectively to regions or features that, during an injection operation, are closer to or remote from, respectively, an injection site of a human or animal patient. The term “axial” or “axis” is used to define a direction that extends through a device, generally aligned with a direction along which a plunger moves during an injection. Figure 2 illustrates an autoinjector 200 configured for use with a multi-chamber cartridge 100 of known general construction and as already discussed with reference to Figure 1. In this example the multi-chamber cartridge 100 is a two-chamber cartridge although the autoinjector 200 may be adapted for use with cartridges having more than two chambers. The autoinjector 200 comprises a main housing 201 which may be in the form of a moulded plastics housing. The housing 201 defines various internal compartments for containing and supporting functional components of the autoinjector. These components include a drive mechanism 202 including a motor (or motors) 203, a battery power source 204 and a controller 205. The drive mechanism 202 comprises a plunger 206 that is aligned with an axis X-X of the autoinjector. In an initial, pre-use state, the plunger 206 is in a rearward position as illustrated, ie. located at a distal end of a range of movement of the plunger. The plunger is provided at a proximal end with a plunger foot 207. Components of the drive mechanism 202 are engaged with the motor 203, e.g. via a gear mechanism or the like, to facilitate driving of the plunger from the illustrated starting position, in a proximal direction (indicated in the arrow in Figure 2). The proximal end of the plunger 206 and the plunger foot 207 may, in the pre-use position, be located fully within the housing 201. The housing is provided with a proximal opening 208 that allows the distal end of the plunger and the plunger foot to extend out of the housing during use. The controller 205 and battery power source 204 are configured to operate the motor 203 according to a desired sequence. Operation may be initiated and to some extend controlled by a user operated button 209 that is electrically connected to the controller 205. For simplicity various mechanical and electrical connections between the components of the autoinjector 200 are omitted from the drawings and from this discussion, although the skilled person will appreciate how these might be implemented to cause the device to operate as described. The autoinjector 200 is configured to cooperate with a cartridge housing 210 that may have a generally cylindrical construction providing an interior space 211 for accommodating the two chamber cartridge 100. The cartridge housing 210 may have an opening 212 in its distal end through which the cartridge 100 can be loaded prior to attachment of the cartridge housing 210 and the main housing 201. Once loaded the cartridge 100 is substantially prevented from rotating within the cartridge housing. Various means to prevent rotation are contemplated including an interference fit or interengaging anti-rotation features of the cartridge and the cartridge housing. A pen-type needle 109 is shown adjacent to the proximal end of the cartridge 100 and the cartridge housing 210. Attachment of the needle 109 will be described below. Illustrated generally in Figure 2 by reference numeral 213 are coupling features of the cartridge housing 210 and the main housing 201. These features are used to securely attach the two housings together such that, when the plunger 206 and the plunger foot 207 are advanced through the main housing 201 in a proximal direction, the plunger foot engages with the second rubber bung 107 of the cartridge 100 and is able to move that bung 107 though the cartridge 100, resulting in the sequence of operations already described with reference to Figure 1, i.e. injection of liquid from the distal chamber into the proximal chamber, and subsequent ejection of the mixed biological through an attached needle. Movement of the plunger 206 in a proximal direction by the drive mechanism 202 is caused and controlled by the controller 205 and button 209. The controller 205 may comprise hardware, e.g. a processor and memory, and software features, e.g. program code stored in the memory, to control movement of the plunger 206 as required. The controller may further comprise a device orientation detector 214 the operation of which is described below. Of course, the orientation detector may be provided by a distinct component that is electrically connected to the controller. An example of an orientation detector is a tilt switch or sensor which relies on movement of a conductive free mass to electrically connect or disconnect conductive elements depending upon the orientation of the tilt switch. Alternative solutions may utilise on or a combination of an accelerometer, gyroscope, pressure sensor (optionally provided on outer surface the device to check resting on correct surface), optical sensor and a potentiometer. The coupling features 213 are further configured to permit rotation of the cartridge housing 210 about the axis X-X relative to the main housing 201, in one or both of a clockwise and an anti-clockwise direction, once connected. The clockwise and I or anticlockwise rotational force is provided via the coupling features 213 from the motor 203. The controller may be configured to selectively apply force to the coupling features to rotate the cartridge housing 210 or to the drive mechanism 203 to move the plunger 206. Of course, different motors may be provided to perform these functions, i.e. rotation of the cartridge housing and movement of the plunger, separately. According to one embodiment, a single motor may be used together with a pair of drive shafts one of which is configured to drive the plunger axially and the other of which is configured to rotate the cartridge housing. A solenoid arrangement may be operated to selectively couple the motor rotor to one or other of the drive shafts. An exemplary operating sequence is as follows: Step 1: A user inserts the two-chamber cartridge 100 into the cartridge housing 210. Step 2: The user attaches the distal end of the cartridge housing 210 to the proximal end of the main housing 201, thereby engaging the coupling features 213. Step 3: The user attaches the pen-type needle 109 to the proximal end of the cartridge, facilitated by an opening 215 in a proximal end of the cartridge housing 210. This causes the piercing end of the needle 109b to penetrate the cartridge septum 110. Step 4: The user presses and releases the button 209 to initiate a mixing sequence. This is done with the device in an upwardly directed orientation, i.e. with the needle tip pointing upwards. Step 5. The button press is detected by the controller 205 which causes the motor 203 to engage with other components of the drive mechanism 202 to advance the plunger 206 by some predefined distance in the proximal direction. This distance is sufficient to (a) cause the plunger foot 207 to engage with the distal bung 107 and advance that bung by a predefined distance into the cartridge body 101, (b) due to the incompressibility of the fluid in the distal chamber, move the proximal bung 106 to an extent that opens the passage 108 previously closed by the proximal bung, and (c) inject liquid from the distal chamber 104 into the proximal chamber 102, thereby bringing the injected liquid into contact with the dried component within the proximal chamber. Injection of liquid into the proximal chamber in turn ejects air from the distal chamber through the attached needle 109. Step 6: Injection of the liquid into the proximal chamber is completed once the two bungs 106,107 are in contact with one another. Step 7: In order to aid rehydration of the dried component and facilitate a thorough mixing, the controller 205 at this point stops further movement of the plunger 206, whilst causing the motor 203 to engage with and rotate the cartridge housing 210 and therefore the cartridge 100, about the axis X-X. Rotation is continued for a predefined time period. Rotation is then stopped and the device is ready for further use. The direction of rotation may be alternated after predefined time periods. Step 8: The user at this point determines that mixing is complete. This may be further indicated, for example, by an audible sound (“beep”) or a visible indication, e.g. a green LED being illuminated. The device is ready for priming. Step 9: The user primes the device in order to substantially remove air from the proximal chamber. This is achieved by depressing the button 209 and holding the button down, again with the device in an upright orientation. The controller 205 detects this action and causes the plunger 206 to further advance slowly into the cartridge body 101. This causes the bungs 106,107 to advance together into the cartridge, pushing liquid and air ahead of them. Step 10: The uses removes pressure from the button 209 when he or she sees liquid emerging from the needle tip, indicating that all air has been dispelled. Of course, some means may be provided to detect when priming is complete, e.g. comprising an optical detector. Step 11: The user can then insert the insertion end 109a of the needle into the injection site. Step 12. The user again depresses the activation button 209. This may be a short press and release action. Step 13. The controller 205 detects the button press and causes the plunger to continue advancing in the proximal direction, in turn causing the biological to be ejected through the insertion end 109a of the needle and into the injection site. Step 14: Injection is completed once the proximal bung 106 reaches the proximal end of the cartridge 100. This may be detected, e.g. using a micro-switch or optical detector, and an end of delivery indication provided to the user. Alternatively, the controller may drive the plunger for some predefined time period determined a priori to eject all of the biological from the cartridge. Step 15: The user can then remove the needle tip from the injection site. If the autoinjector is a disposable device, the user may then safely dispose of the device and the contained cartridge (and needle). Alternatively, if the device is reusable, the cartridge and needle may be removed from the device and disposed. In some cases the cartridge housing 210 may also be disposable. As noted above the autoinjector 200 may comprise a device orientation detector 214. This detector if provided is configured to detect an orientation of the axis X-X of the device relative to the horizontal / vertical. An output signal generated by the detector may be used by the controller 205 to inhibit or enable one or more of the steps of the operating sequence. For example, at step 5, the controller 205 may be configured to inhibit operation of the drive mechanism and advancement of the plunger when an output signal of the device orientation detector 214 indicates that the device is not in an upright position, or at least that the insertion end 109a of the needle is not sufficiently above the cartridge 100. In this event the controller may cause an audible alert to be generated such as to notify the user that the device is not correctly oriented. The controller at this stage continues to poll the device orientation detector 214 output signal to determine when the device is in the correct orientation, whereupon the mixing sequence is continued. A similar procedure may be followed at the priming steps (9 and 10). The device orientation detector 214 may further be utilised at step 7, i.e. mixing by rotation of the cartridge. It may be the case that such mixing is most efficiently carried out with the cartridge (i.e. axis X-X) in a substantially horizontal orientation. As such, when the controller detects a button press at step 7, rotation will only commence when the device orientation detector 214 output indicates that the device is in a horizontal or substantially horizontal orientation. NB. At any one of the steps where the output of the device orientation detector 214 is used to control the device operation, a change in orientation from the desired orientation may interrupt the operation and cause an alert to be generated. Operation may only be continued when the device orientation detector 214 again indicates a correct orientation. The autoinjector 200 may be configured to accept and cooperate with different cartridge housing formats, where these different formats are configured in turn to accept different cartridge formats. For example, different cartridge housings may accept cartridges with different fill volumes, e.g. 1ml, 2.5ml etc. This permits a common autoinjector to be used regardless of cartridge fill volume. In some embodiments the cartridge housing and the needle may be provided as a single, disposable component, such that a cartridge can be inserted into the cartridge housing and subsequently engaged with the needle without requiring a separate step of attaching the needle to the cartridge. This single unit may include a needle boot for safely covering the insertion end of the needle prior to use. Engagement of the cartridge and the needle, including piercing of the septum, may occur as part of the operation sequence controlled by the controller. Additionally, although the invention has been described with reference to a cartridge, the skilled person will understand that the invention may be implemented with a syringe where a body containing the therapeutic agent is provided with a needle or other conduit at one end and a bung at the other end to contain medicament. The body may be multichamber and provided with first and second chambers as described previously in relation to the multi-chamber cartridge. Whilst the device has been described in relation to a multi-chamber syringe the skilled person will appreciate that it may equally be applied to a single chamber syringe where mixing is desirable prior to delivery of the therapeutic agent. Additionally, the mixing may take place between two liquids, a dried component and a rehydration liquid or two powders. It will be appreciated by the skilled person that the cartridge housing may be provided as integral to the main housing with the cartridge or syringe being received in the cartridge housing without disconnecting the main housing and cartridge housing. For example, the cartridge housing may be provided with an aperture through which a cartridge can be inserted. This aperture may, for example, be provided by a hinged mechanism allowing an aperture closure to be moved from the aperture thereby to allow a cartridge to be inserted into the device. The skilled person will understand that any other suitable mechanism may be used to allow the cartridge to be inserted into the cartridge housing. It will also be appreciated that the operating sequence programmed into the controller may be specific to cartridge format and I or therapeutic agent. For example, the piston stroke, piston force, piston speed, rotation speed and duration, may all be configurable. It will be appreciated by the person of skill in the art that various modifications may be made to the above described embodiments without departing from the scope of the present invention. For example, the motor or functions of the motor may be performed by other electromechanical components such as a solenoid. According to an alternative embodiment, the electrically powered drive mechanism described above may be replaced by a mechanically powered drive mechanism, where energy is provided to the drive mechanism from a tensioned spring, e.g. a torsion spring, compression spring, or clock spring. In a further alternative embodiment, the mixing procedure may require a change of orientation of the device at intermediate points. After a given period, rotation may be stopped and only restarted when the device is in a different orientation. The duration and or speed of the or each rotation may be varied, depending upon the angle of orientation.

Claims

1. An autoinjector comprising:a main housing;a drive mechanism contained within the main housing and having a plunger moveable along a drive axis;an energy storage element coupled to the drive mechanism;a controller configured to cause the energy storage element to provide energy to the drive mechanism to perform a set of one or more predefined operations;an orientation detection mechanism for detecting an orientation of the drive axis relative to a horizontal or vertical axis and for providing to said controller a signal indicative of the orientation; anda feature or features for attaching a cartridge housing to the autoinjector;wherein said set of predefined operations include a movement or movements of the plunger along said drive axis into an attached cartridge housing and / or a rotation of the cartridge housing about said axis, relative to said main housing, andwherein said controller is configured to cause the predefined operation or at least one of the predefined operations only when said signal indicates that the autoinjector is in a predefined orientation or within a range of orientations.

2. An autoinjector according to claim 1, wherein a predefined operation is a rotation of an attached cartridge housing about said axis, and said controller is configured to cause the rotation only when said signal indicates that the drive axis is substantially horizontal.

3. An autoinjector according to claim 1 or 2, wherein said drive mechanism is an electrically powered drive mechanism and said energy storage element is an electrical power source.

4. An autoinjector according to any one of the preceding claims, wherein a predefined operation is a movement of the plunger along said drive axis into an attached cartridge housing, and said controller is configured to cause the movement only when said signal indicates that a proximal end of the autoinjector is above a distal end of the autoinjector, and the drive axis is vertical or substantially vertical.

5. An autoinjector according to any one of the preceding claims, wherein said feature or features are configured to accept a plurality of different cartridge housing formats.

6. An autoinjector according to any one of the preceding claims and comprising at least one user actuatable button, wherein said controller is configured to detect user actuation of the button and in response cause a predefined operation or operations subject to said signal indicating that the autoinjector is in a predefined orientation or range of orientations.

7. An autoinjector according to any one of the preceding claims, wherein said electrically powered drive mechanism comprises one or more electrical motors.

8. An autoinjector according to any one of the preceding claims and comprising a first electrical motor for moving the plunger along said drive axis into an attached cartridge housing and a second electrical motor for rotating of the cartridge housing about said axis, relative to said main housing.

9. An autoinjector according to any one of the preceding claims, the controller comprising a memory for storing instructions for performing said set of predefined operations and a processor for reading and executing the instructions.

10. An autoinjector according to any one of the preceding claims, wherein said controller is configured to control parameters of a caused predefined operation according to an orientation of the autoinjector.

11. An autoinjector according to claim 10, wherein a parameter is a speed or direction of a movement.

12. A system comprising an autoinjector according to any one of the preceding claims and a cartridge housing, the cartridge housing having one or more second features for cooperating with said feature or features of the autoinjector to attach the cartridge housing to the autoinjector, the cartridge housing defining an internal space for receiving a cartridge containing a biological or biological components and further comprising a feature or features for preventing relative rotational movement of the cartridge and the cartridge housing.13

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