Patent Application
20240342384
A drug delivery device is provided. Furthermore, a drug reservoir unit for a drug delivery device and a set comprising a drug delivery device and a drug reservoir unit are provided.
Administering an injection is a process which presents a number of risks and challenges for users and healthcare professionals, both mental and physical. A drug delivery device may aim to make self-injection easier for patients. A safe operation of the drug delivery device is desirable.
One object to be achieved is to provide an improved drug delivery device, preferably a drug delivery device which makes operation and handling safer for the user. Further objects to be achieved are to provide a drug reservoir unit for such a drug delivery device and a set comprising such a drug delivery device and such a drug reservoir unit.
These objects are achieved, inter alia, by the subject-matter of the independent claims. Advantageous embodiments and further developments are subject to the dependent claims and can also be extracted from the following description and the figures.
First, the drug delivery device is specified.
The drug delivery device may be an injection device. The drug delivery device may be an autoinjector and/or a variable dose device or a fixed dose device and/or a pen type device, e.g. a dial extension pen.
According to at least one embodiment, the drug delivery device comprises a mechanism unit. The mechanism unit may comprise a dispense mechanism for dispensing a drug dose and/or a setting mechanism for setting a drug dose.
The dispense mechanism and/or the setting mechanism may comprise several elements which interact with each other during dose dispensing or dose setting. For example, a coupling between two or more elements of the mechanism unit is changed when switching from dose setting to dose dispensing or vice versa. For example, two or more elements are splined during dose setting such that they are rotationally fixed to each other, wherein the splined coupling is released for dose dispensing so that these elements rotate relative to each other during dose dispensing.
For example, the dispense mechanism comprises a plunger rod configured to act on a drug reservoir in order to dispense a drug dose. The mechanism unit may be configured such that the plunger rod moves axially in distal direction during dose dispensing. The plunger rod may also rotate during dose dispensing, e.g. due to a threaded engagement with a further element of the mechanism unit, like a drive element. For example, during setting a drug dose, the plunger rod does not move.
The dispense mechanism may also comprise an energy member in order to provide energy for dispensing a drug dose. The energy member may provide energy for moving the plunger rod in distal direction. For example, the energy member is a drive spring, like a compression spring or a torsion spring, or a gas cartridge or an electric motor. Alternatively, no additional energy member for moving the plunger rod is used. The force needed for moving the plunger rod and dispensing a drug dose may then have to be provided by the user.
The dispense mechanism may comprise a drive element, e.g. a drive sleeve. The drive sleeve may circumferentially surround the plunger rod. The drive element may be threadedly engaged with the plunger rod. During dispensing a drug dose, the drive element may move in distal direction, e.g. without rotation, and may thereby force the plunger rod to rotate and also move in distal direction.
The setting mechanism may comprise a setting element, e.g. a dial sleeve and/or a number sleeve. During dose setting, the drive element may be splined to the setting element. For example, during dose setting, the drive element and the setting element move together, e.g. on a helical path, in a proximal direction but may not move relative to each other. During dose dispensing, the splined coupling between the drive element and the setting element may be released. For example, during dose dispensing, the setting element moves back on the helical path in distal direction but the drive element only moves axially in distal direction without rotation. For realizing the splined coupling and for releasing the splined coupling between the drive element and the setting element, the mechanism unit may comprise a clutch and/or a clicker arrangement and/or a clutch spring.
The mechanism unit may comprise a user interface member configured to be operated by a user, e.g. to be touched by a user, in order to dispense a drug dose. For example, the user interface member is a button or a knob. For example, in order to dispense a drug dose, the user interface member has to be pushed in a distal direction by the user. This user interface member may also be referred to as dose dispense member.
The mechanism unit may also comprise a user interface member configured to be operated by a user, e.g. to be touched by a user, in order to set a drug dose. For example, for setting a drug dose, the user has to rotate and/or move the user interface member in a proximal direction. This user interface member may also be referred to as dose setting member.
The user interface member for setting a drug dose may at the same time be the user interface member for dispensing a drug dose.
According to at least one embodiment, the mechanism unit comprises an electrical element. The electrical element is particularly an element through which, during its intended operation, an electrical current or electrical signal flows. The electrical element may comprise or consist of one or more of: a conductor path, a sensor, an electromechanical switch.
According to at least one embodiment, the mechanism unit comprises an arrangement for changing an operational state of the mechanism unit, particularly, for changing from a first operational state into a second operational state or vice versa. The second operational state is, in particular, a state in which at least one functionality of the mechanism unit is enabled or performed which is disabled or not performed in the first operational state.
The arrangement for changing the operational state may comprise one or more components which interact with each other. For example, the arrangement comprises mechanical and/or electrical components. By way of example, the arrangement comprises one or more of: an electromechanical actuator, a control unit, a display, an energy source. The control unit may comprise a processor, e.g. an IC-chip. The control unit may be a micro controller. The energy source may be a battery. The arrangement may be permanently electrically connected with the electrical element.
According to at least one embodiment, the mechanism unit is configured to enable a dispense process for dispensing a drug dose, e.g. a set drug dose. Particularly, the mechanism unit may be configured to act on a drug reservoir, particularly a drug reservoir of a drug reservoir unit, during the dispense process.
The drug reservoir may have a distal end for dispensing the drug. The distal end may be the end comprising a needle or the end to be connected with a needle. The drug reservoir may comprise a stopper sealing the drug reservoir in proximal direction. When the mechanism unit acts on the drug reservoir, the mechanism unit may push the stopper in distal direction in order to dispense a drug dose. For example, the plunger rod of the mechanism unit thereby abuts against the stopper and pushes the stopper in distal direction. Performing the dispense process may require the user to operate the dose dispense member.
According to at least one embodiment, the mechanism unit may be configured to be operatively coupled with a selected drug reservoir unit. The selected drug reservoir unit may comprise or may be a drug reservoir and/or a drug reservoir holder for holding a drug reservoir. The drug reservoir holder may be configured to hold the drug reservoir such that the drug reservoir is not movable relative to the drug reservoir holder. A selected drug reservoir unit is, in particular, a drug reservoir unit which is especially intended or foreseen or selected for the mechanism unit. For example, a selected drug reservoir unit is a drug reservoir unit with an electrical contact element at a correct or predefined position.
“Operatively coupled” particularly means that the mechanism unit and the drug reservoir unit are mechanically coupled or connected, respectively, particularly releasable coupled or connected. For this purpose, the mechanism unit may comprise an interface feature for forming a connection interface connecting the mechanism unit to the drug reservoir unit. The interface feature may comprise a thread configured to engage into a thread of the drug reservoir unit for forming the connection interface. Alternatively, the interface feature may be configured to establish a snap connection to the drug reservoir unit. When coupled, the drug reservoir unit may be fixed with respect to the housing element so that, e.g., the drug reservoir unit is not movable with respect to the housing element in axial direction. Additionally or alternatively, “operatively coupled” may mean that the mechanism unit and the drug reservoir unit are coupled to exchange information, e.g. electrical signals or currents.
According to at least one embodiment, when a selected drug reservoir unit is coupled with the mechanism unit, the selected drug reservoir unit interacts with the electrical element. Thereby, the selected drug reservoir unit particularly changes an electrical property of the electrical element in a characteristic manner. The selected drug reservoir unit may mechanically and/or electrically and/or signally interact with the electrical element. The change of the electrical property may be a change in an electrical resistance and/or a capacity and/or an inductance of the electrical element.
A change in a characteristic manner particularly means that the change is characteristic for the selected drug reservoir unit. For example, the mechanism unit may also be configured to be operatively coupled with an unselected or unintended drug reservoir unit. This unselected drug reservoir unit may also interact with the electrical element and may also change an electrical property of the electrical element. However, this change of the electrical property is different from the change induced by a selected drug reservoir unit. In this way, the mechanism unit may be able to distinguish between a selected and an unselected drug reservoir unit and/or may be configured to react differently when coupled to a selected drug reservoir unit compared to when coupled to an unselected drug reservoir unit.
According to at least one embodiment, the mechanism unit is configured such that operation of the arrangement for changing the operational state of the mechanism unit is prevented unless the electrical property of the electrical element is changed in at least one characteristic manner. For example, the mechanism unit is configured to enable operation of the arrangement for changing the operational state, particularly to only enable it, when the electrical property of the electrical element is changed in at least one characteristic manner. The operation of the arrangement changing the operational state may happen automatically when the electrical property is changed in at least one characteristic manner. Alternatively, enablement of the operation of the arrangement may additionally require a further enabling process to be performed, like receiving an enabling signal from an external device. Particularly, the change of the electrical property of the electrical element in at least one characteristic manner may be a precondition for the operation of the arrangement.
The mechanism unit may be configured to determine whether the electrical property of the electrical element is changed in at least one characteristic manner and to prevent and/or only enable operation of the arrangement unless or when it is determined that the electrical property of the electrical element is changed in at least one characteristic manner, respectively.
The mechanism unit may be configured to be coupled to different kinds of selected/intended drug reservoir units each of which may change the electrical property of the electrical element in a different characteristic manner. Thus, there may be one or more characteristic changes of an electrical property of the electrical element. The mechanism unit may then be configured such that operation of the arrangement for changing the operational state of the mechanism unit is prevented unless the electrical property of the electrical element is changed in any one of the characteristic manners.
In at least one embodiment, the drug delivery device comprises a mechanism unit with an electrical element and an arrangement for changing an operational state of the mechanism unit. The mechanism unit is configured to enable a dispense process for dispensing a drug. Furthermore, the mechanism unit is configured to be operatively coupled with a selected drug reservoir unit which, when coupled with the mechanism unit, interacts with the electrical element and thereby changes an electrical property of the electrical element in a characteristic manner. The mechanism unit is configured such that operation of the arrangement for changing the operational state of the mechanism unit is prevented unless the electrical property of the electrical element is changed in at least one characteristic manner.
With the drug delivery device specified herein it is, inter alia, possible to increase the safety for a user of the drug delivery device. By way of example, only if a drug reservoir unit which is intended for the user, e.g. with a prescribed drug, is coupled to the mechanism unit, the user may be able to use the drug delivery device.
The drug delivery device specified herein may be elongated and/or may comprise a longitudinal axis, e.g. a main extension axis. Additionally or alternatively, the drug delivery device may have a rotational symmetry with respect to the longitudinal axis. A direction parallel to the longitudinal axis is herein called an axial direction. By way of example, the drug delivery device may be cylindrically-shaped.
Furthermore, the drug delivery device may comprise an end, e.g. a longitudinal end, which may be provided to face or to be pressed against a skin region of a human body. This end is herein called the distal end. A drug or medicament may be supplied via the distal end. The opposing end is herein called the proximal end. The proximal end is, during usage, remote from the skin region. The axial direction pointing from the proximal end to the distal end is herein called distal direction. The axial direction pointing from the distal end to the proximal end is herein called proximal direction. A distal end of a member or element or feature of the drug delivery device is herein understood to be the end of the member/element/feature located most distally.
Accordingly, the proximal end of a member or element or feature is herein understood to be the end of the element/member/feature located most proximally.
In other words, distally is used herein to specify directions, ends or surfaces which are arranged or are to be arranged to face or point towards a dispensing end of the drug delivery device or components thereof and/or point away from, are to be arranged to face away from or face away from the proximal end. On the other hand, proximal is herein used to specify directions, ends or surfaces which are arranged or are to be arranged to face away from or point away from the dispensing end and/or from the distal end of the drug delivery device or components thereof. The distal end may be the end closest to the dispensing end and/or furthest away from the proximal end and the proximal end may be the end furthest away from the dispensing end. A proximal surface may face away from the distal end and/or towards the proximal end and a distal surface may face towards the distal end and/or away from the proximal end. The dispensing end may be a needle end where a needle unit is or is to be mounted to the device, for example.
A direction perpendicular to the longitudinal axis and/or intersecting with the longitudinal axis is herein called radial direction. An inward radial direction is a radial direction pointing towards the longitudinal axis. An outward radial direction is a radial direction pointing away from the longitudinal axis. The term “angular direction”, “azimuthal direction” or “rotational direction” are herein used as synonyms. Such a direction is a direction perpendicular to the longitudinal axis and perpendicular to the radial direction.
According to at least one embodiment, the change of the operational state is associated with a mechanical change in the mechanism unit. For example, when the arrangement changes the operational state, an element of the mechanism unit, e.g. an element of the arrangement, e.g. an actuator element of the actuator, is moved.
Additionally or alternatively to a mechanical change, the change in the operational state may be a change in an electrical state of the mechanism unit. For example, when the arrangement changes the operational state, an electrical signal may be transmitted inside the mechanism unit. For example, when changing the operational state, a light-emitting element, like an LED or a display, may be operated in a changed manner.
According to at least one embodiment, the change of the operational state is a change between a state where setting of a drug dose and/or dispensing of a drug dose is prevented (locked state) and a state where setting of a drug dose and/or dispensing of a drug dose is enabled (unlocked state). For example, unless the electrical property of the electrical element is changed in at least one characteristic manner, dose setting and/or dose dispensing is prevented.
According to at least one embodiment, the electrical element comprises a conductor path. The conductor path may comprise metal. For example, the first conductor path is interrupted, i.e. not closed, unless a selected drug reservoir unit is coupled with the mechanism unit.
According to at least one embodiment, the conductor path comprises at least one contact point for contacting at least one contact element of a drug reservoir unit. The contact point may be arranged such that, at least unless the mechanism unit is coupled to a drug reservoir unit, the contact point is freely accessible. The contact point may be an electrically conductive area of the mechanism unit. The contact point may be arranged at a distal end of the mechanism unit and/or may face in distal direction.
For example, the conductor path comprises two contact points for electrically contacting the contact element. The conductor path may be interrupted between the two contact points. The two contact points may be spaced from each other in rotational direction. The two contact points may overlap or may be aligned in axial and/or radial direction.
According to at least one embodiment, when a selected drug reservoir unit with a contact element at a correct position is coupled with the mechanism unit, the at least one contact point electrically contacts the contact element and this changes the electrical property of the conductor path in a characteristic manner. Particularly, the electrical resistance of the conductor path may be changed in a characteristic manner in this way.
By way of example, if an unselected drug reservoir unit is coupled with the mechanism unit with no contact element at the correct position, the electrical property of the conductor path is not changed in a characteristic manner or is not changed at all.
For example, a selected drug reservoir unit comprises a contact element with at least one access point, e.g. two access points. The access points may be electrically conductive areas of the contact element. The access points may constitute ends of the contact element. The access points may be electrically connected via the contact element. The access points may be arranged at a proximal end of the drug reservoir unit and/or may face in proximal direction. A selected drug reservoir unit may comprise a contact element with at least one access point which, when the drug reservoir unit is coupled with the mechanism unit, faces and contacts the at least one contact point. For example, every access point then faces and electrically contacts a different contact point of the mechanism unit. For example, the access points of a selected drug reservoir unit overlap or are aligned in rotational direction with the contact points when the drug reservoir unit and the mechanism unit are coupled.
According to at least one embodiment, the electrical element comprises a sensor, e.g. an inductive sensor or a capacitive sensor. When a selected drug reservoir unit with a coupling element, e.g. a coupling element at the correct position, is coupled to the mechanism unit, this may change the inductance or capacity of the sensor in a characteristic manner. The coupling element may be an electrically conductive element, e.g. a metallic element.
According to at least one embodiment, the arrangement comprises an electromechanical actuator. The actuator may comprise an electric motor and/or an electromagnet.
According to at least one embodiment, operation of the arrangement for changing the operational state comprises operation of the actuator. The actuator may be configured such that, when operated, it moves an actuator element of the actuator between a first position and a second position.
An electromechanical actuator is herein understood to be an actuator which converts an electrical signal into a movement of an actuator element. For example, when operated, the actuator may move the actuator element from the first position into the second position and/or vice versa. The movement between the first position and the second position may be a movement in axial and/or rotational and/or radial direction.
The mechanism unit may comprise a control unit for operating the actuator. For example, for operating the actuator, the control unit sends an electrical signal.
For example, for operating the actuator, the actuator has to be provided with an electrical signal or electrical current. Without being provided with an electrical signal/current, the actuator element may remain in the first position. When the actuator element is in the second position and the actuator is no longer operated or provided with an electrical signal/current, the actuator element may automatically return into the first position. For this purpose, the actuator element in the second position may be pre-biased towards the first position. In other word, the actuator element may be in the first position by default and may only leave the first position when the actuator is operated.
Alternatively, without being provided with an electrical signal/current, the actuator element may be in the second position and when the actuator element is in the first position and the actuator is no longer provided with an electric signal/current, the actuator element may automatically return into the second position.
For example, the mechanism unit is configured to prevent setting a drug dose and/or to dispense a drug dose when the actuator element is in the first position. The mechanism unit may be configured to allow setting a drug dose and/or dispensing a drug dose when the actuator element is in the second position.
By way of example, the mechanism unit comprises a first movable element and a second element, such as a housing element. Dose setting and/or dose dispensing may be associated with a movement of the first movable element relative to the second element in a first and/or second direction. The mechanism unit may be configured to block movement of the first movable element in the first and/or second direction when the actuator element is in the first position in order to prevent dose setting and/or dose dispensing and to allow movement of the first movable element in the first and/or second direction when the actuator element is in the second position as a precondition for dose setting and/or dose dispensing. For example, the first movable element is one of: the drive element, the setting element, the plunger rod, the dose setting member, the dose dispense member.
For the present description, if not stated otherwise, movement of a member or element or feature particularly means a movement relative to the second element and/or the housing element.
According to at least one embodiment, when a selected drug reservoir unit is coupled with the mechanism unit, the conductor path is closed. Closing the conductor path is a change of an electrical property of the conductor path in a characteristic manner. When no drug reservoir unit is coupled with the mechanism unit or an unselected drug reservoir unit is coupled with mechanism unit, the conductor path may not be closed. The first conductor path may, in particular, be closed by the contact element of the selected drug reservoir unit.
According to at least one embodiment, the closed conductor path electrically connects components of the mechanism unit, particularly components of the arrangement. For example, only when the conductor path is closed, the arrangement is operable or operation of the arrangement is enabled.
According to at least one embodiment, the closed conductor path electrically connects an actuator of the mechanism unit with a control unit of the mechanism unit. Additionally or alternatively, the closed conductor path may electrically connect the control unit with an energy source of the mechanism unit and/or may electrically connect the actuator with the energy source and/or electrically connects an output interface of the control unit with an input interface of the control unit. For example, if the conductor path is not closed, the mentioned components may not be electrically connected.
By way of example, when the conductor path is closed due to a coupling of the mechanism unit with a selected drug reservoir unit, the control unit can send a test signal via the output interface along the closed conductor path. The control unit may be configured to receive the test signal via the input interface. The control unit may be configured to operate the arrangement, e.g. the actuator, based on or in response of the received test signal. For example, only when the control unit receives the test signal, the arrangement is operated.
Another possibility is that only when the conductor path is closed, the control unit is electrically connected to an energy source and only then is provided with energy. Yet another possibility is that when the conductor path is closed, the energy source is electrically connected to the actuator and the actuator is then automatically operated without additional operation signals of a control unit.
According to at least one embodiment, the conductor path comprises at least two sections which are arranged movable with respect to each other. The two sections may be electrically connected by a sliding contact.
According to at least one embodiment, the two sections are arranged rotatably and/or axially movable with respect to each other.
The two sections may be assigned to different elements of the mechanism unit, e.g. are arranged on different elements of the mechanism unit. The different elements may be arranged movable with respect to each other. For example, the different elements move with respect to each other during an operation of the mechanism unit so that also the two sections of the conductor path move with respect to each other. The operation of the mechanism unit during which the elements move relative to each other may be a dose setting and/or a dose dispensing event. For example, the two sections move axially and/or rotationally with respect to each other during this operation. By way of example, one section of the first conductor path is assigned to the first movable element.
According to at least one embodiment, during an operation of the mechanism unit, a first section of the conductor path moves on a helical path with respect to a second section of the conductor path.
According to at least one embodiment, the first section comprises a helical conductor track. The helical conductor track may be electrically connected to the second section via the sliding contact.
According to at least one embodiment, the helical conductor track has the same pitch as the helical path so that during operation of the mechanism unit, the two sections of the conductor path stay electrically connected.
According to at least one embodiment, the mechanism unit is configured to enable setting a drug dose to be dispensed. For example, the drug delivery device is a variable dose device where different drug doses can be set or dialed, respectively, by the user. Setting a drug dose may require a user to operate a user interface member.
According to at least one embodiment, during setting a drug dose and/or dispensing a drug dose, the two sections of the conductor path move relative to each other.
According to at least one embodiment, the mechanism unit is configured to be coupled with different kinds of selected drug reservoir units. Each kind of a selected drug reservoir unit may be assigned a different drug. All features disclosed herein for the selected drug reservoir unit are also disclosed for each kind of the selected drug reservoir unit.
According to at least one embodiment, each kind of selected drug reservoir unit is assigned at least one electrical element of the mechanism unit. The mechanism unit may comprise several electrical elements, each assigned to a different kind of selected drug reservoir unit. All features disclosed for the electrical element are also disclosed for the other electrical elements.
For example, each kind of selected drug reservoir unit is assigned at least one electrical element on a one-to-one basis. Alternatively, different kinds of selected drug reservoir units may be assigned at least one common electrical element. Different electrical elements assigned to different kinds of drug reservoir units may share a common part, e.g. a common conductor path section and/or a common contact point.
According to at least one embodiment, each kind of selected drug reservoir changes an electrical property of the at least one assigned electrical element in a characteristic manner when coupled with the mechanism unit.
According to at least one embodiment, the mechanism unit is configured such that operation of the arrangement for changing the operational state of the mechanism unit is prevented unless the electrical property of at least one electrical element assigned to a kind of selected drug reservoir unit is changed in at least one characteristic manner. If the electrical property of at least one electrical element is changed in at least one characteristic manner, operation of the arrangement may be enabled.
According to at least one embodiment, the mechanism unit comprises several electrical elements each having a conductor path. Each of the conductor paths may be assigned to at least one kind of selected drug reservoir unit. Each kind of the selected drug reservoir unit may be assigned at least one conductor path on a one-to-one basis. Different conductor paths may have a common conductor track section.
The different conductor paths may be interrupted and may each comprise two contact points at which the conductor paths are interrupted. The different conductor paths may share one contact point (second contact point) and the associated conductor path section. The different conductor paths may be different in the other contact point (first contact point) and the associated conductor path section. For example, the first contact points of the different conductor paths are offset/spaced from each other in rotational direction. The first contact points of the different conductor paths may overlap or may be aligned in axial and/or radial direction.
Accordingly, different kinds of selected drug reservoir units may, e.g., differ from each other by the position of their contact element, particularly by the position, e.g. the offset in rotational direction, of the respective access points.
According to at least one embodiment, if a selected drug reservoir unit with a contact element at a correct position is coupled with the mechanism unit, an electrical property of the assigned conductor path is changed in a characteristic manner. For example, the assigned conductor path is closed.
According to at least one embodiment, the mechanism unit comprises a guiding structure for interacting with a guide structure of a drug reservoir unit so that when coupling the drug reservoir unit with the mechanism unit, the position of the drug reservoir unit relative to the mechanism unit, particularly relative to the electrical element, is fixed by the interaction between the guiding structure and the guide structure. For example, when the reservoir unit is coupled with the mechanism unit, the interaction between the guide structure and the guiding structure prevents a relative rotation between the reservoir unit and the electrical element.
The guiding structure may be configured to engage with the guide structure. For example, the guiding structure comprises a groove and the guide structure comprises a rib or vice versa. The groove and the rib may be orientated in axial direction.
According to at least one embodiment, the mechanism unit further comprises a communication module for communicating with an external device. The external device may comprise a processor. For example, the external device is a computer or a smartphone or a smartwatch.
The communication module may be electrically coupled with the control unit. There communication module may be configured for a wireless communication with the external device, e.g. for a Bluetooth communication.
According to at least one embodiment, the mechanism unit is configured such that operation of the arrangement in order to change the operational state of the mechanism unit is prevented unless an enabling signal from the external device is received via the communication module. The communication module may then transmit the enabling signal to the control unit and the control unit may, in response to the enabling signal, send an operation signal in order to operate the arrangement, e.g. in order to operate the actuator.
For example, only if the electrical property of at least one electrical element is changed in at least one characteristic manner and only if the enabling signal is received, operation of the arrangement for changing the operational state is enabled or only then the arrangement is operated in order to change the operational state.
For example, the external device may first be used to identify the drug reservoir unit coupled with the mechanism unit, particularly in order to identify the drug of the drug reservoir unit. For this purpose, the drug reservoir unit may comprise a code, like a QR code, which is characteristic for the drug reservoir unit or the kind of the drug reservoir unit. The QR code may be read with the external device in order to identify the drug reservoir unit. The external device may then be configured to decide whether the drug reservoir unit is a correct drug reservoir unit for the user of the external device, e.g. comprising a prescribed drug. Only if this is the case, the enabling signal may be sent by the external device.
In this way, it is possible to provide one mechanism unit which is foreseen for different kind of selected drug reservoir units. However, only if a selected drug reservoir unit is coupled with the mechanism unit and only if this selected drug reservoir unit is indeed intended for the user, the operation of the arrangement in order to change the operational state of the mechanism unit is enabled. This may further increase the safety for the user.
According to at least one embodiment, the drug delivery device comprises a drug reservoir unit coupled with the mechanism unit. The drug reservoir unit may comprise a drug reservoir filled with a drug and/or a drug reservoir holder. The drug reservoir unit may be a selected drug reservoir unit.
Next, a drug reservoir unit for a drug delivery device is specified. The drug reservoir unit may, in particular be, a selected drug reservoir unit as specified herein. Therefore, all features disclosed for the selected drug reservoir unit are also specified for the drug reservoir unit described in the following and vice versa.
According to at least one embodiment, the drug reservoir unit comprises a drug reservoir filled with a drug. Additionally or alternatively, the drug reservoir unit may comprise a drug reservoir holder for holding a drug reservoir. The drug reservoir holder may be configured to hold the drug reservoir such that the drug reservoir is not movable with respect to the drug reservoir holder.
According to at least one embodiment, the drug reservoir unit comprises a coupling element, e.g. contact element, which is arranged such that when the drug reservoir unit is coupled with the mechanism unit of a drug delivery device as described herein, the coupling element changes an electrical property of the electrical element in a characteristic manner.
For example, the coupling element in form of a contact element comprises two access points. The two access points may be arranged at a proximal end of the drug reservoir unit and/or may face in proximal direction. The two access points may be electrically connected to each other via the contact element. As long as the drug reservoir unit is not coupled with the mechanism unit, the access points may be freely accessible. The access points may be configured to be electrically connected to contact points of the mechanism unit in order to close a conductor path of the mechanism unit.
For example, the access points are spaced from each other in rotational direction. The access points may overlap or may be aligned in radial and/or axial direction.
Next, the set is specified. The set comprises a drug delivery device as specified herein and a drug reservoir unit as specified herein. The drug reservoir unit and the mechanism may or may not be coupled with each other.
Hereinafter, the drug delivery device, the drug reservoir unit and the set described herein will be explained in more detail with reference to drawings on the basis of exemplary embodiments. Same reference signs indicate similar, similar acting or same elements in the individual figures. However, the size ratios involved are not necessarily to scale, individual elements may rather be illustrated with exaggerated size for better understanding.
The drug delivery device 100 comprises a mechanism unit MU with a setting mechanism and a dispense mechanism. The setting mechanism is configured for setting a drug dose and the dispense mechanism is configured for dispensing a drug dose. The functional principles of the mechanisms are explained further below.
The mechanism unit MU comprises an inner body 10 and a housing element 11, in the following also referred to as outer body 11. The inner body 10 and the outer body 11 are fixedly connected to each other, i.e. they cannot be rotated or moved axially with respect to each other. The outer body 11 forms an outer surface of the drug delivery device 100 which can be touched or grabbed by a user.
The drug delivery device 100 further comprises a cap 14 and a user interface member 13 in form of a knob 13. The knob 13 is a dose setting member configured to be operated by a user for setting a drug dose. At the same time, the knob 13 is dose dispense member configured to be operated by a user in order to dispense a drug dose.
A drug reservoir unit RU comprising a reservoir 16 and a reservoir holder 15 is received within the cap 14. A drug is filled into the reservoir 16. The reservoir 16 is sealed in proximal direction P by a stopper 17.
The drug reservoir unit RU is operatively coupled or connected, respectively, to the mechanism unit MU. The mechanism unit MU is configured to enable a dispense process for dispensing a drug dose by acting on the drug reservoir 16. For dispensing a drug dose, the stopper 17 is pushed in distal direction D by a plunger rod 29 of the mechanism unit MU. The coupling between the mechanism unit MU and the reservoir unit RU is realized by the inner body 10 being coupled to the reservoir holder 15 via a connection interface which might be a snap connection or a threaded connection. The coupling is preferably reversible. For example, the drug reservoir unit RU is axially and rotationally fixed to the inner body 10 by the coupling.
The mechanism unit MU further comprises a number sleeve 26 and a dial sleeve 27 which are fixedly coupled to each other (e.g. they cannot rotate or move axially relative to each other). The dial sleeve 27 and number sleeve 26 can be implemented by one unitary component. Hence, referrals herein to the number sleeve should be considered as referrals to the dial sleeve and vice versa. The number sleeve 26 may comprise an inner thread which is engaged with an outer thread of the inner body 10. On an outer surface of the number sleeve 26, numbers may be shown, e.g. suitable to indicate the size of the currently set dose. The user can see the numbers through a window 12 of the mechanism unit MU. The window 12 may comprise a lens. The window 12 is formed in the outer body 11. The numbers visible in the window 12 indicate to a user the set/dialed dose. Due to the threaded coupling between the number sleeve 26 and the inner body 10, the dial sleeve 27 and the number sleeve 26 are moved on a helical path in proximal direction relative to the body 10, 11 during setting a drug dose and dispensing a drug dose as will be explained further below.
The mechanism unit MU also comprises a drive sleeve. The drive sleeve comprises a distal drive sleeve 20, a proximal drive sleeve 21 and a drive sleeve coupler 22 coupling the distal drive sleeve 20 to the proximal drive sleeve 21. For setting a drug dose and dispensing a drug dose, the distal drive sleeve 20 and the proximal drive sleeve 21 are fixedly coupled to each other via the drive sleeve coupler 22 so that these elements can neither rotated nor move axially relative to each other during setting and dispensing of a dose. The distal drive sleeve 20 may comprise an inner thread which is engaged with an outer thread of the plunger rod 29. An outer thread of the distal drive sleeve 20 may be engaged to an inner thread of a last dose nut 30, the function of which will be explained further below. The distal drive sleeve and the proximal drive sleeve may be uncoupled, e.g. for a resetting operation when the plunger rod should be moved back into an initial position to reuse the mechanism unit MU for a new reservoir. The uncoupling for the reset, e.g. by moving teeth of the distal and proximal drive sleeves out of engagement, may achieve that the distal drive sleeve can rotate relative to the proximal drive sleeve, thereby enabling a movement of the plunger rod into its initial position. Thus, the drug delivery device can be a reusable device.
Furthermore, the mechanism unit MU comprises a clutch 28, which is fixedly coupled to the knob 13 so that, during setting a drug dose and dispensing a drug dose, the clutch 28 and the knob 13 are not rotated or moved axially relative to each other. A clutch coupler 31 may be provided for this purpose. The clutch coupler 31 expediently rotationally and/or axially locks the knob 13 and the clutch 28 with one another. Clutch 28 and knob 13 could also be integrally formed. Different couplings between clutch and knob than the depicted clutch coupler 31 are possible. The clutch coupler 31 has portions of different outer diameters. In a first portion, the clutch coupler may be connected or engaged to the clutch 28. For example, an inner surface of the clutch coupler 31 may extend along an outer surface of the clutch 28. The clutch 28 or a portion thereof may be received within the first portion of the clutch coupler. A second portion, which may project from the first portion in a central region of the first portion and/or extend proximally, e.g. towards the proximal end of the knob, has an outer diameter which is less than the outer diameter of the first portion. The second portion may have a rod-like configuration. In the second portion, the clutch coupler may extend through an opening in an element is provided within the knob 13 and/or on the dial sleeve 27. This element may be or may comprise a conductor carrier or circuit board (not shown in
A distal clicker 23, a proximal clicker 24 and a clutch spring 25 of the mechanism unit MU are arranged between the clutch 28 and the drive sleeve coupler 22. The clutch spring 25 is coupled to the drive sleeve coupler 22 and to the distal clicker 23. The distal clicker 23 is configured to engage the proximal clicker 24 in proximal direction P. The distal clicker and the proximal clicker can be configured to be coupled via a toothed interface, e.g. via engagable sets of circumferentially disposed teeth (which may be provided at the inner radius or circumference of the clickers 23, 24). The toothed interface may enable rotation of one of the clickers relative to the other one of the clickers under simultaneous axial displacement with the clickers 23 and 24 being biased into engagement via the clutch spring 25 (thereby providing a clicking noise by the rotating teeth). The proximal clicker 24 is configured to abut against the clutch 28 in proximal direction P. Thus, the clutch spring 25 is configured to bias the distal clicker 23, the proximal clicker 24 and the clutch 28 in proximal direction P relative to the drive sleeve coupler 22. The mechanism of the device described herein operates like the device disclosed in WO 2015/028441 A1, the entire disclosure of which is incorporated herein by reference for all purposes. The dial sleeve and the number sleeve as well as the remaining parts of the mechanism are illustrated slightly differently in the figures of the present application but may nevertheless be implemented as depicted and/or described in WO 2015/028441 A1.
The distal clicker 23 may be permanently splined to the proximal drive sleeve 21 so that a relative rotation between these two elements is prevented. However, a certain axial movement between the distal clicker 23 and the proximal drive sleeve 21 may be allowed. The proximal clicker 24 may be permanently splined to the inner body 10 so that a relative rotation between these two elements is prevented, whereas a certain relative axial movement may be allowed.
The distal face of the clutch 28 and the proximal face of the proximal clicker 24 may both be toothed so that these two faces may engage into each other. Furthermore, the distal face of the proximal clicker 24 and the proximal face of the distal clicker 23 may both be toothed so that these two toothed faces can engage into each other. A proximal face of the clutch 28 may be toothed, e.g. dog toothed, and may be arranged to engage a toothed, e.g. dog toothed, distal face of the dial sleeve 27.
Since the proximal drive sleeve 21 is splined to the clutch 28, also the proximal drive sleeve 21 and with it the distal drive sleeve 20 and the drive sleeve coupler 22 are moved on the helical path in proximal direction P relative to the inner body 10.
The plunger rod 29 comprises two outer threads with opposite hand which overlap with each other. The plunger rod 29 is threadedly engaged with the inner thread of the distal drive sleeve 20. The threads are chosen such that during the helical movement of the distal drive sleeve 20 in proximal direction P, the plunger rod 29 does not rotate and is also not moved axially.
The last dose nut 30 may be splined to the inner body 10 and, therefore, cannot rotate relative to the inner body 10. Due to the threaded engagement of the last dose nut 30 with the distal drive sleeve 20, the last dose nut 30 is forced to move in proximal direction P during setting a drug dose. When the maximum dose has been set (e.g. 80 units-independently of whether it has been set in only one drug setting process or several drug setting processes), the last dose nut 30 establishes a rotation-lock interface with the distal drive sleeve 20 so that the last dose nut 30 can no longer rotate relative to the distal drive sleeve 20. As a consequence of this, the distal drive sleeve 20 can no longer be rotated and no further drug dose can be set. The drug delivery device 100 then has to be reset to its initial state.
During setting a drug dose, the toothed faces of the distal clicker 23 and the proximal clicker 24 facing each other ratchet over each other thereby creating a click sound which indicates to a user that a drug dose is set. For this purpose, the teeth of the two faces are preferably formed as shallow triangles so that relative rotation between the clickers 23 and 24 is possible leading to a repeated slight compression and decompression of the clutch spring 25.
After the desired dose has been set, the user can now press on the knob 13 in distal direction D in order to dispense the set drug dose. Thereby, the distally directed force on the knob 13 is transferred from the knob 13 via the clutch 28 to the proximal clicker 24, from there to the distal clicker 23 and this compresses the clutch spring 25. The two clickers 23 and 24 are now pressed against each other and their toothed faces are engaged. When the knob 13 is pressed in the distal direction, the proximal clicker 24 is expediently brought into a splined connection with the proximal drive sleeve 21 to which the distal clicker 23 is permanently splined already. Hence the proximal drive sleeve 21 may be splined to both clickers when the knob 13 is pressed. Relative rotation between the two clickers 23, 24 is then prevented. Since the proximal clicker 24 is splined to the inner body 10 and the distal clicker 23 is splined to the proximal drive sleeve 21, the proximal drive sleeve 21 can no longer rotate relative to the inner body 10.
However, since the proximal drive sleeve 21 is also splined to the clutch 28, also the clutch 28 and the knob 13 can no longer rotate relative to the inner body 10.
The distally directed force applied to the knob 13 has as a consequence that the clutch 28 together with the knob 13 slightly moves in distal direction D relative to the dial sleeve 27 so that the clutch spring 25 is compressed, as already mentioned. The dog toothed engagement between the dial sleeve 27 and the clutch 28 is thereby released so that the dial sleeve 27 is no longer rotationally locked to the clutch 28. Therefore, when the knob 13 is pressed in distal direction D, the dial sleeve 27 together with the number sleeve 26 can still rotate relative to the inner body 10. When the knob 13 is now moved in distal direction D, a stop against the dial sleeve 27 forces the dial sleeve 27 to also move in distal direction D. Due to the threaded engagement of the number sleeve 26 with the inner body 10, the dial sleeve 27 together with the number sleeve 26 moves on a helical path in distal direction D. Thereby, the numbers of the number sleeve 26 visible in the window 12 decrease.
At the same time, the clutch 28, the clickers 23, 24 and the drive sleeve 20, 21, 22 are forced to move in distal direction D (without rotation). The threaded engagement between the plunger rod 29 and the distal drive sleeve 20 forces the plunger rod 29 to rotate. A further threaded engagement between the plunger rod 29 and an inner thread of the inner body 10 may then force the plunger rod 29 to also move distally in order to push the stopper 17 inside the cartridge 16 in distal direction D for dispensing the set drug dose. Since the distal drive sleeve 20 is not rotate during dispensing, the last dose nut 30 moves together with the distal drive sleeve 20 in distal direction D without changing its position relative to the distal drive sleeve 20.
After having dispensed the set drug dose and when the knob 13 has been completely moved back into its initial position, a new drug dose may be set by again rotating the knob 13 on a helical path in proximal direction P. During this, the plunger rod 29 does not change its position. Only when dispensing a dose, the plunger rod 29 is moved in distal direction D.
As explained with respect to
On the proximal face of the dial sleeve 27, a control system comprising a control unit 43A and a battery 43B are arranged. The control unit 43A and the battery 43B may be arranged on a PCB 43C (or conductor carrier) mounted on the proximal face of the dial sleeve 27. The control unit 43A may comprise a processor and/or an IC-chip. The control unit 43A and/or the battery 43B may be electrically connected to the conductor path 41, 44. The elements 43A to 43C may be mounted on the dial sleeve 27. Hence, they may rotate relative to the knob 13 during the dose delivery operation.
As can be best seen in
In order to always maintain an electrical connection between the first section 41A and the second section 41B during dose setting and dose dispensing, a sliding contact 42 is realized between the two sections 41A, 41B. This sliding contact 42 can be best seen in
The helical conductor track of the first section 41A assigned to the dial sleeve 27 and having the same pitch as the helical path on which the dial sleeve 27 moves relative to the body 10, 11 during dose setting and dose dispensing in combination with the sliding contact 42 ensures that the two sections 41A, 41B always stay electrically connected during dose setting and dose dispensing.
As can be further seen in
The closed conductor path 41 may, e.g., electrically connect the control unit 43A to the battery 43B. Alternatively, the control unit 43A may be configured to send an electric test signal via an output interface through the conductor path 41 and only when the conductor path 41 is closed with help of the contact element 4 of the selected drug reservoir unit RU, the test signal is returned to the control unit 43A via an input interface thereof. In this way, it may be determined by the mechanism unit MU that a selected drug reservoir unit RU with a contact element 4 at the correct positions is coupled to the mechanism unit MU. This may then be used to enable a change of the operational state of the mechanism unit MU, which will be explained further below.
As can be seen in
At its free longitudinal end, the arm 50 comprises an electromagnet 52 (see the detailed view of
It is indicated in
As explained with respect to
Instead of using a control unit 43A for operating the actuator 5, it may also be possible that the actuator 5 is automatically operated, for example supplied with electrical current, if the conductor path 41 is closed so that an electric current is transmitted to the electromagnet 52 which changes its magnetization.
As an example, in
As can be further seen in
It can be advantageous to at least partially use the same conductor track, e.g. the same helical conductor track, for the conductor path 41 and the conductor path 44. In this case, the control unit 43A may be configured to differentiate between a current for operating the actuator 5 and a current for verification whether a selected drug reservoir unit RU is coupled to the mechanism unit MU. The differentiation may be based on different frequencies of the different currents. However, we note that systems using just one of the conductor paths 41 and 44 are also within the scope of the present disclosure.
Operation of the actuator 5 may require, additionally or instead of having coupled a selected drug reservoir unit RU, the mechanism unit MU to receive an enabling signal from an external device, like a smartphone or a smartwatch. For this purpose, the mechanism unit MU may comprise a communication module which is, e.g., arranged on the PCB. The communication module may be a wireless communication module, like a Bluetooth module. If the communication module receives an enabling signal from the external device, the control unit 43A may operate the actuator 5 or may enable operation of the actuator 5. For example, the external device may first be used to read a code, like a QR code, e.g. on the drug reservoir unit RU. The external device may then evaluate, based on the read code, if the drug reservoir unit RU is indeed intended for the user, and may then send the enabling signal in order to operate the actuator 5.
We note that the conductor paths 41, 44 or sections thereof could also be comprised by the number sleeve 26, given that the dial sleeve 27 and the number sleeve 26 are expediently axially and rotationally fixed to one another or can be implemented by one unitary component.
In the second exemplary embodiment of the drug delivery device 100, the control unit 43A, the battery 43B and also the PCB are coupled and fixed to the knob 13 so that they move together with the knob 13 during setting and dispensing a drug dose. The actuator 5 comprises an actuator element 50 in form of an elliptical disc 50. This elliptical disc 50 may be rotated with help of an electromotor of the actuator 5. The electromotor is electrically coupled to the control unit 43A so that the control unit 43A can operate the electromotor in order to rotate the elliptical disc 50.
When the elliptical disc 50 is in the first position, the longitudinal ends of the elliptical disc 50 abut against the clamps 55 in radial outward direction which holds the clamps 55 in the lock position. In this lock position, distal ends of the clamps 55 engage into recesses 56 of the outer body 11. This forms a block interface preventing an axial movement of the knob 13 relative to the outer body 11. As explained in connection with
In
As for the first exemplary embodiment, operation of the actuator 5 may only be enabled if a selected drug reservoir unit RU, e.g. with contact elements 4 at correct positions, is coupled to the mechanism unit MU so that the conductor path 41 is closed and/or if an enabling signal of an external device is received by the mechanism unit MU.
As can be seen in
In
It should be emphasized at this point, that a distal movement of the proximal clicker 24 relative to the proximal drive sleeve 21, as it happens when the spindle nut 50 is in the first position and/or when the knob 13 is pressed in distal direction D, may also spline the proximal clicker 24 to the proximal drive sleeve 21 which additionally blocks rotation of the proximal drive sleeve 21 relative to the inner body 10. This may be the case in all exemplary embodiments described herein.
The operation of the actuator 5 may again be controlled by the control unit 43A. This may again be done dependent on whether a selected drug reservoir unit RU is coupled to the mechanism unit MU and/or dependent on whether an enabling signal of an external device has been received.
The mechanism unit MU comprises an intermediate element 58 in form of a blocking sleeve 58 which partially surrounds the distal drive sleeve 20. The blocking sleeve 58 comprises two elongated arms each with a wedge 58.1 protruding in radial outward direction (see
The blocking sleeve spring 59 has pushed the blocking sleeve 58 in distal direction D so that the arms of blocking sleeve 58 are no longer held over the ramps 20.1 and can relax in radial inward direction into a release position. In the release position of the arms of the blocking sleeve 58, the wedges 58.1 of the blocking sleeve 58 do no longer engage into the recesses of the last dose nut 30 so that the block interface is released and rotation of the drive sleeve 20 relative to the last dose nut 30 is allowed. In this way, dose setting is enabled.
The operation of the actuator 5 may again be controlled by the control unit 43A. This may again be done dependent on whether a selected drug reservoir unit RU is coupled with the mechanism unit MU and/or dependent on whether an enabling signal of an external device has been received.
In the fifth exemplary embodiment, the actuator 5 is similar to the actuator 5 of the first exemplary embodiment. Also here, the actuator 5 comprises an actuator element 50 in form of a flexible arm which is at one longitudinal end fixed to the outer body 11 and has one free longitudinal end. A magnet 51 is arranged at the free longitudinal end of the arm 50. An electromagnet 52 is coupled to the outer body 11 and configured to interact with the magnet 51 of the arm 50.
One difference to the actuator 5 of the first exemplary embodiment is that the arm 50 according to the fifth exemplary embodiment is orientated circumferentially instead of axially. For example, the arm 50 extends over at least 90° or at least 150°. A further difference is that the electromagnet 52 is not arranged at the arm 50 but fixed to the outer body 11. However, an arrangement with the electromagnet 52 coupled to the arm 50 and the magnet 51 assigned to the outer body 11 is also conceivable.
The operation of the actuator 5 may again be controlled by the control unit 43A. This may again be done dependent on whether a selected drug reservoir unit RU is coupled with the mechanism unit MU and/or dependent on whether an enabling signal of an external device has been received.
In the sixth exemplary embodiment, the control unit 43A and/or the battery 43B are coupled to the knob 13 so that they move together with the knob 13. The actuator 5 is also part of the knob 13. The actuator element 50 of the actuator 5 is, e.g., a pin which can be moved in radial direction by the actuator 5.
In
In
Also here, the operation of the actuator 5 may be controlled by the control unit 43A. This may again be done dependent on whether a selected drug reservoir unit RU is coupled with the mechanism unit MU and/or dependent on whether an enabling signal of an external device has been received.
Some or all of the actuators 5 described in connection with the first to the sixth exemplary embodiment may also be combined.
The mechanism unit MU is configured to be coupled with three different kinds of selected drug reservoir units RU, to prevent operation of the actuator 5 unless a selected drug reservoir unit RU is coupled thereto and/or to enable operation of the actuator 5 in case any one of the three selected drug reservoir units RU is coupled thereto. For this purpose, the mechanism unit comprises three different conductor paths 41, each having a first contact point 40.1 and a second contact point 40.2. The second contact point 40.2 (lower one in
If a selected drug reservoir unit RU with a contact element 4, particularly with access points 4.1, 4.2, at a correct position (see
If a drug reservoir unit with no contact element 4 at a correct position is coupled with the mechanism unit MU, a change of the operational state may not be prevented.
It shall be emphasized that the structure of the mechanism unit MU comprising several conductor paths 41 and associated contact points 40 for different kind of selected drug reservoir units RU could be realized in every of the previously described exemplary embodiments.
The positions of the access points 4.1, 4.2 of a selected drug reservoir unit RU match with the positions of the contact points 40.1, 40.2 of one conductor path 41 so that when a selected drug reservoir unit RU is coupled with the mechanism unit MU this conductor path 41 is closed via the contact element 4 of the drug reservoir unit RU.
In order to make sure that, when coupling a selected drug reservoir unit RU with the mechanism unit MU, the orientation of the drug reservoir unit RU, particularly in rotational direction, is correct, the mechanism unit MU comprises guiding structures 46 in form of guide grooves (see
The inner body 10 comprises an interface feature 70, e.g. in form of an inner thread 70. The drug reservoir unit RU, in this case the reservoir holder 15 of the drug reservoir unit RU, comprises an interface feature 71, e.g. in form of an outer thread. The two threads 70, 71 may be engaged and thereby establish a connection interface 7 in form of a threaded interface via which the drug reservoir unit RU is releasably connected to the mechanism unit MU. For releasing the connection and the connection interface 7, the drug reservoir unit RU may have to be rotated and/or moved in proximal direction P or distal direction D with respect to the body 10, 11.
In
The coupling element 60 is pivotably suspended in the mechanism unit MU via a joint connection 61 to the inner body 10. Due to this joint connection 61, the coupling element 60 can be rotated out of the lock position of
The coupling element 60 is an elongated element with a main section running essentially in axial direction and a further section 62 running perpendicularly to the main section and to the rotational axis around which the coupling element 60 is rotatable. The coupling element 60 is arranged such that the number sleeve 26, which constitutes a part of the locking mechanism 6 and which moves in axial direction during dose setting and dose dispensing, can, when it reaches a first position (see
As can be seen in
The locking mechanism 6 described in connection with
The concepts proposed in the present disclosure, e.g. the ones for blocking setting and/or dispensing of a dose or the remaining concepts, may not only be applied to the device architecture described above, e.g. in the most detail in conjunction with
The terms “drug” or “medicament” are used synonymously herein and describe a pharmaceutical formulation containing one or more active pharmaceutical ingredients or pharmaceutically acceptable salts or solvates thereof, and optionally a pharmaceutically acceptable carrier. An active pharmaceutical ingredient (“API”), in the broadest terms, is a chemical structure that has a biological effect on humans or animals. In pharmacology, a drug or medicament is used in the treatment, cure, prevention, or diagnosis of disease or used to otherwise enhance physical or mental well-being. A drug or medicament may be used for a limited duration, or on a regular basis for chronic disorders.
As described below, a drug or medicament can include at least one API, or combinations thereof, in various types of formulations, for the treatment of one or more diseases. Examples of API may include small molecules having a molecular weight of 500 Da or less; polypeptides, peptides and proteins (e.g., hormones, growth factors, antibodies, antibody fragments, and enzymes); carbohydrates and polysaccharides; and nucleic acids, double or single stranded DNA (including naked and cDNA), RNA, antisense nucleic acids such as antisense DNA and RNA, small interfering RNA (siRNA), ribozymes, genes, and oligonucleotides. Nucleic acids may be incorporated into molecular delivery systems such as vectors, plasmids, or liposomes. Mixtures of one or more drugs are also contemplated.
The drug or medicament may be contained in a primary package or “drug container” adapted for use with a drug delivery device. The drug container may be, e.g., a cartridge, syringe, reservoir, or other solid or flexible vessel configured to provide a suitable chamber for storage (e.g., short- or long-term storage) of one or more drugs. For example, in some instances, the chamber may be designed to store a drug for at least one day (e.g., 1 to at least 30 days). In some instances, the chamber may be designed to store a drug for about 1 month to about 2 years. Storage may occur at room temperature (e.g., about 20° C.), or refrigerated temperatures (e.g., from about-4° C. to about 4° C.). In some instances, the drug container may be or may include a dual-chamber cartridge configured to store two or more components of the pharmaceutical formulation to-be-administered (e.g., an API and a diluent, or two different drugs) separately, one in each chamber. In such instances, the two chambers of the dual-chamber cartridge may be configured to allow mixing between the two or more components prior to and/or during dispensing into the human or animal body. For example, the two chambers may be configured such that they are in fluid communication with each other (e.g., by way of a conduit between the two chambers) and allow mixing of the two components when desired by a user prior to dispensing. Alternatively or in addition, the two chambers may be configured to allow mixing as the components are being dispensed into the human or animal body.
The drugs or medicaments contained in the drug delivery devices as described herein can be used for the treatment and/or prophylaxis of many different types of medical disorders. Examples of disorders include, e.g., diabetes mellitus or complications associated with diabetes mellitus such as diabetic retinopathy, thromboembolism disorders such as deep vein or pulmonary thromboembolism. Further examples of disorders are acute coronary syndrome (ACS), angina, myocardial infarction, cancer, macular degeneration, inflammation, hay fever, atherosclerosis and/or rheumatoid arthritis. Examples of APIs and drugs are those as described in handbooks such as Rote Liste 2014, for example, without limitation, main groups 12 (anti-diabetic drugs) or 86 (oncology drugs), and Merck Index, 15th edition.
Examples of APIs for the treatment and/or prophylaxis of type 1 or type 2 diabetes mellitus or complications associated with type 1 or type 2 diabetes mellitus include an insulin, e.g., human insulin, or a human insulin analogue or derivative, a glucagon-like peptide (GLP-1), GLP-1 analogues or GLP-1 receptor agonists, or an analogue or derivative thereof, a dipeptidyl peptidase-4 (DPP4) inhibitor, or a pharmaceutically acceptable salt or solvate thereof, or any mixture thereof. As used herein, the terms “analogue” and “derivative” refers to a polypeptide which has a molecular structure which formally can be derived from the structure of a naturally occurring peptide, for example that of human insulin, by deleting and/or exchanging at least one amino acid residue occurring in the naturally occurring peptide and/or by adding at least one amino acid residue. The added and/or exchanged amino acid residue can either be codeable amino acid residues or other naturally occurring residues or purely synthetic amino acid residues. Insulin analogues are also referred to as “insulin receptor ligands”. In particular, the term “derivative” refers to a polypeptide which has a molecular structure which formally can be derived from the structure of a naturally occurring peptide, for example that of human insulin, in which one or more organic substituent (e.g. a fatty acid) is bound to one or more of the amino acids. Optionally, one or more amino acids occurring in the naturally occurring peptide may have been deleted and/or replaced by other amino acids, including non-codeable amino acids, or amino acids, including non-codeable, have been added to the naturally occurring peptide. Examples of insulin analogues are Gly(A21), Arg(B31), Arg(B32) human insulin (insulin glargine); Lys(B3), Glu(B29) human insulin (insulin glulisine); Lys(B28), Pro(B29) human insulin (insulin lispro); Asp(B28) human insulin (insulin aspart); human insulin, wherein proline in position B28 is replaced by Asp, Lys, Leu, Val or Ala and wherein in position B29 Lys may be replaced by Pro; Ala(B26) human insulin; Des(B28-B30) human insulin; Des(B27) human insulin and Des(B30) human insulin.
Examples of insulin derivatives are, for example, B29-N-myristoyl-des(B30) human insulin, Lys(B29) (N-tetradecanoyl)-des(B30) human insulin (insulin detemir, Levemir®); B29-N-palmitoyl-des(B30) human insulin; B29-N-myristoyl human insulin; B29-N-palmitoyl human insulin; B28-N-myristoyl LysB28ProB29 human insulin; B28-N-palmitoyl-LysB28ProB29 human insulin; B30-N-myristoyl-ThrB29LysB30 human insulin; B30-N-palmitoyl-ThrB29LysB30 human insulin; B29-N-(N-palmitoyl-gamma-glutamyl)-des(B30) human insulin, B29-N-omega-carboxypentadecanoyl-gamma-L-glutamyl-des(B30) human insulin (insulin degludec, Tresiba®); B29-N-(N-lithocholyl-gamma-glutamyl)-des(B30) human insulin; B29-N-(ω-carboxyheptadecanoyl)-des (B30) human insulin and B29-N-(ω-carboxyheptadecanoyl) human insulin.
Examples of GLP-1, GLP-1 analogues and GLP-1 receptor agonists are, for example, Lixisenatide (Lyxumia®), Exenatide (Exendin-4, Byetta®, Bydureon®, a 39 amino acid peptide which is produced by the salivary glands of the Gila monster), Liraglutide (Victoza®), Semaglutide, Taspoglutide, Albiglutide (Syncria®), Dulaglutide (Trulicity®), rExendin-4, CJC-1134-PC, PB-1023, TTP-054, Langlenatide/HM-11260C (Efpeglenatide), HM-15211, CM-3, GLP-1 Eligen, ORMD-0901, NN-9423, NN-9709, NN-9924, NN-9926, NN-9927, Nodexen, Viador-GLP-1, CVX-096, ZYOG-1, ZYD-1, GSK-2374697, DA-3091 March-701, MAR709, ZP-2929, ZP-3022, ZP-DI-70, TT-401 (Pegapamodtide), BHM-034. MOD-6030, CAM-2036, DA-15864, ARI-2651, ARI-2255, Tirzepatide (LY3298176), Bamadutide (SAR425899), Exenatide-XTEN and Glucagon-Xten.
An example of an oligonucleotide is, for example: mipomersen sodium (Kynamro®), a cholesterol-reducing antisense therapeutic for the treatment of familial hypercholesterolemia or RG012 for the treatment of Alport syndrome.
Examples of DPP4 inhibitors are Linagliptin, Vildagliptin, Sitagliptin, Denagliptin, Saxagliptin, Berberine.
Examples of hormones include hypophysis hormones or hypothalamus hormones or regulatory active peptides and their antagonists, such as Gonadotropine (Follitropin, Lutropin, Choriongonadotropin, Menotropin), Somatropine (Somatropin), Desmopressin, Terlipressin, Gonadorelin, Triptorelin, Leuprorelin, Buserelin, Nafarelin, and Goserelin.
Examples of polysaccharides include a glucosaminoglycane, a hyaluronic acid, a heparin, a low molecular weight heparin or an ultra-low molecular weight heparin or a derivative thereof, or a sulphated polysaccharide, e.g. a poly-sulphated form of the above-mentioned polysaccharides, and/or a pharmaceutically acceptable salt thereof. An example of a pharmaceutically acceptable salt of a poly-sulphated low molecular weight heparin is enoxaparin sodium. An example of a hyaluronic acid derivative is Hylan G-F 20 (Synvisc®), a sodium hyaluronate. The term “antibody”, as used herein, refers to an immunoglobulin molecule or an antigen-binding portion thereof. Examples of antigen-binding portions of immunoglobulin molecules include F(ab) and F(ab′)2 fragments, which retain the ability to bind antigen. The antibody can be polyclonal, monoclonal, recombinant, chimeric, de-immunized or humanized, fully human, non-human, (e.g., murine), or single chain antibody. In some embodiments, the antibody has effector function and can fix complement. In some embodiments, the antibody has reduced or no ability to bind an Fc receptor. For example, the antibody can be an isotype or subtype, an antibody fragment or mutant, which does not support binding to an Fc receptor, e.g., it has a mutagenized or deleted Fc receptor binding region. The term antibody also includes an antigen-binding molecule based on tetravalent bispecific tandem immunoglobulins (TBTI) and/or a dual variable region antibody-like binding protein having cross-over binding region orientation (CODV).
The terms “fragment” or “antibody fragment” refer to a polypeptide derived from an antibody polypeptide molecule (e.g., an antibody heavy and/or light chain polypeptide) that does not comprise a full-length antibody polypeptide, but that still comprises at least a portion of a full-length antibody polypeptide that is capable of binding to an antigen. Antibody fragments can comprise a cleaved portion of a full length antibody polypeptide, although the term is not limited to such cleaved fragments. Antibody fragments that are useful in the present disclosure include, for example, Fab fragments, F(ab′)2 fragments, scFv (single-chain Fv) fragments, linear antibodies, monospecific or multispecific antibody fragments such as bispecific, trispecific, tetraspecific and multispecific antibodies (e.g., diabodies, triabodies, tetrabodies), monovalent or multivalent antibody fragments such as bivalent, trivalent, tetravalent and multivalent antibodies, minibodies, chelating recombinant antibodies, tribodies or bibodies, intrabodies, nanobodies, small modular immunopharmaceuticals (SMIP), binding-domain immunoglobulin fusion proteins, camelized antibodies, and VHH containing antibodies. Additional examples of antigen-binding antibody fragments are known in the art.
The terms “Complementarity-determining region” or “CDR” refer to short polypeptide sequences within the variable region of both heavy and light chain polypeptides that are primarily responsible for mediating specific antigen recognition. The term “framework region” refers to amino acid sequences within the variable region of both heavy and light chain polypeptides that are not CDR sequences, and are primarily responsible for maintaining correct positioning of the CDR sequences to permit antigen binding. Although the framework regions themselves typically do not directly participate in antigen binding, as is known in the art, certain residues within the framework regions of certain antibodies can directly participate in antigen binding or can affect the ability of one or more amino acids in CDRs to interact with antigen. Examples of antibodies are anti PCSK-9 mAb (e.g., Alirocumab), anti IL-6 mAb (e.g., Sarilumab), and anti IL-4 mAb (e.g., Dupilumab).
Pharmaceutically acceptable salts of any API described herein are also contemplated for use in a drug or medicament in a drug delivery device. Pharmaceutically acceptable salts are for example acid addition salts and basic salts.
Those of skill in the art will understand that modifications (additions and/or removals) of various components of the APIs, formulations, apparatuses, methods, systems and embodiments described herein may be made without departing from the full scope and spirit of the present invention, which encompass such modifications and any and all equivalents thereof. An example drug delivery device may involve a needle-based injection system as described in Table 1 of section 5.2 of ISO 11608-1: 2014 (E). As described in ISO 11608-1: 2014 (E), needle-based injection systems may be broadly distinguished into multi-dose container systems and single-dose (with partial or full evacuation) container systems. The container may be a replaceable container or an integrated non-replaceable container.
As further described in ISO 11608-1: 2014 (E), a multi-dose container system may involve a needle-based injection device with a replaceable container. In such a system, each container holds multiple doses, the size of which may be fixed or variable (pre-set by the user). Another multi-dose container system may involve a needle-based injection device with an integrated non-replaceable container. In such a system, each container holds multiple doses, the size of which may be fixed or variable (pre-set by the user).
As further described in ISO 11608-1:2014 (E), a single-dose container system may involve a needle-based injection device with a replaceable container. In one example for such a system, each container holds a single dose, whereby the entire deliverable volume is expelled (full evacuation). In a further example, each container holds a single dose, whereby a portion of the deliverable volume is expelled (partial evacuation). As also described in ISO 11608-1:2014 (E), a single-dose container system may involve a needle-based injection device with an integrated non-replaceable container. In one example for such a system, each container holds a single dose, whereby the entire deliverable volume is expelled (full evacuation). In a further example, each container holds a single dose, whereby a portion of the deliverable volume is expelled (partial evacuation).
The disclosure described herein is not limited by the description in conjunction with the exemplary embodiments. Rather, the disclosure comprises any new feature as well as any combination of features, particularly including any combination of features in the patent claims, even if said feature or said combination per se is not explicitly stated in the patent claims or exemplary embodiments.
| Number | Date | Country | Kind |
|---|---|---|---|
| 21315216.8 | Nov 2021 | EP | regional |
The present application is the national stage entry of International Patent Application No. PCT/EP2022/080416, filed on Nov. 1, 2022, and claims priority to Application No. EP 21315216.8, filed on Nov. 3, 2021, the disclosures of which are incorporated herein by reference.
| Filing Document | Filing Date | Country | Kind |
|---|---|---|---|
| PCT/EP2022/080416 | 11/1/2022 | WO |
