Patent Grant
12070571
The present application is a United States national stage application of International patent application PCT/IB2019/055742 filed on Jul. 5, 2019 designating the United States, and claims foreign priority to European Patent Application Numbers EP18182850.0 filed on Jul. 11, 2018, EP18215745.3 filed on Dec. 21, 2018, EP19151323.3 filed on Jan. 11, 2019, EP19151324.1 filed on Jan. 11, 2019, EP19151325.8 filed on Jan. 11, 2019, and EP19155800.6 filed on Feb. 6, 2019, and claims also foreign priority to International Patent Application No. PCT/IB2019/051237 filed on Feb. 15, 2019, the contents of all eight (8) documents being herewith incorporated by reference in their entirety.
This disclosure relates to a drug delivery system. In particular, it relates to a drug delivery system which may comprise a drug container and a pressurized means.
Many kinds of delivery device are available such as pen, jet and other device designed to inject a single or multiple dose of drug contained in a cartridge or reservoir. Depending on the application (acute intervention, prevention or long-term treatment) the intended user is a healthcare professional, a caregiver or the patient himself. The main drawback of these devices is that the duration of the injection must be short because the user has to handle the device for the whole duration of the delivery. This means that the solution cannot be viscous, the volume to be injected has to be low, and/or the flow rate must be within a short range.
For example, while pen injectors are preferred to inject aqueous solutions up to 3 mL, on-body-injectors become desirable in case of viscous solutions and/or large volume of drugs. Furthermore, some specific subcutaneous formulations cannot be injected via a pen injector even if they comprise recombinant human hyaluronidase as excipient to lower the resistance of the tissues during the SC injection. As consequence, there is a growing interest in providing an on-body-injector able to infuse various formulations of drugs or solution.
The bolus delivered by an on-body-injector is usually accomplished by moving a plunger inside a cylindrical barrel filled with the drug (the reservoir being prefilled or filled by the user). Various engines are used to move the plunger: preloaded spring, linear motor, stepper motor, induction motor, . . . Usually, the on-body-injectors are fully disposable thus such devices shall ideally comprise no complex engine.
Another type of on-body-injectors comprises a flexible pouch (storing the drug) pressurized by an elastomeric bladder filled with a propellant. Such devices comprise several drawbacks:
Such structure of device is more adapted to very large volume of reservoir (typ. 100 ml or more) in order to maintain the dead volume less than 10%, preferentially less than 5%, more preferentially less than 2%. Moreover, the mechanical constraints related to the large bladder area that is pressurized lead to the use of a reinforced and heavy housing and thus it cannot be wearable.
For a wearable device directly secured to the patient skin, there is a need of an alternative device structure that:
According to a first aspect of the disclosure, the document describes a delivery system configured to be secured on a patient skin comprising:
The first movable wall and the second movable wall are facing each other and define a containers' interface having a cavity. The system may further comprises a vent device having a first venting element (such as one or more aperture) configured to allow a pressure equilibration between the cavity of the containers' interface and the outside of the delivery system when at least one of the first movable wall and the second movable wall moves. For example, the vent device may provide access to the fluid surrounding the delivery system which may be the ambient air/gas at the atmospheric pressure. The first venting element may prevent any (unintended) over pressure on the first movable wall caused by a leak or air trapped in the cavity of the containers' interface. The first venting element may be configured to be enabled and/or disabled at a specific time period(s) of use.
The vent device may be configured to prevent any unintended pressure increase in the first storage compartment.
The first movable wall may be configured to change the volume of the first storage compartment. And, the second movable wall may be configured in such a manner that a change of the second storage volume induces a movement of the second movable wall. At least one of the first and second movable walls may comprise a flexible membrane.
At least one of the first storage compartment and the second storage compartment may be initially empty and the volume of the containers' interface cavity may initially be maximal.
At least one of the first container and the second container may comprise a rigid part. Said rigid part may extend along at least one length of at least one of the first container and the second container in at least one dimension.
In the case where a container comprises a flexible membrane and a rigid part, the flexible membrane may be fixed or attached to the rigid membrane in order to provide the storage compartment. It may be fixed or attached for example at its edge. For example, it can be welded e. g. by ultrasonic, laser or thermal sealing methods or by standard mechanical joining methods.
In the case where a container comprises two flexible membranes, a first flexible membrane may be fixed or attached to a second flexible membrane in order to provide the storage compartment. It may be fixed or attached for example at its edge. For example, it can be welded e. g. by ultrasonic, laser or thermal sealing methods or by standard mechanical joining methods.
The delivery system may comprise a housing in which at least a part of at least one of the first container and the second container may be arranged. For example, the delivery system may comprise a housing including a concave internal structure fitted to at least a part of the external surface of at least one of the first container and the second container.
At least one of the housing of the system, the first container, and the second container may comprise a part or a protrusion including the vent device (for example the first venting element or a second venting element as descried thereafter). The protrusion may extend toward the opposite container. And/or, the protrusion may extend along at least a part of the peripheral edge of the container interface cavity.
At least a part of the first container and/or the second container may form a part of the housing of the delivery system.
At least one of the first container and the second container may comprise a concave internal structure in which at least one of the first movable wall and the second movable wall may move or may collapse. Preferentially, the concave internal structure may be a rigid structure and may comprise a rigid internal wall of the storage compartment.
The medical fluid may be an incompressible fluid such as a liquid or a compressible fluid (such as a gas).
Preferentially, the first container and the second container are in pressure communication via the first movable wall and the second movable wall.
In some embodiments, the first container and the second container may be in pressure communication only when the first movable wall and the second movable wall are at least partially in contact.
The cavity of the containers' interface may comprise a variable volume depending on the movement of at least one of the first movable wall and the second movable wall.
Preferentially, the delivery system comprises a third container configured to store a compressed fluid in a third storage compartment. The delivery system may further comprise at least one of a fluid pathway and a fluid communication device (also called valve device) configured to allow fluid communication between the third storage compartment and the second storage compartment when the fluid communication device is in an open state (also called thereafter second position). Preferentially, the fluid communication device further comprises a closed state (also called thereafter first position) configured to prevent the fluid communication between the third storage compartment and the second storage compartment.
In order to prevent any (unintended) pressure increase into the second storage compartment, the vent device may comprise a second venting element (such as one or more aperture) configured to allow a pressure equilibration between the second storage compartment and the outside of the delivery system. As described above, the vent device may provide access to the fluid surrounding the delivery system (outside of the delivery device) which may be the ambient air/gas at the atmospheric pressure. For example, the second venting element may prevent any over pressure in the second storage compartment during the storage time period, caused by leakage of the compressed gas from the third container. The second venting element may be configured to prevent any unintended pressure increase in the first storage compartment due to an (unintded) increase of at least one of the third variable volume and the second variable volume.
The second venting element may be configured to be enabled and/or disabled at a specific time period(s) of use. For example, the second venting element may be disabled (occluded/closed) during the infusion, at the time of the activation of the infusion or (just) before the transition of the fluid communication device from the first position (closed state) to the second position (open state).
In some embodiments, the vent device (for example at least one of the first venting element and the second element) and the fluid communication device may be operatively coupled. For example, the delivery system may further comprise a control device arranged to close the second venting element when the fluid communication device is open. The control device may comprise at least one of an electronic element and a mechanical element.
Before the activation of the delivery device, the second venting element may provide a pressure equilibration of the second storage and outside of the delivery device (the vent device is, this case, enabled), but when the delivery device is activated, the second venting element is preferentially disabled (for example: automatically closed, clogged or occluded) in order to insure a pressure increase into the second storage compartment in such a manner the second movable wall moves toward the first movable causing the solution to flow.
At the end of the solution delivery, the second venting element (or another device) may be enabled or open in order to discharge the pressure (in the second storage compartment) to the outside.
The delivery system may further comprise a triggering device operable coupled with the fluid communication device and configured to change the status or position of the fluid communication device. The delivery system may further comprise a countdown mechanism configured to activate the triggering device after a predetermined time period.
The delivery system may further comprise a transcutaneous device which is in fluid communication with an outlet of the first storage compartment.
The delivery system may further comprise a valve device which is in fluid communication with an outlet of the first storage compartment.
The delivery system may further comprise a hydrophobic membrane which is in fluid communication with an outlet of the first storage compartment. The hydrophobic membrane may cover the outlet of the first storage compartment.
The delivery system may further comprise a flow restrictor which is in fluid communication with an outlet of the first storage compartment.
The delivery system may further comprise a first status indicator (for example an infusion status indicator as described thereafter) which is in fluid or pressure communication with an outlet (for example) of the first storage compartment.
The delivery system may comprise a second status indicator (for example a filling indicator as described thereafter) which is in fluid or pressure communication with the first storage compartment or the cavity between both flexible membranes.
The delivery system may further comprise a pressure transducer which is in fluid communication with an outlet of the first storage compartment.
Preferentially, the delivery system is configured to be used only once or be non reusable, for example, the third container cannot be refilled, the fluid communication once opened cannot be closed, the valve device cannot be moved at it initial state, . . . Preferentially, the delivery system is configured to infuse the whole content of the first container as a single bolus.
According to a second aspect of the disclosure, the document further describes a delivery system configured to be secured on a patient skin comprising:
The first container is at least partially arranged into the first cavity.
The delivery system further comprises a vent device configured to vent the first cavity and a second flexible membrane having a first side configured to be at least partially in contact with the first flexible membrane in delivery condition. The second variable storage compartment is arranged on another side of the second flexible membrane.
Preferentially, the delivery system is configured to be used only once or be non reusable, for example, the third container cannot be refilled, the fluid communication once opened cannot be closed, the valve device cannot be moved at it initial state, . . . Preferentially, the delivery system is configured to infuse the whole content of the first container as a single bolus.
According to a third aspect of the disclosure, the document describes a delivery system configured to be secured on a patient skin comprising:
The medical device further comprises a containers' interface configured to operatively couple the first container and the second container such that a volume increase of the second variable volume may induce a volume decrease of the first variable volume.
The containers' interface may be defined by a first wall of the first container and a second wall of the second container.
The first wall may comprise a first movable wall, for example, a first flexible membrane. The second wall may comprise a second movable wall, for example, a second flexible membrane.
The containers' interface may comprise a cavity which may be vented by a first venting element. The first venting element may be configured to allow a pressure equilibration between the cavity of the containers' interface and the outside of the delivery system when at least one of the first variable volume and the second variable volume change. For example, the first venting element may provide access to the fluid surrounding the delivery system which may be the ambient air/gas at the atmospheric pressure.
The second container may comprise a second venting element configured to vent the second storage compartment. The second venting element may be configured to allow a pressure equilibration between the second storage compartment and the outside of the delivery system. For example, the second venting element may provide access to the fluid surrounding the delivery system which may be the ambient air/gas at the atmospheric pressure.
The delivery system may comprise a first valve device configured to occlude the second venting element.
The delivery system may comprise a fluid pathway configured to provide fluid communication between the third storage compartment and the second storage compartment. The delivery system may comprise a second valve device having a first position configured to close the fluid pathway and a second position configured to open the fluid pathway. The delivery system may comprise a trigger device configured to change the position of the second valve device.
In some embodiments, the first valve device and the second valve device may be operatively coupled such that:
In some embodiments, the skin adherable unit comprises a cradle unit configured to be secured on the patient skin and to (removably—optional) receive the medical device. The medical device may comprise a first position where the medical device is not fixed to the cradle unit and a second position where the medical device is fixed to the cradle unit.
In some embodiments, the skin adherable unit may be operatively coupled with at least one of the first valve device and the second valve device such that:
Preferentially, the delivery system is configured to be used only once or be non reusable, for example, the third container cannot be refilled, the fluid communication once opened cannot be closed, the valve device cannot be moved at it initial state, . . . Preferentially, the delivery system is configured to infuse the whole content of the first container as a single bolus.
According to a fourth aspect of the disclosure, the document describes a delivery system configured to deliver medical fluid to a patient; The system may comprise at least one of:
The delivery system may further comprise a first valve device having:
The medical device may further comprise a containers' interface configured to operatively couple the first container and the second container such that a volume increase of the second variable volume may induce a volume decrease of the first variable volume.
Preferentially, the system further comprises a vent device configured to prevent any unintended pressure increase in the first storage compartment.
The containers' interface may comprise a first movable wall of the first container and a second movable wall of the second container. At least one of the first movable wall and the second movable wall may comprise a flexible membrane. The containers' interface may comprise a cavity defined by at least the first and the second movable wall.
The cavity of the containers' interface may comprise a third variable volume. The vent device may comprise a first venting element configured to allow a pressure equilibration between the cavity of the containers' interface and the outside of the delivery.
The vent device may comprise a second venting element second venting element configured to allow a pressure equilibration between the second storage compartment and the outside of the delivery.
At least one of the first venting element and the second venting element may be configured to prevent any unintended pressure increase in the first storage compartment due to an (unintended) increase of at least one of the third variable volume and the second variable volume.
In some embodiments, the system comprises a second valve device configured to occlude at least partially the second venting element. The first valve device and the second valve device may be operatively coupled such that:
In some embodiments, the system comprises a trigger device configured to change the position of the first valve device. The second valve device and trigger device may be operatively coupled such that:
In some embodiments, the medical device may comprise a first position and a second position. The medical device may be operatively coupled to at least one of the first valve device, the second valve device, the trigger device, and the skin adherable unit such that:
The position of the medical device may be a position relative to the skin adherable unit (as the cradle unit described in this document) or to the patient skin or to the infusion site. The second position may be required for the infusion, for example, the second position may be the position of the medical system when the medical system is secured on the patient skin and/or ready to use and/or for infusion. The first position may be required during the filling of the first container or all other position before the medical device has been secured on the patient skin.
Preferentially, the delivery system is configured to be used only once or be non reusable, for example, the third container cannot be refilled, the fluid communication once opened cannot be closed, the valve device cannot be moved at it initial state, . . . Preferentially, the delivery system is configured to infuse the whole content of the first container as a single bolus.
The present disclosure will be better understood at the light of the following detailed description which contains non-limiting examples illustrated by the following figures:
In the following detailed description, reference is made to the accompanying drawings that form a part hereof, and in which are shown by way of illustration several embodiments of devices, systems and methods. It is to be understood that other embodiments are contemplated and may be made without departing from the scope or spirit of the present disclosure. The following detailed description, therefore, is not to be taken in a limiting sense.
All scientific and technical terms used herein have meanings commonly used in the art unless otherwise specified. The definitions provided herein are to facilitate understanding of certain terms used frequently herein and are not meant to limit the scope of the present disclosure.
As used in this specification and the appended claims, the singular forms “a”, “an”, and “the” encompass embodiments having plural referents, unless the content clearly dictates otherwise.
As used in this specification and the appended claims, any direction referred to herein, such as “top”, “bottom”, “left”, “right”, “upper”, “lower”, and other directions or orientations are described herein for clarity in reference to the figures and are not intended to be limiting of an actual device or system. Devices and systems described herein may be used in a number of directions and orientations.
As used herein, “have”, “having”, “include”, “including”, “comprise”, “comprising” or the like are used in their open ended sense, and generally mean “including, but not limited to.
As used in this specification and the appended claims, the term “or” is generally employed in its sense including “and/or” unless the content clearly dictates otherwise.
As used in this specification and the appended claims, “at least one of A, B, and C”, “at least one of A, B or C”, “selected from the group consisting of A, B, C, and combinations thereof” or the like are used in their open ended sense including “only A, or only B, or only C, or any combination of A, B and C” unless the content clearly dictates otherwise.
The present application claims the benefit of the priority of PCT/IB2019/051237 filed on 15 Feb. 2019, EP19155800.6 filed on 6 Feb. 2019, EP19151325.8 filed on 11 Jan. 2019, EP19151324.1 filed on 11 Jan. 2019, EP19151323.3 filed on 11 Jan. 2019, EP18157250.4 filed on 16 Feb. 2018, EP18182850.0 filed on 11 Jul. 2018 and of EP18215745.3 filed on 21 Dec. 2018 in the name of Debiotech SA, the entire disclosure of which are incorporated herein by reference.
1.1 General Concept
As shown by the
The delivery system (1) further comprises a pressurization means (14) which may be operatively coupled (6) to the first container (11). For example, the pressurization means (14) may be adapted or configured to pressurize the first container so as to cause the flow of the medical fluid from the first container (11) to the patient (2). For example, if the first container (11) comprises a flexible membrane, the pressurization means (14) may be configured to act on the flexible membrane in order to pressurize the first container.
The delivery system (1) may further comprise an action means (15) which may be operatively coupled to the pressurization means (14). For example, the action means (15) may be adapted or configured to allow the pressurization of the first container preferentially via the pressurization means (14).
According to a preferred embodiment, the pressurization means (14) comprises a container (for example a second container (12)) and the action means (15) comprises a container (for example a third container (13)) in fluid communication or pressure communication with the pressurization means (14). The action means (15) may further comprise at least one of a valve device (4) and a fluid pathway (5) allowing fluid communication between the third container and the second container for example when the valve device (4) is in open position. At least one of the valve device and the fluid pathway may define a fluid communication device as described in this document. The third container may be configured or adapted to store a compressed fluid (in a compressed state) such as a propellant. The propellant may be a liquefied gas that exhibits a large value of vapor pressure at ambient temperature. The pressure range is therefore determined by the evolution of this vapor pressure within a predefined range of functioning temperature, typically from 5° C. to 40° C. Considering isobutane as a potential propellant, this pressure (absolute) is for instance 1.86 bar at 5° C., 3 bar at 20° C. and 5.25 bar at 40° C.
According to another embodiment, the pressurization means (14) may be a spring, an elastic device, an actuator which acts on the first container, a plunger, . . . And the actions means (15) may comprise an element adapted to generate a gas, such as a battery or other chemical elements, or to act on the pressurization means (14) . . .
The delivery system may be intended for single use. Thus, after a single use/delivery, the delivery system may be discarded, for example entirely discarded.
The delivery system (1) may be configured to deliver the entire volume of the solution stored in the first storage compartment in a single bolus. Thus, once the trigger device is activated, the delivery system will infuse the solution to the patient until the first storage compartment is substantially empty.
The delivery system may be adapted to inform the patient about the end of the delivery, via an indicator device (also called status indicator device).
In one embodiment, the delivery system may comprise an electronic device configured to control and/or monitor the delivery. Preferentially, the delivery system does not comprise any electronic element configured to convey the solution and/or to pressurize the first container and/or to control the pressurization means (14) and/or the action means (15). Nevertheless, an indicator device may comprise some electronic elements (embedded electronic device) such as a sensor (pressure sensor or other), a processor and/or a light indicator (LED, . . . ). The embedded electronic may be configured to send information to a tierce device. For example, the embedded electronic may comprise a communication device adapted to send data to a remote device (Smartphone, remote server, PC, PDA, . . . ). The embedded electronic may be configured to send information relative to at least one of a delivery state, a system status, treatment compliance, date and time of the treatment, infused volume, flow rate, end of the infusion, failure, anomaly, occlusion, leak, . . .
In one embodiment, the delivery system may be configured to operate without any electronic element and/or battery.
1.2 General Structure
The delivery system (1), disclosed by at least one of the
Preferentially, the first container (11) comprises a first storage compartment (11a), a first movable wall (for example a flexible wall/membrane) configured to change a capacity of the first container (11) (for example the volume of the storage compartment (11a)) and an outlet port allowing the solution to get out of the storage compartment (11a). The outlet port is configured to be in fluid communication with the transcutaneous device (7), for example when the delivery system delivers the solution to the patient.
The first container may comprise an inlet port to fill the storage compartment (11a) with the solution intended to be delivery to the patient (as shown by
As shown by the
The fluid pathway is preferentially straight but it may comprise one or several curved sections.
The fluid pathway may comprise a hollow rod which may be made from at least one of the following materials: metal, plastic, silicon, ceramic or glass. The hollow rod may comprise a sharp end (such as a needle) configured to be inserted into the transcutaneous device.
Other examples of flow restrictor (which may be implemented in the delivery system) have been described by at least one of the following documents: WO2010020891A1, WO2011098946A1, WO2014108860A1, and WO2011098867A1. The contents of these documents are incorporated by reference in the present document.
The pressure means (14) (for example the second container and the propellant) and the flow restrictor (19) may be configured in order to reach a substantially constant flow rate for substantially the entire duration of the infusion.
The delivery system may comprise a valve device (26) (as shown by the
Preferentially, the second container (12) comprises a second storage compartment (12a), a second movable wall (for example a flexible wall/membrane) configured to change capacity of the second container (12) (for example the volume of the second storage compartment (12a)). More particularly, a change of the volume of the second storage compartment induces a movement of the second movable wall (for example a movement/deformation/stretching of the flexible membrane). The second container may comprise an inlet port. The second container (12) may comprise an outlet port (which may be a vent device as described thereafter) configured to expel the propellant from the second container for example at the end of the delivery.
Preferentially, the first container (11) and the second container (12) comprise a containers' interface (6) configured in such a manner that the first container and the second container are in pressure communication when the first movable wall and the second movable wall are at least partially in contact.
As disclosed by the
The cavity of the containers' interface may have a variable volume depending on the delivery state. This cavity is preferentially vented by a vent device as described below.
The vent device may comprise a first venting element (16) (for example an aperture) intended to allow fluid communication between at least an inside part of the delivery system and the outside environment of the delivery system. The first venting element may be configured to keep the cavity of the containers' interface (6) vented.
In some embodiments, the first venting element may be configured to provide a pressure equilibration of the containers' interface cavity to the (external ambient) atmosphere (for example with the (external) air surrounding the delivery system which may be at the atmospheric pressure), preferentially when at least one of the first storage compartment volume and the second storage compartment volume varies.
In some embodiments (for example shown by
In some embodiments, the first venting element may be configured to expel (outside the delivery system) the air/fluid (trapped) present into the containers' interface cavity when the first movable wall moves towards the second movable wall and/or when the second movable wall moves towards the first movable wall.
In some embodiments, the first venting element may be configured to allow air/fluid entry into the containers' interface cavity when the first movable wall moves away from the second movable wall and/or when the second movable wall moves away from the first movable wall.
In some embodiments, the first venting element may comprise one or more aperture (for example a through hole). The vent device may further comprise a hydrophobic membrane, a filter or a coating configured to prevent the flow of water into the enclosure. The first venting element may comprise a baffle configured to prevent the insertion of a straight and rigid tip through the venting element.
An example of a vent device which may be comprised in the delivery system is described by the United States Patent: U.S. Pat. No. 9,872,955, the entire disclosure of which is incorporated herein by reference.
In some embodiments, the second container may comprise a second venting element (16a) (as shown by the
In case of a (unintended) leakage of the third storage compartment into the second storage compartment, the second venting element (16a) may prevent any unintended pressure increase into the second storage compartment (12a).
During the storage time period, the delivery system may be stored in a cavity of a closed (e.g. sealed) packaging. In this case (and until the packaging is open) the second venting element may provide an air/fluid communication of the second storage compartment (12a) with the cavity of the packaging.
During the filling of the first storage compartment, if the second storage compartment is not empty, the first movable wall may exert a force (due to the volume increase during the filling process) on the second movable wall and may decrease the volume of the second storage compartment. In this case, for example, the second venting element may prevent any (unintended) pressure increase and/or may make the filling process easier and more efficient.
At the end of the infusion (after solution delivery), the second venting element may discharge the pressure present in the second storage compartment. Thus, the delivery system may be discarded without or with a limited pressure in at least one of the first, second and third storage compartment.
The second venting element (16a) may be configured to be enabled and/or disabled, for example, the second venting element may comprise a valve device (4a) having two positions:
The second venting element (16a) may comprise a (slight) controlled leak, for example, one or more small hole(s) and/or a porous material, configured to provide an air/fluid communication with determined fluid resistance. The controlled leak may be configured to ensure that the solution is wholly infused to the patient (after activation of the delivery system) and to allow the pressure to be slightly expelled to the outside (at least after the solution delivery). Thus, the controlled leak is designed in such a manner that the second container comprises or keeps enough propellant (gas at a minimal pressure) to exert a determined pressure to the first container during the whole duration of the infusion.
The porous material and/or the small hole may be arranged on at least a part of the wall of the second container such that a (slight) controlled leak may occur. For example, the second movable wall may comprise a silicone material or other porous material.
In some embodiments, the second venting element may comprise one or more aperture (for example a through hole). As described above, the vent device may further comprise a hydrophobic membrane, a filter or a coating configured to prevent the flow of water into the enclosure. The second venting element may comprise a baffle configured to prevent the insertion of a straight and rigid tip through the venting element.
The
The
A small (slightly) controlled leak may be designed to decrease the pressure after activation and/or, the user may be prompted to act on (e.g. pull) the trigger device (504) to open the fluid pathway (506) at the end of the infusion.
The
The valve device may comprise an elastic device (for example a spring (508)) configured to maintain the valve device in a predetermined position.
For example, the elastic device may maintain the valve device in a second position (closed) and action may be required to open the valve (for example before or during the first container filling or before the activation of the infusion or after the delivery). For example, the user may be prompted to push on the valve device (e.g. the moving body) to open the valve device (507).
The
The
For example,
Preferentially, the second relative position is required the whole duration of the infusion.
In some embodiments, the cradle unit is configured to occlude the fluid pathway when there are in the second relative position.
In some embodiments, the delivery system may comprise a valve device (507) having a moving body (509) configured to open and close a fluid pathway (506) in collaboration with the cradle unit. The valve device may further comprise an elastic device (for example a spring) configured to maintain the valve device in a predetermined position.
In some embodiments, a trigger device (as disclosed above) may be adapted to be also operatively coupled with a cradle unit. Furthermore, the trigger device (504) shown in
Preferentially, as described above (
The delivery system may comprise a valve device (4) (also called fluid communication device) configured to prevent the fluid communication (or to isolate the second storage compartment from the third storage compartment) when the valve device is in a first state/position (for example closed) and to allow the fluid communication between the second storage compartment and the third storage compartment when the valve device in a second state/position (for example open).
The delivery system may comprise a trigger device (8). The trigger device may be configured to initiate a change of delivery system state. Preferentially the trigger device is operatively coupled to the valve device (4) (for example mechanically). The trigger device may be configured to change the state/position of the valve device (4) in order to pass from a first state (first position) to a second state (second position) and/or vice versa.
The trigger device (8) may comprise a button such as a push or a sliding button, a timer, and/or a countdown mechanism. When the trigger device is activated (for example by the user/patient), the trigger device is configured to initiate the change of the delivery system state or to launch the countdown or the timer.
The delivery system may comprise a status indicator (9) as disclosed by the European patent application number EP18157250.4 or international patent application PCT/IB2019/051237, the entire disclosure of which are incorporated herein by reference. The indicator device may be operatively coupled to at least one of the first container, the second container, the third container, and the transcutaneous device. The indicator device (9) may be configured to provide information to the user concerning the status of the delivery system or one of the listed elements, for example: Occlusion, ready, ready to be activated, ready for filling, ready to infuse, delivery in progress, error, full storage compartment, empty storage compartment, delivery finished, . . .
The delivery system may comprise one or several parts. As disclosed by
As disclosed by the
The vent device may be arranged on at least one of the first, the second and the third housing, preferentially in fluid communication with the containers' interface (6).
The housings or the containers may be configured to be coupled there between in order to form the delivery system. The coupling process may be performed during the manufacturing process or by a user before the use.
The housing may comprise rectangular shape, trapezoidal shape, egg shape, butterfly shape, disks shape, triangular shape or ellipsoidal shape. Preferentially the housing is thin with smooth angles.
Preferentially, to solve problems related to the recycling of waste, at least one of the second container and the third container may be configured to be removable from the first container, for example at the end of the treatment. Thus at least one of the containers may be discarded in appropriate waste.
At least one of the third container and the second container may be adapted to the compressed fluid (propellant) and/or to the physical features (volume, viscosity, . . . ) of the solution stored in the first container. In other terms, the features (shape, dimension, material, . . . ) of the third container and/or the second container are designed by taking into account the physical features (volume, viscosity, . . . ) of the compressed fluid (propellant) and/or the physical features (volume, viscosity, . . . ) of the solution stored in the first container.
The delivery system may comprise a skin-adherable unit (3) configured to secure the delivery system to the patient skin. The skin-adherable unit may comprise a first side having an adhesive surface facing toward the skin surface of the patient for adhesion and a removable cover for covering the skin-adherable unit. The skin-adherable unit may further comprise a frame and coupling device configured to (optionally removably) secure the delivery system.
1.3 Containers' Interface
The
In the
In
In
In
According to the
A first cavity (45) may be defined by at least one of a third flexible membrane (6c) and the first flexible membrane (6a). The third flexible membrane (6c) may be configured to move away from and/or toward the first container (11) (or the second container (12)) and to vary the volume of the first cavity (45). The first cavity may comprise a dedicated vent device (16) configured to vent the first cavity for pressure equilibration for example when the first container (11) is being filled.
A second cavity (46) may be defined by at least one of a third flexible membrane (6c) and the second flexible membrane (6b). The third flexible membrane (6c) configured to move away from and/or toward the first container (11) (or the second container (12)) and to vary the volume of the second cavity (46). The second cavity may comprise a dedicated vent device (16) configured to vent the second cavity for pressure equilibration for example when at least one of the second flexible membrane (6b) and the third flexible membrane (6c) moves or when the volume of at least one of the first storage compartment and the second storage compartment varies.
The third flexible membrane may be configured to provide additional insulation (shock and/or thermal) to the first container (11). Furthermore, in the case of second container leakage, the fluid initially stored in the second storage compartment may exit by the dedicated vent device (16).
According to the
According to the
1.4 Delivery System States
The
Initial State:
In one embodiment, as disclosed by the
In another embodiment (for example as the state of the system shown by
In both cases, preferentially, the movable walls of the first and the second containers are not in contact in order to not exert any non-intentional pressure to the first container. Furthermore, as disclosed above, the containers' interface may be vented by first venting element (16).
At the initial state of the delivery system, the gap (17) between the first surface (6a) of the first movable wall and a second surface (6b) of the second movable wall may be maximal and/or the volume of the containers' interface cavity (44) may be maximal.
Preferentially, the volume of the second storage compartment is initially minimal. Nevertheless, the second storage compartment may be non-empty and initially store a fluid such as a gas (for example air trapped during the manufacturing process).
As the third container (not shown by
Filling Step:
If the first storage compartment does not initially store the solution, the user has to fill the first storage compartment before use and the first container may comprise an inlet port (22) configured to fill the first storage compartment with the solution.
The
As disclosed by the
If the third storage compartment does not initially store the compressed fluid, the user has to fill the third storage compartment before use and the third container may comprise an inlet port configured to fill the third storage compartment with the compressed fluid.
In order to monitor the volume injected during the filling, the delivery system may comprise a filling indicator. The filling indicator may display the volume injected as the solution is injected into the first container and/or may indicate the end of the filling (filling volume reached). The filling indicator may be operable coupled to the first container. For example, the filling indicator may be is pressure communication with the first container. In this case, the filling indicator may comprise a pressure transducer and the first venting element may be occluded during the filling such that, as the first variable volume increases, the pressure increases and the filling indicator converts this pressure increase in a visual, tactil or sonor indication for the user.
Full Drug State:
At the end of the filling step, the gap between the first surface (6a) of the first movable wall and a second surface (6b) of the second movable wall is substantially reduced. The first surface (6a) of the first movable wall and a second surface (6b) of the second movable wall may or may not be in contact. The pressure exerted on the first movable wall, if any, must be limited and not induce a flow of the solution to the patient.
As disclosed by
At this state, the indicator device (not shown) may indicate that the delivery system is ready to infuse or the drug container is full.
Activated/Delivery State:
After the trigger device has been activated (for example as soon as or after a predetermined time period), the trigger device initiates a change of the delivery system state. The valve device (4) switches from a first state/position (closed position) to a second state/position (open position). A second state/position of the valve device induces a flow of the compressed fluid from the third storage compartment to the second storage compartment. The second movable wall moves toward the first container due to the fluid pressure of the compressed fluid. The fluid pressure of the compressed fluid into the second container induces a displacement (a bending) of the second movable wall which exerts a pressure on the first movable wall.
At least during the delivery, the second movable wall is configured to come into contact with the first movable wall on at least 50, preferentially at least 80%, more preferentially at least 90% for example (substantially) on 100% of the first movable wall surface.
The fluid pressure of the second container is transmitted (at least partially or substantially) to the first container, in particular to the solution stored in the first storage compartment. Furthermore, the pressure causes a flow of the solution to the transcutaneous device.
The volume of the second storage container and/or the quantity of compressed fluid are adapted in order to have a substantially constant fluid pressure during a predetermined time period of the delivery. For example this predetermined time period may be at least 50% of the time period necessary to substantially drain the first storage compartment, preferentially at least 80%, more preferentially at least 90%, for example at least equal to the time period necessary to substantially drain the first storage compartment. In the latter case, the fluid pressure is constant over the entire duration of the delivery.
1.5 Containers Features
As disclosed above (
The storage compartment may be configured to receive and to store a volume of the solution comprised between 0 and 100 ml, preferentially between 1 and 10 ml for example 5 ml. The viscosity of the solution may be comprised between 0 and 100 cP, preferentially between 1 and 80 cP, more preferentially between 10 and 65 cP at 20° C., for example, 25 cP.
One of the inlet port and the outlet port of the first container may be covered by a filter (27) such as a hydrophilic filter configured to allow the passage of liquid and prevent the passage of gas (for example air).
The outlet port may be covered by a hydrophobic filter configured to prevent the flow of the solution outside of the first storage compartment until the pressure of the solution reaches a predetermined threshold. The hydrophobic filter may be used here as a valve device in order to infuse the solution only when a predetermined pressure is reached into the first and/or the second storage compartment (or a predetermined differential pressure between the pressure in the first storage compartment and the outlet port (downstream the filter)). The hydrophobic filter may be characterized by a threshold pressure that is typically at least 2 times larger than the maximum drug reservoir filling pressure (typically few tenths of mbar due to the reservoir film unfolding) and at least 2 times smaller than the minimum infusion pressure (e.g. the vapour pressure of the propellant at 5° C.)
Preferentially, the first container (11) comprises a rigid part (20) and a flexible sheet (28) (also called flexible membrane), as described by
The concave internal structure (24) is preferentially designed in such a manner that the dead volume of the first storage compartment (the residual volume at the end of the delivery) is minimal for example substantially equal to 0. For example, at the end of the treatment, the wall (of the concave internal structure (24)) intended to be in contact with the solution is covered by the flexible sheet and substantially in contact with the flexible sheet. Thus at the end of the treatment (end of delivery), the first container stores a residual volume of solution which is less than 10% of the solution initially stored in the first container, preferentially less than 8%, more preferentially less than 5%. Furthermore, at the end of the treatment (end of delivery), the delivery system comprises a residual volume of solution which is less than 10% of the solution initially stored in the first container, preferentially less than 8%, more preferentially less than 5%.
Furthermore, as described in
Furthermore, as described in
Furthermore, the flexible sheet may be thermoformed so as to have a substantially similar shape of the internal wall of the concave internal structure. The first container may further comprise a slope (P).
Thus, the shape and the characteristic of the concave internal structure and the flexible sheet may be configured to allow a substantial draining of the first storage compartment.
The second container (12) may comprise similar features to the first container (11).
As described by the
The cavity (30) and/or the channel (31) may be arranged in the internal wall of the rigid part (20) and may be configured to prevent clogging of the outlet by the flexible sheet before the end of the delivery.
In order to prevent the clogging of the outlet (before the end of the delivery), at least one of the first and the second containers may be configured to enable a collapse of the flexible membrane in a determined manner, in a determined direction (29) and/or in determined sequence. For example, the flexible membrane may collapse in a first instance to a remote location from the outlet and then the flexible sheet may collapse toward the outlet (of the container). As described by
Other examples of features which should prevent the clogging of the outlet (before the end of the delivery):
The material of the flexible membrane (single flexible membrane, first flexible membrane or second flexible membrane) may, for example, consist of one or more polymers of the following families: Polypropylene (PP), Polyethylene (PE), Ethylene Vinyl Alcohol (EVOH), Polyamide (PA), Polychlorotrifluoroethylene (PCTFE), Cyclic Olefin Copolymer (COC), Cyclic Olefin Copolymer elastomer (COC elastomer), Polycarbonate (PC), Ethylene Vynil Acetate (EVA), Polyvinyl Chloride (PVC), Polyvinylidene Chloride (PVDC), Polystyrene (PS), Polyethylene Terephthalate (PET), Thermoplastic Elastomer (TPE), Polymethacrylate (PMMA/MABS/MBS), Nitrile Butadiene Rubber (NBR), Natural Rubber (NR), Silicone, or other polymers. The flexible membrane may be thermoformed and may be manufactured for example by extrusion, blown film extrusion, coextrusion or lamination.
The rigid wall part may be an injection molded part. It may for example, consist of one or more polymers of the following families: Polypropylene (PP), Cyclic Olefin Copolymer (COC), Polymethacrylate (PMMA/MABS/MBS), Polyoxymethylene (POM), Acrylonitrile butadiene styrene (ABS), Copolyester (PCTG), Polyethylene Terephthalate (PET) or Polycarbonate (PC). Fillers can be used to reinforce the shell, e.g. glass fibers, Kevlar . . .
In order to reduce the cost of the rigid part of the container, the delivery system may comprise a first layer and a second layer. The first layer may comprise a first surface intended to be in contact with the solution and a second surface intended to be in contact with the second layer. Preferentially the first surface is arranged on another face (for example opposite face) than the face comprising the second surface. The second layer is intended to provide a determined mechanic property (for example a better rigidity) to the container. The first layer may be independent of (it may be removably coupled to) or secured to the second layer (for example rigidly fixed). In this case, the first layer may, for example, consist of one or more polymers of the following families: Polypropylene (PP), Cyclic Olefin Copolymer (COC), Polymethacrylate (PMMA/MABS/MBS), Copolyester (PCTG), Polyethylene Terephthalate (PET) or Polycarbonate (PC). And the second layer may for example, consist of one or more polymers of the following families: Polyethylene (PE, HDPE, LDPE), Polypropylene (PP), Polyethylene Terephthalate (PETE or PET), Acrylonitrile-Butadiene-Styrene (ABS), Polyvinyl Chloride (PVC), Polyamide (PA), Acrylic (PMMA), Polylactic Acid (PLA), Polycarbonate (PC), Polystyrene (PS, GGPS, HIPS), Acetal, Polyoxymethylene (POM), Polyurethane (PU) or glass fibres . . .
The first container (11) may comprise a rigid part and a flexible part as described by the US patent application US20140166528, the content of the patent application is incorporated by reference in the present document.
The second and the third container may be configured to store a compressible fluid (for example in a compressed state) such as a propellant, for example consisting of one or more material of the following families: butane, propane, CFC11, CFC12, CFC114, HFA 134a, HFA 152a, HFA 227, Isobutene, n-butane, HFO1234yf, or HFO1234ze. Thus the flexible membrane (single flexible membrane, first flexible membrane or second flexible membrane) may be configured to be in contact with a compressible fluid such as listed above. In this case, the material (which may be intended to be in contact with the compressed fluid (propellant)), for example, the second flexible membrane, may consist of one or more material of the following families: Natural Rubber, Styrene Butadiene, Ethylene Propylene (EPDM), Nitrile, Neoprene, Fluorocarbon, Fluoro Silicone, Urethane, SBR, Silicone, Butyl, Polyacrylate, Hypalon, Viton, Polyurethane, Fluorosilicone, Aflas, or Kalrez.
When the compressed fluid enters into the second storage compartment, the expansion of the compressed fluid induces shocks which may damage the flexible membrane of the first container or the solution. Thus, the second flexible membrane may be configured to insulate/protect the first flexible membrane and/or the solution from the thermal shock and/or expansion shock when the compressed fluid enters into the second storage compartment. An additional layer arranged between the first and the second flexible membrane may comprise a thermally insulating material.
At least one of the fluid compressed, the fluid pathway (5), the third container (13) and the second container (12) may be adapted to one or several features (volume, viscosity, active agent, life cycle, live time of the solution . . . ) of the solution stored in the first container in order to infuse the solution during a predetermined time period.
The second container may further comprise an outlet configured to drain the second storage compartment at the end of use or delivery. This outlet may be closed by a valve device during the delivery and when the first storage compartment has been drained, this valve device may be open (automatically or by a user).
The first, the second and/or the third container may be arranged into the housing. In one embodiment, the rigid part (or at least a part) of one of the containers may be a part of the housing of the delivery system. In other terms, a part of the rigid part of one of the containers may be configured to be in contact with the external environment of the delivery system. Thus, the mechanical property of the rigid part of the container is designed in such a manner to provide mechanical protection to the delivery system.
The housing may for example, consist of one or more polymers of the following families: Cyclic Olefin Copolymer (COC), Polymethacrylate (PMMA/MABS/MBS), Copolyester (PCTG), Polyethylene (PE, HDPE, LDPE), Polypropylene (PP), Polyethylene Terephthalate (PETE or PET), Acrylonitrile-Butadiene-Styrene (ABS), Polyvinyl Chloride (PVC), Polyamide (PA), Acrylic (PMMA), Polylactic Acid (PLA) Polycarbonate (PC), Polystyrene (PS, GGPS, HIPS), Acetal, Polyoxymethylene (POM), Polyurethane (PU) or glass fibers . . .
The rigid housing and/or at least a part of the container may be translucent or transparent and/or the rigid housing may comprise a window so as to see the container.
The rigid part of at least one of the first container (11) and the second container (12) may define a part of the housing (10) (which may be into contact with the external environment). At least a part of the rigid wall of the third container may be a part of the housing (10) (which may be into contact with the external environment).
Preferentially, the first container and the second container comprise symmetric forms at least in one dimension (for example length and/or width) in such a manner that the second flexible membrane substantially (preferentially perfectly) matches with the concave internal structure of the first container.
Preferentially, the first (resp. second) container or the housing/support of the first (resp. second) container may comprise edge and/or coupling devices (clip or screw or other fixing means) configured to rigidly fix (or to glue or to weld) to the second (resp. first) container or the housing/support of the second (resp. first) container and/or to the third container or the housing/support of the third container.
1.6 Containers Arrangement
Preferentially the first container is adjacent to the second container, more preferentially, the first movable wall is opposite to the second movable wall in such a manner that the first and the second movable walls may be in contact and in pressure communication.
As disclosed by
In one embodiment, at least one rigid part of one of the containers is used as a rigid structure of the delivery system. In this case, the other elements of the delivery system may be secured to this rigid part (for example another container, housing, indicator device, transcutaneous device, skin-adherable unit).
In one embodiment as described by the
The first rigid housing may comprise a concave internal structure configured to receive at least a part of the first container (101). The first container (101) may be secured to the first rigid housing (131). At least a part of the concave internal structure of the first rigid housing may be formed so as to match with a part of the external surface of the first container.
The third container (103) (or the housing comprising the third storage compartment) and/or the indicator device (104) may be secured to the rigid housing (131, 132).
The first container may be a first flexible pouch configured to be in fluid communication with the transcutaneous device and the second container may be a second flexible pouch configured to be in fluid communication with the third container. In this case, the edge of the flexible pouch may be rigidly fixed to the housing at least at two separate locations.
The rigid housing and/or at least a part of the container may be translucent or transparent and/or the rigid housing may comprise a window so as to see the container.
At least a part of the external surface (307) of the rigid part (302) may be a part of the housing.
At least a part of the external surface (307) of the rigid part (302) may be a rigid structure or a frame configured to secure/attach on it other elements of the delivery system such as another container, indicator device, transcutaneous device and/or skin-adherable unit.
According to
The delivery system may comprise a proximal part and a distal part (to the patient skin). Preferentially, the proximal part comprises a lower face and may be configured (for example at least a part of the lower face) to be coupled to the skin-adherable unit or to be secured to the patient skin. The distal part comprises upper face and at least a part of the distal part (for example at least a part of the upper face) is configured to be visible (by the patient or other persons) when the delivery system is fixed on the patient skin.
According to the
According to the
The indicator device (9) is preferentially arranged in such a manner to be visible to the patient when the delivery system is secured on to the patient skin, for example, the indicator device may be arranged in the upper area of the delivery device
1.7 Examples Of Embodiments
According to the
In
The first storage compartment (111) is configured to be in fluid communication with a patient via a first fluid pathway (142) and optionally via a transcutaneous device (not shown). The second storage compartment (112) is configured to be in fluid communication with the third container (103) via the second fluid pathway (143).
The delivery system (100) may further comprise an indicator device (104) which may be in fluid or pressure communication with the first storage compartment (111), preferentially before the main fluidic resistance of the fluid pathway, for example before the flow resctrictor. The delivery system (100) may further comprise a trigger device (145) configured to launch/initiate a delivery sequence. The delivery sequence may comprise a delivery step and an optional countdown step (before the delivery).
At least one of the first flexible membrane (121) and the second flexible membrane (122) defines the cavity of the containers' interface. The cavity (140) is vented by at least one vent (141).
The first container (101) may be arranged at least partially in the distal part (39) of the delivery system (100) and the second container (102) may be arranged at least partially in the proximal part (38) of the delivery system (100).
The
The
The delivery system comprises a first container (401) and a second container (402), both arranged opposite each other. The first container may comprise a rigid part (451) and a part of the rigid part (451) may act as a first rigid shell (431) of the delivery system (400). The second container may comprise a rigid part (452) and a part of the rigid part (452) may act as a second rigid shell (432) of the delivery system (400).
The delivery system may further comprise a third container (403) and a trigger device (445) arranged on the side of at least one of the first container (401) and the second container (402).
The delivery system may further comprise an indicator device (404) arranged on the side of at least one of the first container (401) and the second container (402).
The first rigid shell (431) may comprise a surface configured to be coupled or to be secured to a skin adherable unit (not shown). The indicator device may comprise visible information (LED, Message, level indicator) arranged on a visible part of the delivery system (400) when the delivery system is secured on the patient skin.
At least a part of the second rigid shell (432) may comprise an upper face of the delivery system (400).
The
The
The
The
The “end of injection” indication may be only visible when the reservoir membrane is fully collapsed against the bottom of the reservoir shell. It is not visible in case of cannula occlusion. For a specific medication volume and viscosity, maximum infusion duration will be indicated in the user manual, therefore the user can deduce that the full volume has not been administered (in case of total occlusion for instance) if the infusion status indicator is still showing “injection on-going” after this maximum duration. The high pressure generated by the propellant vapor will limit the occurrence of an occlusion in the cannula.
The
The delivery system (600) comprises a medical device (604) having a first container (601), a second container (602) and a third container (603). As disclosed in this document the third container may comprise a rigid wall adapted to store the propellant. The first and the second container may comprise a movable wall (606). In order to simplify the description, the interface between the first and the second container is called the movable wall (606) but it may be substituted by other features described in this document. For example, as described in this document, the movable wall (606) may comprise a first flexible membrane and a second flexible membrane, both defining at least a part of the containers' interface which may be vented by a vent device (not shown in
Preferentially, the delivery system (600) comprises a cradle unit (605) configured to fix the medical device (605) to the patient skin and a transcutaneous device (607) (which may be a part of the cradle unit) intended to allow the infusion of the solution stored in the first container to the patient.
Preferentially, the delivery system (600) comprises a second venting element (608) configured to provide fluid communication of the second container to the outside of the delivery system (to the ambient air for example). The second venting element may be selectively open or closed via a first valve device (609) which may be a part of the cradle unit (605) or the medical device (604).
The first container is configured to store a medical solution intended to be infused to a patient. In the case where the first container is initially empty (for example delivered or sold empty), the first container may be configured to be filled with the solution before use via for example a cartridge (612).
The delivery system may further comprise a trigger device (610) configured to allow or provide fluid communication between the third container (603) and the second container (602) when the delivery system is activated.
The trigger device may be operatively coupled with a second valve device (611) configured to allow or provide fluid communication between the third container (603) and the second container (602) when the first valve device (609) is closed and/or the trigger device (610) triggered or activated.
In the end, when the medical device is removed from the patient or from the cradle unit, the second venting element may expel the gas stored in the second container, for example, the first valve may be opened.
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