FIELD OF THE INVENTION

The invention relates to a device for transdermal delivery of a liquid via a micro jet. The invention further relates to an apparatus for co-operation with said device. The invention further relates to a system comprising the device and the apparatus.

BACKGROUND OF THE INVENTION

US 5840062 discloses an apparatus for the rapid and repeatable delivery of small quantities of a liquid to an intended target, comprising a first housing and a second housing detachably connected thereto. Herein, the first housing is intended to be a disposable. The first housing comprises a dispensing chamber, a nozzle element defined therein and a liquid reservoir for holding the liquid to be dispensed. The first housing furthermore comprises a valve assembly driven by a piezo electric element for controlling the quantity and rate of transfer of liquid from the liquid reservoir to the dispensing chamber, and pump means for placing pressure on the liquid reservoir. The second housing comprises a piezoelectric element for forcing a predetermined quality of liquid out of the dispensing chamber through the nozzle.

A problem of the apparatus disclosed in US 5840062 is that disposing of the first housing is economically very unattractive. Namely, apart from indispensable features such as the reservoir, the dispensing chamber and the nozzle, the first housing comprises relatively expensive elements such as the piezo based electrically driven valve assembly and an actuator for pressurizing the reservoir.

SUMMARY OF THE INVENTION

It is an object of the invention to provide a device according to the opening paragraph that enables the disposal of a co-operating apparatus to be economically feasible without reducing functionality.

The object of the invention is achieved by the device according to the invention, and the apparatus according to the invention for co-operation therewith. The device according to the invention comprises an ejection actuator for pressurizing an ejection chamber provided with a nozzle for generating the micro jet in response to the ejection actuator, and a pump actuator for actuating a passive pump element. Herein, the passive pump element is situated in an apparatus for co-operation with the device. The apparatus according to the invention comprises a reservoir for storing the liquid and a passive pump element configured for actuation by the pump actuator. Herein, the passive pump element is at least temporarily in fluid communication with the reservoir and at least temporarily in fluid communication with the ejection chamber.

By situating the pump actuator in the device, which pump actuator is configured for actuating the passive pump element situated in the apparatus, the pump system is effectively partitioned into a relatively expensive part, i.e. the pump actuator, and a further relatively inexpensive part, i.e. the passive pump element. Thereby, the device according to the invention effectively enables incorporating relatively expensive components in the device itself, and incorporating only relatively inexpensive components in the co-operating apparatus according to the invention, without reducing functionality for the assembly of the device and the apparatus. That is, owing to the partition of the pump system, the costs of disposing the apparatus are effectively reduced without affecting the assembly's capabilities regarding transporting the liquid from the reservoir towards e.g. an ejection chamber.

Furthermore, the device and the co-operating apparatus according to the invention advantageously reduce the risk of inadvertently releasing the liquid in case of malfunctioning. That is, the reservoir in the apparatus is passive, i.e. there is no overpressure continually applied to the reservoir.

In this text, transdermal implies all layers comprised in a mammal's skin underneath the stratum corneum which performs as the interface with the outside world. In order of increasing depth with regard to the stratum corneum, these layers are the epidermis, the dermis and the hypodermis, wherein the latter layer is also referred to as the subcutis or subcutaneous fat.

In a preferred embodiment of the apparatus according to the invention, the apparatus comprises the ejection chamber configured for pressurization by the ejection actuator, and provided with the nozzle for generating the micro jet in response to the ejection actuator. This embodiment has the advantage of increased hygiene when using the apparatus. Namely, by situating the ejection chamber and the nozzle in the apparatus, the path the liquid is to flow from the reservoir up to and including the nozzle, is effectively realized in a single component. Thus, making temporarily connections between durable and disposable parts constituting the flow path is not required. In addition to that, this embodiment advantageously increases the ease of interconnecting and separating the device and the apparatus. It is to be noted that the ejection chamber and the nozzle are relatively inexpensive components which at least economically justifies their disposal.

In a preferred embodiment of the apparatus according to the invention, the reservoir is collapsible. Because the reservoir is collapsible, no inlet of air is needed to enable easily transporting liquid from the reservoir. This is advantageous since the air could contaminate the fluid.

In a preferred embodiment of the system according to the invention, the combination of the pump actuator and the passive pump element forms a positive

displacement pump. A positive displacement pump causes a liquid to move by repetitively taking a fixed amount of the liquid and by subsequently displacing said fixed amount. This embodiment is advantageous in that it allows for relatively easily synchronizing the pump actuator and the co-operating passive pump element with the ejection actuator or generally, the generation of the microjet. Namely, the continuous operation of a positive displacement pump operation is marked by a phase in which liquid is being taken, and a phase in which said liquid is further transported, e.g. to the ejection chamber. This enables the phase in which liquid is taken to simultaneously occur with the generation of the microjet and enables the phase in which liquid is transported to the ejection chamber to take place just after the microjet has been generated.

In a preferred embodiment of the system according to the invention, the passive pump element comprises a pump chamber provided with a partially openable membrane for alternatingly switching between a first state in which the pump chamber is in fluid communication with the reservoir, and a second state in which the pump chamber is in fluid communication with the injection chamber, wherein the pump actuator is configured for pressurizing the pump chamber. This embodiment is advantageous in that it further reduces the costs of disposing the apparatus according to the invention. Namely, the pump chamber and the membrane comprised in the passive pump element are relatively inexpensive components. That is, the costs of the pump chamber are mainly determined by its

manufacturing costs which are limited to the costs for removing a specific volume from a slab of material. The material thus removed, may be employed to manufacture the membrane, which will minimize its purchase price.

In a further preferred embodiment of the system according to the invention, the first state is obtained in case the pressure in the reservoir exceeds the pressure in the pump chamber, and wherein the second state is obtained in case the pressure in the pump chamber exceeds the pressure in the reservoir. This embodiment has the advantage of reducing the complexity of the pump actuator and thereby increasing its reliability of operation. Namely, by switching between the first and second state on the basis of pressure changes caused by the pump actuator itself, no further actuation mechanisms are required.

In a practical embodiment of the system according to the invention, the membrane comprises a first opening coverable with a first cover and a second opening coverable with a second cover, wherein the second opening is covered by the second cover during the first state, and wherein the first opening is covered by the first cover during the second state.

In a further preferred embodiment of the system according to the invention, the passive pump element comprises an internal gear pump having an inner rotor and an outer rotor, wherein the pump actuator is configured for mutually rotating the inner and outer rotors. This embodiment has the advantage that it is capable of instantaneously generating a relatively high pressure. Furthermore, this embodiment allows for a very flat design which advantageously enhances the wearability of the device and apparatus by the patient at hand.

In a further preferred embodiment of the system according to the invention, the inner rotor is provided with at least two magnetizable elements that are situated eccentrically, wherein the pump actuator is configured for generating a magnetic coupling with the inner rotor. This embodiment advantageously allows for contactless actuation of the passive pump element. Such contactless actuation not only facilitates easily connecting and disconnecting the device and the apparatus according to the invention, it also enhances hygiene and enables maintaining sterile conditions for the liquid in which the drug is solved. That is, by employing contactless actuation, the possibly contaminated durable parts comprised in the device will not affect the liquid.

In a further preferred embodiment of the system according to the invention, the passive pump element comprises a first syringe, and the pump actuator is configured for driving the first syringe. This embodiment has the advantage that it is capable of generating high pressures while transporting relatively small volumes of liquid by the pump actuator and the co-operating pump passive pump element.

In a further preferred embodiment of the system according to the invention, the passive pump element comprises a second syringe and a valve for alternatingly switching between a first state and a second state. Herein, the first state implies that the first syringe is in fluid communication with the ejection chamber while the second syringe is in fluid communication with the reservoir, and the second state entails that the first syringe is in fluid communication with the reservoir while the second syringe is in fluid communication with the ejection chamber. Herein the pump actuator is configured for driving the first and second syringes as well as the valve. This embodiment advantageously enables a very productive operation of the passive pump element. Namely, by incorporating the first and second states and by alternatingly switching between these two states, the first syringe is enabled to deliver the liquid to the ejection chamber while the second syringe is allowed to be refilled through connecting it with the reservoir, and vice versa.

BRIEF DESCRIPTION OF THE DRAWINGS

These and other aspects of the invention will be apparent from and elucidated with reference to the exemplary embodiments described hereinafter. In the accompanying drawings:

Figure IA schematically shows an embodiment of the system according to the invention, wherein the passive pump element comprises a pump chamber provided with a partially openable membrane,

Figure IB schematically shows the pump actuator and the passive pump element comprised in the system depicted in Figure IA, during the first state,

Figure 1C schematically displays the pump actuator and the passive pump element comprised in the system depicted in Figure IA, during the second state,

Figure 2 provides a plan view of the membrane for application the passive pump element in the system displayed in Figure IA,

Figure 3 schematically depicts an embodiment of the system according to the invention, wherein the passive pump element comprises an internal gear pump,

Figure 4 provides a plan view of the internal gear pump for application in the system depicted in Figure 3,

Figure 5 schematically displays an embodiment of the system according to the invention, wherein the passive pump element comprises first and second syringes,

Figure 6 provides a plan view of the valve and the first and second syringes for application in the system depicted in Figure 5.

DETAILED DESCRIPTION OF THE EMBODIMENTS

Figure IA schematically depicts a system 102 for transdermal delivery, comprising a device 104 and an apparatus 106, which device 104 is durable and which apparatus 106 is intended for being disposed once a reservoir 108 situated therein is emptied. In this particular example, the device 104 and the apparatus 106 are connectable to each other via a connecting member 110 such as a mechanically flexible membrane. The connecting member 110 may either be durable or intended for disposal. In case the connecting member 110 is intended for durable use, it may be mounted to the device 104. Otherwise, the connecting member 110 may be mounted on the apparatus 106. The device 104, the apparatus 106 and the connection member 110 may all be manufactured by injection molding techniques. In this particular embodiment, the reservoir 108 is collapsible. In this specific example, the apparatus 106 comprises a passive pump element 112 provided with a pump chamber 114. The pump chamber 114 is sealed by the connecting member 110 on one side, and is provided with a partially openable membrane 116 on an opposing side.

During operation, the membrane 116 enables alternatingly switching between a first state in which the pump chamber 114 is in fluid communication with the reservoir 108 in order to fill the pump chamber 114 with a liquid 118 stored in the reservoir 108, see Figure IB, and a second state in which the pump chamber 114 is in fluid communication with an ejection chamber 120 situated in the apparatus 106 as to deliver the liquid 118 thereto, see Figure 1C. For this purpose, the membrane 116 is provided with a first opening 122 connecting the pump chamber 114 with the reservoir 108 and a second opening 124 for connecting the pump chamber 114 and the ejection chamber 120 as depicted in Figures IB and 1C. Herein, the first opening 122 is coverable by a first cover 126 whereas the second opening 124 is coverable by a second cover 128. Referring to Figure 2, the first and second covers 126 and 128 are realized by flaps, i.e. the membrane 116 is perforated such that portions of it are allowed to rotate with regard to the membrane 116. Herein, the first and second covers' axes of rotation are indicated by ARl and AR2, respectively. Obviously, this way of manufacturing will result in reduced manufacturing complexity as well as increased robustness of the passive pump element 112. Referring to Figure 1, the first opening 122 is closed in case the second opening 124 is opened, and vice versa. The liquid 118 is guaranteed to flow only from the reservoir 108 towards the ejection chamber 120 by restricting the first and second covers 126 and 128 to be merely movable in directions towards the reservoir 108 and the ejection chamber 120, respectively.

During operation, a pump actuator 130 comprised in the device 104 pressurizes the pump chamber 114 via the connecting member 110. The pump actuator 130 may be embodied by a piezo electric element; however, other types of electro mechanic, hydraulic, magnetic or pneumatic actuators are feasible as well. In case the pump actuator 130 exerts pressure on the pump chamber 114, the first flap 126 will close the first opening 122 while the second flap 128 will open the second opening 124 by moving towards the ejection chamber 120. As a result, the liquid 118 contained in the pump chamber will be transported to the ejection chamber 120. Once the pump actuator 130 removes pressure from the pump chamber 114, the first flap 126 will open the first opening 122 through being moved towards the reservoir 108 while the second flap 128 will cover the second opening 124. Consequently, liquid 118 will be force to flow from the reservoir 108 to the pump chamber 114 while the reservoir 108 will accordingly collapse. The reservoir 108 may be formed by a fluid pouch for the purpose of making the reservoir 108 collapsible.

In this specific example, during operation, an ejection actuator 132 is situated in the device 104 and pressurizes the ejection chamber 120 via the connecting member 110 during operation. The ejection actuator 132 may be embodied by a piezo electric element; however, other types of electro mechanic, hydraulic, magnetic or pneumatic actuators are feasible. A nozzle 134 in fluid communication with the ejection chamber 120 is provided for the purpose of generating a microjet 136 in response to the pressure built up in the ejection chamber 120 by the ejection actuator 132.

The system 102 is mountable or wearable on a patient's skin 134. More precisely, the nozzle 134 is directed towards the stratum corneum 138 which performs as an interface with the outside world for causing the microjet 136 to penetrate the stratum corneum 138 and skin layers 140 underneath it, i.e. the epidermis, the dermis and the hypodermis, and to subsequently deliver the liquid 118 at that place. Accordingly, depending on the concentration of the drug in the liquid 118, an amount of drug is delivered

transdermally in that way.

After generating a microjet, the ejection actuator 132 removes pressure from the ejection chamber. The device 102 has a controller 142 for mutually coordinating the pump actuator 130 and the ejection actuator 132. That is, the controller 142 is to synchronize the second state in which the pump chamber 114 is in fluid communication with the ejection chamber 120 in order to deliver liquid 118 thereto, and the pressurization of the ejection chamber 120 by the ejection actuator 136, such that said second state and said pressurization take place alternatingly.

The device 104 and the co-operating apparatus 106 advantageously enable repetitive transdermal delivery of the liquid 118. Namely, such repetitive operation requires the liquid 118 ejected from the ejection chamber 120 to be replenished in a quick way. For that reason, pumping concepts based on capillary refilling are less feasible since capillary forces generally instigate fluid flow having a relatively low velocity. In addition to that, capillary refilling will be strongly dependent on both temperature and the liquid at hand. Furthermore, the device 104 and the co-operating apparatus 106 advantageously guarantee reliable refilling of the ejection chamber 120. After generation of the microjet 136 ejection of the liquid from the ejection chamber 120, air will be sucked in the nozzle 134. If an interface between the air sucked in and the liquid 118 that has not been ejected from the ejection chamber 120 remains in contact with the atmosphere, capillary refilling may be feasible from this point of view. However, due to clogging of e.g. water at the nozzle 134, the air will be enclosed. To force the air thus trapped in the nozzle 134 out of it, the application of an external pressure is required. Herein, relying on capillary forces is not a feasible option since the water clogged in the nozzle 134 provides a significant barrier.

Figure 3 schematically depicts a system 302 for transdermal delivery of a liquid 303, comprising a device 304 and an apparatus 306, which device 304 is durable and which apparatus 306 is intended for disposal e.g. in case a liquid reservoir 308 comprised in the apparatus 306 is emptied. The apparatus 306 comprises a passive pump element 310 which is in fluid communication with both the reservoir 308 and an ejection chamber 312. In this specific example, the ejection chamber 312 is situated in the apparatus 306. The device 304 and the apparatus 306 are mutually connected in a disconnectable manner via a bayonet coupling 313. The device 304 comprises a pump actuator 314 for actuating the passive pump element 310. In this specific example, the passive pump element 310 comprises an internal gear pump 316 having an inner rotor 402 and an outer rotor 404, see Figure 4.

The inner rotor 402 is configured to fit within the outer rotor 404. The inner rotor 402 is provided with N lobs whereas the outer rotor 404 is provided with N +1 lobes, i.e. the outer rotor's number of lobes exceeds the inner rotor's number of lobes with 1. The pump actuator 314 is configured for mutually rotating the inner and outer rotors 402 and 404. That is, during operation the pump actuator 314 directly drives the inner rotor 404. As a result, the outer rotor 404 will also be caused to rotate and hence, the pump actuator 314 indirectly drives the outer rotor 404 during operation. Through mutually rotating the inner and outer rotors 402 and 404, suction is created at locations where the inner rotor' lobes and the outer rotor's lobe mutually diverge whereas pressure comes into being at locations where the inner rotor' lobes and the outer rotor's lobe mutually converge. In this particular example, the inner rotor 402 is provided with two magnetizable elements 406 and 408, see Figure 4. Referring to Figure 3, the pump actuator 314 is configured for directly driving the inner rotor 402 through magnetic coupling with the magnetizable elements 406 and 408. That is, during operation the pump actuator 314 effectuates a magnetic field having a continually changing direction, thereby causing the inner rotor 402 to rotate directly and the outer rotor 404 to rotate indirectly. The latter magnetic field may be realized e.g. by rotating a permanent magnet.

The device 302 furthermore comprises an ejection actuator 318 for repetitively pressuring the ejection chamber 312 via a connecting member 320 such as a mechanically flexible membrane in order to generate a microjet via a nozzle 322, which nozzle 322 is in fluid communication with the ejection chamber 312. During operation, said microjet is to transdermally deliver a drug that is solved in the liquid 303. After generating the microjet or a series of microjets, the ejection actuator 318 removes the pressure from the ejection chamber 312. The device 302 comprises a controller 324 known per se for synchronizing the pump actuator 314 and the ejection actuator 318, such that the transport of the liquid 303 to the ejection chamber 312 and the generation of microjets take place alternatingly.

Figure 5 schematically displays a system 502 for transdermally delivering a liquid 503 comprising a device 504 and an apparatus 506, which apparatus 506 is

disconnectably mounted to the device 504 via a bayonet mount 508. Herein, the device 504 is intended for durable application and the apparatus 506 is intended for disposal. The apparatus 506 may e.g. be disposed once the reservoir 510 comprised in the apparatus 506 is emptied. In this particular embodiment, the reservoir 510 is foldable. In this specific example, the apparatus 506 comprises a passive pump element 512 provided with a first syringe 602, a second syringe 604 and a valve 606, see Figure 6. During operation, the valve 606 is caused to rotate by a pump actuator 514 comprised in the apparatus 506 with the purpose of alternatingly switching between a first state and a second state. Referring to Figure 5, during operation the valve 606 is driven by the pump actuator 514 via a shaft.

In the first state, as depicted in Figure 6, the first syringe 602 is in fluid communication with an ejection chamber 516 via a first micro channel 608 while the second syringe 606 is in fluid communication with the reservoir 510 via a second micro channel 610. During the first state, the first syringe 602 is to deliver the fluid 503 to the ejection chamber 516 whereas the second syringe 604 is to be replenished with the liquid 503 from the reservoir 510. The second state is obtained starting from the first state by rotating the valve 606 a quarter of a full rotation in either direction, see the arrow 612. During the second state the first syringe 602 is in fluid communication with the reservoir 510 via the second micro channel 610 while the second syringe 604 is in fluid communication with the ejection chamber 516 via the first micro channel 608. During the second state, the first syringe 602 is to be replenished with the liquid 503 from the reservoir 510 whereas the second syringe 604 is to deliver the liquid 503 to the ejection chamber 516. It is to be noted that a subsequent first state is obtainable from the second state by rotating the valve 606 either reversely or forwardly along a quarter of a full rotation.

During operation, the pump actuator 514 furthermore drives the first and second syringes 602 and 604. That is, during the first state as depicted in Figure 6, the pump actuator 514 mutually translates the piston 614 and the cylinder 616 such that the volume of the first syringe 602 is being decreased as indicated by the arrow 618. Simultaneously, the pump actuator 514 mutually translates the piston 620 and the cylinder 622 such that the volume of the second syringe 604 is being increased, which is graphically indicated by the arrow 624. During the second state, the first and second syringes 602 and 604 are actuated in a reverse manner compared to the first state.

In operational conditions, an ejection actuator 518 situated in the device 504 repetitively pressurizes the ejection chamber 516 via a connecting member 520. In this particular example the ejection actuator 518 is embodied by a piezo electric element. The ejection chamber 516 is provided with a nozzle 522 in fluid communication therewith for the purpose of generating a microjet 524 in response to the pressure build up in the ejection chamber 516 by the ejection actuator 518. The system 502 is installable on a patient's skin 526. More precisely the nozzle 522 is directed towards the stratum corneum 528 which performs as an interface with the outside world for causing the microjet 524 to penetrate the stratum corneum 528 and skin layers 530 underneath it, i.e. the epidermis, the dermis and the hypodermis, and to subsequently deliver the liquid 503 there. The device 502 has a controller 532 for mutually coordinating the pump actuator 514 and the ejection actuator 518. That is, the controller 532 is to synchronize the and the pressurization of the ejection chamber 516 by the ejection actuator 518 and the delivery of the liquid 503 by either the first syringe 602 and the second syringe 604 thereto, such that said pressurization and said liquid delivery take place in an alternating manner.

While the invention has been illustrated and described in detail in the drawings and in the foregoing description, the illustrations and the description are to be considered illustrative or exemplary and not restrictive. It is noted that the device, the apparatus and the system according to the invention and all their components can be made by applying processes and materials known per se. In the set of claims and the description the word "comprising" does not exclude other elements and the indefinite article "a" or "an" does not exclude a plurality. Any reference signs in the claims should not be construed as limiting the scope. It is further noted that all possible combinations of features defined in the set of claims are part of the invention.