WO2009150594A1

WO2009150594A1 - Micro-jet injection device for local submucosal drug application

Info

Publication number: WO2009150594A1
Application number: PCT/IB2009/052390
Authority: WO
Inventors: Chetan Mittal; Roelf Kassies
Original assignee: Koninklijke Philips Electronics NV
Current assignee: Koninklijke Philips NV
Priority date: 2008-06-11
Filing date: 2009-06-05
Publication date: 2009-12-17
Anticipated expiration: 2010-12-11

Abstract

The application relates to the field of micro- jet drug delivery devices, in particular it relates to a micro- jet drug delivery device for local submucosal drug applications. A pressure drop occurs in a micro- jet drug delivery device implemented in a catheter when a fluid is pumped out of a pump chamber located at a proximal end of a catheter to a nozzle being located at the distal end of the catheter. In order to prevent such pressure drop it is suggested to provide a micro -jet drug delivery device comprising a catheter (1) having a distal end (14) and a proximal end (15), a micro -jet pump (2) located in the catheter comprising a pump cavity, wherein the pump cavity is located closer to the distal end than to the proximal end, a drug reservoir (22) located at the proximal end of the catheter, and a tube connecting the drug reservoir and the micro- jet -pump.

Description

Micro -jet injection device for local submucosal drug application

FIELD OF THE INVENTION

The invention relates to the field of micro -jet drug delivery devices, in particular it relates to a micro-jet drug delivery device for local submucosal drug applications.

BACKGROUND OF THE INVENTION

While oral application is the most common standard for drug delivery, many drugs cannot easily be formulated in a format suitable for oral administration. For example, treatment of diabetes, genetic disorders, and novel cancer treatments are based on (poly) peptides, which are destroyed in the gastro intestinal tract. For these drugs, the preferred way of administration is usually an injection. One way of injecting a drug is by micro-jet injection which is one of the technologies known in the field of transdermal drug delivery. However, the common concepts for transdermal drug delivery fail whenever a drug must be provided very locally within a patient's body and cannot be easily administered subcutaneously. WO 2006/096654 A2 discloses a fluid delivery system including a reservoir, a delivery actuator, and at least one delivery nozzle of a micro -jet having an exit opening with a diameter between about 1 μm and about 500 μm. The delivery actuator may be configured to deliver a quantity of fluid contained in the reservoir into tissue of an individual through the nozzle or nozzles at a pre-determined velocity, and to desired depth. The quantity of fluid may contain one or more therapeutic agents, such as medications, drugs, bio-reactive agents, etc. The delivery actuator may also be configured to repeatedly deliver a quantity of the fluid contained in the reservoir through at least one delivery nozzle at pre-determined intervals.

Figure 3 of WO 2006/096654 discloses an embodiment of a micro-jet device having a catheter and/or endoscope portion, wherein a nozzle of the micro-jet device is located at the distal end of the catheter and the micro-jet pump cavity as well as the reservoir are located at the proximal end of the catheter, i.e. outside the patient's body. This arrangement requires a long path for the drug being expelled from the pump cavity to the nozzle leading to a reduced speed and momentum for the drug passing through the nozzle into a patient's body. SUMMARY OF THE INVENTION

It would be advantageous to provide a micro -jet drug delivery device enabling high speed drug ejection at any point of the patient's body being accessible from outside the body through a natural or artificial opening in the body.

It would also be desirable to have a micro -jet drug delivery device enabling selective application of drugs into very precisely localized areas within a patient's gut.

To better address one or more of these concerns, in a first aspect of the invention a micro -jet drug delivery device comprising a catheter having a distal end and a proximal end, a micro -jet pump located in the catheter comprising a pump cavity, wherein the pump cavity of the micro -jet pump is located closer to the distal end than to the proximal end, a drug reservoir located at the proximal end of the catheter, and a tube connecting the drug reservoir and the pump cavity of the micro -jet pump is provided.

This way the necessary pressure for high speed ejection is generated close to the tissue to be disrupted reducing any pressure drop or energy loss occurring between the pump and the outlet opening of the nozzle.

A catheter in the sense of the present application is a tubular device which can be inserted into a natural or artificial body cavity allowing access to part of the human or animal body otherwise not accessible conveniently. In embodiments a catheter is a thin, flexible tube (a "soft" catheter) or a larger solid tube (a "hard" catheter).

In the sense of the present invention distal end of the catheter or tube shall denote the tip thereof to be inserted in a patient's body. Proximal end in the sense of the present invention shall mean the end of a catheter remaining outside a patient's body. In a further embodiment of the invention the catheter may comprise an endoscope in order to enable vision into the patient's body when applying the medication with the micro-jet drug delivery device. This is in particular advantageous if the medication or drug shall be delivered very locally to a particular section of a patient's body. By incorporating micro-jet injection technology into an endoscope the medication can be accurately delivered locally into a lesion during endoscopic procedures, particularly as an alternative for systemic treatment of lesions with substances which are toxic for the rest of the body.

The micro -jet pump in an embodiment of the invention comprises a pump cavity being in fluid communication with the tube, a pump membrane or plunger connected to the pump cavity, a nozzle for ejection of a drug being in fluid communication with the pump cavity, and an actuator to drive the pump membrane. Such a micro-jet pump according to an embodiment enables needle-less drug delivery through any type of surface of a patient's body, for example, but not limited to skin, gut wall, or inner lung surface. In an embodiment the actuator may be a piezoelectric actuator. However in alternative embodiments any other type of actuator may be used, for example an electromagnetic actuator.

In order to penetrate the patient's surface, a medication for needle-less application must be accelerated to high velocities to carry enough momentum to disrupt the layers of the patient's tissue. In an embodiment the micro-jet pump is therefore designed such that it enables acceleration of the medication up to velocities in a range from 60 m/s to 200m/s measured behind the outlet opening of the nozzle in air.

In order to enable these high ejection velocities in an embodiment of the present invention the pump cavity and the nozzle of the micro -jet pump are located at the distal end of the catheter.

In an embodiment the distance between the pump cavity and the outlet opening of the nozzle is less than 10 mm. In an embodiment the nozzle is an integral part of the pump cavity.

In an embodiment of the invention the pump cavity has a volume in a range from 1 e-4 ml to 0.1 ml.

In an embodiment of the present invention the tube may have any length. However in an embodiment the tube has a length of more than 80 cm providing access even to parts of a human or animal body being further away from any natural opening in the body than 80 cm, e.g. the duodenum (upper GI endoscopy), left colon (colonoscopy) or smaller bronchi (bronchoscopy) of a human body.

The nozzle for the ejection of a medication is a nozzle for high speed ejection and thus an embodiment of the invention is designed according to several design rules.

In an embodiment the nozzle has a centrally symmetric shape.

Desirably, in an embodiment of the invention the diameter of the nozzle is in a range from 10 μm to 200 μm and preferably in a range from 40 μm to 100 μm.

In order to optimize the nozzle for high speed ejection of the medication according to an embodiment of the invention, the nozzle and the inlet channel fulfill the following relationship:

Ii/ai«l₂/a₂, wherein Ii is the length of the nozzle, ai is a cross sectional surface area of the nozzle, I₂ is the length of the inlet channel and a₂ is the cross sectional surface area of the inlet channel. Typically the relation "«" will be fulfilled if the two sides of the relation differ by at least a factor of 100. Fulfillment of this relation is in particular important when the pump cavity, tube and reservoir do not form a closed fluid system, e.g. with cavity refilling based on capillary forces.

In an embodiment of the invention the micro -jet drug delivery device comprises a feed pump located on the tube between the drug reservoir and the pump cavity of the micro -jet pump. This feed pump will provide a flow of a fluidic drug or medication from the drug reservoir to the pump cavity of the micro -jet pump in order to support possible capillary forces in the tube between the drug reservoir and the pump cavity of the micro-jet pump.

In an alternative embodiment the feed pump may be connected to the reservoir in order to pressurize the fluid contained in the reservoir. In an embodiment the pump mechanism could be a mechanism that provides continuous pressure (e.g. gas, mechanical spring, flexible balloon etc). In an embodiment the continuous pump mechanism could work in combination with an (electronically) controlled valve connected to the tube that determines when and which amount of fluid can enter the pump cavity. In an alternative embodiment the pump mechanism could be a mechanism that stepwise pumps out the liquid medication towards to pump cavity (e.g. step motor, syringe pump). Also in this case an (electronically) controlled valve or check valve attached to the tube and providing a controlled filling of the pump cavity could still be useful.

In a further embodiment the feed pump is located on the tube between the drug reservoir and the pump cavity of the micro -jet pump at the proximal end of the catheter. Thus this way the feed pump can be located outside the patient's body and does not have to fulfill any strict construction requirements according to size and weight.

In a further embodiment the micro-jet drug delivery device comprises a valve in fluid communication with the micro-jet pump preventing a backflow of a fluidic drug or medication from the micro-jet pump towards the reservoir when pressure is build up in the pump cavity. In an embodiment this valve can either be electronically controlled or be a check valve.

Under a second aspect of the invention a method for ejection of a drug out of a micro-jet drug delivery device is provided, comprising the steps: transporting the drug to be ejected from a drug reservoir located at the proximal end of a catheter through a tube to the pump cavity of a micro -jet pump being located at the distal end of the catheter, activating the micro-jet pump to eject the drug from the pump cavity through an outlet opening of a nozzle. These and other aspects of the invention will be apparent from and elucidated with reference to the embodiments described herein after.

BRIEF DESCRIPTION OF DRAWINGS

Figure 1 schematically shows part of a micro-jet drug delivery device according to an embodiment of the present invention. Figure 2 schematically shows part of an alternative embodiment of a micro-jet drug delivery device according to the present invention.

Figure 3 schematically shows an overall view of the embodiment according to Figure 1.

DETAILED DESCRIPTION OF EMBODIMENTS

In figure 1 a cross sectional view through the tip of a catheter 1 of a micro -jet drug delivery device according to the present invention is shown. The essential part of the drug delivery device is the micro-jet pump 2 located at the very front or distal end 14 of the catheter 1. The micro -jet pump 2 comprises a nozzle 3 for ejection of a fluidic drug 4 into a patient's tissue. The nozzle 3 is in direct fluid communication with the pump cavity 5, i.e. it forms the outlet of the pump cavity 5. Opposite the nozzle 3 the pump cavity 5 is terminated by a pump membrane 6 or plunger. The pump membrane may be activated via a piezo actuator 7 providing a compressive force on the pump membrane towards the nozzle 3 in order to push a fluidic drug 4 contained in the pump cavity 5 out of the nozzle 3. In the embodiment depicted in figure 1 the pump cavity 5 is connected via an inlet channel 8 to a tube 9. The tube 9 guides a fluidic drug from a drug reservoir (not shown in figure 1) located at the proximal end of the catheter 1, i.e. outside the person's body, to the inlet channel 8 of the micro -jet pump 2. The tube 9 is made of a flexible material in order to provide a soft catheter. The piezoelectric actuator 7 is connected via wires 10, 11 to an electronic control located at the proximal end of the catheter.

In the embodiment according to figure 1 the inlet channel 8 as well as the nozzle 3 are designed such that they fulfill the following relationship: Ii/ai«l₂/a₂, wherein Ii is the length of the nozzle 3, ai is the cross sectional surface area of the nozzle 3, 1₂ is the length of the inlet channel 8 and a₂ is the cross sectional surface area of the inlet channel 8. When compared to the tube 9 and to the further inlet duct 12 the inlet channel 8 has a reduced diameter. The above design rules enable ejection of the drug through the nozzle avoiding the backflow of a substantial amount of drug through the inlet channel 8 and back into the tube 9.

Fig. 2 depicts an alternative embodiment, wherein identical parts have been denoted by identical reference numbers. In the embodiment according to Figure 2 the problem of backflow occurring from the pump cavity 5' through the inlet channel 8' towards the tube 9' has been solved by providing a check valve 13' in the inlet channel 8'. Therefore the inlet channel 8' can have a diameter equal or approximately equal to the diameter of the tube 9' or the inlet duct 12'.

Figure 3 is an overall view of a micro-jet drug delivery device having a tip as depicted in Figure 1, whereas the micro-jet pump 2 is located at the distal end 14 of the catheter 1 a support unit 20 is located at the proximal end 15 of the catheter 1.

The support unit 20 comprises an electronic control 21 providing control of the actuator 7 (not shown in Figure 3). Furthermore the support unit comprises a drug reservoir 22 connected to the upper or proximal end of the tube and thus being in fluidic connection to the micro-jet pump 2 at the distal end 14 of the catheter. The support unit further comprises a feed pump 23 enabling transmission of a fluidic drug from the drug reservoir 22 towards the micro-jet pump 2 supporting the capillary forces in the tube 9.

While the invention has been illustrated and described in detail in the drawings and foregoing description, such illustration and description are to be considered illustrative or exemplary and not restrictive; the invention is not limited to the disclosed embodiments. Other variations to the disclosed embodiments can be understood and effected by those skilled in the art in practicing the claimed invention, from a study of the drawings, disclosure and the appended claims. In the claims, the word "comprising" does not exclude other elements or steps, and the indefinite article "a" or "an" does not exclude a plurality. The mere fact, that certain measures are recited in mutually different dependent claims does not indicate that the combination of these measures cannot be used to advantage. Any reference signs in the claims should not be construed as limiting the scope. REFERENCELIST:

1, 1' Catheter

2,2' Micor-jet pump

3,3' Nozzle

4,4' Drug 5,5' Pump cavity

6,6' Pump membrane

7,7 Piezoelectric actuator

8,8' Inlet channel

9,9' Tube 10, 10" Wire

11, 11" Wire

12, 12' Inlet duct

13' Check valve

14 Distal end 15 Proximal end

20 Support unit

21 Electronic control

22 Drug reservoir

23 Feed pump

Claims

CLAIMS:

1. Micro -jet drug delivery device comprising a catheter (1, 1 ') having a distal end (14) and a proximal end (15), a micro-jet pump (2, 2') located in the catheter (1, 1 ') comprising a pump cavity (5, 5'), wherein the pump cavity (5, 5') is located closer to the distal end (14) than to the proximal end (15), and a tube (9, 9') connecting the micro-jet-pump (2, 2') to a drug reservoir (22).

2. Micro -jet drug delivery device according to claim 1, characterized in that the pump cavity is located at the distal end of the catheter.

3. Micro -jet drug delivery device according to claim 1, characterized in that the micro-jet pump comprises a nozzle (3, 3') being located at the distal end of the catheter.

4. Micro -jet drug delivery device according to claim 1, characterized in that the catheter comprises an endoscope.

5. Micro -jet drug delivery device according to claim 1, characterized in that the tube has a length of more than 80 cm.

6. Micro -jet drug delivery device according to claim 1, characterized in that the micro-jet pump is arranged such that it provides an acceleration of the medication to velocities in a range from 60 m/s to 200m/s behind an outlet opening of a nozzle.

7. Micro -jet drug delivery device according to claim 1, characterized in that it comprises a feed pump (23) located on the tube between the drug reservoir and the pump cavity of the micro-jet pump.

8. Micro -jet drug delivery device according to claim 1, characterized in that it comprises a feed pump (23) located on the tube between the drug reservoir and the pump cavity of the micro-jet pump at the proximal end of the catheter.

9. Micro -jet drug delivery device according to claim 1, characterized in that it comprises a feed pump (23) connected to the drug reservoir in order to pressurize a fluid contained in the drug reservoir.

10. Micro -jet drug delivery device according to claim 1, characterized in that the micro-jet pump (2, 2') comprises a pump cavity (5, 5') being in fluid communication with the tube (9, 9'), a pump membrane (6, 6') connected to the pump cavity (5, 5'), an actuator (7, T) for actuation of the pump membrane (6, 6'), and a nozzle (3, 3') for ejection of a drug (4, 4') being in fluid communication with the pump cavity (5, 5').

11. Micro -jet drug delivery device according to claim 1, characterized in that it comprises a valve in fluid communication with the pump cavity of the micro-jet pump preventing a backflow of a fluid from the micro-jet pump towards the reservoir.

12. Method for ejection of a drug out of a micro-jet drug delivery device, comprising the steps: transporting the drug to be ejected from a drug reservoir located at the proximal end of a catheter through a tube to the pump cavity of a micro-jet pump being located at the distal end of the catheter, activating the micro -jet pump to eject the drug from the pump cavity through an outlet opening of a nozzle.