WO2009069063A1

WO2009069063A1 - Implantable therapeutic substance delivery device

Info

Publication number: WO2009069063A1
Application number: PCT/IB2008/054920
Authority: WO
Inventors: Ventzeslav P. Iordanov; Jozef C. M. Versleegers; Arnold Aalders
Original assignee: Koninklijke Philips Electronics N.V.
Priority date: 2007-11-27
Filing date: 2008-11-24
Publication date: 2009-06-04

Abstract

An implantable therapeutic substance delivery device (1) comprising a reservoir (3) and a pump (7, 200) configured to pump a substance from the reservoir to an outlet. The pump (7, 200) comprises a piston (71, 271) having one end disposed in a cylinder (73, 273) with and outlet (75, 275) and an inlet (74, 274) providing a connection to the reservoir. The cylinder (73, 273) is closed at one end. The piston end is provided with an axially extending recess (92, 292). The piston (271) is rotatable passing a first position closing off the inlet (74, 274) with the recess (92, 292) leaving the outlet (75, 275) open, and a second position closing off the outlet (75, 275) with the recess (92, 292) leaving the inlet open. The piston (71, 271) is reciprocated to enhance the space between the recessed piston end and the cylinder end wall (91, 291) when the inlet is open, and subsequently reduce the space when the outlet (75, 275) is open.

Description

Implantable therapeutic substance delivery device

FIELD OF THE INVENTION

This disclosure relates to an implantable therapeutic substance delivery device comprising a therapeutic substance reservoir, and a pump configured to pump a therapeutic substance from the reservoir to an outlet. The device can be implanted in a patient for controlled delivery of the therapeutic substance.

BACKGROUND OF THE INVENTION

An implantable therapeutic substance delivery pump is typically implanted by a clinician into a patient at a location appropriate for the therapy that interferes as little as practicable with patient activity such as subcutaneous in the lower abdomen. The device can be implanted to infuse the therapeutic substance or other therapeutic substance at a programmed infusion rate and predetermined location to treat the medical condition. Such devices allow reliable and accurate delivery of the therapeutic substance preventing patient complications caused by inadequate or unintended therapeutic substance delivery. The optimum concentration of the therapeutic substance can vary greatly from patient to patient as well as during the course of the treatment. Therefore, an ideal delivery system should be able to control the concentration of the therapeutic substance at the optimum therapeutic level during the course of the treatment. This can be done by constant infusion or by pulsatile time-varying infusion. The major advantages of implantable therapeutic substance delivery devices include both targeted and local delivery of therapeutic substances at a constant rate, less therapeutic substance required to treat the disease state, minimization of possible side effects, and enhanced efficacy of treatment. Also, these delivery devices are capable of protecting therapeutic substances which are unstable in vivo and which would normally require frequent dosing.

Implantable delivery devices are particularly desirable where compliance with a prescribed drug regimen is critical. Such devices allow a therapeutic substance to be delivered at a specific rate without regular physician or patient intervention. Implantable therapeutic substance delivery devices can be used to treat conditions such as pain, spasticity, cancer, and a wide variety of other medical conditions. The therapeutic substance can for example be a medicine, a mixture of medicines or co-reactive components of a medicine, a placebo, a non-medicinal substance, dietary supplements, contrast agents, nutrients, probiotics, gases, fluids, liquids, radiological agents, imaging or medical markers, etc.. The therapeutic substance can be administrated as a liquid, but also as nano-particles or encapsulated in nano-spheres or micro-spheres which can be suspended in liquid carrier, such as an oil.

Implantable therapeutic substance delivery devices are typically provided with a pump to transport the therapeutic substance from a reservoir to an outlet of the device. An example of an implantable therapeutic substance pump is disclosed in WO 02/083208.

The object of the present invention is to provide a compact but reliable pump for an implantable therapeutic substance delivery device.

SUMMARY OF THE INVENTION The object of the invention is achieved with an implantable therapeutic substance delivery device comprising a reservoir and a pump configured to pump a substance from the reservoir to a delivery outlet, the pump comprising a piston having one end disposed in a cylinder with an outlet and an inlet providing a connection to the reservoir, the cylinder being closed at one end. The piston end is provided with an axially extending recess. The piston is configured to rotate passing a first position closing off the inlet with the recess leaving the outlet open, and a second position closing off the outlet with the recess leaving the inlet open. During every rotation from the first to the second position the piston is reciprocated to enhance the space between the recessed piston end and the cylinder end wall when the inlet is open, and subsequently reduce the space when the outlet is open. This way, therapeutic substance is evacuated from the reservoir into the piston chamber during the time that the inlet is open and the space between the piston and the cylinder end is increased. When the piston is further rotated, the inlet is closed off and the outlet is opened when it is passed by the recessed part of the piston. When the outlet is open, the space between the cylinder end and the piston end is reduced, thus squeezing out the therapeutic substance via the outlet.

Rotation and translation of the piston can take place simultaneously in a continuous movement. Alternatively, the rotation and translation movements can take place step-by- step. The piston can for example have one axial recess, while the inlet and outlet are arranged in such a way that in a full 360 degrees rotation, the recess reciprocates a single stroke backwards and forwards passing the first position and the second position once. Alternatively, the piston and the inlet and outlet can be arranged in such a way that more than one dosing step takes place during a full rotation. For instance, the piston chamber can be provided with more than one set of inlets and outlets arranged in such a way that during a full rotation the recess passes a first position and a second position more than one time, while it is reciprocated backwards and forwards every time it moves from a first position to a next first position passing a second position. Alternatively, or additionally, the piston can be provided with a number of axially extending recesses. Every time one of the recesses passes the inlet, the piston is retracted and every time the piston recess passes the outlet, it is moved back further into the cylinder.

To superpose the translation movement upon the rotation movement, the piston can for example be provided with a lateral projection guided along an annular surface surrounding the piston configured to induce the reciprocating movement of the piston during rotation. To that end, the annular surface can for instance at least partly be waved, inclined and/or wobbled.

The piston can for example comprise an annular wall and two longitudinal walls extending from the annular wall to the piston end form two separate spaces, one space forming the recess and the other space being closed off by a second annular wall segment which is interrupted to leave the recess open. The annular and longitudinal walls can be dimensioned in such a way that they effectively seal off the enclosed spaces with reduced friction against the interior cylinder wall during rotation and translation of the piston.

Optionally, the actuator driver and the piston can bee arranged such that the rotating direction alternates. This way the piston does not rotate in one direction but alternates between clockwise and counter-clockwise rotation. This makes it possible to use a flexible membrane isolating the therapeutic substance reservoir from the driving means wherein the piston runs through the membrane while the membrane is attached to the piston in a leak tight manner. A catheter can be used to create a pathway for the therapeutic substance to flow from the pump to the delivery site. Optionally, two or more catheters can be used to allow site specific and independent delivery of the therapeutic substance to be administered to different body sites. To further enhance controllability of the therapeutic substance outflow, a capillary flow restrictor can be placed directly at the end of the therapeutic substance channel or at the end of the catheter, if so desired.

Optionally, the delivery device is provided with a refill port or septum. This way it can be replenished with the therapeutic substance, so the period the pump can be implanted may not be limited by therapeutic substance capacity.

The therapeutic substance delivery device according to the present invention can comprise an actuator driver to drive the pump. The actuator driver can for example be a stepper motor, particularly if pulsatile delivery is required. A power source can be used to provide power to the pump and optionally other components of the implantable device. The power source can for instance be a battery. An exemplary battery is a thin film lithium battery (e.g., available from Frontedge Technologies TM, located in Baldwin Park, California, US), having a small footprint and a suitable shelf life (e.g., 1% discharge/year). The battery may further be selected from other known batteries, such as photo lithium, silver oxide, lithium coin cells, zinc air cells, alkaline, etc.. Alternatively or additionally the device may use passive power. It is contemplated that the power source includes a device configured for scavenging power from another device, which may employ electrostatic, micro fuel cells, micro-heat, temperature gradient, etc.. The delivery device can comprise electronic circuitry to control the pump. Optionally, the electronic circuitry is capable of receiving and transmitting data, which include device identification number, sensor(s) data, remaining drug quantity, remaining battery power, time and date of last refill. The electronic circuitry can be programmed prior to implantation or after implantation, e.g. via a wireless link. The circuitry can be programmed to work in several modes, such as single shot delivery, continuous flow delivery, complex profiled delivery, sensor triggered delivery, or combinations thereof.

BRIEF DESCRIPTION OF THE DRAWINGS

The present invention will be elucidated with reference to the figures wherein:

Figure 1 shows in longitudinal cross section a therapeutic substance delivery device according to the present invention;

Figure 2 shows in exploded view the pump part of the therapeutic substance delivery device of Figure 1 ;

Figures 3A-D show the piston and the cylinder of the device of Figure 1 in four consecutive pumping steps. Figure 4 shows a pump for an alternative embodiment of a therapeutic substance delivery device according to the invention.

DETAILED DESCRIPTION OF THE EMBODIMENTS Figure 1 shows in cross section an exemplary embodiment of a therapeutic substance delivery device 1 according to the present invention. The device 1 comprises a housing 2 encasing a reservoir 3, a power source 4, electronic control circuitry 5, an actuator driver 6 and a pump 7.

The housing 2 has a cylindrical shape with rounded outer ends 21 to prevent sharp shape transitions and edges, which may irritate or damage surrounding tissue. The housing 2 is provided with a refill port 22 and an outlet 23 in one of the rounded end sections 21.

A flexible membrane 31 isolates a pressurized gas part 32 of the interior of housing 2 from a compressible reservoir section 33 which is in open connection with a non- compressible reservoir section 34. The power source 4, control circuitry 5 and actuator driver 6 are located between the compressible section 33 and non-compressible section 34. A second flexible membrane 35 isolates a second pressurized gas part 36 between the compressible reservoir 33 and a surface of the power source 4. Via the flexible membranes 31, 35 the pressurized gas maintains a pressure within the reservoir when therapeutic substance is discharged.

The pressure balance may also be obtained by adding a dedicated ventil valve to the rounded end sections 21, which will allow transportation of water or gas from the surrounding, compensating the vacuum created by drug displacement.

The power source 4 is a battery, which provides power to the actuator driver 6 and control circuitry 5. The battery can be thin film lithium battery photo lithium, silver oxide, lithium coin cells, zinc air cells, alkaline, or any other suitable type of battery.

The electronic control circuitry 4 serves to control actuator driver 6 and the pump 7. The electronic control circuitry 4 is capable of receiving and transmitting data and can be programmed prior to implantation or after implantation, e.g. via a wireless link. Actuator driver 6 is shown in more detail in Figure 2. In Figure 2, showing the part of the delivery device 1 housing the pump 7 in exploded view, housing 2 is partly broken away to show the encased parts. Pump 7 comprises a piston 71 with an end which is flattened at one side recess 72 extending from the outer end in axial direction. The piston 71 is encased in a cylinder 73. Near the outlet 23 of the delivery device 1, the cylinder is provided with an inlet opening. Opposite the inlet opening 74 is an outlet opening 75 (see Figure 3A - D) operatively connected to outlet 23. The cylinder 73 is coaxially mounted on a bus 76 defining the outlet 23.

The other outer end of the piston 71 is coaxially mounted in a cylindrical body 77 provided with a lateral projection 78. The cylindrical body is provided with an annular shoulder 79 and a coaxial cylindrical extension 80 of reduced diameter. The cylindrical extension 80 is provided with a central rectangular opening 81. A spring coil 82 surrounds the cylindrical extension and rests on the shoulder 79. A drive key 83 of actuator driver 6 grips into the rectangular opening 81 having freedom of sliding movement in axial direction. Drive key 83 is provided with a disk shaped section 84. The spring coil 82 is sandwiched between shoulder 79 and disk section 84.

The piston 71 passes a central opening of a mounting ring 85 with an outer diameter tightly fitting into the interior of the housing 2. The mounting ring 85 is provided with a coaxial annular extension 86 comprising two opposite segments 87, 88 of different length with two opposite slanting segments 89, 90 joining them. When the piston 71 is rotated the lateral extension 78 is moved along the annular extension 86 of the mounting ring 85. Passing slanting segment 90, the pin is guided to move the piston away from the outlet 23, while it is maintained in that position when the lateral extension passes flat segment 87. The piston 71 is moved back in the direction of outlet 23 when during rotation of the piston 71 the lateral pin 78 passes slanting segment 89. The piston 71 is maintained in that position when during rotation the pin 78 passes flat segment 88 of the annular extension 86 of mounting ring 85. This way, a translation movement in axial direction is superposed on the rotational movement of the piston 71.

In an alternative embodiment, the above described combined rotational and trans lational movement of the piston can also be obtained using a reciprocating actuator driver driving the piston while the piston and piston cylinder are provided with cooperating guiding means inducing a rotational movement of the piston during the reciprocating stroke. In such a construction, the actuator driver as such performs a translational movement only, e.g. as in a ball point pen. The pumping mechanism of the delivery device 1 is schematically shown in

Figures 3 A - D. The outer end of piston 71 with axial recess 72 is encased in cylinder 73 closed off by an end wall 91. Recess 72, the interior wall of the cylinder 73 and its end wall 91 define an enclosure 92. At a distance from its end wall 91 the cylinder 73 is provided with an inlet 74. Opposite to the inlet 74 is an outlet 75 operatively connected to a discharge line 93 leading to outlet 23 of the therapeutic substance delivery device 1.

In the position shown in Figure 3A, the enclosure 92 is in open communication with the inlet 74 and the outlet 75 is closed off. When the piston is retracted to a position away from the cylinder end wall 91, as shown in Figure 3B, the enclosure 92 is expanded creating an vacuum which evacuates therapeutic substance from the reservoir 3 into the enclosure 92. When the piston 71 is further rotated, inlet 74 is closed off and enclosure 92 turns into open connection with outlet 75, as shown in Figure 3C. The piston 71 is then translated back into the direction of the cylinder end wall 91, reducing the volume of enclosure 92. As a result, the enclosed therapeutic substance is squeezed through the outlet 75 to be discharged.

In the Figures 3A - D, the translation steps and rotation movements are described as discrete steps. However, they can be superposed to form an integral continuous movement. Figure 4 shows an alternative piston end for a therapeutic substance delivery device 200 according to the present invention. The mechanism comprises a piston 271 and a cylinder 273, which is shown in the drawing a as a transparent part to show the interior and the end of the piston 271 within the cylinder 273. Cylinder 273 is provided with an end wall 291, an inlet 274 and an outlet 275 opposite the inlet 274. The piston 271 has a terminal section 301 with reduced diameter provided with a first annular wall 302 close to the outer end of the piston 273, and a second annular wall 303 more distant from the outer end of the piston 273. Both annular walls 302, 303 are under right angles with the longitudinal axis of the piston 271. The two annular walls 302, 303 fit tightly in the interior of the cylinder 273. Two longitudinal wall sections 304, 305 extending parallel to the longitudinal piston axis bridge the two annular walls 302, 303. The height of the longitudinal wall sections 304, 305 is the same as the height of the annular walls 302, 303, also forming a tight fit with the interior of the interior wall of the cylinder 273. This way, the longitudinal wall sections 304, 305 and the annular walls 302, 303 form a smaller first enclosure 292 and a larger second enclosure 294 with the interior wall of the cylinder 273. The annular wall 302 closest to the outer end of the piston 273 is interrupted by an opening 306 connecting the smaller enclosure 292 with the space between the cylinder end wall 291 and the outer end of the piston 271.

In the position shown in Figure 4, the enclosure 292 is in open communication with the inlet 274 but isolated from the outlet 275. When the piston 271 is retracted to a position away from the cylinder end wall 291, the space between the cylinder end wall 291 and the annular wall 302 is expanded creating a vacuum which evacuates therapeutic substance from the surrounding reservoir into the enclosure 292. When the piston 271 is further rotated, enclosure 292 turns into open connection with outlet 275. The piston 271 is then translated back into the direction of the cylinder end wall 291, reducing the volume of the space formed by enclosure 292 and the space between cylinder end wall 291 and annular wall 302. As a result, the enclosed therapeutic substance is squeezed through the outlet 275 to be discharged.

In the embodiment of Figure 4, the piston 271 can for example be made of a rubber or rubber- like material. With the piston tightly fitting in the interior of the cylinder 273, the rubber material effectively closes off the enclosures 292, 294.

Claims

CLAIMS:

1. An implantable therapeutic substance delivery device (1) comprising a reservoir (3) and a pump (7, 200) configured to pump a substance from the reservoir to an outlet, the pump (7, 200) comprising a piston (71, 271) having one end disposed in a cylinder (73, 273) with an outlet (75, 275) and an inlet (74, 274) providing a connection to the reservoir, the cylinder (73, 273) being closed at one end, wherein said piston end is provided with an axially extending recess (92, 292) and wherein the piston (271) is rotatable passing a first position closing off the inlet (74, 274) with the recess (92, 292) leaving the outlet (75, 275) open, and a second position closing off the outlet (75, 275) with the recess (92, 292) leaving the inlet open, and wherein the piston (71, 271) is configured to be reciprocated to enhance the space between the recessed piston end and the cylinder end wall (91, 291) when the inlet is open, and subsequently reduce the space when the outlet (75, 275) is open.

2. A therapeutic substance delivery device according to claim 1 wherein the piston is driven by a rotating actuator driver (6).

3. A therapeutic substance delivery device according to claim 2 wherein the actuator driver (6) is a stepper motor.

4. A therapeutic substance delivery device according to claim 1 wherein the piston (7) is driven by a reciprocating actuator driver and the piston (7) and piston cylinder are provided with cooperating guiding means inducing a rotational movement of the piston during the reciprocating stroke.

5. A therapeutic substance delivery device according to any one of the preceding claims wherein the piston end is provided with a number of axially extending recesses and wherein every time one of the recesses passes the inlet, the piston is retracted and every time the piston recess passes the outlet, it is moved back further into the cylinder.

6. A therapeutic substance delivery device according to any one of the preceding claims wherein the piston chamber is provided with more than one set of inlets and outlets arranged in such a way that during a full rotation the recess passes a first position and a second position more than one time, and wherein every time the recess passes an inlet, the piston is retracted and every time the piston recess passes an outlet, the piston is moved back further into the cylinder.

7. A therapeutic substance delivery device according to any one of the preceding claims wherein the piston (71) is provided with a lateral projection (78) guided along an annular surface (86) surrounding the piston (71) configured to induce the reciprocating movement of the piston (71) during rotation.

8. A therapeutic substance delivery device according to any one of the preceding claims wherein an annular wall (303) and two longitudinal walls (304, 305) extending from the annular wall to the piston end form two separate spaces (292, 294), one forming the recess (292) and the other one being closed off by a second annular wall (302) which is interrupted to leave the recess (292) open.

9. A therapeutic substance delivery device according to any one of the preceding claims wherein the actuator driver and the piston (6) are arranged such that the rotating direction alternates.

10. A therapeutic substance delivery device according to claim 9 wherein a flexible membrane isolates the therapeutic substance reservoir from the driving means and wherein the piston runs through the membrane while the membrane is attached to the piston in a leak tight manner.