WO2002076533A1

WO2002076533A1 - Magnetically operated, subcutaneously implantable drug infusion device

Info

Publication number: WO2002076533A1
Application number: PCT/IT2001/000153
Authority: WO
Inventors: Alessandro Giannessi; Paolo Poli; Massimo Moschini
Original assignee: Alessandro Giannessi; Paolo Poli; Massimo Moschini
Priority date: 2001-03-27
Filing date: 2001-03-27
Publication date: 2002-10-03

Abstract

A subcutaneously implanted device for the infusion of a drug comprising a tank (1) for the drug accessible through a port (2) for the injection of the drug through a syringe, a catherer (5) positioned for the infusion of the drug in an infusion site of the body (B) of patient, pump means (3) connected to the tank, and to the caterer for administering the drug in the infusion site, means (6) for shutting off the flow of the drug located downstream of the pump means, micro-controller means (10) for controlling the pump means and the shutt-off means. The pump means are controlled in such a way as to administer the drug at a basic delivery rate and a greater delivery rate. To activate the administration of drug at the greater rate, a magnetically operated switch (11) is provided, connected to the micro-controller (10) and able to be operated from outside the body by means of a magnet (12) approached directly by the patient to the magnetic switch (11) and maintained in this position for a time no shorter than a predetermined time

Description

TITLE MAGNETICALLY OPERATED, SUBCUTANEOUSLY IMPLANTABLE DRUG

INFUSION DEVICE DESCRIPTION Technical Field

The present invention relates to a subcutaneously implanted and magnetically controlled device for the infusion of drugs. More specifically, the present invention relates to a device for the infusion of drugs and/or analgesics for containing pain symptoms in patients suffering from cancer or chronic pain. Background Art

As is well known, an effective therapy for treating patients suffering from intractable chronic pain of malignant aetiology consists of the intrathecal and epidural administration of morphine or its derivatives or of synthetic opioids . The same therapy has also been successfully employed for treating intractable chronic pain of a non malignant nature, for instance consequent to lumbar arachnoiditis, vertebral collapse due to osteoporosis, reflex-symphathetic dystrophy, multiple sclerosis, rheumatoid arthritis and post-herpetic neuralgia. The intraspinal infusion of opioids exercises a strong analgesic effect through the spinal and supraspinal receptors without significantly influencing motor, sensorial and sympathetic reflexes. Moreover, because dosage is considerably lower than the one required in the case of systemic administration, the risk of addiction to the drug is considerably reduced. The widespread use of the intraspinal administration of opioids and other therapeutic agents at constant dosages and for long periods of time has been made possible by the availability of devices for the continuous infusion of drugs implanted in the patient's body. The continuous, low-dosage administration of opioids leads to a constant liquor or haemic concentration, thereby allowing to reduce the phenomenon of the oscillation of the pain symptoms, necessarily associated with the fractionated administration of analgesic drugs.

In general, a device for the infusion of a drug into a bodily site comprises a tank for the drug, a catheter to carry the drug into the required site, for instance the intrathecal region of the spine in the case of a pain suppressing drug, and a source of mechanical energy to transfer the drug from the tank to the infusion site through the catheter. The device is usually implanted surgically in a subcutaneous abdominal region and there are provisions for a possibility of accessing the device at least for refilling or emptying the tank.

Currently, mechanical and electronic devices for the infusion of drugs are available. In the devices of the first kind the tank is of the bellows type and/or made of elastic material and is housed in a sealed chamber containing a gas, for instance freon, which is pressurised when the tank is refilled. The flow of the drug through the capillary duct is assured by the pressure existing in the chamber within which the tank is housed. The electronic devices comprise a tank for the drug, a peristaltic pump for extracting the drug from the tank and a catheter for transporting the pumped drug into the infusion site. Devices of this kind further comprise a battery for operating the pump and an electronic unit for controlling the delivery rate of the pump. Some known devices further comprise an antenna through which they can be programmed by an external control system, for instance a computer.

The need to vary the hourly quantity of drug administered within ranges that can even be wide is deeply felt in numerous therapeutic treatments and also in the case of pain therapy. In the case of the administration of opioids, the device releases a quantity of drug deemed optimal by the physician (for instance 2 mg/day) . On the other hand, such a dosage may not be adequate to cover the whole 24-hour period. If the patient is provided with a mechanical type of infusion device, drug dosage cannot be varied in any way. In this case, the physician injects a supplementary dose, or bolus, of drug through a port implanted near the device and connected to the catheter. If an electronic infusion device has been implanted, instead, it is possible to change pump velocity externally and hence to increase drug dosage through the control computer.

In both cases the patient is forced to ask the physician or the health care facility every time the need arises. Moreover, if an electronic device has been implanted, there is the additional problem that any further change to the dosage of the drug must be made in the health care facility where the computerised control system is available. As a result, infusion devices of the prior art are not suited for the application of the PCA

(Patient Controlled Analgesia) technique which is considered optimal for the controlled administration of pain suppressing drugs, since it allows to adapt, over time, the administration of the drug to the patient's actual requirements.

It should also be noted that in the case of mechanical infusion devices, administration of the drug cannot be interrupted except by emptying the tank, whilst in the case of electronic infusion devices this operation can be performed only in the controlling health care facility. The possibility of using radio-switches associated with the electronic devices and able to be operated by the patient has been discarded both because of cost considerations and of possible risks of interference. Manually operated subcutaneous systems applied in some infusion devices functioning with the pressure exerted from the exterior by the patient appear equally inadequate, and thus are not used.

Another drawback of known infusion devices is their high cost, especially in the case of programmable electronic devices, which constitutes a hurdle for their widespread use particularly for terminal patients with a relatively short life expectancy, also in view of the impossibility to use such devices on another patient. Summary of the Invention The aim of the present invention is to provide a device for the infusion of drugs with subcutaneous implantation in which the dosage of the administered drug can be maintained constant over 24 hours and can also be increased in a manner controlled directly by the patient for time intervals of predetermined duration, with no risk of overdose .

Another object of the present invention is to provide a device for the infusion of drugs of the aforementioned type in which the administration of the drug can be temporarily interrupted by the physician without having to provide interruption devices operated through computerised systems . A further object of the present invention is to provide a device for the infusion of drugs of the aforementioned type which can be made available at lower costs that those of known similar devices. Yet another object of the present invention is to provide a device for the infusion of drugs in the intrathecal region of the spine of the aforementioned type, which further allows periodically to draw liquor through it . An additional object of the present invention is to provide a device for the infusion of drugs which can be rapidly and completely emptied if the concentration of the drug, or the drug itself, is to be changed.

Another object of the present invention is to provide a method for the infusion of a drug that allows the patient directly to control the infusion of a bolus of drug when he/she feels the need for it, without thereby running the risk of dangerous drug overdoses .

These objects are achieved with the device for the infusion of drugs with subcutaneous implantation according to the present invention and with the related infusion method whose main features are set out in claims 1 and 9. Further particular features of the device and of the method are set out in the claims that depend therefrom. Brief Description of the Drawings

The features and advantages of the device for the infusion of drugs with subcutaneous implantation according to the present invention shall become more readily apparent from the description that follows of an embodiment thereof, made purely by way of non limiting example with reference to the accompanying drawings in which: Figure 1 schematically shows the device of the invention and the block diagram of the related electronic control circuit;

Figure 2 is a section view of a switch of the device;

Figures 3a, 3b and 3c show the operative flowchart of the device of the invention. Description of a Preferred Embodiment

With reference to Figure 1, the reference number 1 indicates a tank for the drug to be administered, bi- directionally connected to a port 2 for refilling the drug, while the reference number 3 indicates a preferably peristaltic pump operated by a direct current or stepped motor, not shown herein, and connected to the tank 1 through a conduit 4. The pump can be operated to provide a variable flow rate of the drug under the control of a micro-controller unit 10, in particular a continuous basic flow rate, defined by the physician according to the patient's prevailing conditions, and a greater, peak, flow rate or bolus, to be administered under particular conditions. The reference number 5 indicates a capillary catheter through which the drug is pumped by the peristaltic pump to the site of infusion into the patient's body, generically indicated as B. An on-off bi- stable valve 6 is installed on the catheter 5 immediately downstream of pump 3 to interrupt communication between the pump and the infusion site, as required in certain operating modes of the device, described farther on. Downstream of valve 6 can be installed, on catheter 5, a drawing port 7 whose function shall be described farther on. The aforesaid components of the device are all conventional and available on the market and thus will not be described in any greater detail, as their structure is obvious to a person skilled in the art. They are destined to be implanted, generally, into the patient's abdomen in subcutaneous position and ports 2 and 7, also implanted subcutaneously, comprise a septum that can be punctured with an Uber hypodermic needle to access tank 1 or, respectively, catheter 5.

The components of the device can be enclosed in compact form in a single implantable case, or the drug tank can be kept separate, so that, depending on requirements, it is possible to choose among different volumes of the tank to be implanted.

Electrical power to the system is provided by a battery 8 connected in PS1 to micro-controller 10, which through the output OUTl drives a power control unit 15 to be able to vary the velocity of the motor of pump 3 as requirements demand. To achieve such control, a switch 11 is provided, connected in IN2 to micro-controller 10 and able to be operated by means of a magnet 12 which the patient approaches to skin S in correspondence with the switch from outside his/her body. Through an output OUT2 , micro-controller 10 controls a bi-stable actuator 16 associated with valve 6 to command it to open and close. The system is activated and deactivated through a switch 9 connected to micro-controller 10 through the input INI.

With reference to Figure 2, switch 9 allows the physician to activate and deactivate the system through a simple injection of a predetermined quantity of twice- distilled water or other inert sterile liquid into the patient's abdomen through a port 17 implanted therein and conventionally provided with a septum that can be punctured with a hypodermic Uber needle. Port 17 is connected to a cylinder 21 in which is able to slide in sealed fashion a piston 22 that subdivides the cylinder into two chambers 21a and 21b. Chamber 21a communicates with the exterior through port 17, whilst in chamber 21b are located electrical contacts 23a, integral with piston 22 and 23b connected to input INI of micro-controller 10 and supported by a plug 24 that closes chamber 21b. The sliding motion of the piston due to the inflow of liquid into chamber 21a, achieved by injection through port 17, performed by the physician, causes the electrical power supply circuit to be closed and hence the activation of the device, which can be deactivated by the physician simply by drawing the liquid with a syringe through the same port 17. A compression spring 25, situated between piston 22 and plug 24, favours the inverse sliding of piston 22 when the liquid is drawn.

An acoustic indicator device 13 is connected in OUT3 to the micro-controller to emit sound signals audible from the exterior under different circumstances, as shall be described farther on.

In a preferred embodiment of the invention, the motor of pump 3 is controlled in such a way as to provide at least two different flow rates, control over flow rates being preferably achieved with PWM techniques, easily controllable in digital fashion and free of power losses and hence energy losses of the battery, as would be the case if the motor were driven in analogic fashion.

Amongst the numerous micro-controllers available on the market, a PIC16C73 micro-controller, marketed by Microchip Technology, Inc., or its equivalents, has proven to be particularly advantageous. The programming of this type of micro-controllers in machine code is well known to anyone who is versed in sequential logic digital electronic techniques. For the sake of completeness, but without thereby intending in any way to restrict the scope of the invention, Figures 3a, 3b and 3c show the functional flowchart whence the codes for programming micro-controller 10 can easily be obtained.

The operation of the device for the infusion of drugs according to the present invention shall now be described with reference to Figures 3a, 3b and 3c. Preliminarily the device is programmed setting the two operating rates, a slow and a fast one, of pump 3 and then the physician fills tank 1 by injecting the drug into it through port 2. The device is then activated acting on switch 9. The control circuit verifies that valve 6 is open and activates the slow operating rate of the pump which, at this point, is implanted in the patient's abdomen. If no circumstances arise that would require a change in the operating rate of the pump, (for instance, an increase in the level of pain) the device continues to administer the drug until the content of the tank drops below a pre-set value (for instance 10 cc) . The timer of the control system is set in such a way that, when this condition is reached, sound indicator 13 is activated and emits an acoustic signal, for instance consisting of a number of beeps corresponding to the number of cc ' s of drug remaining in the tank every 6 hours, or another mode such as to provide an indication of the residual content of the tank. At this point, the patient has enough time to see his/her doctor who will provide for refilling the tank. If the drug in the tank is exhausted altogether, valve 6 is shut, pump 3 is turned off and the bolus administration function is disabled so that, if a bolus is required under such conditions, an acoustic signal is emitted that indicates the impossibility of administering it. If switch 9 is open, all alarms are also disabled and the device is completely inoperative. If the need arises to shift to the fast operating rate of the pump to administer a drug bolus, the patient approaches magnet 12 to switch 11. The control systems verifies that within a pre-set previous time interval, for instance six hours, another bolus has not been administered already and that there is a pre-set volume (for instance, no less than 1 cc) of drug in the tank. If so, it measures the time of permanence of the magnet in contact with switch 11 and, if it exceeds a pre-set value, for example two minutes, the control system enables the activation of the fast operating rate of the pump through a timer that measures the duration of the administration of the bolus to compare it with a predetermined duration, emitting a conventional confirmation acoustic signal. If not, the control system acoustically advises the patient, for example by emitting, in the first case, a sequence of three sound signals lasting two seconds each and, in the second case, a sequence of three sound signals lasting one second each. After this administration duration is reached, the slow operating rate of the pump is resumed and the fast operation option is disabled for a predetermined minimum time interval, for instance six hours .

At this point, if the switch 9 is closed, the device continues with the slow administration of the drug after updating the residual quantity of drug in the tank, i.e. the variable indicated as "drug time" . If switch 9 is opened instead, for instance when the drug has to be replaced with a different one or with the same one, but at a different concentration, or when liquor needs to be drawn from the infusion site, as shall be described farther on, valve 6 is shut, pump 3 is stopped and the drug bolus administration function is disabled, along with the alarms connected thereto. It should be noted that every time the switch 9 is closed the "drug time" variable is automatically reset to the volume corresponding to the usable volume of the tank, so that the physician will have to fill the tank every time the device is deactivated.

The fact that the alarms are off (as can be noted from the absence of beeps when magnet 12 is approached to the patient's abdomen) and switch 9 is open (as can be noted by the fact that the liquid has been drawn from chamber 21a of cylinder 21) , constitutes for the physician the confirmation that the pump is actually deactivated.

When switch 9 is closed again, valve 6 is open, the low-rate administration of the drug is restored and the bolus administration function is enabled again, along with the alarms connected thereto, storing in the memory the time elapsed since the last administration of the bolus. Lastly, the content of the tank is reset, i.e. the "drug time" variable is updated, as stated above.

A typical capacity value for tank 1 is 50 cc . The control system computes the residual content of tank 1 based on the volume of drug administered by pump 3, both in the slow and in the fast operating condition.

The device according to the invention can also comprise the additional drawing port 7 installed on capillary catheter 5 for diagnostic interventions. Downstream of drawing port 7 is provided a valve 18 with related bi-stable on-off actuator 19 connected to an output OUT4 of micro-controller 10.

Port 7 can be used for drawing liquor for diagnostic purposes and it also allows immediately to fill the catheter downstream of the system when replacing the drug. In case of extreme need, for instance a system failure, port 7 can be used as an emergency access for the immediate infusion of the drug. When drawing liquor, pump 3 is stopped and valve 6 is shut. Valve 18 instead remains open for a sufficient period of time to allow the drawing operation, whereupon it also shuts. It is important for the deactivation of the system also to entail the closure, albeit delayed, of valve 18, in order to prevent, when refilling the tank, the accidental use of port 7 instead of port 2 with severe injury to the patient. From the above description it is clear that the device according to the invention achieves all its set aims. The device allows the continuous infusion of the drug both at a pre-set dose and upon the patient's request, at a greater dose (bolus) for a predetermined time and at time intervals no shorter than a given value. The possibility of varying the dosage is entrusted directly to the patient by means of a simple command from the exterior with no need for the physician's intervention. The risk of overdose for increased dosages administered at shortened time intervals is excluded because, after each administration of a bolus, this function is disabled for a predetermined time. Moreover, the activation and deactivation of the device is achieved with a much more economical system than the one provided in the electronic devices for the infusion of drugs currently available in the market. A system of acoustic alarms allows the patient to monitor the operating conditions of the device and alerts him/her when servicing is required, for instance refilling the tank.

The device for the infusion of drugs with subcutaneous implantation according to the present invention can be subject to variations and/or modifications, without thereby departing from the scope of the invention as defined in the appended claims.

Claims

CLAIMS 1. A subcutaneously implanted drug infusion device comprising a tank (1) for the drug accessible through a port (2) from which the drug can be injected, a catheter (5) positioned for the infusion of the drug in an infusion site of the body (B) of a patient, pump means (3) connected to said tank and to said catheter to dispense said drug in said infusion site, means (6) for shutting off the flow of said drug situated downstream from said pump means, micro-controller means (10) for controlling said pump means and said shut-off means, characterised in that said pump means are controlled in such a way as to administer said drug at a basic delivery rate and at least at a rate greater than said basic rate, the administration of said drug at said greater rate, occurring for a prefixed time interval, the time interval between two consecutive drug administrations being not lower than a prefixed value, said device comprising a magnetically operated switch (11) for enabling said drug administration at a greater rate connected to said micro-controller able to be operated from the outside of the patient's body by means of a magnet (12) approached by the patient him/herself to said switch (11) and maintained in said position for a time no shorter than a pre-set time.

2. A device as claimed in claim 1, wherein said microcontroller means (10) are connected to a switch (9) implanted in the patient's abdomen and communicating with the exterior through a port (17) able to be punctured with a syringe needle, said switch (9) comprising a pair of fixed contacts (23b) positioned to co-operate with a movable contact (23a) integral with actuator means (22) able to be controlled hydraulically through said port (17) to achieve a connection between said fixed contacts and said movable contact .

3. A device as claimed in claim 2, wherein said hydraulically controlled actuator means comprise a piston (22) able to slide in sealed fashion within a cylinder (21) subdivided by said piston into two chambers (21a, 21b) , one of said chambers (21b) containing said electrical contacts (23a, 23b) , the other chamber (21a) being able to receive a pressurised inert liquid through said port (17) , in the first of said chamber (21b) also being provided elastic means (25) operating antagonistically to the motion of said piston (22) caused by the insertion of said pressurised inert liquid into said chamber (21a) .

4. A device as claimed in claim 1, wherein the delivery rate of said pump is controlled with a PWM technique.

5. A device as claimed in claim 1, wherein acoustic signalling means (13) are provided, connected to said micro-controller means (10) to provide acoustic signals audible from the exterior, differently modulated according to the function the device is serving or to the alarm to be signalled.

6. A device as claimed in claim 1, wherein downstream of said means (6) for shutting off the flow of drug supplied to the infusion site, means (7) are provided for drawing liquor from said infusion site connected to said catheter (5) and implanted in the patient's abdomen, comprising a drawing port (7) through which the liquor can be drawn through a syringe, and a shut-off valve (18) downstream of said port (7) able to remain open for a predetermined period of time when the device is deactivated, to allow the drawing of the liquor.

7. A device as claimed in any of the previous claims, wherein said micro-controller means (10) comprise a microcontroller of the PIC type.

8. A device as claimed in claim 7, wherein said micro- controller is programmed as illustrated previously and shown in Figures 3a, 3b, 3c.

9. A method for the controlled administration of a drug to a patient by means of an infusion device comprising a tank (1) able to contain a pre-set volume of said drug accessible through a port (2) for injecting the drug into said tank, a catheter (5) positioned for the infusion of the drug in an infusion site of the body (B) of a patient, pump means (3) connected to said tank and to said catheter to dispense said drug in said infusion site, means (6) for shutting off the flow of said drug located downstream of said pump means, micro-controller means (10) for controlling said pump means and said shut-off means, said method comprising the following phases: activating said pump means for the administration of a base rate of delivery of said drug; comparing the drug content present in the tank with a predetermined value and, if said content is lesser than said predetermined value, emitting a corresponding acoustic signal; - deactivating the device if the drug content in the tank drops to 0 ; and characterised by the following phases: receiving a request for the administration of the drug at a greater delivery rate than said basic rate, said request being routed to said micro-controller means (10) through a switch able to be operated from outside the body directly by the patient by means of a magnet (12) ; verifying whether at least a predetermined time interval has elapsed since the patient's last similar request ; if so, verifying whether the drug content in the tank exceeds a predetermined value; if so, verifying whether the patient has been operating said switch for a time interval no shorter than a predetermined interval ; if so, sending a command signal to said pump means (3) able to activate the administration of the drug at said greater delivery rate; interrupting said administration at greater delivery rate when a predetermined time interval has elapsed and resuming the administration of the drug at said basic delivery rate.

10. The method as claimed in claim 9, wherein in order to activate/deactivate the administration of said drug, an inert sterile liquid is injected/drawn by means of a syringe into/from a hydraulically operated switch (9) implanted in the patient's abdomen, through a port (17) able to be punctured.

11. The method as claimed in claim 9 or 10, wherein said device further comprises means for drawing the liquor from the infusion site, connected to said catheter and implanted in the patient's abdomen, situated downstream of said means (6) for shutting off the flow of drug supplied to the infusion site, comprising a drawing port (7) through which liquor can be drawn by means of a syringe and a shut-off valve (18) , downstream of said drawing port, the drawing operation comprising the following phases : deactivating the device, closing also said shut-off means (6) but leaving open said valve (18) for shutting off said drawing means, carrying out the drawing operation with a syringe through said drawing port (7) and within a predetermined time interval; closing said shut-off valve (18) once said predetermined time has elapsed.

12. The method as claimed in any of the previous claims 9, 10 or 11, wherein the content of said tank is continuously updated based on the operating time of said pump means at said basic delivery rate and at said greater rate .

13. The method as claimed in any of the previous claims from 9 to 12, wherein the content of the tank is reset to a value corresponding to said predetermined value, after each deactivation of the device.

14. The method as claimed in any of the previous claims, wherein the administered drug is morphine or its derivatives or a synthetic opioid.