WO1994014487A1

WO1994014487A1 - Improved pulsed infusion system

Info

Publication number: WO1994014487A1
Application number: PCT/AU1993/000669
Authority: WO
Inventors: John Elvin Teasdale; David Eric Dale Baker
Original assignee: John Elvin Teasdale; David Eric Dale Baker
Priority date: 1992-12-21
Filing date: 1993-12-20
Publication date: 1994-07-07

Abstract

A pulsed infusion apparatus comprising a drug delivery means (13), an automatically controllable valve means (14) and a catheter (10) or the like. The drug delivery means (13) is capable of delivering the drug through the valve means (14) to the catheter (10) and the catheter (10) is capable of intravenously administering the drug to the region of a thrombus. The apparatus also includes a drug supply means (50) connected thereto in constant fluid communication via a flow restricting means (64) with each of the drug delivery means (13) includes a relatively small chamber (36) capable of being pressurised to deliver the drug therefrom such that on opening of the valve means (14) the drug passes into the catheter (10) for a predetermined time prior to the valve means (14) closing. The drug supply means (50) includes a relatively large chamber (62) capable of being pressurised to a greater extent that the small chamber (36) of the drug delivery means (13) such that the drug is continuously urged towards and into the small chamber (36) from the large chamber (62) while the valve means (14) is closed.

Description

"IMPROVED PULSED INFUSION SYSTEM"

This invention relates to a pulsed infusion method for the infusion of therapeutic solutions into the cardiovascular system, together with apparatus for use therewith.

The invention relates particularly to the dispensing of a drug intraarterially or intravenously in timed high pressure bursts to assist in the dispersion or destruction of vascular thrombosis.

A common treatment for vascular thrombosis lies in the insertion of intravenous solutions which attack and disperse a blood clot. In the past, solutions were given systemically- in other words by injection in high dosage into the whole body circulation via a vein (or artery) and such high doses were liable to produce bleeding elsewhere in the body and other serious complications due to the high dose required. Further, these solutions had to be administered for relatively long durations of hours or even several days with high cost of hospitalisation, usually in intensive care beds rather than in the lower cost general hospital beds. There was also the high cost present due to use of large quantities of the solutions used.

A further development has been to intraluminally insert a catheter in the region of the blood clot (in the artery or vein), the catheter having one or more exit orifices at or towards the end thereof through which the drug may be sprayed. This assists in rapidly dispersing the drug throughout the blood clot and in breaking down the blood clot by physical means, in addition to "lacing" the clot with the drug to maximise the thrombolytic action thereof.

However, due to the nature of these blood clots, and the efficacy of the drugs being used, there is a need to continuously administer the drugs for short periods of time over long intervals. This is normally conducted manually and is thus time consuming and labour intensive.

It is an object of the present invention to provide a pulsed infusion method and apparatus therefor that overcomes, or at least partly alleviates, the above mentioned difficulty.

The present invention provides a pulsed infusion apparatus comprising a drug delivery means, an automatically controllable valve means and a catheter or the like, the drug delivery means being capable of delivering the drug through the valve means to the catheter, the catheter being capable of intravenously administering the drug to the region of a thrombus, the apparatus also including a drug supply means connected thereto in constant fluid communication via a flow restricting means with each of the drug delivery means and the valve means, wherein the drug delivery means includes a relatively small chamber capable of being pressurised to deliver the drug therefrom such that on opening of the valve means the drug passes into the catheter for a predetermined time prior to the valve means closing, and wherein the drug supply means includes a relatively large chamber capable of being pressurised to a greater extent than the small chamber of the drug delivery means such that the drug is continuously urged towards and into the small chamber from the large chamber while the valve means is closed.

By utilising a flow restricting means through which the drug must pass from the drug supply means, the volume of drug provided to the apparatus thereby is extremely low. Thus, when the valve means opens to allow the drug to be delivered to the catheter, the major volume of drug is provided by the drug delivery means. However, while the valve means is closed, the increased pressure on the drug in the large chamber of the drug supply means causes a low volume of drug at relatively high pressure to be passed into the upstream portion of the system so as to refill the small chamber of the drug delivery means. It is the increased pressure of the drug supply means that allows the drug therefrom to overcome the pressure of the drug delivery means.

As a result, the small chamber of the drug delivery means may be provided by a normal syringe. In this respect, the plunger thereof only ever moves through a small range of movement when delivering the drug, which in turn means that the force applied by the plunger to the drug when delivering the drug remains substantially constant. This ensures that the correct volume of drug is administered each time the valve means opens.

Furthermore, by only utilising a small chamber in the drug delivery means, and by including the flow restriction means in the system to restrict the flow of the drug from the large chamber of the drug supply means, if there is a failure in the valve means or in any other part of the system that results in the system remaining open, it will only be the volume of the small chamber of the drug delivery means that is administered to the patient during the failure. In this respect, the volume of the drug that would then be provided via the flow restricting means of the drug supply means would certainly be continuous until the failure was identified and corrected, but would only be minimal.

For example, it is preferred that the small chamber of the drug delivery means holds in the order of 1 millilitre of the drug, whereas the large chamber of the drug supply means preferably holds in the order of at least 10 millilitres. Furthermore, it is preferred that both the drug supply means and the drug delivery means comprise a normal syringe having attached thereto a pressurising member. Preferably, the pressurising member provides a substantially constant force to the plunger of the syringe, the force being able to be predetermined and/or adjusted as necessary. Preferably the automatically controllable valve means comprises a solenoid valve connected to a timing circuit such that the timing circuit is capable of being set to automatically control the frequency of opening of the valve and also the periods for which the valve is open. The pulsed infusion system may also include a bypass means located between the drug supply means and the flow restriction means. The bypass means is preferably connectable to a major drug source such that prior to the exhaustion of the drug in the drug supply means, the bypass means may be operated to allow drug from the major drug source to be inserted into the drug supply means to allow continual operation. In a preferred form of the invention, the bypass means is provided in the form of a manual bypass valve.

By utilising the apparatus of the invention as described above, a pulsed infusion method may be adopted that allows a volume of a drug to be supplied under pressure to a catheter for the continuous administering thereof for fixed periods of time at predetermined intervals to maximise the efficacy of the drug in order to properly disperse or destruct a blood clot. In this respect, the preferred drug for use with the method and apparatus of this invention is UROKINASE, although other drugs such as STREPTOKINASE or rTPA may also be used. In this respect, it will be understood by a person skilled in the art that the method of the invention may be used with any appropriate drug, whether it be an existing drug or a drug developed in the future, or even with water alone if that is appropriate.

The invention will now be described in relation to a preferred embodiment illustrated in the accompanying drawings. However, it is to be understood that the following description is not to limit the generality of the above description. Figure 1 schematically illustrates the apparatus according to a preferred embodiment of the present invention.

Illustrated in Figure 1 is a pulsed infusion apparatus capable of connection to a catheter at one end 10 and to a drug delivery means 13 at the other end 12. Located intermediate the ends 10 and 12 are an automatically controllable valve means 14 and an open junction 16.

The automatically controllable valve means 14 comprises a solenoid valve 18 actuatable by a solenoid 20 which in turn is controlled by a timing means 22 having a power supply 24. An alarm is preferably connected to the solenoid 18 so that whenever it pulses an audible warning is heard. In this way, if the timing circuit malfunctions so as to keep the valve open, the alarm will continuously sound to alert staff.

When in use, the drug delivery means 13 connected at end 12 is constantly under pressure such that the drug may be provided to the catheter at end 10 also under pressure. Furthermore, this allows the opening and closing of the valve 18 to control the duration and frequency of the pulses of drug that are allowed to pass to the catheter 10. In this respect, the pressure exerted on the drug by the drug supply means is sufficient to cause these pulses whenever valve 18 is opened. In this respect, an adjustable timing circuit is preferably provided within timing means 22 which enables the solenoid to open the solenoid valve for periods in the range of 0.1 seconds to 0.5 seconds, or for periods that allow pulses of about 0.1 ml to about 0.4 ml, at preferred intervals in the order of 15 seconds to 3 minutes, and for total treatment times in the order of about 0.75 hour to 1.5 hours. Of course, the duration of the pulses and frequency of the pulses may vary depending upon the particular drug being used and the particular treatment regime required. It will also be understood that a continuous purge mechanism, or at least a continuous purging system, will be utilised by the operator in order to initially prime the system with the drug to eliminate all air from the apparatus.

The drug delivery means 13 is shown including a normal syringe 34 having a relatively small chamber 36 and a plunger

38 having a pressurising member 40 connected thereto. The pressurising member 40 includes an outer housing having a platform 42 which is constantly urged towards the plunger 38 of the syringe 34 by virtue of spring 44.

As will be seen from the drawing, the interaction of the neck

46 of member 40 with the finger grip portions 48 of the syringe, together with the interaction of the platform 42 on the plunger 38 caused by the resilience of spring 44, continuously urges the plunger 38 into the small chamber 36.

The apparatus of the invention also includes a drug supply means 50 which includes a syringe 52 and a pressurising member 54 having the same general components as illustrated in relation to the drug delivery means 13. Thus, there is a spring 56, a platform 58, a plunger 60 and a relatively large chamber 62.

Of course, it will be appreciated by a person skilled in the art that the reference to a "relatively small chamber" and a "relatively large chamber" is to indicate the general sizes of the two chambers relative to each other. Thus, the sizes may vary provided that the chamber of the drug delivery means is smaller than the chamber of the drug supply means and provided that the volume of the chamber of the drug delivery means is not of a size that may include a volume of drug that would be dangerous if injected into a patient in one pulse.

Located between the inlet 30 to the open junction 16 and the drug supply means 50 is a flow restriction means 64, a manually operable bypass valve 66, and a major source of the drug 68. The manually operable bypass valve 66 may be operated to close off the fluid communication between the inlet 30 and the drug supply means 50 to open fluid communication between the major source of drug 68 and the large chamber 62. The major source of drug may then be operated to resupply and refill the large chamber 62 once that large chamber has been exhausted. On completion, the manual valve may again be opened allowing fluid communication between the large chamber 62 and the inlet 30.

The flow restricting means 64 may be any type of flow restricting means that is insertable in this location and that only allows a reduced flow of drug to pass therethrough. In particular, the flow restricting means may be a flexible tube comprising a flexible wall defining a bore for throughflow of fluid, the cross sectional dimensions of the wall and the bore being such as to maintain the bore substantially uniform in cross section during flexing of the tube. Such a flow restricting means is described in Australian Patent 606092.

The different forces applied to pressurise the drug delivery means and the drug supply means may be provided by utilising pressurising members 40 and 54 having different characteristics. These different characteristics may be adjustable or may be fixed in relation to the particular member. In particular, by utilising a spring 56 in the drug supply means 50 having a greater spring force F than the spring force f of the spring 44 of the drug delivery means 13, the appropriate difference in pressure may be provided. In this respect, the spring force F equals a spring constant K times the compression distance of spring 56, while the spring force f equals a spring constant k times the compression distance of spring 44. However, it will of course be appreciated that any such mechanism may be utilised to provide the appropriate pressures. In particular, it will be appreciated that the drug delivery means and the drug supply means may utilise syringes and/or plungers of a variety of sizes and areas. With this in mind a person skilled in the art will understand that the appropriate configurations of spring sizes and the like will be required to be determined, provided that the general operation described above of the apparatus is adhered to.

It can thus be seen from the above description that the lack of a flow restriction means in the path between the drug delivery means 13 and the catheter 10 allows the major volume of drug passed to the catheter when the valve 18 is open to be delivered by the drug delivery means. While there will also be some drug delivered from the drug supply means 50 via inlet 30, that amount will be minimal due to the presence of the flow restricting means 64.

Further, while the valve 18 is closed, the greater pressure of the pressurising member 54 than the pressure of the pressurising member 40 allows the minimal flow of drug through the flow restricting means 64 and into the inlet 30 to ensure that the drug is resupplied to the small chamber 36 of the drug deliver means 13 to keep that small chamber 36 full. Thus, the plunger 38 will only be required to move a small distance to deliver the required dose of drug whilst the valve 18 is open, thus ensuring that the variation in force applied by the plunger to the drug in the small chamber remains minimal. The volume of drug thus administered in that pulse may be carefully determined and monitored.

From the above description it can be seen that the pulsed infusion method and apparatus of the present invention allow for accurate intravenous administering of a virtually continuous supply of drug in short periods of time at frequent intervals. The system need only be primed and switched on, having been set for the appropriate periods of time and frequency of intervals, and then only needs further attention prior to the drug being exhausted from the drug supply means. At that time, the simple operation of a manual bypass valve, allows the drug supply means to be resupplied for further operation. Thus, the apparatus allows an operator to only be present infrequently while administering a drug according to a required program.

Furthermore, the apparatus allows for the periods of each pulse and the frequency of each pulse to be readily altered according to particular treatment regimes, and also allows for the pressure of the pulses to be accurately predetermined. In this respect, it is of course possible to include normal calibration techniques on the drug supply means as described above.

It will be understood that there may be other modifications and variations to the configurations described above that may also be within the scope of the present invention.

Claims

THE CLAIMS defining the invention are as follows:-

1. A pulsed infusion apparatus comprising a drug delivery means, an automatically controllable valve means and a catheter or the like, the drug delivery means being capable of delivering the drug through the valve means to the catheter, the catheter being capable of intravenously administering the drug to the region of a thrombus, the apparatus also including a drug supply means connected thereto in constant fluid communication via a flow restricting means with each of the drug delivery means and the valve means, wherein the drug delivery means includes a relatively small chamber capable of being pressurised to deliver the drug therefrom such that on opening of the valve means the drug passes into the catheter for a predetermined time prior to the valve means closing, and wherein the drug supply means includes a relatively large chamber capable of being pressurised to a greater extent than the small chamber of the drug delivery means such that the drug is continuously urged towards and into the small chamber from the large chamber while the valve means is closed.

2. A pulsed infusion apparatus according to claim 1 wherein the drug delivery means comprises a syringe and a pressurising member, the drug delivery means syringe including a plunger, and the drug delivery means pressurising member being adapted to provide a substantially constant force to the plunger, the force being able to be predetermined and/or adjusted if necessary.

3. A pulsed infusion apparatus according to claim 1 or claim 2 wherein the drug supply means comprises a syringe and a pressurising member, the drug supply means syringe including a plunger, and the drug supply means pressurising member being adapted to provide a substantially constant force to the drug supply means plunger, the force being able to be predetermined and/or adjusted if necessary.

4. A pulsed infusion apparatus according to claim 2 or claim 3 wherein the drug delivery means pressurising member comprises a platform which is constantly urged towards the drug delivery means plunger by virtue of a biasing means. »

5. A pulsed inf sion apparatus according to claim 2 or claim 3 wherein the drug supply means pressurising member comprises a platform which is constantly urged towards the drug supply means plunger by virtue of a biasing means.

6. A pulsed infusion apparatus according to any one of claims 1 to 5 wherein the small chamber of the drug delivery means is capable of holding only about 1 millilitre of the drug.

7. A pulsed infusion apparatus according to any one of claims 1 to 6 wherein the large chamber of the drug supply is capable of holding at least about 10 millilitres of the drug.

8. A pulsed infusion apparatus according to any one of claims 1 to 7 wherein the automatically controllable valve means comprises a solenoid valve connected to a timing circuit such that the timing circuit is capable of being set to automatically control the frequency of opening of the valve and the periods for which the valve is open.

9. A pulsed infusion apparatus according to any one of claims 1 to 8 wherein the apparatus also comprises a bypass means located between the drug supply means and the flow restriction means.

10. A pulsed infusion apparatus according to claim 9 wherein the bypass means is connectable to a major drug source such that, prior to the exhaustion of the drug in the drug supply means, the bypass means may be operated to allow drug from the major drug source to be inserted into the drug supply means to allow continual operation.

11. A pulsed infusion apparatus according to claim 9 or claim 10 wherein the bypass means is provided in the form of a manual bypass valve.

12. A method for the infusion of therapeutic solutions into the cardiovascular system by application of the pulsed infusion apparatus according to any one of the above claims.

13. A pulsed infusion apparatus according to claim 1 substantially as herein described with reference to the accompanying drawing.

14. A method according to claim 12 substantially as herein described with reference to the accompanying drawing.