DE2544884A1 - MEDICAL TREATMENT DEVICE AND METHOD - Google Patents

Description

PATENT LAWYERS DIPL.-ING. LEO FLEUCHAUS

β MÖNCHEN 71st October 7th 7th!)

Melchiorstrasse 42 M..nZe.cb.n _: OL3P-1339

Everett Hews EUinwood, Jr.

3519 Tonbridge Way Durham, North Carolina 27705

United States

Device and method for medical

treatment

The present invention relates to an independent, self-sustaining device which, as a whole, is incorporated into a particular Body of a living being, in particular in a human or animal body, is used to select, internal Periodically evaluate physiological conditions of the body and selected treatment agents depending on the body conditions to be administered periodically, with the body being treated on an outpatient basis for the entire duration of the treatment. the The invention further relates to a method for using the device to measure selected internal physiological states of a body of a living being, in particular a human or animal body, to periodically evaluate and to

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to periodically release treatment agents into the body in accordance with these conditions, the body over the entire treatment time is treated away on an outpatient basis.

The present invention thus relates to the internal administration of medicinal or physiological substances or substances and in particular a device for administering these substances or substances over a long period of time according to the special needs of the patient at the times when the substances and Substances are administered.

Known techniques are disclosed in commonly assigned U.S. Patent 3,692,027 and describe methods for delivering medicinal substances within the body. On the Reference is made to U.S. Patent 3,692,027. U.S. Patent 3,692,027 gives a self-sustaining device that can be inserted into a body and that contains medicinal substances administered in pre-measured doses over a long period of time at certain time intervals. In the magazine An article appeared in "Fortune" in June 1973 in which diffusion capsules for dispensing devices are described which Continuously dispensing medical substances.This article clearly states that there is a very great need for delivery devices that can be used for long periods of time for treatment and the drugs to certain organs or parts of the body. Further details are provided in US Pat. No. 3,379,996 made with diffusion devices in which a polysiloxane carrier is intended for the controlled dispensing of drugs and other agents and substances. The device according to this US Pat. No. 3,379,996 consists of a silicone rubber container in which a soluble drug is contained is. The drug can diffuse through the silicone rubber of the container to the outer surface of the container. Another

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The design of this vessel is described in "Annals of the New York Academy of Sciences", Volume 111, 1963-64, pages 857-868 described by Judah IPolkman and David Long. With this device an electrical voltage is applied to the container and to an electrode located outside the container, around the diffusion of the treatment agent through the fibrous Fibrous scar tissue raised around the container because the container is in the heart muscle is inserted. In the manner of treatment described, the treatment agent or the drug is used pulled through the fibrous crevice tissue of the heart muscle by iontophoresis or electrophoresis. In this application the drug is constantly diffusing and is not or cannot be in limited doses at certain times not even limited according to the physiological requirements Doses are given at specific time intervals.

The present invention is based on experience with usable Devices are based that determine the cardiac conditions through the electrical heart processes and electrical impulses release to influence the heartbeat according to the sensed data. These devices are generally known by the term "pacemaker" and have been used in their use It has been found that the human body can tolerate deployed devices without the need for the deployment process human life is endangered. The pacemakers have also shown that feedback is possible. Both The output signal is paced by the pacemaker circuitry controlled or regulated, the decisions depending on the electrical processes of the heart performs. The following shows that the necessary pacemakers can be used in the human body specified publications:

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1) Goetz, E. H .: Goldstein, J. V. Frater, R.W.M.Berkovits, B. "Demand Pacemaking in Intermittant Heart-Block, "Journal of the American Medical Association, Volume 10, pages 657 to 662, 1968.

2) Nathan, D.A .; Center, S .; Wu, C; Keller W .; "To Implantable, Synchronous Pacemaker for the Long Term Correction of Complete Heart-Block. "Circulation, Volume XXVII, pp to 685, 1963.

3) Fischler, H .; Barr, I.M .; Auerback, Yerushalmi S .; Neufeld, H.N. - "Atrial-Sychornized Demand Heart Pacing" IEEE Transactions on Biomedical Engineering, Volume BME-16, Pages 64 to 69.

The invention is also related to various types of sensing devices, some of which are already commercially available are obtainable. These sensing devices can be used to accurately sense the physiological and chemical states of the body can be used. At this point in time, the output signals from most of these devices are showing changes feel, recorded and / or in or on the body used to exert influence through devices located outside the body. Already existing, in practice Used sensing devices are, for example, for measuring, detecting or determining sugar, the pH value, ion changes, blood pressure or blood flow, electrical processes, breathing processes and gastrointestinal activity been used.

It should also be noted that there are already deployed devices with a battery supply, whereby the battery can be recharged electrically without the Device must be removed. In U.S. Patent 3,692,027 issued The same inventor has also described a device for the medicament container when a supply device is used to replenish. So it is known both one;

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used battery to charge, as well as a memory for to refill the drug.

From the description of the prior art it can thus be seen that the implantation techniques already in many respects is well advanced. So there are both diffusion devices that continuously release the treatment agent than also known the self-sufficiency technology going back to the same inventor, and the facilities leads to medicinal substances and substances in pre-measured doses either constantly or in predetermined regular Hand in intervals. However, they are not devices and methods known for the administration of medicinal substances that enable medicinal substances according to the special medical requirements and needs of the Administering patients through an implanted device in which the device itself meets these needs and needs notices.

The invention is therefore based, inter alia, on the object of specifying a device and a method which do the aforementioned Has features.

A device that solves this problem is characterized by

(a) a single housing which is inserted and secured in the body as a whole at a selected location and has different departments,

(b) a storage unit housed in the installed housing,

(c) a micro supply source housed in the inserted housing,

(d) an electromechanical one housed in the inserted housing Drive device that works with the micro-supply

. source is connected and fed by it,

(e) a dispensing device accommodated in the inserted housing

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miniature design,

(f) one outside the inserted housing on a selected one Sensing device located in the body,

(g) connections passing through the wall of the housing and communicating with the sensing device,

(h) a data evaluation and control circuit in miniature design that is inserted within the housing used, is connected to and powered by the micro supply source.

A method for solving the problem is indicated through the following process steps:

(a) Insertion of the one filled with a specific treatment agent Housing the device to a selected location in the body,

(b) inserting the sensing device of the device in the same body at a selected location outside the housing, wherein the sensing device is connected to the circuitry of the device via connections, and

(c) Operating the sensing device to generate signals that correspond to the physiological conditions in the body, and delivering the treatment agent to selected points in the body ■ according to a scheme that is determined by the data evaluation and control circuitry is established, wherein the operation of the sensing device and the dispensing of the treating agent takes place in the form mentioned over a long period of time.

The device according to the invention and the method according to the invention are therefore based on a device which as a whole is implanted in a body. Either one sensing device or several sensing devices are provided, each of which sense a certain physical condition in certain parts of the body. Furthermore is a self-sufficient, the treatment agent-releasing device provided, which depends on the evaluation

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the changes in the sensed data is operated. In the dispensing device according to the invention and in the one according to the invention Procedure can be several medicinal substances or substances in powdery, liquid form, in the form of a suspension or used in another administrable form. The circuit arrangements leading to the decisions according to the invention, which operate in response to changes in the sensed data, control the operation of the Dispensing device and therefore also the dispensing of the treatment agent according to the special needs and requirements of the patient and at special times or time intervals.

The invention thus provides an apparatus for administering drugs and other treatment agents within one Body. The device is implanted as a whole in the body and releases the substances over a long period of time, for example over several years, according to the actual needs of the patient. A self-sufficient one Dispensing device stores a single substance or several substances in powder, liquid or form otherwise administrable form. A logic circuit arrangement with a self-control controls the administration the substance or substances by monitoring and interrogating a single or several sensing devices used in the body and by evaluating the sensed data in order to identify both the conditions in which the administration was carried out will control, as well as the mode of administration.

The features and advantages of the invention also emerge from the following descriptions of exemplary embodiments in connection with the claims and drawings. Show it:

■ Fig. 1 is a block diagram showing the basic building blocks of the

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appropriate device reproduces,

FIG. 2 is a block diagram illustrating the application of the present invention Reproduces invention in cardiac monitoring and treatment,

Pig. 3 is a block diagram showing the practice of the invention in blood pressure monitoring and treatment,

Figure 4 is a block diagram illustrating the practice of the invention in the monitoring and treatment of the chemical composition,

Fig. 5 is a block diagram showing the application of the invention in Relation to the administration of drugs from several drug stores at the same location of the body.

6 is a block diagram showing the application of the invention in connection with the administration of various Returns medication to different parts of the body,

7 shows a schematic and enlarged representation of a pump device with a bellows in miniature construction, which can be used advantageously in connection with the invention,

8 shows a schematic, enlarged representation of a Purr.-pe using multiple bellows to apply the same treatment agent to the same part of the body but in different ways To be administered in quantities and under different conditions,

9 shows a schematic, enlarged representation of a Pu "; pe using multiple bellows to accommodate different types of treatment agents to different parts of the body in different amounts and with separate Give up control,

FIG. 10 is an enlarged representation of a diaphragm pump with several separate chambers to the treatment agent in different amounts

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and to be administered to different parts of the body, wherein the bellows pump has a single drive,

Pig. 11 is a schematic, enlarged illustration of an insertable System according to the invention for different treatment agents from different stores to deliver with different controls,

12 shows a schematic representation of the device according to the invention as it is used in the treatment of supraventricular Tachycardia can be used with quinidine,

FIG. 13 shows a cross-sectional representation of the device shown in FIG. 12,

14 and 14A schematically an arrangement for the openings, to replenish the treatment agent in the system,

Figure 15 is a block diagram of the decision making Circuit,

FIG. 16 shows a more detailed illustration of that shown in FIG Circuit arrangement,

Figure 17 is a timing diagram for multiple doses of treating agent to administer.

Medical principles for a better understanding of the preferred embodiments of the invention described below ;:

Before the device according to the invention and the Method is to be described, first of all the medical problems and tasks under consideration here described that the inventive method and the device according to the invention are based. With these general medical designs are the facilities and procedures to be described below can be better understood.

The general concept underlying the applications being described

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underlying, revolves around sensing and providing and determining biological signals that refer to abnormal processes or changes in normal processes in the body. These biological signals can be used to determine or to calculate whether it is necessary to use a particular drug, hormone, or other chemical agent to deliver to a certain organ in the body or to bring it to certain places. By dispensing a drug To certain organ sites by means of a small catheter it is of course possible that small amounts at these sites are essential are more effective without causing side effects on the body. In addition, the concept includes the delivery of To regulate or to regulate medication by means of a feedback process change, possible to administer the drug intermittently, so that in this way much lower doses are delivered will need, as in the case when the drug is administered continuously over a period of time without paying close attention to it Attention is paid to whether this is from the therapeutic point of view is necessary, and whether various toxic effects occur, or whether the drug is still working or no longer working. For example In the following, an application is to be described in which a change in blood pressure in the blood vessels is determined is to provide information to the person making the decision To create part of the logic and control circuitry in the device that turns on a battery operated pump, to release a predetermined amount of a drug that lowers blood pressure. The decision to administer the drug occurs only when blood pressure rises above a certain level. This operating mode offers the possibility of to suppress undesirable effects of drugs, for example the undesirable effects of adrenergic Blocking agents to reduce the adverse side effects of chronic use, especially psychological ones Produce depression and orthostatic hypotension. The same is true of various other lowering medicines. of

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Blood pressure. In other forms of application to be described below can use physiological signals that predict the toxic effects of a particular drug Device can be used to determine and calculate the required drug administration. Hence can the toxic effects that occur during the administration of therapeutically necessary drugs due to the logical system of the invention are counteracted.

In connection with the biological sensing of blood pressure or other physiological changes that the device determined or determined, it is possible to have physiological reactions, effects or behavior-changing effects by means of suitable programming of such a device to practice and train with small logic circuits. The type of signal that is detected and in the logical Circuits processed can consist of either a signal or a combination of bio-signals, with one being or several of these signals are required for controlling the pump device to be described later for the administration are. For example, by inserting or implanting a suitable device in the body An addict may experience a variety of physiological changes that occur from injection of a narcotic. For example, using a miniature strain gauge attached to the diaphragm, respiratory problems or a reduced Determine breathing activity, a strain gauge attached to the abdomen or upper duodenum measures gastrointestinal activity and the type of activity or mobility, and a pressure transmitter measures the increase in pressure in the bile duct « The combination of these signals is used to determine when an anesthetic has been injected. The one administering a drug The pump can then expel an antidote to the narcotic and / or it can be used to practice or train the Behavior, or to bring about a change in behavior

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give off a drug that causes nausea and vomiting, thus bringing about a change in behavior or conditioning is avoided.

The forms of application that are used to generate biological signals according to the invention can have the following devices: 1) Chemical converters and chemical feedback devices, for example for detection; blood sugar, pH value, ion exchange; 2) Temperature, pressure or mechanical transducers that detect a change, for example that detect blood pressure, blood flow or bowel activity, and 3) Devices that detect electrical effects, for example, the electrical measured values in an electrocardiogram or in an electroencephalogram measure up. With the electroencephalogram or the electrocardiogram, according to the invention no. special logic circuits in miniature size can be provided to analyze abnormal signals or an abnormal rhythm and then to administer a certain amount of drug to a certain organ. For example, in the case of certain cardiac arrhythmias, the invention makes it possible to detect and determine these abnormalities with very simple logic circuits and then to deliver a drug into the pericardium in a manner similar to that required for the pacemakers already in use.

One of the types of diseases closely related to the present invention is malignant hypertension. Malignant hypertension, if untreated, has a two-year mortality rate of 90% and a five-year mortality rate of nearly 100%. By & Durchtr.ea s of Synpathikuses or may lionen by removing the sympathetic Gan ^ the two-year mortality rate at 50% and rti ο Five year mortality rate at 80% are reduced. These anti-hypertension drugs are more effective than the surgical method. The present invention provides

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a *

Method of treating malignant hypertension based on sensors within the body and on the administration of Medicines based, which are pumped to different sites of action. The sensors can have the following devices:

1) Facilities that determine blood pressure and look at the Neck and / or located on the lower extremities, 2) sensors that take electrical values from the carotid artery or the Tapping the aorta, 3) possibly sensors, the electrical values of the outflow of the sympathetic system (sympathetic outflow) determine and 4) facilities that perform the electrocardiogram take up. Blood measurements make it possible that the invention Facility, for example, can distinguish between the dystolic and the systolic ratio. The combinations the information received from the sensors can be used in the micro-implemented logic circuits can be programmed to create a range of treatment decisions based on the individual characteristics of the Patient based.

From the effector posts. ago is the doctor with the present Invention given a wide range of options to tackle malignant hypertension in various areas: 1) the outflow of the sympathetic system (sympathetic outflow) can be blocked with ganglionic blockers,

2) the adrenal outflow or delivery mechanisms can be with ganglionic blockers are blocked, 3) they are appropriate Medications exist that can be administered systematically to target the adrenergic receptors all over the body to block, and 4) there are other groups of drugs known as Varatrum Virid components, present, which can be released according to the invention in order to inhibit the pressure centers in the brain itself. If only you can Taking two of the examples mentioned, it is now possible to Herven endpoints (effector sites) in 1) the sympathetic Chain or the sympathetic discharge and 2) to find out at the body sites via an intraperitoneal administration.

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that or to think up. If four sensors and two effector sites are used, it is now possible to set up a range of possibilities, only a few of which should be described. For example, if the dystolic blood pressure rises above a certain value, the body's circulation can especially at one point in the interperitoneal cavity (abdominal cavity.) a dose of an antihypertensive Drug delivered with a beta-adrenergic blocker; in addition, it is by means of one over one Carefully monitored drug delivery to the sympathetic outflow is now possible to test the effect of the catheter antihypertensive medication to increase this by blocking this discharge. As shown earlier, this could topical application contribute to many serious side effects of the systemic ganglionic blocking drug to prevent. Difficulty in hypotension could be with blood pressure devices on the neck or with electrical ones Values discharged from the carotid artery are monitored. Numerous features of these possibilities can be found on the normal movement behavior of the individual person, for example based on people who have severe mobility restrictions or loads (heavy exercise load). The logic Mechanism of the invention can only be every 2 or 5 or even Respond for 4 hours with increasing dystolic pressure so that movement over a relatively extended period of time is possible with slightly increased pressure. Combinations of the devices shown in the drawings can be used are used to deliver drugs to different nerve endings or to bring effector sites.

In a special application, the blood pressure monitor senses both the systolic as well as the dystolic blood pressure values, which are then amplified, or for which at least the ..analog signals are amplified .-- These amplified values are sent to a detector and a logical control system where logical

Systems

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Systems in microform used are fed by various Decision-making processes are carried out:

1. If the blood pressure above a critical value is less than 30% of the heartbeats over a specified period of time away? If the answer is no, then the Purap system, which will be described below, does not become a drug submitted. It should be remembered that the pump system operates six times a day or twelve times a day could work so that the decision-making process of whether or not to dispense a drug could be every 2 or 4 hours, or even less than 1 hour apart.

2. Is the blood pressure above a critical value available for more than 30 % of the period? If so, the drug is released into the body system.

3 · Is the blood pressure above the critical value more than 90 % of the specified period? One might assume that the decision-making process finds only a very small number of possibilities, but if the decision is made then another drug, a ganglionic blocking agent, is applied directly to the sympathetic discharge in the sacral region and to the first five of the thoracic lumbai outflows.

The self-powered dispensing device According to the invention, two major improvements can be made in the treatment of hypertension possible are: 1) The drug is delivered to selected sites within the body, eliminating many of the side effects of the more effective hypertensive drugs be, 2) a much more precise titration of the hypotensive effects of the drug is possible so that the Number of undesirable hypotensive secondary treatments, particularly those related to postural hypotension

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stand, is diminished. One way by which this can be accomplished is to do this for the hypotensive Effects used drug to act for a shorter period of time, thus creating a blood pressure feedback is possible to regulate the dosage.

A notable example of the process or method described above is the treatment severe hypertension. Currently the most widely used drug in the treatment of severe hypertension is guanethidine, which is and is a long-acting drug tends to build up in tissues and is slow to clear out will. When stopping a dose of this drug, only a clot appears for several hours after stopping. Effect, whereby the significant side effects continue to occur for a considerable period of time. Medication like Bretylium, which is a short-acting hypertensive agent, is no longer used because of the significant amount Side effects and the low absorption when taken orally. However, these effects can occur in the case of the erfindäsc.e.a Dispensing device are titrated. In addition, annere Medicines similar to this composition, for example bethanidine (1-benzyl-2,3-dimethylguanethidine) and other derivatives or relatives of this compound were used with significantly better results by means of selective titration be, with the selective titration for the invention The method and the device according to the invention is suitable.

Other groups of drugs that increase efficacy depend on the selective ability of the device of the invention to deliver the drug to a particular site. These drugs groups contain ganglionic _Blockierun: -r.-medium, such as hexamethonium and related compounds or mixtures. The blockage of the sympathetic ganglions results in a significant disruption or

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Inhibiting effect in the adrenergic regulation of the little ones Arteries (arterioles) and leads to a vasodilation and better peripheral blood flow in the blood supply of organs or areas, as well as a blood pressure sample, The effectiveness of these drugs is partly due to the small proportion of ρraganglionic neurites (axons) postgangionic neurites related. Therefore, the ganglionic blockage has a very great effect. the Major difficulty with ganglionic blocking agents consists in that these agents act equally on both the parasycpathetic and the sympathetic ganglions act without a difference. This group of drugs is also only absorbed by the gastrointestinal tract with little hate, and these quaternary ammonium ions generally only penetrate penetrates cell membranes to a limited extent. Because the outflow opening of a polyethylene catheter of the invention Delivery device to the sacral ganglion and to the first four ganglions of the thoracic discharge or Lumbar region (thoracοlumbar outflow) is directed, can the mediciners the blood vessels in the large muscles of the extremities block selectively without affecting the gastrointestinal tract, the urogenital system or the heart and affects the lungs significantly.

With the inventive method and the inventive Device can also be used to treat cancer. For example, it may be necessary on different parts of the body To dispense different drugs depending on the sensitivity of each site. To this end the two or three-part bellows bags described below can be used. In other forms of application can reduce the radioactivity of certain radioactive anti-cancer compounds can be monitored and the drug can be given depending on the radioactive concentrations Cancer site to be submitted.

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Another possible application is in connection with Stomach ulcer. For example, the pH according to Invention found in the stomach and the antrium of the stomach rinsed or bathed in an anti-cholinergic. at Another form of application can be painful spinal dorsal nerves for nerve damage with a treatment agent be rinsed or bathed, whereby this process is controlled from the outside by the patient, but with the possibility of to control this also by the control and logic circuits according to the invention in order to avoid overdoses. In In this case, the patient's pain threshold or the patient's sensation of pain is used as a feeler, so to speak. The patient actuates a reed switch to the device to turn on. In the case of kidney stones, a drainage catheter can be attached in the renal pelvis itself, whereby the pH value of this Body area is determined and changed to dissolve the kidney stones. Certain forms of epilepsy or Various forms of mental illness may also be possible with intraventicular treatment or delivery can be treated more effectively from very small doses to certain positions. This treatment, or the delivery of a drug can be controlled in the case of epilepsy when abnormal electrical values occur. Other abnormal brain conditions can be treated by turning off abnormal slow waves (while awake) or through programs to help certain forms of electrical processes, for example to maintain alpha waves or certain subcortical rhythms. It goes without saying that the possible applications on the central nervous system can only be used carefully after many years Investigations and experiments are carried out.

In the case of certain spastic vascular diseases, for example in the Berger ¹ see or the Raynand ¹ see disease, it now appears possible to carry out a periodic lumbar or cervical sympathetic block with the present invention by delivering a drug to this area.

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respectively. The drug can be administered by the onset of the discharge at the time of surgery on the vessels carried out, fed to the artery itself. The drug may be used depending on the blood stream being withdrawn be delivered.

A heart stroke can be sensed with sensors that sense venous pressure and electrical heart activity the. Heart stroke can then be controlled with digoxin, which is passed from the catheter directly to the pericardium. In other Cases can be carried out - depending on the results - from examinations - Vascular dilators or vasodilators are released into the pericardium by external control of the patient, and if the patient has heart spasm or other difficulties or senses that the patient may experience and pain.

After all, there are different "heart conditions," in particular Cardiac arrhythmias that can be treated by taking a drug in response to abnormal electrical signals is released from the heart into or through the pericardium. For example, the "device according to the invention Quinadin Occurrence of supra-ventricular tachycardia (above the gastric or Excessive heart function or rapid heartbeat), which is based on electrophysiological cardiac activity. This example is given below in order to to illustrate the present application of the concept described above in connection with a special device, whose mode of operation and operation can be fully documented.

In summary, it can be said that many possible forms of application arise by themselves, and that many years are required are to full the invention in all details and for all forms and areas of medical application

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to develop. The advantages and usefulness of the basic concept this invention is also readily apparent. The person skilled in the art knows that individual parts and components are required and examines individual procedural steps required independently of one another in other medical areas became. In the present invention, these parts, components and process steps are combined and brought together, so that previously unknown results and modes of operation arise.

Description of preferred embodiments

The invention is intended first in a larger context and in With reference to certain forms of application are explained in connection with the structural details of the individual, special components to put the invention into practice. Finally, an individually described form of application should then be used can be specified.

In Fig. Λ the basic components of a usable system according to the invention are shown schematically. A micro supply source 28, a medicament store 29, a measuring sensor 30, a delivery control circuit 31 and a delivery device 32 are provided. Besides the sensor 30 are all other components in a suitable housing 33 ■> the body is employed persons to be treated the in. The system is supplied with voltage by a suitable micro-supply source 28, which is described, for example, in US Pat. No. 3,692,027. The measuring sensor 30 is used to sense certain physiological, chemical, electrical and other conditions at certain points in and on the body; it generates data corresponding to the sensed conditions at the sensed locations. These data are then brought together in accordance with the method according to the invention and stored in a suitable delivery control circuit 31? for example in a logical ochal

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evaluation evaluated; depending on the sensed data indicating whether drugs are required or not the delivery control circuit -31 that the delivery device 32 either switched off or remains closed, or a predetermined one Amount of drug from the drug store 29 delivers according to the needs of the patient.

In Fig. 2 is a more specific and somewhat more complicated form of application of the invention for cardiac monitoring and cardiac treatment shown schematically. The micro supply source, for the sake of clarity and simplicity is not shown, but is part of the systems shown in FIGS. In the application form shown in FIG a medicament storage 40 and a measuring sensor for electrical voltages 41 is provided, as it is for example in the case of electroencephalogrammatic and electrocardiogrammatic examinations are used. Although only a single sensor is shown, the measuring sensor 41 can also consist of several, for example three or more measuring sensors. The sensed Information is fed to a suitable logic circuit 42, which selects the sensed data as key factors. Since the logic circuits themselves are known and one skilled in the art can make these logic circuits, the description is intended to focus more on the medical ones in general Aspects than relate to the details of the circuit, although in the context of one to be described further below Example of a complete circuit is to be described.

It is known that the sensed electrical voltage data, for example in conjunction with an electroencephalogram and an electrocardiogram are several Contain or reveal factors. In Fig. 2, it was assumed that there are three factors A, B and C that are selected and in suitable logic circuit parts 43, 44, 45 with normal

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paint limit values can be compared. For example, the subcircuit 43 can determine whether the factor A is within normal limits (WML) or not, and accordingly produce a "no" or a "yes" output signal. The sub-circuits 44 and 45 can be used for corresponding processes be designed with respect to the factors B and C, in such a way that when the factors A, B and C are all are outside the normal limits, an output signal is generated at connection point 46, which is used for control the dispenser 47 can be used. Other circuit compositions are possible. Except for the sensor shown in Fig. 2, all components should be in a suitable, Housing 48 insertable into the body may be included.

In Fig. 3, a further form of application of the invention is shown, blood pressure monitoring and treatment serves. In this form of application, a pressure transducer 51 is used provided with a housing 50 that can be inserted appropriate logic circuit 52 contained therein is connected, wherein the pressure transducer 51 and / or the logic circuit 52 are trained so that they are due to the systolic and diastolic properties make decisions. When the blood pressure is not within the specified limits is, a "no" output signal is generated, which activates a suitable output device 53 so that the from Memory 5 ^ selected drug delivered and thereby blood pressure is decreased.

A chemical monitoring system is shown in FIG. In this embodiment, a suitable chemical Value-detecting sensor 60 used, for example, pH changes, ion changes, the sugar value or other chemical factors of the body that are amenable to sensing. The probe 60 is with a suitable threshold value discriminator and a logical

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see circuit 61 connected, which in turn is connected to a dispensing device 62 for the drug is connected. Except for the measuring sensor, all components are in a suitable one insertable housing 63, in which also the medicament storage 59 is included. In this embodiment, logic circuit 61 determines whether the sensed chemical factor is within acceptable normal threshold limits or not, and in the event that this is not the case, the medicament dispenser 62 is put into operation, by the factor again within to bring acceptable threshold limits.

In Fig. 5, a form of application of the invention is schematically shown in which doses of the same drug can be dispensed from different dispensers. at In this embodiment, the sensor 64 is compatible with a suitable one logic circuit 65 connected, which the periodic sensing, the evaluation of the sensed data and the dispensing of medication from a common medication memory 66 via a delivery device 67 or a delivery device 68 separate therefrom controls. For example, the delivery device 67 serve to dispense a relatively small amount of medication that is normally to be dispensed, while the dispensing device 63 serves for an additional delivery of the drug to the same treated area.

In Fig. 6, the sensor 70 is with an appropriate logic Circuit 71 connected, which is an output device 72 for Controls delivery of a drug A, for example, which is contained in a drug store 73. The circuit 71 also controls the delivery device 73 », for example Medication B dispenses in another medication store 74 is included. In this form of application, different Medicines are delivered to the same treated site or to different treated sites, with a drug one and the other drug for a different purpose

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serves. A housing 76 encloses the device.

From the above description it can be seen that the various Application forms of the invention are in each case suitable Time control and sensing devices, suitable circuits for evaluating the sensed data and for deciding on the sensed data, as well as suitable dispensing facilities require the medication depending on the evaluation of the submit sensed data. Measuring sensors which can be used in the body are known for various purposes and the person skilled in the art can will quickly recognize the applicability of these probes in the context of the present invention. It is to the expert It is also possible to easily create other types of usable measuring sensors that are and will be adapted accordingly also the parameters required for other types of probes can determine.

The following are those required for the concept of the invention logic circuits are briefly described, which can be easily made by one skilled in the art. the Logical circuit must be designed in a suitable manner for the respective application in order to receive the sensed data to be able to process that of a measuring sensor, for example a measuring transducer, in one of the particular application forms Come shape. The data coming from the measuring sensor or arriving at the logic circuit are for example Print data, chemical data, electrical data, etc. The logic circuit generates depending on the data evaluation an output signal. In some cases, as noted for example in connection with FIG. 2, multiple output data signals from a single signal output signal are formed, the only output signal for different data, for example for the factors A, B and C can be selected by means of different circuit parts, as shown in FIG. Logical switch

- 2Pr - -dunk

709815/0565

services of the type required for the present invention, which are available in miniature, are both in electronic Circuit books, as well as in the medical literature, for example in connection with pacemakers, described. Since the present invention has a wide range of uses, there is freedom in the Choice of circuit types with which the logical processes and functions can be carried out.

Another important consideration is substitutability the sensor used in a body, the usability of the housing, in which the drug storage and the dispensing device is included, and the usability of a catheter or other devices that are used for delivery or administration of the drug can be used on the treated area. Since measuring sensors, especially electrical measuring sensors, Exchange or diffusion devices and the like that have been used for long periods of time have all been used, and the difficulties and problems of inserting such devices into a body are well known, are the Those skilled in the art are familiar with the parameters and conditions required for use. Because pacemakers already used in body are also the usual parameters and conditions for inserting a housing for the present Invention required type known. The medication that takes place inside over a long period of time used catheters and the like, in which the drug is supplied from external drug containers or sources, has also already been applied. Hence the difficulties associated with tissue growth and tissue blockage, and other difficulties encountered with known methods and techniques of the present invention are contemplated and the same techniques previously developed are also contemplated useful with the present invention.

- 25 - At

709815/0 5 65

544884

In each application of the present invention are devices required to convert a substance intended for the treatment into powdery, liquid or otherwise processable Save shape under pressure. Furthermore, there are facilities that take predetermined amounts from such a memory pumping or otherwise fetching from the memory, as well as facilities required to measure the measured dose to the appropriate organ or site best suited to administering the dose. The size of the The pressure can be different for the different drugs because the drugs have different viscosity, Have dose dimensions, etc. Lots of arrangements on are known in the field of pumping technology, arise by themselves. For example, the drug can be in an elastic Bags are located, with inert gas being introduced into the storage area, which creates the required overpressure.

U.S. Patent 3,692,027, assigned to the same inventor as the present invention Invention describes a device which, in connection with the present invention, is suitable for the medicament to save and submit. For example, such a device as described in the aforementioned patent is described, the delivery device 32 shown in FIG. 1 and the delivery control also shown in FIG 3 ^ included, with a switch provided that the battery which, according to the aforementioned patent specification, feeds the device, connects to the device or from it separates. In this form of application, the sensor shown in FIG. 1 feels Sensor 30 at controlled time intervals the respective State from and the delivery control 31 according to FIG. 1 causes that the delivery device, as it is for example in of the aforementioned patent specification is shown and described, depending on the evaluation and the decision, based on the sensed data, turned on or not

- 26 - switched on

709815 / 056S

is switched on. Corresponding controls are for the Circuit logic is advantageously provided to prevent overdosing when the sensed physiological changes do not occur quickly enough after the drug dose has been delivered, d. H. if between the physiological change and the drug delivery corresponding time delays or corresponding dose-time dependencies occur.

A wide variety of dispensing devices can be used in the present invention be used. The device described in US Pat. No. 3,692,027 has already been mentioned. Another Device for pumping a liquid medicament is shown in FIG. Fig. 7 shows on a greatly enlarged scale a housing 80 in which a piston 81 is arranged, the is attached to a bellows container 82. The bellows container is made of polyvinyl plastic or another suitable one Material made. A piston rod 83 is on the piston 81 attached and is moved inwards by a suitable magnetic coil 84 and outwards by a suitable spring 85, the spring 85 exerting pressure on the head portion 86 on the piston rod 83 exercises. This arrangement is shown schematically in FIG. The flow of current through the solenoid 84 is of course controlled by suitable logic circuitry as previously described. Via an inlet port 87 and a disposable shut-off device 88, the medicament enters the bellows 82 and the medicament is dispensed via a disposable Shut-off element 89 and an outlet pipe 90 are released. Naturally the pump arrangement shown in FIG. 7 is accommodated in the practical case in the built-in housing described above and has the particular advantage that no seal is required between the piston 81 and the housing 80, which requires a frictional pressure, since all of the medicament is contained in the interior of the bellows 82 and from it the medicament cannot escape. Such bellows pumps are known and have already proven themselves in practice.

- 27 - a

709815/0565

A problem with many physical disabilities and ailments occurs, consists in the requirement to take a mean daily dose, for example insulin, regularly and, if it becomes necessary to administer doses of short-term drugs, for example insulin, in the meantime. In Fig. 8 a device is shown schematically, which is provided and suitable for this requirement. At this Apparatus is a cam 100 by a suitable micromotor such as that described in US Pat. No. 3,692,027 was driven. The micromotor is driven by a suitable, logic circuit not shown switched on. When the cam 100 rotates, it comes into contact with a roller 101 and exerts pressure on the arm 102, which moves the piston 105 so that the bellows 104- a predetermined dose of the previous from the medicament input from the medicament memory 106 Drug storage area 105 releases. The cam 100 rotates, and after the bellows 104- dispenses the amount of medication has, he withdraws and fills the chamber 105 at an appropriate time when the cam 100 is not rotating. Control appropriate one-way shut-off devices 107 and 108 the inlet and outlet. Such a cam driven arrangement can be provided for the required provide medium daily doses. In order to provide an additional amount of the medicament in the meantime if necessary, one with the corresponding one, not shown Logic circuit related solenoid 110 is provided. When this coil 110 is energized, it moves Piston rod 111 and displaces the piston 112 so that a smaller amount than that dispensed by means of the cam 100 amount and so that a smaller dose is administered. At the end of the piston stroke for delivery, the coil 110 is de-energized and the spring 113 causes the storage area 114 to be refilled.

In Fig. 9 a device is shown with which two different

- 28 - -different

7098 15/0565

Different drugs can be administered. The in Fig. The crouch 120 shown and the coil 121 operate in a corresponding manner as the cam and the coil in the case of the previous reference of FIG. 8 shown device. In the application according to FIG. 9, the cam 120 acts on the bellows 123 and the spool 121 on the bellows 124. In the case of the dispensing devices according to FIGS. 7, 8 and 9, the one for the drive is the corresponding one Drive members such as piston rod 83 and cam 100 require power from the aforementioned micro-supply source provided. A certain drug, for example a long-acting drug, can be in the one Memory 125 and another drug, for example a short-acting drug, can be stored in a separate memory 126 must be saved. Therefore, one drug can be supplied by means of the coil 121 and the other drug by means of the cam 120 can be administered. Of course, suitable one-way shut-off devices or other features and components can be known mechanical devices are used, even if they are not shown or not described in detail will.

In Fig. 10, a pump arrangement with a bellows is shown, which has two compartments 130, 131, which in a common Housing 132 are housed and operated with a piston 133 " will. From the drawings it can be seen that this arrangement, as in the arrangement shown in FIG. 9,

Deliver two or more different drugs to two or more parts of the body. The arrangement shown in FIG allows the drug in two places with different To deliver pressure using two pressure generating devices. In contrast, the in 10, the drug is delivered to two or more locations with unequal pressure, with only one Drive shaft is used. In addition, it is in the arrangement shown in Fig. 10 with a bellows with several

- 29 - chambers

709815/0565

Chambers possible to dispense two or more drugs without that this significantly increases the frictional force that would otherwise be relative when using several cylinders and pistons is high. In addition to the good sealing of the bellows chamber, the bellows chamber enables a great variety and the possibility of variation in implant surgery to obtain, namely by the fact that different bellows designs can be used instead of others Bellows designs are used in the pump. This means that the surgeon only needs to have a few types of pumps in stock, which are then adapted to the respective circumstances and requirements by inserting the corresponding bellows can. It can take a wide variety of bellows shapes and dimensions be advantageous, these different bellows for the different treatment purposes in the pump cylinder can be used.

FIG. 11 shows a system similar to that shown in FIG. 6, schematically Application form corresponds. It should also be noted here that the arrangement shown schematically in FIG Practice corresponds to a device that has much smaller dimensions. In the arrangement shown in FIG a housing 150 with suitable anchorages 151 is shown. A suitable compartment 152 is provided within the housing 150, in which there is a predetermined amount of the medicament that is given off over a long period of time for chronic treatment, with even Doses are required, the dimensions of which can be specified and specified. Compartment 155 represents one Storage container for a special drug, for example is required for unusual and temporary conditions in a particular patient. The previously mentioned Evaluation and control circuit is housed in a separate compartment 154- and is available with a suitable measuring sensor 155 in connection within the body to be treated,

- 30 -. However

7098 1 S / 05SS

but is outside the housing 150. For the controlled treatment or administration of medicaments, the micro-unit 160 _{1 of} the type described in US Pat turned on and rotates the cam 161 so that the cam tips against the roller

180 press, which is attached to the piston rod 162

The medication contained in the storage area 152 is then transferred a suitable outlet pipe.164- delivered. During the outlet the flap valve 170 closes when the piston 162 moves to the right in FIG. 11 and a cylindrical, sliding valve member 171 slides upward so that a connection is established between lines 175 and 176. If When the cam 161 rotates, the roller 180 runs due to the spring

181 constantly crouching 161. The flap valve 170 opens down, slide valve 171 moves down and a new one Charge is stored in storage area 163. The inputs 158 and 159 are used to refill the memory.

When the specific drug is requested, based on the evaluation of the information provided by the probe in the logic circuit contained in compartment 154, When the coil 190 is energized, it moves the piston 191 to the right in FIG. 11 against the resistance of the spring 192. The flap valve 193 closes and the slide valve 194 slides afterwards at the top, in the position shown in FIG. 11, and the tubes 196 and 197 are in communication with one another, so that the special Drug can escape via line 196. As the piston moves back, slide valve 194 moves downward, the flap valve 192 opens and there is a new load of the special medicament is sucked into the storage area 200. In this way, by switching the unit 160 on and off, the body to be treated can be periodically

- 31 - submitted

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dispensed drug and treated by energizing and de-energizing coil 190 with the particular drug.

In the following, a pump device for the treatment of heart diseases will be described in detail to a medicament to prevent recurrent excessive cardiac functions (recurrent tachycardias). It should be noted that quinidine is administered long-term, for the recurrence of atrial fibrillation and flutter, as well as preventing supra-ventricular tachycardias that do not due to digitalitis toxicity. Quinidine, as well as procainamide, is also used to advantage to keep recurring prevent ventricular tachycardia. Quinidine is also used to treat recurrent ventricular fibrillation or prevent flutter, except when the ventricular flutter occurs during an entire heart failure this flutter inevitably occurs. The treatment of cardiac arrhythmias is described in "Drugs used in the Treatment of Cardiac Arrythmias "in the book" Treatment of Heart Disease in the Adult ", second edition, Rubin, T. L .; Gross, H.; Work, S. R., Lea and Febriger, Philadelphia, pp. 297-324, 1972. One of the difficulties of use of these drugs is to be seen in the fact that the therapeutic ratio, or the therapeutic amount, i.e. the ratio between the therapeutic dose and the toxic dose is quite small. The pump feedback system according to Invention, however, is intended to very carefully consider the heart condition and the toxic effects of the drugs Monitor and maintain medication dosages at a level that lowers the complications associated with this treatment connected, to be kept as low as possible, or to be switched off completely. The device according to the invention and the device according to the invention Processes enable these drugs to be used more generally than for other uses lead to quite serious and life threatening heart conditions

- 32 - can.

709815 / 056S

25A4884

can. The invention relates to a system required for the application of these medicaments, namely to a Evaluation system with feedback to provide the maximum required therapeutic dose, which is nevertheless below the toxic dose of the drug at which toxic phenomena occur.

The object described can be achieved by monitoring the state of the disease and the administration of medication is regulated in order to treat the disease state in this way according to the invention, with nonetheless toxic phenomena When using the drug should be avoided by changing the dose depending on these phenomena is additionally monitored and regulated. Supraventricular tachycardia is an example of the disease being treated. The present example is directed to the toxic changes induced by quinidine in cardiac condition to counteract, d. H. a widening of the QRS complex (this is a component of the electrocardiogram) to counteract. The dose of quinidine can be monitored and decreased when using the present invention an enlargement or broadening of the QRS complex occurs, namely when the quinidine dose reaches the limit at which toxic effects are triggered.

Figs. 12 and 13 show the basic structure and operation the device used to treat supraventricular tachycardia with the administration of quinidine. The pump motor 210 is described in US Pat. No. 3,692,027 and rotates the one formed in the shape of an equilateral triangle Cam 211, for example eight or more times per day by 360 °, so that the pump is actuated a total of 24 times via the roller 230, which sets the piston 212 in motion. So the pump can Work once an hour so that 24 possible doses can be dispensed per day. In this example, the following

- 33 - Company boards

λ A Λ Ji t * # Λ fr *

Operations carried out when one is in a two-hour rhythm to dispense the drug works, so if you give the drug every 2 hours, if not is changed by an evaluation of the information coming from the sensors (the two-hour rhythm becomes performed by running the pump motor 210 every 2 hours is switched on): 1. The device delivers the medication every 2 hours as an average dose division. 2. In dependence from the evaluation of the feedback process, the delivery of the drug must be suppressed for 2 hours, leaving a period of 4 hours between the delivery of two doses occurs when indicated. 3 · Additional doses can be given every hour, if this is necessary. During operation, the cam 211 is driven by the pump motor 210 and it becomes a first Dose delivered. Then the control mechanism turns the device off for 1 hour, if there are no conditions that require an additional dose of medication, in which case the facility works in the next Hour and provides an additional dose. So under normal operating conditions, the facility gives all 2 hours, and thus one dose 12 times a day. Should toxic phenomena occur during the administration of quinidine, so the device can be switched off for a sufficiently long period to cover the period between the delivery of the drug to 4 hours.

In the treatment of supraventricular tachycardia, the electrodes 250 shown in FIG. 13 practice heart feel even the electrical cardiac activities and the cardiac signals are amplifiers in the electronic assembly via wires 251, which are attached in or on the catheter 248. An electronic, logical program for recognition is provided to identify the QRS complex and another The program then determines the size of the QRS period and

- 34 - des

of the RR interval, as will be described with reference to the diagram shown in FIG. During operation, the heart rate (RR interval) is monitored, determined and averaged for every hour over a 24-hour period and stored in a memory. The lowest mean frequency for a 1 hour during the 24-hour period is compared with the lowest frequency per hour of the control periods, and it is determined whether this lowest mean frequency has risen by 10 to 20% above the standard control level, the norms being set when the device is inserted into the body. So when the frequency has increased by 20 % , the device will deliver three additional hourly doses over the next 24 hours, one dose every 8 hours. The logic control circuit which brings about the decision is provided in the system for this process. The quinidine toxicity is determined using the QRS period. The QRS period is summarized and evaluated every hour and if this period rises above the normal level (in% of control), or if premature ventricular contractions occur (which are indicated by very broad QRS complexes above 150% of control), in particular If the quinidine effect is monitored, then the next dose period is suppressed by switching off the pump motor 210 and, secondly, the additional dose is stopped for the 8 hour period that is currently occurring because of the criterion used for the first series of feedback decisions is provided.

The diagram shown in FIG. 17 will now be explained will:

State I = the pump is working in normal operation, namely

every 2 hours to even-numbered hours.

• State II = the heart rate has risen to 10 to 20% , which means that the RR interval has decreased

- 35 - 10

70981S / 056S

Has decreased by 10 to 20%. The hour with the lowest frequency during the previous 24 hour day is compared to the control value to make this decision. If this smallest hourly frequency in the 24 hours is 10 to 20 % higher than the control value, the logic circuit then causes three additional doses to be dispensed for the next day, namely every 8 hours in the 1st, 9th and 17th · Hour.

State III = the sampled QRS period is during the past Greater than normal for an hour on the following basis: The QRS complex period is divided into percentages of the control value and gives a value according to the following list:

1) 110 % or less than the control variable gives a value of zero

2) 110 to 120% larger than the control variable gives a value of one

3) 120 to 130% larger than the control variable gives a value of two

4) 130 to 150 % larger than the control variable gives a value eight

5) shows greater than 150% of the control size indicates a premature ventricular contraction and gives a variable value of

8 or 16. If over the next hour, the 257 QRS periods sampled results in a total of 256 for the values or weightings, or a larger total, the pump is switched off for the next even-numbered hour operation and the Delivery of the additional dose for this 8-hour period in which the operation is currently in progress

- 36 - carried out

7Q981S / 05GS

can be carried out, set, because of the created for state II Criterion. So if the dose is not delivered at hour 4, the Dose to be delivered at hour 9 was also not delivered.

The three inputs 252, 253, 254 shown in FIGS. 12 and 13 will be described below. The entrance 252 consists of a rotary switch with 8 positions and a needle contact. The rotary switch and the needle contact are actuated by means of a needle (not shown) with a solid core, the tip area of which is round to triangular to a round outer diameter, and which is inserted into the inlet 252, which, as shown, has an adapted Has triangular hole. The switch is operated by moving the needle over one of the 8 different positions is rotated. The connection to the switch is via the contacts on uen three triangular surfaces of the needle, which make the triangular hole contacts are approximately approximated. The lines to the triangular needle surfaces are routed along the long axis of the needle and shielded by suitable insulating means. The switch position no. 1 of the rotary switch is used to charge the battery via the needle contacts. Switch position no.2 is used for recording or sensing the electrocardiogram, generated by the electrodes used. The switch position No. 3 is used to stimulate the heart via the heart electrodes when pacemaker effects are required. Switch position no. 4 creates a connection to the logic circuit system relating to the logic circuit calibrate the parameters responsive to the heart. Switch position no. 5 is used to monitor and display de Output signal from the logic circuit and the number of doses per day. Switch position no. 6 is used to switch off of the whole system. The switch positions no. 7 and 8 are

- 37 - still

7 η Q a 1 S / η t; ft K

still free for further requirements.

The catheter entry opening 253 is a by-pass catheter inlet and serves the following tasks: (1) The medical professional is enabled to generate increased pressure in the catheter when the catheter is mechanically blocked or clogged. (2) The medical professional is enabled to insert a wire stylet if the catheter is mechanically blocked or clogged. (3) It will allow the medical professional to add additional to the pericardium Introduce medication if necessary. The catheter entry opening and how it works will be described with reference to Figs. 14 and 14A. A needle provided with an inner bore, not shown, with a round to square to round tip area is passed through the patient's skin with the aid of hump 306 and then inserted into the square hole 303. The segment of the square needle engages the sides of the square hole 303. By rotating the needle around its longitudinal axis the small gear 302, which meshes with and rotates the partial ring gear 301, is rotated. When the part ring gear 301 has been turned counterclockwise as far as it will go, the opening 307 for the hole in the needle is or aligned with the inner diameter of the needle so that one has access to the catheter 304 and the pump outlet port 305 Has. The "O" rings 308 and 309 both seal the passage in the open as well as in the closed position. The small gear 302 is held in place by the top plate 310. In Fig. 14, the outer housing of the device is through the line 311 indicated.

In order to be able to refill the medication container, an inlet opening 254 is provided. Since feeding from under Pressurized medicament in the medicament container has already been described in US Pat. No. 3,692,027, as well as an inlet suitable therefor in this context, the labor

- 38 - -wise

wise and the opening for refilling the container does not will be explained again in detail.

In Fig. 15 further details of the by-pass system are shown, in particular the attachment of the catheter system to the pericardium is shown. The O-rings 255 below the inlet opening are provided for sealing. A one-way shut-off device 256 in the catheter, that in the one leading to the pump Line is, is used to keep the by-pass system rising pressure away from the pump device. The catheter system is attached or sewn to the pericardial envelope with an inlet 247 which is attached to the catheter 248 is appropriate. The catheter has both a catheter area with a uniform diameter and an adjoining, widening, trumpet-shaped area 249. The Increased catheter diameter results in an enlarged surface area and reduces the risk of clogging or blockage by the tissue fibers surrounding the exit opening of the catheter. In the vicinity of the catheter 248 there are also lines 251 »from the two sensing electrodes 250 to the amplifier and the logic System lead. These lines are embedded in the catheter and provide additional stiffening and support for the catheter. The electrodes 250 and the wires connected to them are surrounded by a polyvinyl layer after them emerge from the catheter.

15 is a block diagram showing the mode of operation and the execution of the decisions as they occur in the control of the pump for the heart treatment. Those referred to as the "sense electrode" and the "amplifier" Components are customary standard components that are used, for example, in the known cardiac pacemaker circuits. The remainder of the block diagram shown in FIG is, so to speak, the brain of the system and serves to control

- 39 - amendment

70981S / 0S6S

eration of the "pump" when the conditions described above are present I, II or III. The type and construction of the components required for the circuit shown in FIG are generally known and have already been mentioned in the preceding description. Since Fig. 16 is a detailed 15 shows the circuit arrangement of FIG. 15 and its mode of operation the following description is understandable.

In Fig. 16 is a. logical flowchart shown, the for the application forms shown in FIGS. 12 to 15 and 17 suitable is. Since the components shown in FIG. 16 are designated in the figure and are known to those skilled in the art and since their relationship to each other is also shown in the circuit in Fig. 16, hereinafter will mainly be the operation of the circuit shown in Fig. 16 will be described. The "detector for the possible QRS complexes "which has an output (a), determines the beginning and the end of all" possible "QRS complexes The beginning of a "possible" QRS complex is detected by the "start detector for the possible QRS complexes", which has an output (b), determined and the end of a "possible" QRS complex is determined by the "end detector for the possible QRS complexes" detected, which has an output (d). The decision as to whether the "possible" QRS complex that has been identified is a "real" QRS complex is performed in the "true QRS complex detector" which has an output (c). The output signals at the outputs (c) and (d) are then fed to an AND gate with an output (e). The on Output signal occurring at output (s) then represents the end of a "real" QRS complex.

The QRS complex is analyzed in two different ways: (1) The period time of the QRS complex is measured and (2) the period time between two consecutive QRS complexes, i.e. H. the R-R interval, measured.

- 40 - The

70981S / 0S6S

The measurement of the holiday time of the QRS complexes is carried out with the "Classifier for the percentage control time division". The classifier is reset by the signal at output (b) and then begins to divide or classify the time period of a QRS complex into one of the five time intervals; (I) 110% or a lower percentage of the control time, (II) 110 % to 120% of the control time, (III) 120% to 130 % of the control time, (IV) I30 % to 150% of the control time, or (V) 15Ο % or a greater percentage of the control time. The control time is the time period of a normal QRS complex for a particular patient. At node (f) the end of a "real" QRS complex occurs 256 times per hour. The pulse at node (f) is the signal that is added in the "addition counter for the QRS period time". Depending on the percentage of the control time classification of the QRS complexes, this counter is incremented by 0, 1, 2, 4, 8 or 16 counters. Each classification adds a counter number to the counter. With the classification (V) there is the additional possibility that its counter value can be changed to 4, 8 or 16 via the "memory latch control 1". This memory latch control can be set or influenced with the aforementioned rotary switch 252 which can be operated from outside. The rotary switch 252 is not shown in FIG. 16, but is shown in FIGS. 12 and 13. If the count of the "addition counter for the QRS period time" exceeds the value 256 in one hour, a digital "one" occurs at output (g), otherwise a digital "zero".

The R-R interval is measured by the "R-R pulse generator" which selects two consecutive "real" QRS complexes, each occurring 256 times in one hour and a digital output signal at node "h" Provides "one" pulse whose pulse width is the same

- 41 - the

η η η a <* irtr-A

is the period time between the end pulses of these successive "real" end pulses. This pulse at circuit point (h) is then passed through an AND element with a 1000 Hz clock sequence and the pulses resulting at circuit point (i) then reproduce the number of 1000 Hz pulses that are generated 256 times during an RR interval occur in an hour. These pulses at node (i) are added up in the "RR interval counter" which has an output (j). At the end of each hour, the content of the "RR interval counter" is compared with the "RR control value". This control value reflects the number of 1000 Hz pulses that occur during a period that is 20 % smaller than a normal RR interval for a specific patient (i.e. the period corresponds to an RR frequency that is 20 % smaller higher than the normal period time). This control value is entered into the "memory latch control 2" via the previously mentioned externally operable ^{T rotary switch 252.} If the hourly counter number is greater than the counter value, then the "RR status for the present day" (which is normally a digital "one") changes to a digital "zero". Once the logical "zero" is set, the logical "zero" is maintained for the remainder of the day. At the end of the 24th hour, this value is stored in the "RR status for the previous day" in order to be used in making decisions about the pump operation for the current day at the beginning of hours 1, 9 and 17. This output signal at node (k) is a digital "zero" if the RR interval count for any hour of the previous 24-hour day was greater than the "RR control value" for a particular patient Frequency during one hour of the 24-hour day was lower than the normal control value plus 20%).

The two output signals at circuit points (g) and (k)

- 42 - taxes

control the pump operation. During normal operation, the pump delivers the drug every even hour (state I in the diagram shown in Fig. 17). As the frequency increases, for the lowest "hourly frequency" of the 24-hour period from the previous day (which means that a greater amount of medication is required) occurs at the switching point (k) a digital "one" on which causes the pump to add an extra dose at hours 1.9 and 17 releases (state II in the diagram shown in Fig. I7). These two operating states occur in the following way on: If either the output signal at the switching point (s) or the output signal at node (q) is a digital "one", then the input signal of the "pump control" is a digital "one" at the node (r). -If a digital "one" pulse occurs at node (r), with this signal the pump is switched on. This signal at the switching point (r) is normally at every even hour (at exit (m)) and in state II of the diagram shown in Fig. 17 for hours 1, 9 and 17 (at exit (p)) a digital "one", provided that these states are not changed by one of the following influences: If the output at node (g) is a digital "one" every hour, the output will be the "Two-hour memory" at the switching point (1) for the next 2 hours converted to a digital "zero" (normally the output signal at node (1) is a digital "one"). This signal (1) is then due to the pulse switched through for the even hours at the switching point (m) by an AND element which has an output (n). If the output signal at node (g) is a digital "one" for every hour, the output signal of the "eight-hour memory" brought into the digital "zero" state for 8 hours at the switching point (o) (normally this is Output signal (o) a digital "one"). This output signal (o) is then sent to the switch by means of the logical "one" pulse

- 45 - point

70981 B / 066S

point (ρ) for hours 1, 9 and 17 and by means of the on the line (k) occurring pulse passed through an AND gate which has an output (q).

In connection with the above, it should be noted that that the drive unit 210 is shown in FIGS. 12 and 13 Arrangement similar to that shown in Figs Circuit arrangements is connected, is set or adapted in a suitable manner so that they are in contrast to 60 minute hour of logic circuit with a 50 minute hour is working. In this way one gets between the end of the drive unit hour and the end of the hour of the logi-r systems see a time interval of 10 minutes, so that there is a time control margin for error in the movement of the drive unit, which occurs due to increased workload or utilization, can be created.

A system that can be used in a body and a special method that is used to treat the human and animal body can be used in a unique way. The "source of supply" can be varied Form be formed. The source of supply may, for example, be of the miniature form described in US Pat. No. 3,692,027 own, or other, corresponding supply sources in miniature format can be used, the one have a long service life, for example at least on the order of days and preferably years, and the electrical energy for operating the electronic circuit and provide for the operation of the drive devices with which the delivery device is driven. the The device can be used in a wide variety of ways and the necessary pharmacologically active drugs, Part of the body, active ingredients, radioactive substances, etc. are used.

- 44 - It

709815 / 056S

It should also be noted that with that used in the claims The term "body" and "animal body" includes both animal and human and other bodies of living beings The term "body" includes all types of bodies, whether they are living bodies or Body parts and the like, providing a facility with micro-self-sufficiency and a control can receive in order to administer substances or substances in addition to such a body or supply.

Patent claims:

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Claims (28)

CL3P -1339 claims 1. Independent, self-sustaining device known as * "Whole in a particular body of a living being, in particular is used in a human or animal body to restore selected internal physiological states periodically evaluate the body and selected treatment agents To be administered periodically depending on the body conditions, the body over the entire Treatment time, is treated on an outpatient basis, indicated by (a) a single housing (35 »150) which is attached as a whole to a selected point is inserted into the body and fastened in it and has different departments, (b) one housed in the inserted housing (33 »150) Memory (29, 152), (c) one housed in the inserted housing (33, 150) Micro supply source (28), (d) an electromechanical drive device in miniature design accommodated in the inserted housing (33 »150), which is connected to the micro-supply source (28) and is fed by it, (e) a miniature dispensing device (32) housed in the inserted housing (33 »150), (f) one arranged outside the inserted housing (33 »150) at a selected location in the body Sensing device (30, 155), (g) through the wall of the housing (33 »150) and in communication with the sensing device (30, 155) - 46 - 709815/0585 ORIGINAL INSPECTED standing connections, (h) a data evaluation and control circuit (31 »154) ia Miniature construction which is inserted within the inserted housing (33, 150) with the micro supply source (28) is connected and fed by it. 2. Device according to claim 1, characterized in that in the housing (33, 150) a memory (29 »152) for the treatment agent, a micro supply source (28), a drive and dispensing device (32) in miniature design, which are fed by the micro supply source (28) and deliver the treatment agent from the memory (29 »152), and data evaluation and control circuits (31, 154) are housed in miniature construction, which are from the micro-supply source (28) are fed, and physiological data including that of the outside of the housing (33 »150) located sensing device (30, 155) provided Process data to control the operation of the drive and delivery devices (32), and that through the wall of the housing (33, 150) connections from the outside of the housing (33 »150) attached Pass through the sensing device (30). 3- devices according to at least one of claims 1 and 2, characterized in that the Sepicher (29 »152) stores selected treatment agents that are in certain Quantities are to be delivered. 4. Device according to one of claims 1 to 3, characterized in that that the micro-supply source (28) is attached in the vicinity of the memory (29 »152) and one Operating time in the order of at least a few Days. - 47 - 70981 5. Device according to at least one of claims 1 to 4-, characterized in that the dispensing device is in communication with and from the store (29, 152) the treatment agent is supplied and is driven at certain times by the drive device and measured one after the other from the memory (29 »152) at these times Amounts of the selected treatment agent decreases and the treatment agent from the housing used (35 »150) releases into the body. 6. Device according to at least one of claims 1 to 5 » characterized in that the sensing device (30, 155) corresponding to a sensed state in the body generates sensed signals that are converted into electrical data signals 'nale can be implemented. 7. Device according to at least one of claims 1 to 6, characterized in that the connections transmit the signals generated by the sensing device (30, 155) into the housing (33 »150) in which they are processed. 8. The device according to at least one of claims 1 to 7 »characterized in that the data evaluation and control circuits (31,154) an electrical circuit in miniature construction have, which is via the connections with the sensing device (30, 155) in connection, selected Data supplied by the sensing device (30, 155) receives and converts this data into an electrically processable form and electrically at selected times evaluates. 9 · Device according to at least one of claims 1 to 8, characterized in that the data evaluation and control circuits (31 »154) have a timing circuit, which is connected to the electrical circuit and 709815 / 056B 25U884 this provides electrical time base signals, the drive device in accordance with the respective Evaluations is switched on and the output device (32) is actuated. 10. The device according to claim 1, characterized by a catheter (248) which is outside the inserted housing (33> 150) is arranged in the body and that of the delivery device (32) picks up the treatment agent dispensed and forwards it to a specific location to be treated (Pig. 13). 11. The device according to at least one of claims 1 to 10, characterized in that the drive device (32) a spool (84) having a spool core (83); and the dispenser comprises a dispenser which is passed through the spool core (83) is actuated. 12. Device according to at least one of claims 1 to 11, characterized in that the dispenser comprises a compressible and expandable bellows (82) which takes up the treatment agent inside, measures it in terms of quantity and releases it. 13. The device according to at least one of claims 1 to 12, characterized in that the memory (29) 1 is the dispensing device (32), the sensing device (30) and the data evaluation and control circuits (31) are adapted to selectively receive treatment agents from a plurality of memories hand over. 14. The device according to at least one of claims 1 to 13, characterized in that the drive device from an electric motor (160) with a bracket (161), and the dispenser is actuated by a cam (161). - 49 70981 5 / 056S 15 device according to at least one of claims 1 to 14, characterized in that the memory (29) »the sensing device (30), the dispensing device (32) and the evaluation and control circuits (31) are designed so that If they are storing multiple treatments, determine if multiple treatment doses are required and dispense doses of multiple treatments. 16. The device according to at least one of claims 1 to, characterized in that the dispensing device (32) Deliver doses of multiple treatments to separate locations in the body. 17 device according to at least one of claims 1 to 16, characterized in that the treatment agent is dispensed according to several sensing schemes. 18. The device according to at least one of claims 1 to 17 »characterized in that openings which can be reached from the outside (158, 159 »214) are provided to refill the treatment agent in the stores (152, 153) (Fig. 11, 12) 19 device according to at least one of claims 1 to 18, characterized in that the sensing device (30) electrical signals according to several medical factors senses and generates, and the data evaluation and control circuits (31) evaluate these factors electrically, and the treatment agent is released according to this evaluation. 20. The device according to at least one of claims 1 to 19 »characterized in that the sensing device (3Ό feels the pressure in the body. - 50 - 709815/0565 21. Device according to at least one of claims 1 to 19, characterized in that the sensing device (31) senses an electrical process in the body. 22. Device according to at least one of claims 1 to 19 » characterized in that the sensing device (31) senses a chemical process in the body. Device according to at least one of claims 1 to 22, characterized in that the memory (66, 106) stores a single treatment agent, that the delivery device (33) stores several delivery devices (67 »68) and that the data evaluation and control circuits (65) determine the need for separate actuation of the dispensing device (67, 68) and actuate the dispensing devices (67, 68) separately, so that the ^; Treatment agent from one or the other dispensing device (67, 68) is dispensed independently in each case (Fig. 5, 8). 24. Device according to at least »one of claims 1 to 22, characterized in that the memories (73, 74; 125, 126), the sensing device (70), the output devices (72, 73) and the data evaluation and control circuits (71) are designed so that they have a first treatment agent according to a regular time base and a second treatment agent according to a special time base and determine the necessity for these processes (Fig. 6, 9). 25 · Device according to at least one. of claims 1 to 24, characterized in that the dispensing device (32) has an outlet opening and an opening accessible from the outside (253) through which a suitable object - 51 - 709815/0565 can be introduced to clean the outlet opening (Fig. 13, 14). 26. Device according to at least one of claims 1 to 25 » characterized in that the memory (29) the sensing device (30), the dispensing device (32) and the Evaluation and control circuits (31) are designed in such a way that the treatment agent can be used in various combinations is delivered, both in a single dose and in multiple doses, both as a single treatment agent as well as in the form of multiple treatment agents, depending on a single sensed condition or condition of several sensed states, in only one or in several places in the body, and according to a single time schedule or more time schedules. 27 · Device according to at least one of claims 1 to 26, characterized in that the device for administration Treatment agents are used to prevent recurring tachycardias and arrhythmias that the sensing device is a heart sensor and the data evaluation and control circuits one with the sensing device communicating amplifiers have a first QES detector connected to the amplifier is that a second circuit for analyzing the QRS period and comparing it with the control value with the first QRS detector is connected to a circuit that analyzes the E-R interval and compares it with the control value is connected to the first QRS detector and to the circuit for analyzing the QRS period that a Logical evaluation circuit with the second circuit for analyzing the QRS period and with the circuit for analysis of the R-R interval that a timing circuit with the second circuit for analyzing the QRS period, as well as with the circuit for analyzing the R-R- - 52 - 709815/0565 17,? F (9 -i Interval and connected to the logic evaluation circuit is to control this in terms of time, and that the dispensing device is controlled by the logic evaluation circuit. 28 Vo- ~ -d € hg ~ ¥ r &-riusp ^ rüchen 1 to 27 to selected internal physiological states of a body of a living being, human insbesondere''eines metallic or animal body, periodically evaluate ⁷ and periodically according to these states treatment agent to be released into the body, where the body is treated on an outpatient basis throughout the entire treatment period, characterized by the following procedural steps: (a) Insertion of the housing of the device, which is filled with a specific treatment agent, onto a selected one Place in the body, (b) Inserting the sensing device of the device in the the same body at a selected point outside the housing, the sensing device via connections is connected to the circuitry of the device, and (c) operating the sensing device to generate signals, which corresponds to the physiological conditions in the body, and dispensing of the treatment agent selected places in the body according to a scheme that includes the data evaluation and control circuits is determined, with the operation of the sensing device and the dispensing of the treatment agent in the Jf η τ »τη ΐΐ Vn - 53 - 70981S / O56S