Medical implantable arrangement in the form of a wrap cuff

Abstract

The invention relates to a medical implantable arrangement in the form of a wrap cuff for applying electrical signals along an intracorporeal vessel or a nerve fibre bundle. The invention is characterised in that: at least 2·n electrodes, where n ≥ 2, are arranged in serial spatial succession along at least one virtual line on a support structure and are wired to a current generator; the current generator supplies the 2·n electrodes with high-frequency stimulation signals in such a way that a first group of n electrodes is supplied with high-frequency stimulation signals of the same polarity, while simultaneously a second group of n electrodes is supplied with high-frequency stimulation signals of opposite polarity to the first group; the electrodes of the first and second groups are each arranged in an alternating sequence along the virtual line; and the at least one virtual line, along which the at least 2·n electrodes are arranged in serial spatial succession, has one of the following shapes and arrangements: - straight and parallel to a wrap-around longitudinal axis (8) that can be associated with the wrap cuff, - straight and inclined to a wrap-around longitudinal axis (8) that can be associated with the wrap cuff, - wave-shaped with a wave baseline (9) that is orientated parallel to a wrap-around longitudinal axis (8) that can be associated with the wrap cuff, - wave-shaped with a wave baseline (9) that is orientated inclined to a wrap-around longitudinal axis (8) that can be associated with the wrap cuff.

Description

[0001] Medical implantable device in the form of a wrap-around cuff

[0002] Technical area

[0003] The invention relates to a medical implantable device in the form of a wound cuff for applying electrical signals along an intracorporeal vessel or a nerve fiber bundle.

[0004] State of the art

[0005] The document EP 3204 105 B1 discloses a cuff electrode arrangement, also referred to as a cuff electrode, consisting of a flexible, biocompatible, foil-like carrier substrate. A plurality of individual electrodes are arranged on at least one surface of the carrier substrate. The known cuff electrode serves for the spatially resolved detection of neuronal electrical signals and for the selective electrical stimulation of individual nerve fibers running within a nerve fiber bundle. The cuff electrode arrangement, formed into a wound cuff, encloses a nerve fiber bundle, preferably the vagus nerve, radially from the outside in the form of a straight hollow cylinder, on the inner surface of which the plurality of electrodes are arranged, which come into direct contact with the epineurium of the vagus nerve.The plurality of electrodes is divided into a first and a second electrode array, of which the first electrode array serves for the location-selective detection of neuronal electrical signals propagating along baroreceptive nerve fibers and for the selective electrical stimulation of at least one nerve fiber. Since the electrical stimulation along the baroreceptive nerve fibers occurs isotropically, i.e., without specifying a fixed signal propagation direction, the second electrode array serves for the selective inhibition of efferent nerve fibers, i.e., those leading to the heart, in order to avoid possible side effects caused by uncontrolled signal propagation effects.For this purpose, the second electrode arrangement arranged directly next to the first electrode arrangement on the common carrier substrate provides at least two axially spaced-apart electrode strips extending in the circumferential direction of the straight-cylindrical winding sleeve and each assuming a ring shape. Between these electrode strips, at least two, preferably many, electrode surfaces are arranged evenly distributed in the circumferential direction. Both the ring-shaped electrode strips and the electrode surfaces arranged between the two electrode strips are connected to a signal generator for their coordinated electrical polarization.

[0006] An electrical stimulation arrangement for the vagus nerve is also disclosed in the document US 2013 / 0172973 A1, which provides a wound cuff with electrodes on the inner side of the wound cuff wound into a hollow cylinder, facing the vagus nerve.

[0007] The theory of inhibition of efferent nerve fibers dates back to experiments by Rattay from 1986, see the article "High frequency electrostimulation of excitable cells" (doi:10.1016 / S0022-5193(86)80234-X). This article proposed that high-frequency excitation of nerve fibers with high-frequency excitation signals of > 10 kHz can lead to a block through sustained depolarization rather than hyperpolarization of the corresponding nerve membrane.

[0008] In an article by KL Kilgore, N. Bhadra, “Nerve conduction block utilising high-frequency alternating current”, Medical and Biological Engineering and Computing volume 42, pages 394-406 (2004) the idea is formulated that tonic depolarisation of a nerve over a large area along the myelinated axon (up to 20 nodes of Ranvier) leads to an effective block of the action potentials propagating past. In a number of subsequent publications the idea of ​​preferring a bipolar arrangement of two structurally identical electrodes to a monopolar or tripolar electrode was taken up. Relevant publications that deal with the topic in more detail using simulations and measurements include Ackermann et al., Effect of Bipolar Cuff Electrode Design on Block Thresholds in High-Frequency Electrical Neural Conduction Block, IEEE Transactions on Neural Systems and Rehabilitation Engineering ( Volume: 17, Issue: 5, October 2009) or Aristovich, et al., Model-based geometrical optimization and in vivo validation of a spatially selective multielectrode cuff array for vagus nerve neuromodulation, J Neurosci Methods, 2021 Mar 15.

[0009] The hypothesis derived from the relevant publications is that the bipolar response has an average depolarizing effect on the membrane potential due to the non-linear transfer function of the excitation pulse (the "activation function") and that this depolarization, if maintained for a longer period, leads to an effective blockage of stimulus transmission in the nerve.

[0010] Description of the invention

[0011] The invention is based on the object of providing a medical implantable arrangement in the form of a wound cuff for applying electrical signals along an intracorporeal vessel or a nerve fiber bundle, which is suitable for controlling or blocking nerve signal propagation in at least one propagation direction along a nerve fiber bundle or along one or more individual nerve fibers, and is designed in such a way that the efficiency of the blocking effect is improved compared to known generic arrangements. Thus, the aim is to largely or preferably completely prevent or suppress at least unidirectional nerve signal propagation along a nerve fiber bundle or along one or more individual nerve fibers using the same or lower electrical voltage potentials as previously used.

[0012] The solution to the problem underlying the invention is specified in claim 1. Features that advantageously further develop the inventive concept are specified in the subclaims and in the further description with reference to illustrated embodiments.

[0013] The medical implantable arrangement according to the invention, in the form of a wound cuff for applying electrical signals along an intracorporeal vessel or a nerve fiber bundle, is characterized in that at least 2 x n electrodes, with n > 2 electrodes, are arranged on a support structure along at least one virtual line in serial spatial sequence. These electrodes are connected by wire to a current generator. The current generator simultaneously applies high-frequency stimulation signals to the 2 x n electrodes in such a way that a first group of n electrodes can each receive equally polarized high-frequency stimulation signals, and a second group of n electrodes can each receive high-frequency stimulation signals polarized opposite to the first group.The electrodes of the first and second groups are each arranged in an alternating sequence along the at least one virtual line, wherein the at least one virtual line, along which the at least 2 n electrodes are arranged in serial spatial sequence, has one of the following shapes and arrangements: rectilinear and parallel to a winding longitudinal axis assignable to the winding sleeve, rectilinear and inclined to a winding longitudinal axis assignable to the winding sleeve, undulating with a wave base line oriented parallel to a winding longitudinal axis assignable to the winding sleeve, undulating with a wave base line oriented inclined to a winding longitudinal axis assignable to the winding sleeve.

[0014] The idea underlying the proposed medical implantable device is derived from extensive studies conducted by the applicant, which involved stimulation electrodes arranged along a nerve fiber strand, each of which was subjected to high-frequency stimulation signals. Different electrode arrangements were investigated, resulting in different electrical effects along the individual nerve strands, which have a decisive influence on signal propagation or signal propagation suppression along a nerve strand.

[0015] For further explanation of the findings obtained in these preliminary tests, reference is made to Figures 2a to d and 3a to c.

[0016] Figures 2a to d each show a nerve cord 1, in the immediate vicinity of which one or more electrodes 2 are arranged. In the case of Figure 2A, a monopolar electrode arrangement is provided, in which a single electrode 2 is arranged in the immediate vicinity along the nerve cord 1. It is assumed that the counter electrode for closing the circuit is symbolically arranged at infinity. In Figure 2B, a bipolar electrode arrangement with two equally sized electrodes 2 is provided, which are arranged next to one another along the nerve cord 1. In the case of Figure 2C, a tripolar electrode arrangement is selected, with a smaller driver electrode 2" arranged centrally between two similarly designed counter electrodes 2', each arranged at the edge, and attached at the same distance from both counter electrodes 2'.Figure 2 D shows a multipolar electrode arrangement which provides several small, equally sized electrodes 2 arranged along the nerve cord 1.

[0017] The individual electrodes 2 or 2', 2" are connected to a current generator (not shown in Figure 2) and are supplied with high-frequency stimulation signals. The current of a phase applied to the electrode 2 or to the electrodes 2, 2', 2" at a specific time is schematically designated as anodal, indicated by "A", or as cathodic, indicated by "K". These current directions symbolically represent the electrical polarity at a specific time during high-frequency stimulation. In the case of the monopolar electrode arrangement according to Figure 2a, the polarity of the single electrode 2 alternates between an anodic and a cathodic potential A or K. In the case of the bipolar electrode arrangement, according to Figure 2b, both electrodes 2 are polarized with different potentials K, A at any given time.In the case of the tripolar electrode arrangement according to Figure 2c, the two counter electrodes 2' arranged at the edges are subjected to the same polarization, whereas the centrally arranged driver electrode 2" is subjected to opposite polarization. In the case of the multipole electrode arrangement according to Figure 2d, the polarization types alternate from cathodic to anodic in their serial arrangement.

[0018] Figures 3a to c illustrate the electrical effects of the four different electrode arrangements AD on nerve cord 2 in different diagrams. Figure 3a shows the different electrical voltage profiles V ex t, which are applied along a nerve cord 2 by means of the respective electrode arrangements A to D at a specific time. Along the ordinate, the electrical voltage V applied to the electrode(s) is ext and the longitudinal extension of the nerve cord is shown along the abscissa. Thus, the dotted potential curve A corresponds to the voltage curve induced by the monopolar electrode arrangement along nerve cord 1. At the location of electrode 2, at a time when electrode 2 is negatively, i.e., cathodically polarized, a maximum negative voltage develops in the immediate vicinity of nerve cord 1. This voltage approximates to zero potential on both sides along nerve cord 1 with increasing distance from the electrode.

[0019] The dashed potential profile B corresponds to the bipolar electrode arrangement shown in Figure 2b and provides a cathodic or anodic voltage increase at those points where the electrodes 2 with the corresponding cathodic and anodic polarization are located. Corresponding voltage profiles also occur for the tripolar arrangement (see dashed potential profile C) and for the multipole electrode arrangement (see solid potential profile D).

[0020] In Figure 3b, representing the monopolar electrode arrangement, see Figure 2 A, as well as the multipolar electrode arrangement, see Figure 2 D, the second derivative of the voltage profiles shown in Figure 3a d 2 V ex t / dx 2The second derivative of these voltage profiles can be considered as an activation function, which in the case of the monopolar electrode arrangement A only shows a local activation function maximum in the area of ​​the monopolar electrode 2, whereas the multipole electrode arrangement according to Figure 2 D has a multitude of activation function maxima arranged next to one another along the entire course of the nerve cord, both positive and negative maxima.

[0021] Figure 3c shows the membrane polarization VM developing along nerve cord 1 for high-frequency stimulation signals in the range > 1 kHz. It can be seen that with the multipole electrode arrangement shown in Figure 2D, a membrane polarization develops that is almost uniform across the entire length of the electrode arrangement. In contrast, the membrane polarization A that develops with the monopole electrode arrangement is shown in dotted lines.

[0022] It can therefore be stated that in the case of a multipolar electrode arrangement D, the blocking function for preventing nerve signal propagation along a nerve cord is significantly more effective and complete than in the case of all other electrode arrangements shown in Figures 2a to c. It has been shown that a tonic (temporarily sustained) depolarization of the nerve cord over a larger spatial area along the nerve to be blocked is only possible with as many electrodes as possible, each alternately connected, and not with just a few.

[0023] Based on this knowledge gained through experimental testing, the proposed medical implantable device is designed in the form of a wound cuff, which provides a support structure suitable for direct attachment around a cord-like vessel or nerve fiber bundle, in which 2 x n electrodes, with n > 2, are arranged on a cuff surface oriented toward the vessel or nerve fiber bundle. In the implanted state, the wound cuff assumes a straight hollow cylindrical shape with a hollow cylinder longitudinal axis that simultaneously corresponds to the winding longitudinal axis, at which the wound cuff fully touches or contacts the cord-like vessel or nerve fiber bundle with its inner surface.On this inner surface of the casing, the at least 2 xn electrodes are arranged in serial spatial sequence at least along a virtual line, wherein the shape and arrangement of the at least 2 n-electrodes can take on one of the following configurations:.

[0024] Particularly preferably, the 2 x n electrodes are identical in shape and size. Furthermore, the 2 x n electrodes are arranged along a straight virtual line and parallel to a longitudinal winding axis attributable to the wound cuff. Such an arrangement is based on the assumption that the multitude of individual nerve fibers running within the nerve fiber bundle are oriented as straight as possible and parallel to the longitudinal winding axis of the wound cuff.

[0025] It is also advantageous to arrange the 2 x n electrodes along a straight virtual line, which, however, is oriented at an inclination relative to a longitudinal winding axis associated with the winding sleeve. The inclination of the virtual line relative to the longitudinal winding axis must be adjusted according to the spatial position of the individual nerve fibers contained within the nerve fiber bundle, which also do not necessarily all run parallel to each other. Typical inclination angles relative to the longitudinal winding axis should not exceed ±10°.

[0026] The individual nerve fibers within a nerve fiber bundle do not necessarily run in a perfectly straight line. This deviating nature of the nerve fibers from mathematically exact straightness can be reflected in the geometry of the virtual line. Thus, curved or wavy lines are included in the solution concept, which can be designed and arranged in the direction of the longitudinal winding axis or inclined to it, along which the 2 x n electrodes are to be arranged.

[0027] Preferably, the shape and dimensions of the 2 x n electrodes arranged along the virtual line are adapted accordingly, taking into account the geometric spacing of the nodes of Ranvier arranged along a myelinated axon, at which the cell membrane of the respective axon is exposed. Typically, the spacing can be between 10 pm < d < 2000 pm. Preferably, the individual electrodes are uniform and of the same size. For nerve inhibition, it has proven particularly effective to select the number n of electrodes per cm along a virtual line depending on the geometric spacing of the nodes of Ranvier, i.e. 5 < n < 1000 per centimeter.

[0028] A further variant according to the solution provides that in addition to the multipole electrode arrangement along a first virtual line, at least one further multipole electrode arrangement is provided which is arranged offset laterally to this on the support structure and which also provides a plurality, preferably 2 x n electrodes, along a further virtual line parallel or inclined to the first virtual line.

[0029] To ensure that the n electrodes of the first group, arranged in series along the virtual line, are always polarized opposite to the n electrodes of the second group, regardless of the type and form of the current signal applied to the 2 x n electrodes, which is generated by a high-frequency current generator, the electrical electrodes assigned to the first group are electrically connected to one another and, via a connecting line, to an output of the current generator. In the same way, the electrodes of the second group are electrically connected to one another and, via a connecting line, to the other output of the current generator. The current generator is capable of generating high-frequency current wave pulses, preferably in the form of square-wave signals or similar RF alternating current signals.Depending on the application and use case, the current generator can be designed either in the form of an extracorporeal current generator or in the form of an implantable pulse generator, or IPG for short.

[0030] Brief description of the invention

[0031] The invention is described below, without limiting the general inventive concept, using exemplary embodiments with reference to the drawings. They show:

[0032] Fig. 1 Representation of a solution-based embodiment for a medically implantable arrangement with a support structure designed as a wound cuff,

[0033] Fig. 2a to d Illustration of different electrode arrangements along a nerve bundle, A-monopole, B-bipolar, C-tripolar and D-multipole electrode arrangement,

[0034] Fig. 3 Diagrams with different potential curves, as well as

[0035] Fig. 4 to 6 different designs for multipole electrode arrangements and

[0036] Ways of carrying out the invention, industrial applicability Figure 1 shows a support structure 3 designed as a wound cuff, which is placed around a nerve fiber bundle 1 and on whose wound cuff surface facing the nerve fiber bundle 1, six electrodes 2 are arranged along a linear virtual line 4, each in a serial sequence and equally spaced from one another. The electrodes 2 are all connected to a high-frequency current generator 5, preferably in the form of a function generator. The function generator is capable of generating rectangular current pulses with a frequency of 1 - 100 kHz. A first group of n=3 electrodes 2, which is marked with "+" in Figure 1, is connected to one output of the HF current generator 5 via a common connecting line 6, and a second group, which is marked with in Figure 1, is connected to the other output of the HF current generator 5 via a common connecting line 7.It is assumed that in the polarization state shown in Figure 1, the electrodes 2 are polarized or charged with the polarizations indicated by "+" and "+". In principle, the electrodes 2 arranged along the virtual line 4 are alternately polarized in a serial sequence due to the given connection to the current generator 5.

[0037] Regardless of the alternating current form chosen, it is essential that the waveform is symmetrical or at least charge-balanced, ie the polarization along the nerve fiber bundle 1 is canceled out in the sum over all electrodes 2.

[0038] In principle, the number of electrodes should be greater than 2, i.e. the multipolar electrode arrangement extends over a macroscopic distance along a nerve fiber bundle, preferably of one or a few centimeters.

[0039] For the explanation of Figures 2 and 3, reference is made to the above description. Figure 4 shows a support structure 3 designed as a winding sleeve with at least two multipole electrode arrangements, each with six electrodes 2 along two virtual lines 4. The electrical interconnection of the electrodes 2 has been omitted for illustrative purposes. In the illustrated case, the virtual lines 4 are oriented parallel to the winding longitudinal axis. Nevertheless, it is possible to arrange the virtual lines 4 at an angle relative to the winding longitudinal axis 8, for example, at an angle a of up to ± 10°.

[0040] Figure 5 shows a support structure 3 designed as a winding sleeve with a multi-pole electrode arrangement, in which the virtual line 4, along which a plurality of electrodes 2 are arranged, helically encircles the inner surface of the winding sleeve.

[0041] Figure 6 shows a support structure 3 designed as a winding sleeve with a multipole electrode arrangement, in which the virtual line 4, along which a plurality of electrodes 2 are arranged, is wave-shaped. In the illustrated case, the wave base line 9 associated with the wave-shaped virtual line 4 is oriented parallel to the winding longitudinal axis 8. Of course, the wave base line 8 can also be arranged at an angle to the winding longitudinal axis.

[0042] List of reference symbols Nerve fiber bundle Electrode Supporting structure Virtual line RF current generator Common connecting cable Common connecting cable Winding longitudinal axis Wave baseline

Claims

Patent claims 1. A medical implantable device in the form of a wound cuff for applying electrical signals along an intracorporeal vessel or a nerve fiber bundle (1), characterized in that on a support structure (3) along at least one virtual line (4) in serial spatial sequence at least 2 n electrodes (2) with n > 2 electrodes are arranged, which are connected by wire to a current generator (5), that the current generator (5) simultaneously applies high-frequency stimulation signals to the 2 n electrodes (2) in such a way that a first group of n electrodes (2) can each be applied with equally polarized, high-frequency stimulation signals and a second group of n electrodes (2) can each be applied with high-frequency stimulation signals polarized opposite to the first group, that the electrodes (2) of the first and second groups are each arranged in an alternating sequence along the virtual line,and that the at least one virtual line along which the at least 2 n electrodes are arranged in serial spatial sequence has one of the following shapes and arrangements: straight and parallel to a winding longitudinal axis (8) assignable to the winding sleeve, straight and inclined to a winding longitudinal axis (8) assignable to the winding sleeve, wave-shaped with a wave base line (9) oriented parallel to a winding longitudinal axis (8) assignable to the winding sleeve, wave-shaped with a wave base line (9) oriented inclined to a winding longitudinal axis (8) assignable to the winding sleeve.

2. Medical implantable arrangement according to claim 1, characterized in that the electrodes (2) of the first group are electrically connected to one another and connected to the current generator (5) via a connecting line (6), and that the electrodes (2) of the second group are electrically connected to one another and connected to the current generator (5) via a connecting line (7).

3. Medical implantable arrangement according to claim 1 or 2, characterized in that the current generator (5) is capable of generating high-frequency current wave pulses and is designed in the form of an extracorporeal current generator or an implantable pulse generator, IPG for short.

4. Medical implantable arrangement according to one of claims 1 to 3, characterized in that the support structure (3) is a wound cuff for attachment around a strand-shaped vessel or the nerve fiber bundle (1), in which the 2 n electrodes (2) are arranged on a cuff surface oriented towards the vessel or the nerve fiber bundle (1).

5. Medical implantable device according to one of claims 1 to 4, characterized in that the electrodes along the virtual line have a mutual distance d, with 10 pm < d < 2000 pm.

6. Medical implantable device according to one of claims 1 to 5, characterized in that the electrodes are each uniform and of the same dimensions.

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