Implantable device and method for treating gastroesophageal reflux disease and digestive system

Abstract

A method and apparatus for treating digestive system diseases, the method comprising: subcutaneously implanting a pulse generator and a plurality of electrodes into the abdomen of a patient, the plurality of electrodes being in electrical contact with a plurality of target areas of the abdomen of the patient; and applying an electrical stimulus to activate the plurality of target regions.

Description

[0001] TECHNICAL FIELD The present disclosure relates to general medical devices, in particular medical devices related to the digestive system and gastroesophageal reflux disease (GERD).

[0002] BACKGROUND Among other digestive system diseases, gastroesophageal reflux disease (GERD) is the most common outpatient gastroenterology diagnosis in the United States, with a prevalence of up to 10% to 30% in Western countries and an annual incidence of 0.38% to 0.45%. In the United States, 20% of adults experience GERD-related symptoms each week, and 7% of adults experience these symptoms every day. GERD significantly reduces the health-related quality of life of patients and places a heavy economic burden on the healthcare system.

[0003] GERD is caused by the undesired movement of gastric acid into the esophagus. This reflux is usually caused by changes in the barrier function between the stomach and the esophagus, including abnormal relaxation of the lower esophageal sphincter (LES), obstruction of gastric reflux discharge, or hiatal hernia. In addition to this, symptoms of GERD can include abdominal pain, heartburn, regurgitation, chest pain, pungent taste, and asthma, among others. Complications of GERD can include mucosal damage, erosive esophagitis (EE), Barrett’s disease, and esophageal cancer.

[0004] Typical treatment methods for GERD include lifestyle changes, taking medications such as proton pump inhibitors (PPIs), H2 receptor blockers, or antacids, and surgery.

[0005] Despite the widespread recognition of the effectiveness of current treatments for GERD, there are still unmet needs and significant challenges. About 10% to 15% of adult patients with erosive esophagitis (EE) do not fully recover after 8 weeks of treatment. In addition, even if the initial treatment dose is continued, 15% to 23% of adult EE patients with Los Angeles grade A and B will relapse within 6 months of treatment, while the relapse rate for grade C and D is as high as 24% to 41%. In addition, up to 40% of adult patients with non-erosive reflux disease (NERD) still have symptoms during treatment with standard doses (once daily) of proton pump inhibitors (PPIs).

[0006] There are concerns about the safety of long-term use of PPIs. These concerns are related to various possible side effects, such as osteoporosis, kidney disease, nervous system disease, dementia, liver disease, anemia, etc.

[0007] Surgical treatment of GERD usually includes fundoplication, which can be performed by open and endoscopic intervention. Fundoplication provides an alternative for patients who do not respond to drug therapy or are unwilling to take drugs for a long time. In recent years, various endoscopic intervention methods have been developed and used to treat GERD in a minimally invasive manner. However, its efficacy is still controversial, and there may be complications, which limit its application in clinical practice.

[0008] U.S. Patent No. 10,426,955 discloses an implanted electrode and method of treating a patient with gastroesophageal reflux disease. The patent discloses a device and method for treating transient lower esophageal sphincter relaxations (tLESR).

[0009] U.S. Patent No. 7,660,636 discloses an electrical stimulation device and method for treating dysphagia. In some embodiments, the electrical stimulation device includes one or more electrode channels, each electrode channel including a first electrode in electrical contact with tissue of a target region of a patient and a second electrode in electrical contact with tissue of a posterior neck or posterior chest of the patient. Then, a series of electrical pulses is applied to the patient through the one or more electrode channels according to a procedure for treating dysphagia.

[0010] U.S. Patent No. 5,716,385 discloses an electronic pacemaker for countering diaphragmatic crus relaxation to prevent and / or treat gastroesophageal reflux. The pacemaker can be implanted in the body or connected through the skin to the skeletal muscle of the diaphragmatic crus. A sensor is used to identify spontaneous intermittent relaxations of the diaphragm. During these spontaneous intermittent relaxations, the skeletal muscle of the diaphragmatic crus is stimulated using one or more electrodes, causing the lower esophageal sphincter to contract. SUMMARY

[0011] According to an aspect of some embodiments of the present application, there is provided a method of treating a patient with a digestive system disease, comprising: subcutaneously implanting a pulse generator and a plurality of electrodes in the abdomen of the patient, the plurality of electrodes being in electrical contact with a plurality of target regions of the abdomen of the patient; and applying electrical stimulation to activate the plurality of target regions.

[0012] According to some embodiments of the present application, the plurality of target regions includes a muscle, a nerve, a muscle-nerve junction, or any combination thereof.

[0013] According to some embodiments of the application, the electrical stimulation is optimized for manipulating the patient's digestive system to change the flow rate of chyme and direct it in a desired direction.

[0014] According to some embodiments of the application, the electrical stimulation comprises a series of current-controlled asymmetric pulses aimed at producing asymmetric contraction of selected abdominal muscles; wherein the fast phase of the pulses is directed upward and the slow phase of the pulses is directed downward.

[0015] According to some embodiments of the application, the change is a reduction in the reflux of chyme from the patient's stomach to the esophagus to alleviate GERD symptoms.

[0016] According to some embodiments of the application, the change is an increase in the flow of chyme from the patient's stomach to the duodenum to alleviate gastroparesis symptoms.

[0017] According to some embodiments of the application, the change is an increase in the flow of chyme from the patient's colon to the rectum to alleviate constipation symptoms.

[0018] According to some embodiments of the application, the electrical stimulation comprises a series of current-controlled asymmetric pulse trains aimed at producing asymmetric contraction of selected abdominal muscles; wherein the fast phase of the pulse trains is directed upward and the slow phase of the pulses is directed downward.

[0019] According to some embodiments of the application, the method further comprises implanting at least one sensor, wherein the stimulation is synchronized with at least one body signal acquired by the at least one sensor.

[0020] According to some embodiments of the application, the sensor comprises at least one of the following members: an accelerometer, a gyroscope, a magnetic compass, an inclinometer, a piezoelectric sensor, an electrocardiogram (ECG), an electroencephalogram (EEG), an electromyograph (EMG), a microphone, an electrical impedance sensor, an oximeter, an optical interferometer, a pH meter, and a photoelectric sensor.

[0021] According to some embodiments of the application, the body signal comprises at least one of the following members: respiration, heartbeat, blood pressure, muscle or ligament tension, body posture, wakefulness state, or muscle activity level.

[0022] According to some embodiments of the application, the activation of the plurality of target regions is adapted to induce a body reflex.

[0023] According to some embodiments of the application, the reflexes include at least one of the following members: straining esophageal reflex and straining crural reflex.

[0024] According to an aspect of some embodiments of the application, there is provided a subcutaneously implantable device for treating a digestive system disorder, the device comprising a control unit; a power source; a pulse generator; and a plurality of subcutaneously implantable electrodes adapted to be in electrical contact with a plurality of target areas of the abdomen; wherein the pulse generator is designed for delivering stimulation signals through the plurality of electrodes to activate the target areas.

[0025] According to some embodiments of the application, the electrical stimulation is characterized by a maximum voltage of +20V, a maximum current of 20mA, a pulse frequency range of 20Hz-50Hz, a burst frequency range of 0.2Hz-4Hz, and a pulse width of 25-300µs.

[0026] According to some embodiments of the application, the digestive system disorder is at least one of the following: gastroesophageal reflux disease (GERD), gastroparesis, obesity, incontinence, and constipation.

[0027] According to some embodiments of the application, the electrical stimulation includes repeated bursts, and the shape of the bursts is set according to the desired physiological effect.

[0028] According to some embodiments of the application, the implantable device further comprises at least one sensor.

[0029] According to some embodiments of the application, the electrical stimulation is synchronized with at least one body signal collected by the sensor.

[0030] According to some embodiments of the application, the sensor includes at least one of the following members: an accelerometer, a gyroscope, a magnetic compass, an inclinometer, a piezoelectric sensor, an electrocardiogram (ECG), an electroencephalogram (EEG), an electromyogram (EMG), a microphone, an electrical impedance sensor, an oximeter, an optical interferometer, a pH meter, and a photoelectric sensor.

[0031] According to some embodiments of the application, the body signal includes at least one of the following members: respiration, heartbeat, blood pressure, muscle or ligament tension, body posture, wakefulness state, or muscle activity level.

[0032] Unless otherwise defined, all technical and / or scientific terms used herein have the meanings commonly understood by one of ordinary skill in the art to which this invention pertains. Although similar or equivalent methods and materials may be used in carrying out or testing embodiments of this invention, only exemplary methods and / or materials are described below. In case of conflict, the patent specification (including definitions) shall prevail. Furthermore, the materials, methods, and examples described are merely illustrative and not intended to limit the scope of the invention.

[0033] Brief description of the attached diagram A more complete understanding and appreciation of the subject matter of this disclosure will be achieved by reading the following detailed description in conjunction with the accompanying drawings. In the drawings, corresponding numbers or characters denote corresponding parts. Unless otherwise stated, the drawings provide only exemplary embodiments or aspects of this disclosure and do not limit its scope.

[0034] In the attached diagram: Figure 1A An apparatus for treating patients with digestive system diseases is schematically illustrated according to some exemplary embodiments of the disclosed subject matter; Figure 1B The illustrations schematically depict some exemplary embodiments based on the disclosed subject matter. Figure 1A A partial cross-sectional view of the housing of the device shown; Figure 2 Exemplary devices for treating digestive system diseases, implanted in the abdomen of a patient, are shown according to some exemplary embodiments of the disclosed subject matter; Figure 3A and 3B Exemplary electrical stimulation waveforms comprising asymmetric pulse trains are shown in accordance with some exemplary embodiments of the disclosed subject matter; Figure 3C Exemplary electrical stimulation waveforms comprising symmetrical pulse trains are shown in accordance with some exemplary embodiments of the disclosed subject matter; Figure 3D Some exemplary embodiments based on the disclosed subject matter are shown. Figure 3A –A detailed view of the pulse train for any diagram in 3C; and Figure 4 The illustration schematically shows a portion of exemplary data collected by sensors according to some embodiments of the disclosed subject matter. Detailed Implementation

[0035] Embodiments of the present invention disclose a method for treating a patient for a digestive system disorder, particularly for gastroesophageal reflux disease (GERD), gastroparesis, constipation, incontinence, and obesity. The method includes implanting a pulse generator and a plurality of electrodes subcutaneously and delivering electrical stimulation through the plurality of electrodes to activate a selected target muscle.

[0036] Additionally, or alternatively, the electrical stimulation in the disclosed methods can be applied to a nerve or neuromuscular junction.

[0037] In some embodiments, the disclosed methods further include implanting at least one sensor in the patient. Optionally, the method further includes synchronizing the electrical stimulation with at least one body signal collected by the at least one sensor.

[0038] In one exemplary embodiment, the disclosed method is used to treat GERD by enhancing esophageal motility, thereby enhancing the movement of chyme from the esophagus into the stomach.

[0039] In one exemplary embodiment, the disclosed method is used to treat GERD or gastroparesis by enhancing gastric motility, thereby enhancing the movement of chyme from the stomach into the duodenum.

[0040] In one exemplary embodiment, the disclosed method is used to treat GERD by enhancing the contractility of the lower esophageal sphincter (LES), thereby reducing the reflux of chyme from the stomach into the esophagus.

[0041] In one exemplary embodiment, the disclosed method is used to treat GERD by enhancing the contractility of the upper esophageal sphincter (UES), thereby reducing the reflux of chyme from the esophagus into the pharynx.

[0042] In one exemplary embodiment, the disclosed method is used to treat fecal incontinence by enhancing the contractility of the anal sphincter.

[0043] In one exemplary embodiment, the disclosed method is used to treat urinary incontinence by enhancing the contractility of the urinary sphincter.

[0044] In one exemplary embodiment, the disclosed method is used to treat obesity or being overweight by inducing the reflux of chyme from the stomach into the esophagus, causing discomfort, thereby reducing appetite.

[0045] In one exemplary embodiment, the disclosed method is used to treat obesity or being overweight by increasing the pressure within the stomach, thereby enhancing satiety.

[0046] In embodiments where the disclosed methods are used to treat obesity or overweight, the electrical stimulation can be applied before, during or after a meal. Alternatively, the electrical stimulation can be applied between meals.

[0047] In one exemplary embodiment, the disclosed methods treat constipation by enhancing intestinal motility, thereby enhancing the power of chyme to flow along the digestive tract toward the rectum.

[0048] In some embodiments, the disclosed methods include applying electrical stimulation in synchronization with a motor or sensory event associated with the digestive tract (e.g., eating, bloating, defecation or urination). In addition, or as an alternative, the stimulation can be applied at a specific time or continuously. In addition, or as an alternative, the stimulation can be applied at the discretion of the user, a physician, a machine or any combination thereof.

[0049] One exemplary embodiment of the disclosed subject matter is a subcutaneously implantable device for treating patients with digestive system disorders, the device comprising a signal generator and a plurality of electrodes. When activated, the implantable device can generate electrical stimulation to treat various digestive system symptoms or disorders.

[0050] In some embodiments, the disclosed device further comprises at least one sensor. In one embodiment, the sensor is an implantable sensor adapted to be implanted within the esophageal wall of a patient and used to detect esophageal acidity. The sensor is configured to output the acidity level to the processor via a wired or wireless connection. In some embodiments, the controller of the device receives the acidity monitoring data for use in controlling the treatment parameters, such as stimulation time, stimulation intensity, stimulation waveform, stimulation frequency, etc., to optimize the treatment effect. In some embodiments, the sensor is only temporarily implanted.

[0051] In some embodiments, the disclosed device comprises a biocompatible, hermetically sealed shell that encloses components such as mechanical elements, circuitry, a processor or computing unit, a power source, a sensing element and a plurality of electrodes.

[0052] In other embodiments, the disclosed device comprises a main shell that encloses a processor or computing unit and at least one additional shell, and the components enclosed in the at least one additional shell are controlled by the main shell. Communication between the main shell and the at least one additional shell can be established via a wired connection, a wireless connection or a combination of both.

[0053] In some embodiments, the shell is sized to be suitable for subcutaneous implantation.

[0054] In some embodiments, the shell has a maximum longitudinal, lateral or depth dimension of less than 10 mm, 7 mm, 5 mm, 3 mm and 2 mm, respectively.

[0055] In some embodiments, the disclosed device includes a rechargeable battery. In some embodiments, the rechargeable battery can be wirelessly charged by a charger located outside the patient's body. In other embodiments, a charging port connected to the implanted device is placed transcutaneously so that it can be operated from outside the patient's body. In other embodiments, the rechargeable battery is charged using mechanical energy generated by human motion, eliminating the need for an external charger. In other embodiments, the disclosed device includes a non-rechargeable battery.

[0056] In some embodiments, the disclosed device includes at least two electrodes. The electrodes are implanted in a manner that makes electrical contact with at least one target region during the device installation process. The multiple target regions can include muscle, nerve, neuromuscular junction, or a combination thereof.

[0057] In some embodiments, the multiple electrodes are designed as intramuscular electrodes, epimysial electrodes, or nerve cuff electrodes. Additionally, or alternatively, the multiple electrodes can be designed in any other manner known in the art for providing electrical stimulation to muscle, nerve, or neuromuscular junction.

[0058] In some embodiments, the multiple electrodes are also designed to collect electrical signals from the target regions and transmit them to the device.

[0059] In some embodiments, the multiple electrodes transmit the electrical stimulation generated by the device signal generator to the multiple target regions such that the electrical current flows from one electrode to at least one other electrode and through a portion of the patient's body.

[0060] In some embodiments, the electrical stimulation includes current-controlled or voltage-controlled pulses. The pulses can be monophasic, biphasic, or any combination thereof. The biphasic pulses can be asymmetric or symmetric with respect to a reference voltage or current. The pulses can take any shape known in the art that can be used in electrical stimulation devices, such as rectangular pulses, triangular pulses, or sinusoidal pulses.

[0061] In some embodiments, the stimulation pulses are characterized by a maximum voltage of 10 V, 20 V, 30 V, or 40 V (fundamental to peak), and a maximum current of 0.1 mA, 1 mA, 5 mA, 10 mA, or 20 mA.

[0062] In some embodiments, the stimulation pulses are repeated cyclically for a predetermined duration.

[0063] In some embodiments, the electrical stimulation includes repeated pulse trains. The stimulation pulse trains can be modulated such that they contain substantially identical pulses, progressively increasing pulses, progressively decreasing pulses, or any other desired modulation method.

[0064] In some embodiments, the pulse repetition frequency can be in the range of 10 Hz to 200 Hz.

[0065] In some embodiments, the pulse width can be in the range of 20 ps to 1000 ps.

[0066] In some embodiments, the stimulation pulse train is characterized by its pulse train repetition frequency in the range of 0.1 Hz to 10 Hz.

[0067] In some embodiments, the stimulation pulse can be symmetric, asymmetric, or any combination of the two, where a symmetric pulse refers to a current or voltage waveform with different rise and fall times.

[0068] In some embodiments, any of the parameters of the disclosed devices can be fine-tuned for optimal therapeutic effect. The optimized parameters include, but are not limited to, implant location, electrode placement location, device activation time, and electrical stimulation characteristics. In some embodiments, an initial setup can be required, and the optimized parameters can be determined based on the setup results.

[0069] In some embodiments, the parameters characterizing the disclosed device structure and electrical stimulation are set according to the desired physiological effect. The settable parameters include the number and location of electrodes, electrode activation sequence, pulse control method (current control or voltage control), stimulation intensity, pulse shape, pulse frequency, pulse train shape, pulse train frequency, and stimulation timing.

[0070] In one embodiment, multiple electrodes are placed at different locations of the abdominal muscles, and stimulation is applied through these electrodes in sequence, thereby inducing abdominal muscle contractions in the desired sequence. In one exemplary embodiment, stimulation is applied through electrodes placed at different levels of the rectus abdominis and external oblique muscles, such that the abdominal muscles contract in sequence from the upper to the lower abdomen, thereby enhancing the transport of chyme within the digestive tract in the desired direction toward the rectum.

[0071] In one embodiment, the shape of the stimulation pulse is set according to the desired physiological effect. In one exemplary embodiment, the electrical stimulation includes a series of controlled current pulses set in an asymmetric shape, such that the pulse rise time is much shorter than the pulse fall time. This stimulation can potentially enhance esophageal motility and alleviate GERD symptoms. This enhancement can be achieved through a vibration transport mechanism, in which a structure carrying a movable substance undergoes linear displacement in a cyclic manner, such that its movement speed is faster in one direction and slower in the other direction. With this mechanism, the substance can undergo a net displacement in the slow movement direction. In theory, applying a stimulation pulse of a specific shape can induce chyme to flow from the esophagus to the stomach through this mechanism.

[0072] In another exemplary embodiment, similar stimulation is applied, but the rise time of the burst is significantly longer than the fall time of the burst. Such stimulation can enhance the reflux of chyme from the stomach into the esophagus, or induce nausea or vomiting.

[0073] In another exemplary embodiment, electrical stimulation is applied to the lower abdominal muscles, including a series of controlled current bursts in an asymmetric shape such that the rise time of the burst is significantly shorter than the fall time of the burst. Such stimulation can enhance peristalsis in the lower digestive tract and push chyme towards the rectum and anus.

[0074] In some embodiments, the structure and stimulation parameters of the disclosed devices are optimized to improve the function of one or more digestive tract sphincters.

[0075] In one exemplary embodiment, electrical stimulation is applied to the rectus abdominis and external oblique muscles, for example to repeatedly and rapidly increase intra-abdominal pressure. Rapid increases in intra-abdominal pressure can induce natural physiological reflexes, such as the forceful esophageal reflex or the forceful diaphragmatic split reflex, which in turn increase the tone of the LES or UES. Alternatively, repeated contractions of the LES can be induced by means other than natural reflexes. Optionally, repeated activation of the LES and / or UES, mediated by reflexes or otherwise, can lead to long-term improvement in sphincter function. Optionally, the frequency and intensity of the contractions can be set to induce the desired level of LES muscle loading and rest, in order to optimize LES strengthening training. In another exemplary embodiment, similar stimulation is applied to the lower abdominal muscles, in order to induce repeated contractions of the pelvic floor muscles, which in turn enhance the anal sphincter and / or the urinary sphincter.

[0076] In some embodiments, the disclosed devices include at least one sensor adapted to acquire a body signal.

[0077] In some embodiments, the at least one sensor is based on any one of the following sensors: accelerometer, gyroscope, magnetic compass, inclinometer, piezoelectric sensor, electrocardiogram (ECG), electroencephalogram (EEG), electromyograph (EMG), microphone, electrical impedance sensor, oximeter, optical interferometer, pH meter, and photoelectric sensor.

[0078] In some embodiments, the acquired at least one signal is a result of a physiological phenomenon that can affect the effectiveness of the electrical stimulation therapy. These phenomena can include, but are not limited to, respiration, heart beat, blood pressure, muscle or ligament tension, body posture, wakefulness state, or muscle activity level.

[0079] In some embodiments, the electrical stimulation is synchronized with one or more acquired signals.

[0080] The potential advantage of synchronizing electrical stimulation with a physiological phenomenon is to improve the effectiveness of the electrical stimulation therapy. For example, electrical stimulation of the abdominal muscles during the expiratory phase can result in reduced contractile force of the lower esophageal sphincter (LES) due to increased abdominal pressure and simultaneous diaphragmatic relaxation, which can result in regurgitation of chyme from the stomach into the esophagus. On the other hand, electrical stimulation of the abdominal muscles during the inspiratory phase can result in increased effectiveness of the mechanical effects of the abdominal muscle contraction being transmitted to the LES due to increased abdominal tension and / or stiffness. Thus, if the purpose of the stimulation is to reduce GERD symptoms, synchronizing the stimulation with the respiratory cycle such that the stimulation is only during the inspiratory phase can help improve the effectiveness of the therapy. Conversely, if the purpose of the stimulation is to reduce appetite, synchronizing the stimulation with the respiratory cycle such that the stimulation is during the expiratory phase can help improve the effectiveness of the therapy.

[0081] In some embodiments, the electrical stimulation is synchronized with the respiratory cycle such that the stimulation is in the active state during the inspiratory phase. Alternatively, the electrical stimulation is synchronized with the respiratory cycle such that the stimulation is in the active state during the expiratory phase.

[0082] In some embodiments, the electrical stimulation is synchronized with the intra-abdominal pressure such that the stimulation is in the active state when the intra-abdominal pressure is at a maximum. Alternatively, the electrical stimulation is synchronized with the intra-abdominal pressure such that the stimulation is in the active state when the intra-abdominal pressure is at a minimum.

[0083] In some embodiments, the disclosed device can be controlled by the user through wireless communication. The communication can be achieved through any available wireless communication technology. For example, Wi-Fi, Bluetooth, Bluetooth low energy (BLE), or near field communication (NFC). In addition, or as an alternative, a custom communication protocol can also be used.

[0084] In some embodiments, a smartphone can be used as a communication device to control the implanted device. Alternatively, other independent remote control devices can also be used.

[0085] One exemplary embodiment of the disclosed subject matter is a method of treating gastroesophageal reflux disease (GERD), comprising: implanting at least two intramuscular electrodes in the rectus abdominis and the external oblique abdominis muscles; implanting a control unit subcutaneously and connecting the at least two electrodes to the control unit through subcutaneous leads; and applying a series of electrical pulses to the electrodes, the electrical pulses being adapted to electrically stimulate target muscles and / or nerves of the patient, thereby reducing regurgitation of chyme from the stomach into the esophagus and alleviating GERD symptoms.

[0086] According to some embodiments, the method further comprises applying a series of asymmetric electrical pulses, thereby producing asymmetric contraction of the target muscles.

[0087] In some embodiments, the fast phase of the electrical pulse is directed upwards and the slow phase is directed downwards. Such electrical pulses can be capable of inducing movement of the patient's digestive system.

[0088] In some embodiments, the movements are to reflux esophageal contents into the stomach, thereby alleviating GERD symptoms.

[0089] According to some embodiments, the fast-slow phase sequence of the pulses can be interchanged, thereby changing the direction of movement of the chyme within the digestive tract.

[0090] According to some embodiments, the stimulation pulses are symmetrical.

[0091] According to some embodiments, the method further comprises including in the control unit a pulse generator for generating the electrical stimulation.

[0092] According to some embodiments, the electrical stimulation is characterized by a maximum voltage range of 10V, 20V, 30V, 40V (fundamental to peak), a maximum current range of 0.1 mA, 1 mA, 5 mA, 10 mA, 20 mA, a pulse frequency range of 10 Hz to 200 Hz, a burst frequency range of 0.1 Hz to 10 Hz, and a pulse duration range of 20 µS to 1000 µS.

[0093] According to some embodiments, the method further comprises at least one sensor for collecting a body signal.

[0094] According to some embodiments, the body signal comprises at least one member of the group consisting of: respiration, heart rate, electrocardiogram, blood pressure, gastroesophageal pressure and position, monotonic movement, and body posture.

[0095] According to some embodiments, the sensor is at least one member of the group consisting of: a piezoelectric sensor, an accelerometer, an electrocardiogram sensor, an electroencephalogram sensor, an electromyogram sensor, a gyroscope, and a photoelectric sensor.

[0096] According to some embodiments, the method further comprises synchronizing the stimulation with the body signal.

[0097] According to some embodiments, the synchronization comprises activating the electrical stimulation when the diaphragm is tensed. In other embodiments, the electrical stimulation is activated when the diaphragm is relaxed. Additionally, or alternatively, the synchronization comprises activating the electrical stimulation when abdominal pressure is elevated. In other embodiments, the electrical stimulation is activated when abdominal pressure is reduced. Additionally, or alternatively, the synchronization comprises activating the electrical stimulation during the inhalation phase. In other embodiments, the electrical stimulation is activated during the exhalation phase.

[0098] According to some embodiments, the implanted device can be wirelessly controlled by a device user. In some embodiments, the control includes activation and deactivation of electrical stimulation and setting of stimulation intensity. In some embodiments, the wireless control is implemented through a smartphone.

[0099] Another exemplary embodiment of the disclosed subject matter is a device for treating obesity; the device includes subcutaneously implanted electrodes and a control unit, the control unit further includes a pulse generator for providing electrical stimulation signals to the electrodes, wherein the electrical stimulation pulses are adapted to induce chyme reflux from the stomach to the esophagus. In other embodiments, the electrical stimulation pulses are adapted to increase intra-abdominal pressure, thereby enhancing satiety.

[0100] Another exemplary embodiment of the disclosed subject matter is a device for treating constipation or gastroparesis; the device includes subcutaneously implanted electrodes and a control unit, the control unit further includes a pulse generator for providing electrical stimulation signals to the electrodes; wherein the electrical stimulation pulses are adapted to enhance gastric motility and facilitate chyme passage from the stomach to the duodenum. In other embodiments, the electrical stimulation pulses are adapted to facilitate chyme passage from the transverse colon to the sigmoid colon.

[0101] One technical problem disclosed in the present invention is how to reduce the risk or complexity caused by deep implantation of electrodes to electrically stimulate internal muscles (e.g. LES or crura).

[0102] One technical solution is to implant subcutaneous electrodes in the region of external muscles such as the external oblique and rectus abdominis muscles, to electrically stimulate these muscles, thereby inducing a reflex that acts on the target internal muscle.

[0103] Before at least one embodiment of the present invention is explained in detail, it is to be understood that the application is not limited in its application to the details of construction, the arrangement of components, and / or the methodology set forth in the following description and / or illustrated in the drawings. The application is capable of other embodiments and of being practiced or being carried out in various ways.

[0104] Reference is now made to the following descriptions taken in conjunction with the accompanying drawings, in which: Figure 1A , Figure 1A A device 100 for treating digestive system disorders according to some embodiments of the disclosed subject matter is shown. The device 100 includes a control unit 103 encapsulated within a housing 106; a plurality of electrodes 101, 102 and a sensor 104. Optionally, the electrodes 101, 102 and the sensor 104 are connected to the control unit 103 by wires 110. In some embodiments, the sensor 114 is disposed on the internal or external surface of the housing 106. Optionally, the electrodes 101, 102 are made of biocompatible, non-irritating material.

[0105] In some embodiments, the device 100 can be controlled by a remote control device 130 through wireless communication.

[0106] Referring now to Figure 1B , Figure 1B The structure of the housing 106 is shown in more detail. In some embodiments, the housing 106 is designed to house the circuitry and electrical components required to generate and control the electrical stimulation. Optionally, the housing 106 is sealed to prevent the ingress of body fluids or particulate matter when implanted in the patient. Optionally, the housing 106 is made of a flexible or semi-flexible material so as to conform well to the patient’s body. Optionally, the housing 106 is made of a biocompatible material. Optionally, the housing 106 is made of an electrically insulating material.

[0107] In some embodiments, the control unit 103 is disposed within the housing 106. The housing 106 optionally includes a circuit board 108 and a power source, such as a battery 105. The circuit board 108 optionally includes the pulse generator 107, as well as other electronic components, such as a microcontroller, digital circuitry, memory, communication circuitry, high-voltage circuitry, analog circuitry, high-voltage switches and bridges, protection circuitry. In some embodiments, any one or some combination of the control unit 103, the circuit board 108, the battery 105, and / or the pulse generator 107 are mounted in a separate housing.

[0108] Referring now to Figure 2 , Figure 2 An exemplary embodiment of the device 200 for treating a digestive system disorder after implantation in a patient is shown. The device 200 includes a housing 206 and two electrodes 201, 202. During implantation, the electrodes 201 and 202 are brought into electrical contact with the target regions of the rectus abdominis muscle 221 and the external oblique muscle 222, respectively. Optionally, leads 211, 212 connect the electrodes to the housing 206.

[0109] Optionally, the lead 211 is designed to have at least one electrical property that depends on mechanical tension or elongation, such as a tension-dependent resistance or a tension-dependent capacitance. In such embodiments, the lead 211 functions as a mechanical tension or elongation sensor. Optionally, the lead 211 is designed to provide an electrical signal that corresponds to body movements related to respiration. Optionally or alternatively, a respiration sensor is included as a separate component in the device 200 (not shown).

[0110] When activated, the device 200 generates an electrical stimulation that is transmitted through the leads 211, 212 and the electrodes 201, 202 to the target regions, causing the selected abdominal muscles to contract and relax in a predetermined pattern. Optionally, the electrical stimulation generated by the device 200 is controllable by wireless communication through a remote control 230. The remote control 230 can be a smartphone.

[0111] Referring now to Figures 3A-3B wherein exemplary electrical stimulation waveforms are shown that include asymmetric pulse trains, the fast phase of the pulse trains being directed upward and the slow phase being directed downward; andFigure 3C wherein an exemplary electrical stimulation waveform comprising an asymmetric burst is shown, the fast phase of the burst is directed downward and the slow phase is directed upward.

[0112] In Figure 3A , a graphical representation of two examples of an exemplary asymmetric burst 300 is shown, the burst comprising a series of sequentially decreasing biphasic pulses. The horizontal axis of the graphical representation represents time and the vertical axis can represent voltage or current. Optionally, the voltage or current of the first pulse 301 of the burst corresponds to a desired intensity level 302. Optionally, the intensity level 302 can be adjusted by the device user. Optionally, the voltage or current of the pulses decreases linearly from the first pulse to the last pulse of the burst. Alternatively, a differential burst is employed. Optionally, an inter-burst duration 303 is maintained between two consecutive bursts. Optionally, the inter-burst duration 303 can be adjusted by the device user. Alternatively, the inter-burst duration 303 can be adjusted by the machine.

[0113] In Figure 3B , a graphical representation of two examples of an exemplary asymmetric burst 310 is shown. The burst 310 is similar to the burst 300, but the voltage or current of the pulses increases linearly from the first pulse to the last pulse.

[0114] In Figure 3C , a graphical representation of one example of an exemplary symmetric burst 320 is shown. The burst 320 is similar to the bursts 300 and 310, but the voltage or current of the pulses increases linearly from the first pulse to the last pulse and then decreases linearly. The burst 320 can also be constructed by applying the burst 310 first and then applying the burst 300.

[0115] Figure 3D A detailed view of two consecutive biphasic pulses in any of the bursts 300, 310 or 320 is shown. The pulse shape is optionally rectangular, representing constant current or constant voltage, respectively. Each pulse optionally comprises a positive phase 330 and a negative phase 331. Alternatively, the order of the positive and negative phases can be interchanged. The phases of the pulses can be designed such that no net charge transfer occurs during the pulse. The positive phase duration 332 can be the same as the negative phase duration 333. An inter-pulse interval 334 can be maintained between two consecutive pulses. The inter-pulse interval 334 can be adjusted by the device user. Alternatively, the inter-pulse interval 334 can be adjusted by the machine.

[0116] Reference is now made to Figure 4Fig. 4, shows a portion of an exemplary signal 400 acquired by a respiration sensor comprised in an implantable device for treating a digestive system disease, in accordance with some embodiments of the disclosed subject matter. Optionally, the signal 400 is a voltage signal output by a tension-dependent respiration sensor implanted in the abdomen or chest of a patient. Optionally, a control unit comprised in the device can analyze the signal 400, for example by identifying local maxima 401 and minima 402 of the signal, in order to synchronize electrical stimulation with the patient's respiratory cycle.

Claims

1. A subcutaneous implantable device for treating digestive system diseases, characterized in that: The device comprises a control unit, a power source, a pulse generator and a plurality of subcutaneously implanted electrodes adapted for electrical contact with a plurality of target areas of the patient's abdomen; wherein the pulse generator is adapted to be implanted in the plurality of target areas and to deliver stimulation signals through the plurality of electrodes to activate the plurality of target areas, wherein the power source is adapted to provide power to the pulse generator, wherein the control unit is adapted to control the power source.

2. The apparatus of claim 1, wherein: The electrical stimulation is characterized by a maximum voltage of +20V, a maximum current of 20mA, a pulse frequency range of 20Hz-50Hz, a burst frequency range of 0.2Hz-4Hz, and a pulse width of 25µs-300µs.

3. The apparatus of claim 1, wherein: The digestive system disease is at least one of gastroesophageal reflux disease (GERD), gastroparesis, obesity, incontinence and constipation.

4. The apparatus of claim 1, wherein: The electrical stimulation comprises repeated bursts of pulses, and wherein the shape of the bursts of pulses is set according to the desired physiological effect.

5. The apparatus of claim 1, wherein: Further comprising at least one sensor; wherein the stimulation is synchronized with at least one body signal acquired by the at least one sensor, wherein the body signal comprises at least one of the following members: respiration, heartbeat, blood pressure, muscle or ligament tension, body posture, wakefulness state or muscle activity level, wherein the sensor comprises at least one member selected from the following group: accelerometer, gyroscope, magnetic compass, inclinometer, piezoelectric sensor, electrocardiogram, electroencephalogram, electromyogram, microphone, electrical impedance sensor, oximeter, optical interferometer, pH meter and photoelectric sensor.

6. The apparatus of claim 1, wherein: The device comprises an implantable sensor adapted to be implanted within the esophageal wall and adapted to sense esophageal acidity level; wherein the sensor is further configured to output the acidity level, wherein the controller is further configured to control at least one parameter related to the disease according to the acidity level.

7. The apparatus of claim 1, wherein: The electrodes are adapted to be implanted in the target areas of the rectus abdominis and the external oblique abdominis muscles.

8. A method of treating a digestive system disorder, comprising: administering to a subject in need thereof a therapeutically effective amount of a compound of claim 1. The method comprises: Implanting a pulse generator and a plurality of electrodes subcutaneously in the patient's abdomen, the plurality of electrodes being in electrical contact with a plurality of target areas of the patient's abdomen; and Applying electrical stimulation to activate the plurality of target areas.

9. The method of claim 8, wherein: The plurality of target areas comprises muscles, nerves, muscle-nerves junctions or any combination thereof.

10. The method of claim 8, wherein: The electrical stimulation is optimized for manipulating the patient's digestive system to change the flow rate of chyme and direct it in a desired direction.

11. The method of claim 8, wherein: The electrical stimulation comprises a series of current-controlled asymmetric pulses aimed at producing asymmetric contractions of selected abdominal muscles; wherein the fast phase of the pulses is directed upwards and the slow phase of the pulses is directed downwards.

12. The method of claim 10, wherein: The change is a reduction in the reflux of chyme from the patient's stomach to the esophagus, thereby relieving GERD symptoms.

13. The method of claim 11, wherein: The change is an increase in the flow of chyme from the patient's stomach to the duodenum, thereby relieving gastroparesis symptoms.

14. The method of claim 11, wherein: The change is an increase in the flow of chyme from the patient's colon to the rectum, thereby relieving constipation symptoms.

15. The method of claim 10, wherein: The electrical stimulation comprises a series of current-controlled asymmetric pulses aimed at producing asymmetric contractions of selected abdominal muscles; wherein the fast phase of the pulses is directed upwards and the slow phase of the pulses is directed downwards.

16. The method of claim 10, wherein: implanting at least one sensor, and wherein the stimulation is synchronized with at least one body signal collected by the at least one sensor; wherein the sensor comprises at least one of the following members: accelerometer, gyroscope, magnetic compass, inclinometer, piezoelectric sensor, electrocardiogram, electroencephalogram, electromyogram, microphone, electrical impedance sensor, oximeter, optical interferometer, pH meter, and photoelectric sensor; wherein the body signal comprises at least one of the following members: respiration, heartbeat, blood pressure, muscle or ligament tension, body posture, wakefulness state, or muscle activity level.

17. The method of claim 10, wherein: The activation of the multiple target areas is adapted to induce a body reflex.

18. The method of claim 10, wherein: The reflex comprises at least one of the following members: forceful esophageal reflex and forceful diaphragmatic split reflex.

19. The method of claim 10, wherein: Measuring an acidity level is further included to control at least one parameter related to the disease.

20. A method of treating a digestive system disease, comprising: administering to a subject in need thereof a therapeutically effective amount of a compound of any one of claims 1-19. The method comprises: applying electrical stimulation to a target area of the patient's abdomen by a pulse generator, the electrical stimulation being applied through a plurality of electrodes in electrical contact with the target area of the patient's abdomen; detecting an acidity level of the esophagus by a sensor and outputting the acidity level to a controller; and controlling at least one parameter related to the electrical stimulation by the controller and in accordance with the acidity level. The method comprises: applying electrical stimulation to a target area of the patient's abdomen by a pulse generator, the electrical stimulation being applied through a plurality of electrodes in electrical contact with the target area of the patient's abdomen; detecting an acidity level of the esophagus by a sensor and outputting the acidity level to a controller; and controlling at least one parameter related to the electrical stimulation by the controller and in accordance with the acidity level.

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