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EP-4740996-A2 - IMPLANTABLE AND NON-INVASIVE STIMULATORS FOR GASTROINTESTINAL THERAPEUTICS

EP4740996A2EP 4740996 A2EP4740996 A2EP 4740996A2EP-4740996-A2

Abstract

Systems and methods for implementation of a disposable miniaturized implant for treatment of PostOperative Ileums (POI), a miniaturized implant for treating chronic GI dysmotility (e.g., dysphagia, gastroesophageal reflux disease (GERD), nausea, functional dyspepsia, blockage of transit, and gastroparesis, inflammatory bowel disease) and obesity, by providing electrical stimulation to the part of bowel going through surgery to expedite the healing process while recording the smooth muscle activities simultaneously, or providing stimulation on a treatment location of the GI tract or the branch of the vagus nerve. Systems and methods are also provided for non-invasive, transcutaneous stimulation of anatomy within the abdomen of the patient.

Inventors

  • LO, Yi-kai
  • LIU, WENTAI

Assignees

  • The Regents of the University of California

Dates

Publication Date
20260513
Application Date
20171212

Claims (15)

  1. A system comprising: a multi-channel stimulator comprising multiple channels; multiple electrodes, each electrode of the multiple electrodes is independently addressable and connected to one of the multiple channels to deliver a stimulation with different onset times, wherein when two or more of the multiple channels are turned on simultaneously, stimulations delivered by the two or more channels of the multiple channels to two or more independently addressable electrodes have different onset times.
  2. The system of claim 1, wherein the stimulations delivered by the two or more channels of the multiple channels are each stepwise pulse trains.
  3. The system of claim 2, wherein onset times of pulses of each of the two or more stepwise pulse trains are interleaved with one another.
  4. The system of claim 3, wherein the onset times of pulses of each of the two or more stepwise pulse trains are interleaved with one another to avoid concurrent firing of the pulse trains to ensure an overall stimulation current does not exceed a safe stimulation limit.
  5. The system of claim 2, wherein the stepwise pulse trains each comprise a series of step up stimulation pulses each having a current that incrementally increases until a specified peak stimulation current is achieved.
  6. The system of claim 2, wherein the stepwise pulse trains have the different onset times to mitigate an uncontrolled strong stimulation.
  7. The system of claim 2, wherein each of the stepwise pulse trains is adjustable based on a feedback signal related to treatment efficiency.
  8. The system of claim 2, wherein the different onset times are used to avoid concurrent firing within a target to avoid damage to the target.
  9. The system of claim 1, wherein a portion of the multiple channels are turned on simultaneously at a first time and another portion of the multiple channels are turned on simultaneously at a second time to establish an onset sequence of electrodes.
  10. The system of claim 9, wherein the onset sequence enables spatial steering of injected electrical charge to target locations and/or tissues of interest within anatomy.
  11. The system of claim 1, wherein an output of the multi-channel stimulator is connected to a digital-to-analog converter (DAC) for a one-to-N output de-multiplexer to allow connection to a greater number of the multiple electrodes.
  12. The system of claim 1, wherein the one-to-N output de-multiplexer allows connection to at least eight of the multiple electrodes.
  13. The system of claim 1, wherein a compliance voltage is adaptively adjusted based on an electrode-tissue impedance.
  14. The system of claim 1, wherein the two of more electrodes stimulate a surface of a patient's skin.
  15. The system of claim 14, wherein stimulating the surface of the patient's skin stimulates one or more spinal nerves and/or ganglions.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS This application claims priority to, and the benefit of, U.S. provisional patent application serial number 62/433,122 filed on December 12, 2016, incorporated herein by reference in its entirety. This application is related to PCT International Application No. PCT/US2016/063886 filed on November 28, 2016 and published as WO 2017/091828 on June 1, 2017, incorporated herein by reference in its entirety, which claims priority to, and the benefit of, U.S. provisional patent application serial number 62/260,624 filed on November 29, 2015, incorporated herein by reference in its entirety. STATEMENT REGARDING FEDERALLY SPONSORED RESEARCH OR DEVELOPMENT Not Applicable NOTICE OF MATERIAL SUBJECT TO COPYRIGHT PROTECTION A portion of the material in this patent document may be subject to copyright protection under the copyright laws of the United States and of other countries. The owner of the copyright rights has no objection to the facsimile reproduction by anyone of the patent document or the patent disclosure, as it appears in the United States Patent and Trademark Office publicly available file or records, but otherwise reserves all copyright rights whatsoever. The copyright owner does not hereby waive any of its rights to have this patent document maintained in secrecy, including without limitation its rights pursuant to 37 C.F.R. § 1.14. BACKGROUND 1. Technical Field The technology of this disclosure pertains generally to therapeutic stimulation systems and methods, and more particularly to systems and methods for therapeutic stimulation in treatment of gastrointestinal disorders. 2. Background Discussion Gastrointestinal neuromuscular disorder (GND) is a set of disorders characterized by the absence or poor function of the intestinal muscularis (IM), involving any segment of the gastrointestinal (GI) tract. GND may affect the enteric nervous system, smooth muscle cells, and/or the interstitial cells of Cajal (ICC), which are the pacemaker cells in the GI tract, thus resulting in functional GI diseases and dysmotility. Patients with GND may present with dysphagia, gastroesophageal reflux disease (GERD), nausea, functional dyspepsia, blockage of transit, and obstruction of the GI tract (e.g., gastroparesis), which accounts for 40% of GI tract illness that patients seek health care for in gastroenterology clinics. The current limitation in the treatment of GND associated GI dysmotility is the lack of understanding of the pathophysiology involving the neurons, ICC, and smooth muscle cells combined with the paucity of effective medications that can improve GI motility. The clinical alternative for pharmaceutically intractable GI dysmotility is usually the total or subtotal resection of the affected GI segments. On the other hand, GI dysmotility can also be transiently induced through surgical operation (e.g., bowel resection surgery), leading to post-operative ileus (POI). POI leads to the inflammation of the bowel wall that occurs following abdominal surgery and its economic impact is estimated to be between $3/4 billion and $1 billion per year in the United States. Patients with POI manifest abdominal pain, nausea, vomiting, as well as the inability of coordinated propulsive mobility while the current treatment is restricted to the spontaneous recovery of the patient. POI is not only limited to patients receiving abdominal surgery. There are patients receiving open-heart surgery also reporting symptoms similar to POI, possibly because the sympathetic and parasympathetic nerves governing the GI tack are affected by the surgery. BRIEF SUMMARY A primary premise of the system and methods disclosed herein is that electrical stimulation in the vagus nerve reduces the level of tumor necrosis factor (TNF), indicating the decrease of inflammation or the direct stimulation on the enteric nervous system and smooth muscles to adapting GI motility. Thus, an aspect of the present technology is a system and method configured to treat GI dysmotility through electrophysiological intervention by stimulating the bowel wall where the nerve ending of VN is located or the vagus nerve at the cervical or celiac branch. For the therapeutic treatment of POI that presents a transient GI dysmotility, the device performing stimulation is small and easily/conveniently removable after a course of POI treatment; for the diseases associated with chronic GI dysmotility, the miniaturized device can be implanted permanently. In one embodiment, an SoC implant of the present description targets motor function of GI tract smooth muscles, with versatile functionalities and highly compact form factor (<0.5cm3 and <0.7g) for various medical applications. In another embodiment, anon-invasive, transcutaneous stimulation system is provided for stimulation of anatomy within the abdomen of the patient Further aspects of the technology described herein will be brought out in the following portions of the specification, w