Patent Application
20250177752
Impaired swallowing is observed in many patients who have suffered a stroke or a brain injury. Animal studies have shown that the central influence of the nervous system is not necessary to initiate a swallowing reflex when direct local electrical stimulation is performed. The swallowing mechanism is important for clearance of oral secretions, pharyngeal secretions as well as secretions coming from the sinuses. When patients are put on artificial respiration, they usually have a breathing tube that is inserted down their mouth or nose into the trachea. To tolerate the presence of the breathing tube and to facilitate successful patient breathing with the ventilator, sedatives and other paralytic drugs are given to the patient which inhibit the central pathway for swallowing. A normal human being produces 700 to 1200 CC of salivary secretions and additional secretions from the sinuses. These secretions tend to collect in the posterior pharynx and these patients are usually recumbent, so these secretions are at risk of entering the breathing system and causing pneumonia in the lung.
In addition, patients who have a breathing tube and are on ventilators have impaired clearance of gastric juices which typically amounts to 1-1.5 liters per day. The clearance of the stomach contents is dependent on the adequate functioning of duodenum and jejunum. The relaxation of the upper and the lower food pipe valve causes these stomach contents to freely regurgitate in the trachea and subsequently in the lungs causing aspiration or pneumonia, also known as ventilator associated pneumonia. Simply stimulating the food pipe is inadequate for achieving coordinated emptying of the oral secretions, gastric secretions, duodenal contents, and Jejunal clearance.
Stimulation of nerves such as the superior laryngeal nerve and branches of the glossopharyngeal nerve are important in initiating the swallowing. Subsequent relaxation of the upper esophagus sphincter is initiated with this stimulation, creating a secondary peristaltic wave within the esophagus which in turn relaxes the lower sphincter, thus clearing the secretions and pushing them into the stomach. Clearance of the stomach is more complicated with the antral portion of the stomach playing an important role in the emptying of the stomach. However, emptying of the stomach is dependent on jejunal clearance and hence stimulation of the jejunum in turn will lead to increased stomach clearance.
Thus, what is needed in the art is a device that can detect physiological feedback along an anatomical lumen, while having the ability to generate stimulation signals coinciding with the proximity of target stimulation point along the anatomical lumen.
In one embodiment, a stimulation catheter includes an elongate flexible member having a proximal end, a distal end, and resonator coils configured therebetween; a cathode connected to each of the resonator coils; anodes each connected to and corresponding with one of the resonator coils; stimulation elements each connected to and corresponding with one of the resonator coils; and a control unit coupled to the cathode and the anodes, wherein the control unit is configured to generate a stimulation signal based on feedback signals generated from the resonator coils. In one embodiment, the control unit comprises a controller communicatively coupled to each of the plurality of anodes and each of the plurality of stimulation elements. In one embodiment, the controller is configured to generate a sequence of stimulation signals for the stimulation elements. In one embodiment, the sequence is based on detecting a predetermined threshold sequence of physiological feedback from the two or more of the resonator coils. In one embodiment, the sequence activates the plurality of stimulation elements in an order moving in a distal direction. In one embodiment, the sequence activates the stimulation elements in an order moving in a proximal direction. In one embodiment, the sequence activates combinations of two or more of the plurality of stimulation elements at different times. In one embodiment, the control unit includes a multiplexer connected to each of the anodes. In one embodiment, the feedback signals includes at least one of a resistance, admittance, impedance, reactance, susceptance, capacitance, or conductance between inductively coupled electrode measurement signal. In one embodiment, at least one of the feedback signals includes a zero-value measurement. In one embodiment, the resonator coils are spaced apart by a uniform distance. In one embodiment, the resonator coils are spaced apart by different distances. In one embodiment, the resonator coils are configured on an outer surface of the elongate flexible member. In one embodiment, each of the resonator coils wraps around the outer surface at least one time in a spiral formation. In one embodiment, each of the resonator coils wraps around an outer surface at least two times time in a spiral formation. In one embodiment, the elongate flexible member includes a lumen extending from the proximal end to a distal tip. In one embodiment, the elongate flexible member includes a medical grade polymer. In one embodiment, the medical grade polymer is polyamide. In one embodiment, at least one of the stimulation elements is a capacitor. In one embodiment, the capacitor is a surface mount device capacitor configured on a surface of at least one of the plurality of resonator coils. In one embodiment, a stimulation catheter system includes an elongate flexible sheath having a sheath lumen connected to a distal sheath opening, and multiple sheath stimulation elements surrounding the sheath lumen. In one embodiment, a stimulation catheter system includes the catheter and an elongate flexible internal body having a distal tip sensor. In one embodiment, the distal tip sensor is a pH sensor. In one embodiment, the elongate flexible internal body comprises a plurality of body stimulation elements. In one embodiment, the control unit is configured to predict a media type based on a detected resistance. In one embodiment, the control unit is configured to amplify detection by spatially tuning adjacent electrodes. In one embodiment, the device includes embedded pressure sensors on an external aspect of the hollow longitudinal tube configured to detect pressure at different levels of the esophagus, stomach, intestine or urinary bladder corresponding to a site of use. In one embodiment, the device includes an obturator within the outer sheath, where the obturator has a distal end viewing camera. In one embodiment, the device includes an obturator tip can having a pH sensor, optical fluorescence sensor and a pressure sensor, wherein the sheath is configured to be a carrier for a tube like structure within its lumen after the removal of the obturator.
The foregoing purposes and features, as well as other purposes and features, will become apparent with reference to the description and accompanying figures below, which are included to provide an understanding of the invention and constitute a part of the specification, in which like numerals represent like elements, and in which:
It is to be understood that the figures and descriptions of the present invention have been simplified to illustrate elements that are relevant for a more clear comprehension of the present invention, while eliminating, for the purpose of clarity, many other elements found in sensing and stimulation devices. Those of ordinary skill in the art may recognize that other elements and/or steps are desirable and/or required in implementing the present invention. However, because such elements and steps are well known in the art, and because they do not facilitate a better understanding of the present invention, a discussion of such elements and steps is not provided herein. The disclosure herein is directed to all such variations and modifications to such elements and methods known to those skilled in the art.
Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. Although any methods and materials similar or equivalent to those described herein can be used in the practice or testing of the present invention, the preferred methods and materials are described.
As used herein, each of the following terms has the meaning associated with it in this section.
The articles “a” and “an” are used herein to refer to one or to more than one (i.e., to at least one) of the grammatical object of the article. By way of example, “an element” means one element or more than one element.
“About” as used herein when referring to a measurable value such as an amount, a temporal duration, and the like, is meant to encompass variations of ±20%, ±10%, ±5%, ±1%, and ±0.1% from the specified value, as such variations are appropriate.
Ranges: throughout this disclosure, various aspects of the invention can be presented in a range format. It should be understood that the description in range format is merely for convenience and brevity and should not be construed as an inflexible limitation on the scope of the invention. Where appropriate, the description of a range should be considered to have specifically disclosed all the possible subranges as well as individual numerical values within that range. For example, description of a range such as from 1 to 6 should be considered to have specifically disclosed subranges such as from 1 to 3, from 1 to 4, from 1 to 5, from 2 to 4, from 2 to 6, from 3 to 6 etc., as well as individual numbers within that range, for example, 1, 2, 2.7, 3, 4, 5, 5.3, and 6. This applies regardless of the breadth of the range.
Referring now in detail to the drawings, in which like reference numerals indicate like parts or elements throughout the several views, in various embodiments, presented herein is a sensing and stimulation device and system.
Embodiments of the device can detect physiological feedback along an anatomical lumen as a basis for generating stimulation signals coinciding with the proximity of target stimulation point along the anatomical lumen. Embodiments of the device can be utilized for several different treatments in various parts of the body. For example, embodiments of the device can be used to restore bladder emptying, bladder function, improving bladder neck tone, and for treating urinary incontinence when used intravesically (urinary bladder and intra virginal). In one embodiment, a rectal application is implemented for treating constipation and pelvic floor exercises in recumbent patient who are chronically recumbent with loss of rectal tone and resultant absence of defecation reflex. In one embodiment, an external ear application is implemented to treat tinnitus, trigeminal neuralgia and TM joint pain. In one embodiment, oral, pharyngeal and laryngeal application is implemented to treat impaired swallowing and dysphagia. The obturator can be modified to be an end viewing telescope, camera or a sensor for pH, pressure or able to induce a EM force field that is detectable by the electrodes mounted on the outer sleeve of the tube. The electrode shapes may be for example ring, longitudinal, crown or spiral shaped. The controller is able to give fixed output of electrical stimulus with for example square, triangular, or sinusoidal waves with varying voltage, amperage, time duration and amplitude.
With reference now to
The controller can be programmed to selectively generate a sequence of stimulation signals the stimulation elements based on detecting a predetermined threshold sequence of physiological feedback from the resonator coils. A sensing block diagram and a pacing block diagram are shown according to one embodiment in
With reference now to
Accordingly, in one embodiment, the device provides a closed loop, autofeedback, multi-site, multi-organ, intra luminal electrical pacing and sensing system and device. This is controlled by a microcontroller, initiated by a function generator, and consists of electronics which detects the resistance, admittance, impedance, reactance, susceptance, capacitance, and conductance between inductively coupled electrode regimen. The inductively coupled regimen of the electrodes provides information between the electrodes of admittance, inductance, impedance, capacitance and susceptance which characterizes the intra luminal contents and motion. Interaction, physiological feedback and relationships between the electrodes can be configured to provide size, position and empty or filled status of the hollow organ. The device records the response to bio stimulation and conveys the information in real time. A graphic display can be utilized to allow more information in real time, which can be transmitted over to any device via Bluetooth, wifi or radio signals. In one embodiment, the electrodes are specially designed with a geometry to increase the contact area and surface area.
Embodiments of the device take advantage of physiological observations that were gathered in part during device development and experimental activity as explained in further detail below. The main purpose of the food pipe is to push the swallowed food or fluid towards the stomach. The esophagus has two valves, one is at the top where the voice box is and one at the bottom where it enters the stomach. The purpose of these two valves is to prevent entry of the swallowed food into the voice box and contaminating the lungs, and the purpose of the lower valves is to prevent the contents of the stomach from coming up into the food pipe also called esophagus. Since the stomach contents are extremely acidic, any regurgitation or reflux of these contents into the food pipe and the lungs can cause severe damage. Proper forward squeezing of the contents within the stomach is important. The stomach after mixing the food and storing the food empties into the duodenum. That duodenum contains alkaline environment which neutralizes the acid from the stomach. The contents from the duodenum are then delivered to the jejunum which is a part of the small intestine.
Esophageal peristalsis, that is, coordinated squeezing of the esophageal muscle, is a complex mechanism. The process is started by the swallowing of food. The beginning of this phase is voluntary when food is swallowed, then mixed with saliva to form a bolus of the food and then pushed by the tongue to the posterior pharynx. The next phase is involuntary, which involves a sequential squeezing of the muscles of the upper head and neck. The food bolus is then pushed forward by the esophagus and by the pharyngeal muscles. Simultaneously, movement of the muscles of the palate and elevation of the larynx is initiated so that the food does not enter the nasal cavity or the larynx. When the deglutition reflex is initiated, the upper esophageal valve also known as upper esophageal sphincter gets activated and relaxes to allow the food bolus to pass into the body of the esophagus. The sequential contraction of the circular smooth muscles initiates the peristaltic activity. The speed of this activity is about 3 centimeter per second in the upper part of the esophagus and five centimeter per second in the middle part of the esophagus, and then it becomes 2.5 centimeter per second in the last part of the esophagus. This peristaltic activity is reflected in the pressure changes in the tubular esophagus. The highest pressures are mean of 54 plus minus 8 millimeter of mercury in the upper part, 35+/−5 millimeter of mercury in the middle part and 70+/−12 millimeter of mercury in the lowest part of the esophagus. The peristaltic activity of the esophagus is affected by factors such as the food bolus size, with a larger bolus causing more stronger peristaltic contractions while a smaller bolus leads to slower peristaltic contraction. Temperatures such as warmer boluses enhances the peristaltic activity while colder boluses have a inhibit reaction on the peristaltic process.
The striated muscle fibers of the esophagus are controlled by the excitatory nerve activity from the lower motor neurons, and this is affected through the nucleus ambiguous and nucleus retro facials via the vagus nerve. Inhibition or destruction of the vagus nerve bilaterally in the cervical region can eliminate the primary peristaltic wave. However secondary peristalsis can happen independently of the central nervous system control and the secondary peristaltic waves can be independently generated. Isolated smooth muscle strips have shown that there is a latency gradient of contraction along the esophagus that appears to contribute to generation of the peristaltic waves. Short duration of electrical stimulation of the intrinsic nerves of the circular smooth muscle strip results in a contraction that occurs after the stimulus has ended also called the off response.
The secondary phase is activated by the distention of the lumen. This can occur with the left behind food after the primary wave has subsided or it can also happen with the reflux contents from the stomach. This secondary wave or secondary phase is not associated with deglutition or pharyngeal or upper sphincter stimulation. The longitudinal smooth muscle contraction effects peristalsis by shortening the esophagus and by longitudinal contraction which slide this over the bolus. The contraction of the longitudinal muscles is longer distally than proximally.
The lower esophageal sphincter extending from 2 to 5 centimeters above the junction with the stomach and has circular muscle functions as a sphincter. It normally remains tonically constructed with a pressure at this point of about 30 millimeter of mercury. This is in stark contrast to the mid portion of the esophagus between the upper and lower sphincters which would normally remain relaxed. The tonic constriction of the lower esophageal sphincter helps to prevent any reflux from the stomach into the esophagus. When stimulated, the lower esophageal sphincter can have a sustained tone lasting several minutes, and can persist even after the stimulus is long past.
The smooth muscle of the gastrointestinal tract shows two basic types of electrical waves-slow waves and spikes. The voltage of the resting membrane potential of the gastrointestinal smooth muscle can change to different levels and this can have an impact on the activity off the tract. They always occur rhythmically. This rhythm is the frequency of the slow waves in the smooth muscle. These are however not action potentials, these are usually slow, until rating changes in the resting membrane potential which stop these slow waves are characterized by 5 to 15 millivolts of intensity and their frequency ranges from 3 to 12 per minute. It is about 3 three waves per minute in the body of the stomach and as much as 12 per minute in duodenum, and then it ranges from eight or nine in the jejunum and ileum. The slow waves cause muscle contraction in the stomach, however in the rest of the part of the gastrointestinal tract they mainly control the appearance of intermittent spike potentials, and these spike potentials in turn actually cause most of the muscle contractions. The frequency of slow waves drops to about 5 in colon before dramatically increasing to more than 15 per minute in the rectum.
Spike potentials are true action potentials and they happen because of the resting membrane potential of the gastrointestinal smooth muscle becomes more positive, 40 millivolts the normal resting membrane potential is somewhere between 52-60 millivolts. The frequency of the spike potential ranges between 1 to 10 spikes per second. Spike potential last about 10 to 40 times as long in the gastrointestinal muscle similar to the action potentials in the nerves.
The slow waves are termed the basic electric rhythm of the stomach, this is well characterized in the distal portion of the stomach. The fundus, proximal third of the stomach exhibits a sustained and non-phasic electrical activity. The gastric slow waves are generated by an area in mid corpus of the stomach along the greater curvature. They only move distally and are thus important in the emptying of the stomach. These waves travel myogenically and are not dependent on specialized nerve fibers such as the heart. The electrogastrogram can depict these changes from transcutaneous recordings, however, direct mucosal and serosal probes give a more accurate recording.
Embodiments of the device can initiate swallowing independently of the stimulation of the stomach. The device can stimulate and maintain stimulation of the lower esophageal sphincter to maintain its tone and prevent reflux. The series of esophageal electrodes/resonators act as sensors to sense ECG signals and any other biological electrical signal, amplifying it to prevent any inadvertent electrical stimulation that can interfere with cardiac activity or diaphragmatic activity. The electrodes which also act as an inductively coupled regimen can detect the gastric lumen, its contents, the direction of its flow and its response to the stimulation. Gastric stimulation is done on the basis of the signal information from the #9 and resultant effects are simultaneously measured in the duodenum, jejunum and pylorus creating an auto feedback loop. Jejunal stimulation effects and promoted gastric emptying, hence the jejunal feedback loop is created based on the electrode/resonators with inductive parameters to create effective bio-stimulation. Similar applications use stimulation in reverse order when one compares the upper, mid and lower rectum to treat constipation. The series of electrodes and resonators help to titrate the electrical signal, frequency, amplitude, and duration needed for effective defecation. The information and position of the electrodes/resonators can be accurately determined by a surface coil which can detect the EMF signal from various signals emitted. This configuration can also create a topographic map of organs the electrodes/resonators are near or within intraluminal.
Stimulation of any intraluminal organ can thus be customized based on application for example: intravesical (inside urinary bladder by mounted on a urinary catheter), within a ureter (on a ureteric catheter), external ear canal, external nasal passage, oral and pharyngeal cavities, thus it can be used for any cavity or organ with a lumen. More specifically, examples of application of use include:
Stimulating swallowing reflex by stimulating the posterior pharyngeal wall and above upper esophageal sphincter by stimulating the recurrent laryngeal nerve and glossopharyngeal nerve.
Feeding tube use for restoring GI peristalsis.
Intravesical use for acute urinary retention and to influence/increase urine output.
Intra-vaginal use to improve bladder neck tone, to correct urinary incontinence.
Endotracheal tube use for treating swallowing reflex dysfunction and to check nerve integrity.
Rectal tube use for treating constipation and to stimulate defecation.
External ear use for treating tinnitus.
Oral, pharyngeal use for treatment of dysphagia.
Post-operative use via nasogastric tube to stimulate appetite and food intake where the stimulating coils are placed at intervals to stimulate stomach and duodenal, jejunal contractions/stimulation. Gastric reflux can cause VAP and aspiration pneumonia, thus embodiments of the invention can be used to prevent this.
Post-operative use via nasogastric tube/endotracheal tube/tracheostomy tube to prevent aspiration. Paralysis weakness of the posterior pharyngeal sphincter and incomplete emptying or GI tract is responsible for majority of patients getting aspiration pneumonia, by periodically stimulating the emptying and contractions, aspiration can be avoided and prevented.
Post-operative use for periodic bowel emptying to prevent paralytic ileus and bowel impaction with fees. As a major cause of prolonged illness, narcotics use post operatively and prolonged recumbency can lead to slower bowel clearance which can lead to constipation and bowel organism translocation, this can be prevented by pacing stimulator coils within a rectal tube to stimulate bowel evacuation.
In one embodiment, with reference now to
The invention is now described with reference to the following Examples. These Examples are provided for the purpose of illustration only and the invention should in no way be construed as being limited to these Examples, but rather should be construed to encompass any and all variations which become evident as a result of the teaching provided herein.
Without further description, it is believed that one of ordinary skill in the art can, using the preceding description and the following illustrative examples, make and utilize the present invention and practice the claimed methods. The following working examples therefore, specifically point out the preferred embodiments of the present invention, and are not to be construed as limiting in any way the remainder of the disclosure.
Animals were acclimatized in a central animal facility for 2 weeks before the experiment. All procedures were performed under aseptic conditions and anesthesia was achieved using a combination of ketamine and xylazine. Animals received humane care in compliance with the “Guide for Care and use of Laboratory Animals”, published by the National Research Council (National Academy Press, 1996).
Various reflux was induced in 10-week-old, male Sprague Dawley rats, (200-250 gms, Harlan, Indianapolis, IN). The animals were allowed two weeks to acclimatize, and were housed at temperature of 20-22° C., humidity of 70%- and 12-hour alternating light-dark cycle. The rats were fasted overnight but allowed water ad-libitum till the surgery. Briefly, the esophagus was mobilized preserving the vagus nerves. The following models that were created to increase the severity of reflux of gastric contents:
Once the animals awoke, they were allowed water ad-libitum. Feeding recommenced the following day. Animals received appropriate analgesia during the peri-operative and postoperative period.
Large animal preparation included, Yorkshire pigs which were anesthetized and intubated. A 110 cm long tube was then inserted via esophagus, then advanced to the stomach, duodenum, and jejunum to measure electrical activity within the structures and to provide electrical stimuli.
Gross appearance of reflux leading to increased oral secretions soiling the mouth and nasal area is shown in the image of
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Accordingly, the concept of putting a tube with the obturator within it has several advantages. That obturator can be disposed at the tip, it can have a conventional glass pH electrode, or it can also have optical fluorescence and or pressure transducer. In conventional methods, when you put the feeding tube, one of the biggest mistakes involves advancing it somewhere it's not supposed to go, such as an trachea, bronchus or even via lungs, blind passage can also go towards the brain upwards than downwards in the esophagus which is dangerous. This eliminates that need because by providing a roadmap to the stomach under vision (by rod lense, flexible optical fiber based, CMOS based camera system), or by detected pH levels, or by detecting optical fluorescence or by detecting pressure differential. Now, once you know you're in the stomach, it's safe to manipulate the device as needed. This safety feature ensures advancement into the stomach instead of e.g. the lungs or any other organs. In one embodiment, the device includes embedded pressure sensors on an external aspect of the hollow longitudinal tube configured to detect pressure at different levels of the esophagus, stomach, intestine or urinary bladder corresponding to a site of use. In one embodiment, the device includes an obturator within the outer sheath, where the obturator has a distal end viewing camera. In one embodiment, the device includes an obturator tip can having a pH sensor, optical fluorescence sensor and a pressure sensor, wherein the sheath is configured to be a carrier for a tube like structure within its lumen after the removal of the obturator.
The disclosures of each and every patent, patent application, and publication cited herein are hereby incorporated herein by reference in their entirety. While this invention has been disclosed with reference to specific embodiments, it is apparent that other embodiments and variations of this invention may be devised by others skilled in the art without departing from the true spirit and scope of the invention.
This application claims priority to U.S. provisional application No. 63/312,497 filed on Feb. 22, 2022 incorporated herein by reference in its entirety.
| Filing Document | Filing Date | Country | Kind |
|---|---|---|---|
| PCT/US2023/062988 | 2/22/2023 | WO |
| Number | Date | Country | |
|---|---|---|---|
| 63312497 | Feb 2022 | US |
