EP4178671A1

EP4178671A1 - Acoustic gastroenterology therapy

Info

Publication number: EP4178671A1
Application number: EP21838606.8A
Authority: EP
Inventors: Yvon Robert; Hugo Charbonneau; Richard Boudreault
Original assignee: Dymedso Inc
Current assignee: Dymedso Inc
Priority date: 2020-07-10
Filing date: 2021-07-12
Publication date: 2023-05-17
Also published as: WO2022006684A1

Abstract

This disclosure pertains to a new medical therapy, using acoustics, for post-operative constipation, CIC, IBS and other conditions of reduced colonic transit. Acoustic waves are propagated to the intestines at between 20-60Hz, an intensity based on the patient being treated and a patterned waveform. The acoustic waves help in dislodging blockage in the intestines and in re-establishing normal bowel functions. Furthermore, this disclosure describes an acoustic device with a specially shaped applicator for the abdomen, which increases the coupling efficiency with the abdomen.

Description

ACOUSTIC GASTROENTEROLOGY THERAPY

Cross-Reference to Related Applications

[001] This patent application claims priority to US provisional patent applications 63/050,554 filed July 10, 2020 and 63/113,027 filed November 12, 2020, the contents of which are hereby incorporated by reference.

Technical Field

[002] The present application relates to medical devices and treatments and, more particularly, to acoustic gastrointestinal devices and treatments for postoperative ileus, constipation, irritable bowel syndrome and other reduced colonic transit conditions.

Backqround

[003] Gastrointestinal disorders, such as heartburn, indigestion/dyspepsia, abdominal pain syndrome and constipation are common disorders experienced throughout the world. Chronic idiopathic constipation (CIC) and irritable bowel syndrome (IBS), which may include constipation (IBS-C), affect a large portion of the population. As a matter of fact, the American College of Gastroenterology (ACG) reports that the prevalence of IBS alone is estimated to be somewhere between 10% and 15% of the United States’ population. The ACG details IBS impacts on patients as having a high degree of impairment in the quality of life, as it may affect the patient’s physical functioning, their ability to participate in the activities of daily living, their level of emotional distress, as well as their sexual functioning and other components of a healthy life.

[004] Furthermore, IBS not only has a significant impact on the health of the patients, but its associated costs and losses are also some of the most important in the medical field. In the United States, the ACG has estimated that IBS causes a loss of $30 to $90 billion USD per year in productivity, being the second most frequent medical reason people take days off from work (the first being the common cold). In 2017, a study was published in the Journal of Medical Economics on the medical costs of CIC and IBS-C for the healthcare system, see Herrick, Linda M et al. “A case-control comparison of direct healthcare-provider medical costs of chronic idiopathic constipation and irritable bowel syndrome with constipation in a community-based cohort.” Journal of medical economics vol. 20,3 (2017): 273-279. doi:10.1080/13696998.2016.1253584. In this study, it was found that patients with constipation account for 3.1 million United States physician visits a year, each of which have a significantly higher outpatient costs over 2- year and 10-year periods compared to controls after adjustments to account for co morbidities, age and sex. It will also be understood, from the study, that although not achieving statistical significance due to the sampling size and the sometimes large variances in the cost variables, the hospital costs, inpatient costs and ER (emergency room) costs also tend to be significantly higher for IBS-C and CIC patients than control patients.

[005] As for chronic constipation, studies have shown that it may affect between 2% to 27% of the worldwide population, with a significant increase in elderly patients. Being a symptom-based disorder with a mainly subjective definition, there is often a lack of agreement between physicians and patients’ perception when defining constipation, which partly explains the wide range of prevalence. Similar to IBS, the economic impact of chronic constipation is significant, both from the perspective of the health care system and the loss of productivity. Constipation related symptoms account for more than 2.5 million physician annual visits in North America alone, leading to testing costs of $6.9 billion USD and more than $500 million on laxative treatments, see Sanchez, Maria Ines Pinto, and Premysl Bercik. “Epidemiology and burden of chronic constipation.” Canadian journal of gastroenterology = Journal canadien de gastroenterologie vol. 25 Suppl B,Suppl B (2011): 11B-15B. doi: 10.1155/2011/974573. Studies have further reported a mean total annual cost of $7,522 for health care provided to each constipated patient, which is higher than the mean total annual cost for patients with IBS, see Nyrop KA, Palsson OS, Levy RL, et al. “Costs of healthcare for irritable bowel syndrome, chronic constipation, functional diarrhea and functional abdominal pain.” Aliment Pharmacol Ther. 2007;26:237-48. Furthermore, the productivity impact of chronic constipation has been estimated as averaging 13.7 million workdays of restricted activities in the United States each year, see Belsey J, Greenfield S, Candy D, Geraint M. “Systematic review: Impact of constipation on quality of life in adults and children.” Aliment Pharmacol Ther. 2010;31:938-49.

[006] In addition to CIC and IBS, constipation is an extremely frequent disorder experienced by post-operative patients. As a matter of fact, opioids (some studies have demonstrated that nearly 40% of patients on opioids suffer from opioid-induced constipation), general anesthesia, inflammatory stimulus and prolonged inactivity may all lead to constipation after surgery. Patients in post-operative care may require longer stays in the hospital due to constipation and its serious potential complications (e.g. anal fissures, hemorrhoids, fecal impaction, rectal prolapse, etc.). These patients suffering from constipation may not only have important and detrimental physical effects, but also incur significant medical costs for themselves, their insurers, and the hospital.

[007] Post-operative ileus, which is the loss of peristaltic activity after surgery, is another common condition after abdominal surgery. This condition is also associated with increased morbidity and prolonged hospital length of stay.

[008] Currently, constipation is mainly treated by the use of laxatives (e.g. fiber laxative, stimulant laxative, etc.), stool softeners and dietary control. While these treatments may work for certain patients, they are not efficient in all patients or may only produce beneficial outcomes after a significant amount of time (ranging from hours to days). Many common laxatives lack efficacy while several others can be associated with serious side-effects. Bulk-former type laxative often lack efficacy and must be taken with enough water to avoid worsening the condition. Osmotic laxatives can cause dehydration and electrolyte disturbance. Long-term use of osmotic or lubricant laxatives is also associated with vitamin and other deficiencies. Stimulant laxatives can cause damage to the Gl nervous networks and lead to intestinal hypomobility after prolonged used. Salt- based laxatives either taken orally or intra-rectally can cause dangerous electrolyte abnormalities and have been associated with death.

[009] As such, there is a need for improved gastrointestinal treatments with increased efficiency (i.e. time to regain normal bowel functions) and minimal secondary effects.

[0010] Acoustic therapy is a treatment known in the art as an efficient way to treat, or supplement conventional treatments, numerous medical conditions. For example, extracorporeal shockwave therapy (ESWT) are typically ultrasonic shockwave therapies used to remove kidney stones and gallstones and infrasonic therapies are used in physiotherapy to treat musculoskeletal conditions (e.g. plantar fasciitis, tendonitis, bursitis, etc.). Another example of acoustic therapy includes pulmonary treatments to dislodge phlegm and other secretions using acoustic waves at about 40 Hz. For example, the device and method from the applicant’s patent application WO 2017/087824 presents one such device and medical application. In this latter type of device, the acoustic wave is generated in air in a chamber coupled to the chest wall. For efficient coupling, the chamber is pressed against the ribcage of the patient.

Summary

[0011] Applicant has discovered a new medical therapy, using acoustics, that overcomes the limitations of traditional treatments for post-operative constipation, CIC, IBS and other conditions of reduced colonic transit. The use of acoustic waves propagated to the intestines at around 40Hz, and an intensity based on the patient being treated, is an efficient way to treat constipation. Applicant has found that the acoustic waves helped in dislodging blockage in the intestines and in re-establishing normal bowel functions.

[0012] Furthermore, the applicant has found that using an acoustic device with an applicator shaped for the abdomen can be more efficiently coupled to the abdomen. This can involve an applicator that has a contact surface that is curved instead of flat, and it can involve a perimeter of the applicator with side tabs or an acoustic coupling chamber that may be obround, oval or rectangular to have the perimeter engage a larger area of the abdominal skin. In this way, when pressing the applicator against the abdominal skin, good acoustic coupling is achieved while not sinking the applicator into the abdomen to an amount that might be uncomfortable or apply pressure to the lower intestines and bowel region.

[0013] The abdominal region is limited by the ribcage and the pelvis, such that the region is the width of the subject’s body but limited in height. Flaving the surface area of the applicator wider in one direction and narrower in the orthogonal direction can allow for a better fit within the abdominal region. Thus, an applicator that is significantly larger than the typical applicator used for pulmonary treatment may be advantageous. The larger applicator may effectively provide a large enough area such that the applicator does not sink significantly inside the target area of the patient’s body. Additionally, a larger applicator may provide a larger treatment area, which may be particularly advantageous for intestine treatments (as certain conditions may not necessarily have localised issues). The size of the applicator may vary depending on different parameters, such as the patient to be treated (e.g. an applicator for a child may have a smaller applicator than one for an adult). Similarly, different sizes of applicator may be provided to account for the distribution of patient’s shapes and physiology.

[0014] This new acoustic therapy has shown, in a pre-test clinical study, significant results in all patients, such that all patients resumed normal bowel functions after treatment. Following treatments of 20 minutes, consisting of 5 minutes for each colon sites (left lower, left upper, right upper, right lower), bowel movements was restored. All patients had postoperative ileus due to visceral surgeries. A total of 10 patients were treated in the pre-test clinical study.

[0015] A first broad aspect is a gastrointestinal acoustic wave therapy device applicator configured to apply an acoustic wave to a patient, wherein an interface of the applicator with the patient is shaped to be at least one of wider in one lateral direction than an orthogonal lateral direction and concavely curved.

[0016] In some embodiments, the interface of the applicator has an oval shape.

[0017] In some embodiments, the interface of the applicator has a rounded rectangular shape.

[0018] In some embodiments, the applicator comprises a sealing membrane at the interface of the applicator with the patient.

[0019] In some embodiments, the interface is curved to adapt to a body area over intestines of the patient.

[0020] In some embodiments, the applicator comprises at least one handle part.

[0021] In some embodiments, the interface is longer than a distance from pelvis to ribcage of an average adult human subject, while the orthogonal dimension of the interface is shorter than the distance.

[0022] A second broad aspect is a gastrointestinal acoustic wave therapy device including: an acoustic wave generator operable to receive an input frequency, intensity and waveform and to generate an acoustic wave at the input frequency and intensity; and an applicator configured to apply the acoustic wave to a patient, wherein an interface of the applicator with the patient is shaped to be at least one of wider in one lateral direction than an orthogonal lateral direction and concavely curved.

[0023] In some embodiments, the applicator is a gastrointestinal acoustic wave therapy device applicator as previously defined.

[0024] In some embodiments, the gastrointestinal acoustic wave therapy device further includes an acoustic waveguide operably connecting the acoustic wave generator to the applicator.

[0025] In some embodiments, the acoustic wave generator is directly mounted to the applicator.

[0026] In some embodiments, the applicator is replaceable.

[0027] A third broad aspect is a method for an acoustic therapy for treating a gastrointestinal condition, including the steps of: selecting at least one of a first frequency, a first intensity and a first waveform for the acoustic therapy; applying an acoustic wave device to an area over a patient’s intestines; and providing acoustic waves at the first frequency and the first intensity to the area for a treatment time.

[0028] In some embodiments, the first frequency is between 20 Hz and 60 Hz.

[0029] In some embodiments, the first frequency is 40 Hz.

[0030] In some embodiments, the method further includes adjusting at least one of the first frequency, the first intensity and the first waveform to at least one of a second frequency, a second intensity and a second waveform depending on a treatment response from the patient and providing acoustic waves at the adjusted frequency and intensity.

[0031] In some embodiments, the treatment time is between 2 to 30 minutes.

[0032] In some embodiments, the treatment time lasts until an activation of bowel movement.

[0033] In some embodiments, the method further includes repeating the applying the acoustic wave device and the providing acoustic waves for a second area over a patient’s intestines.

[0034] In some embodiments, the acoustic wave device is a gastrointestinal acoustic wave therapy device as previously defined.

[0035] A fourth broad aspect is a method for treating a post-operative patient, including the steps of: admitting a patient for a surgery; providing anesthesia to the patient; performing the surgery; providing a gastrointestinal acoustic therapy to the patient; and discharging the patient. [0036] In some embodiments, there is provided an apparatus comprising a signal generator configured to generate an electrical signal, an acoustic transducer operably coupled to the signal generator, the acoustic transducer configured to convert the electrical signal into an acoustic signal, and an applicator operably coupled to the acoustic transducer. The applicator may be configured to receive the acoustic signal from the acoustic transducer, the applicator including a wave diffuser with an applicator membrane defining a curved applicator interface shape to conform to an abdomen of a patient, the wave diffuser applying acoustic waves to the abdomen of the patient. The apparatus may further comprise conical elements and tubes of variable diameters for optimizing the acoustic waves. The apparatus may further comprise an acoustic wave sensor allowing the apparatus to identify areas of obstruction of the abdomen of the patient and determine the severity of the obstruction.

Brief Description of the Drawings [0037] The invention will be better understood by way of the following detailed description of embodiments of the invention with reference to the appended drawings, in which:

[0038] Figure 1 is a flowchart of an exemplary acoustic wave therapy method;

[0039] Figure 2 is a flowchart of an exemplary acoustic wave therapy parameters adjustment;

[0040] Figure 3A is an illustration of an exemplary gastrointestinal acoustic wave device in which the gastrointestinal applicator is connected to an acoustic wave generator through an acoustic waveguide;

[0041 ] Figures 3B and 3C are schematic representations of adapters that can be used in gastroenterology treatment systems in accordance with an illustrative embodiment of the present disclosure.

[0042] Figure 4A is an illustration of an exemplary internal structure of an exemplary gastrointestinal acoustic wave device in which the gastrointestinal applicator is connected to an acoustic wave generator through an acoustic waveguide;

[0043] Figure 4B is a bottom perspective view of the device of Figure 4A;

[0044] Figure 4C is a side exploded view of the device of Figure 4A;

[0045] Figure 5 (appearing on the same drawing sheet as Figure 4A) is an illustration of an exemplary gastrointestinal acoustic wave device with the acoustic wave generator shown;

[0046] Figure 6 is an illustration of an exemplary gastrointestinal acoustic wave device in which the gastrointestinal applicator is directly mounted to an acoustic wave generator; [0047] Figure 7A is a drawing of an exemplary gastrointestinal applicator which may be directly mounted to an acoustic wave generator;

[0048] Figure 7B is side view of the applicator of Figure 7A;

[0049] Figure 7C is bottom perspective view of the applicator of Figure 7A;

[0050] Figure 7D is bottom view of the applicator of Figure 7A;

[0051 ] Figure 7E is short side view of the applicator of Figure 7A;

[0052] Figure 7F is top view of the applicator of Figure 7A;

[0053] Figure 7G is top perspective view of the applicator of Figure 7A;

[0054] Figure 8 illustrates a separate gastroenterology treatment device;

[0055] Figure 9 illustrates a system for calibration and noise reduction for airway treatment, according to embodiments; and

[0056] Figure 10 illustrates a method for calibration and noise reduction for [0057] airway treatment, according to embodiments

Detailed Description

[0058] The present disclosure relates to an acoustic gastroenterology therapy providing relief for patients suffering from postoperative ileus or post-operative constipation, constipation, chronic idiopathic constipation, irritable bowel syndrome with constipation and other intestinal problems. Treating constipation by the use of drugs (i.e. laxatives, stool softeners, etc.) and by dietary control is well known in the art and have been used for decades. Flowever, these treatments may only induce a slow physiological response or may have undesirable side effects and may be inefficient for certain patients. [0059] Constipation Treatment Prior Art

[0060] As detailed herein, typical treatment for constipation and other related gastroenterological disorders often features laxatives and dietary control which are not effective in many cases. For non-anecdotal constipation conditions, the physiological functions of the colon and pelvic floor may be in cause and therefore less prone to successfully react to conventional laxatives. [0061] In addition to conventional laxatives (such as polyethylene glycol and bisacodyl), new pharmacologic agents are being used and tested to treat constipation, see Ryu, Han Seung, and Suck Chei Choi. “Recent Updates on the Treatment of

Constipation.” Intestinal research, vol. 13,4 (2015): 297-305. doi: 10.5217/ir.2015.13.4.297. For example, different serotonergic agents (agonists to 5- hydroxytryptamine type 4 (5-HΪ4) receptors) have been demonstrated to efficiently reduce constipation and have been undergoing further clinical trials to evaluate potential side effects. Notably, Tegaserod, a partial 5-HΪ4 receptor agonist, has seen its general use regulated by the FDA owing to risks of cardiovascular side effects. However, other drugs, such as Prucalopride and Velusetrag, have successfully demonstrated positive early results without severe side effects.

[0062] It should be noted that, although currently deemed more efficient than conventional treatments, the new drugs acting as 5-HΪ4 receptor agonist remain far from providing relief in the majority of patients. As a matter of fact, phase III clinical trials of Prucalopride have shown that only around twice as many patients taking prucalopride 2 or 4 mg have achieved the primary efficacy endpoint compared to the placebo patients (24% vs 12%), see Quigley EM, Vandeplassche L, Kerstens R, et al. “Clinical trial: The efficacy, impact on quality of life, and safety and tolerability of prucalopride in severe chronic constipation - a 12-week, randomized, double-blind, placebo-controlled study.” Aliment Pharmacol Ther. 2009;29:315-28. Additionally, treatment-related minor adverse effects, such as headaches, abdominal pain, nausea and diarrhea, were experienced by patients.

[0063] Acoustic Therapy Prior Art

[0064] Acoustic therapy is a treatment known in the art as an efficient way to treat, or supplement conventional treatments, numerous medical conditions. For example, extracorporeal shock wave therapy (ESWT) is typically ultrasonic shock wave therapy used to remove kidney stones and gallstones and infrasonic therapies are used in physiotherapy to treat musculoskeletal conditions (e.g. plantar fasciitis, tendonitis, bursitis, etc.). Another example of acoustic therapy includes pulmonary treatments to dislodge phlegm and other secretions using acoustic waves at about 40 Hz. For example, the device and method from the applicant’s patent application WO 2017/087824 presents one such device and medical application.

[0065] Low Frequency Gastroenterology Acoustic Therapy

[0066] The Applicant has found a novel application of acoustic wave therapy. Using low frequencies in the range of 40 Hz and an appropriate intensity for the patient undergoing treatment, an acoustic wave directed towards the intestines of a constipated patient may significantly help in treating the constipation. The low frequency constipation treatment may be delivered for a duration prescribed by a physician and repeated, with an adequate time between each treatment, until satisfactory results are reached.

[0067] Reference is now made to Figure 1 , which is a flowchart of an exemplary acoustic wave therapy method. When a physician prescribes the use of acoustic waves to treat constipation, the treatment of the patient may begin by positioning the patient adequately 51 . The patient may receive the treatment in a mostly horizontal position, such as on a hospital bed, surgical bed, stretcher, or the likes. It will be appreciated that the patient may alternatively receive the treatment in a sitting position or while standing, but that the subsequent positioning of the acoustic therapy applicator over the target zone for the prescribed duration may be more challenging.

[0068] Once the patient is positioned adequately 51 , the physician or technician providing the treatment may select the acoustic wave parameters 53 (e.g. frequency, intensity, duration, waveform, etc.). Someone skilled in the art would understand that a patient or a non-medically trained person could provide the treatment for therapies delivered outside a hospital or clinic environment. As a matter of fact, constipation being a very common condition not necessarily requiring treatments in a specialized environment, the acoustic wave devices may be available for domestic use. As such, the selection of acoustic therapy parameters 53 may be limited depending on the type of the device (e.g. a domestic device may be restricted to only allow slight tweaking of parameters whereas a hospital device may allow for adjustments of any parameters). [0069] The acoustic wave therapy parameters being set, the acoustic wave device’s applicator (i.e. the end delivering the acoustic wave to the patient) may be positioned over the patient’s intestines at the desired target location 55. The target location may be a location of the intestine for which a potential blockage has been identified (e.g. bowel obstructions, fecaloma, etc.) through physical examination or any imaging device. However, it will be understood that in many cases of postoperative ileus, chronic constipation or IBS, no single location of the intestine may be identified as the source of constipation. As such, the positioning of the applicator over the target location 55 may be done in a first general area over the patient’s intestines.

[0070] The acoustic waves may now be delivered to the patient’s target location 57 by starting the generation of acoustic waves by the device, at the pre-selected parameters 53. The acoustic therapy may be delivered to the target of the patient for a duration predetermined by the physician prescribing the treatment. While varying between patients (physiology, age, sex, comorbidities, etc.), their condition being treated and the device being used, the duration of the treatment may be between 2 and 20 minutes and may be repeated multiple times per day or per week, as required by the patient’s condition. [0071] Once the treatment has been applied to the first target location for the prescribed amount of time, the process may be re-started, at the positioning step 55, at a second position and thereafter any number of subsequent times 59. Depending on the area being covered by the device’s applicator, the number of repeats may be different to cover the range of targets (e.g. some applicators may include wider or narrower ends, such as to provide varying degrees of intestine coverage).

[0072] The acoustic wave therapy detailed herein may thereafter be repeated at any prescribed interval, such that the condition or constipation may be treated. It will be understood that chronic disorders, such as chronic constipation or IBS may repeat the therapy not only to treat one episode of constipation but may repeat the therapy at each episode of constipation.

[0073] In some embodiments, the gastrointestinal acoustic treatment may be delivered to post-operation patients. As a matter of fact, patients undergoing surgery often experience ileus as an adverse effect of the anaesthesia (whether it be general, local, rachis or other). As such, it may be beneficial to treat post-operative patients against postoperative ileus with the acoustic therapy. The acoustic therapy may be delivered as a prophylaxis directly after surgery before any indication that the patient may suffer from ileus. This may effectively prevent or reduce the severity of the ileus and may allow the patient to be discharged from the post-operative care quicker. The acoustic therapy may be otherwise performed on patients upon diagnosis of ileus or constipation. The use of gastrointestinal acoustic therapy may therefore significantly reduce the time patients spend in hospitals, from their admission to surgery to their discharge from the hospital. [0074] Reference is now made to Figure 2, which is a flowchart of an exemplary acoustic wave therapy parameters adjustment. When providing acoustic wave therapy as detailed herein, the device may be initially set to the adequate acoustic wave frequency 61 . Such frequency may be the default of 40 Hz, which has proven effective in the clinical studies, or may vary slightly in a band around 40 Hz, such as between 20 and 60 Hz. Some acoustic wave devices may provide this adjustment of frequency, which may be included in order to account for the use of different parts in the device, while some other devices may have a single acoustic wave frequency at which it may function.

[0075] The selection of the acoustic parameters 53 may further require selecting an initial acoustic wave intensity 63. The initial setting of the intensity may be based on the evaluation of the patient (e.g. weight, physiology, disorder, etc.) or may be initialized to a default value. As the intensity at which the acoustic wave is transferred to the patient’s intestines may define its efficiency to penetrate the tissues and affect the desired structures, the intensity may be further adjusted based on the patient’s response to the treatment 65. Adjustments to other parameters of the acoustic wave, such as for the frequency and waveform, may also be done due to the patient’s response to the treatment 65.

[0076] It will be understood by someone skilled in the art that the adjusting of the acoustic wave parameters 65, and similarly for the duration of the treatment 57, may be done by a person (i.e. physician, technician, patient, etc.) or may be done automatically by the device. As a matter of fact, an acoustic wave device may have sensors (or may be operably connected to such) allowing the detection of bowel movements, muscular activity or the such, and may vary the intensity and/or length of the therapy automatically based on the sensors’ readings. Automatic variations by the device may be done either on the frequency, on the amplitude or on both settings at the same time. In some embodiments, the automatic variations may be based on recognizable patterns detectable through sensors, a computing system included in the acoustic device control unit being able to perform necessary calculations and comparison between detected patterns and reference patterns being stored in its non-volatile memory. In some embodiments, the computing system includes a processor, memory (volatile and non volatile), input/output ports, and any other electronic components required to perform the calculations and controls of the acoustic device parameters.

[0077] In some embodiments, the adjusting of the intensity, frequency and waveform 65 may include patterned adjustments which varies episodically the treatment parameters throughout the treatment. For example, patterns of a variation of frequency from 38 Hz to 42 Hz during the treatment may be beneficial. The frequency sweep from 38 Hz to 42 Hz may be done once or may be done multiple time, sweeping to the maximum selected frequency and thereafter down to the minimum selected frequency. Another example is a pattern of a fixed selected frequency and a variation of the intensity from -10% to +10% of selected intensity. Similarly, another example includes an intensity variation from 0% to a selected level and back to 0% within 5 seconds, with a pause of 10 seconds between. A person skilled in the art will appreciate that any patterns may be used without departing from the teachings of this disclosure.

[0078] Although reference is made to constipation, chronic constipation and IBS throughout the disclosure, it will be understood that the therapy detailed herein may be used for treating a number of other gastrointestinal disorders. Providing acoustic waves at 40 Hz over the zone of the intestines has been proven to be effective to reinstate normal bowel movements and may thus be used in treating any other disorders affecting bowels.

[0079] Pre-Test Clinical Study

[0080] The gastrointestinal acoustic therapy described herein has shown, in a pre-test clinical study, significant results. A pre-test clinical study was performed on a total of 10 patients experiencing postoperative ileus as a result of visceral surgeries (e.g. intestinal surgery, liver surgery, etc.). The tested therapy included providing acoustic waves in four general areas of the colon: left lower, left upper, right upper and right lower. Each area was treated for 5 minutes (total treatment time of 20 minutes) with acoustic waves set at 40 Hz and an intensity fixed at low settings.

[0081] All 10 patients resumed normal bowel functions after the 20 minutes treatment. Patients further indicated their appreciation of the painless treatment and requested the device for further usage after resorption of the ileus, since they felt it also reduced the pain of bowel movements.

[0082] Gastrointestinal Acoustic Wave Device

[0083] In order to efficiently treat gastrointestinal conditions, the applicator of the acoustic wave device may be significantly different from the applicator used in other applications. As a matter of fact, the area of the body over which the applicator is applied, between the ribcage and the pelvis, is mainly composed of soft tissues and organs. Therefore, the body’s response to acoustic waves and induced vibrations in this region may be significantly different than in other parts of the body such as a pulmonary treatment in which the applicator is pressed against the ribcage.

[0084] As the pressure with which the applicator is applied to the target area plays an important role in the efficiency of the treatment. While the applicator end of the device is required to be pressed against the target area with enough pressure to have a good seal around the acoustic wave transfer area, too great a pressure may impact negatively the treatment (e.g. soft tissue may be pressed into the central cavity and may reflect acoustic waves inside the applicator’s chamber which may result in interferences). The applicators known in the prior art essentially have small round contact surfaces, which may result in the issues of providing a good seal without impacting the transferred acoustic wave. Additionally, an applicator with a larger contact surface area may be beneficial for treating a larger portion of the intestine at a given time. As some conditions may not feature a localized intestine issue, an acoustic therapy may require the treatment of a significant portion of the intestine. Thus, the larger applicator may reduce the time required for the treatment to be efficient. Therefore, a large applicator surface area is desirable.

[0085] As mentioned herein, the target treatment area resides between the ribcage and the pelvis. In order to avoid contacting the bones of such structures, as this may significantly impact the acoustic wave treatment (e.g. by modifying the transferred acoustic waves and/or the induced vibrations), the applicator-patient interface end may have side extensions (e.g. flaps) such that it may generally be shaped like an oval. [0086] Reference is now made to Figure 3A which is an illustration of an exemplary gastrointestinal acoustic wave device in which the gastrointestinal applicator 68 is connected to an acoustic wave generator through an acoustic waveguide 67. As detailed herein, the applicator 68 may be connected to an acoustic waveguide 67. The acoustic waveguide 67 may thereafter be connected to any acoustic wave generator device as further shown in Figure 5 herein. The acoustic wave generator may thus generate acoustic waves at a given frequency and intensity, and the acoustic waves may be propagated to the applicator 68 through the acoustic waveguide 67.

[0087] FIGS. 3B and 3C are illustrations of adapters 401 and 402 that can be used in gastroenterology treatment systems, according to embodiments. The adapter 401 includes a side wall 411 defining a chamber 421 , in which acoustic waves can be amplified or attenuated. The adapter 402 includes a side wall 412 defining a chamber 422 having a nonlinear shape, in which acoustic waves can be amplified or attenuated. In some embodiments, at least a portion of the side wall 412 can be parabolic. In some embodiments, at least a portion of the side wall 412 can be hyperbolic. In some embodiments, at least a portion of the side wall 412 can be elliptical. In some embodiments, at least a portion of the side wall 412 can be polynomial. In some embodiments, at least a portion of the side wall 412 can be exponential. [0072] In some embodiments, the angle at which the waveguide connects to the adapters 401 and/or 402 can be about 1 degree to about 60 degrees, including any values and sub ranges in between.

[0088] The acoustic waveguide 67 may be connected to an applicator expansion chamber 69 of the applicator 68. The applicator expansion chamber 69 may propagate and expand the acoustic wave received from the acoustic waveguide 67. Additionally, the applicator expansion chamber 69 may include structure capable of modifying the input acoustic wave (e.g. a diaphragm or any other structure). In the embodiment of Figure 3, the applicator expansion chamber 69 may be directly mounted to the applicator frame 71 . In some embodiments, the applicator expansion chamber 69 and the applicator frame 71 may be a single part.

[0089] The applicator frame 71 may be a part in which the acoustic wave further gets expanded, such that it covers the larger area that may be in contact with the patient. In some embodiments, the acoustic wave may not be expanded and the applicator frame 71 may simply provide the necessary structure to support a large applicator membrane 73. In some embodiments, the applicator frame 71 may have a circular middle section, at the connection to the applicator expansion chamber 69, which may be expanded in all directions and particularly towards two opposing sections. The applicator frame 71 may therefore have flaps on two opposing sides, such that the general contact area with the patient is substantially of oval shape or of a rounded rectangular shape. An applicator membrane 73 may be fixed to a bottom portion of the applicator frame 71 , such that the contact with the patient’s skin and soft tissues is done through this membrane 73.

[0090] The width of the applicator interface 73 can be shorter than an average distance from the pelvis to the ribcage of an adult human subject, while the orthogonal dimension of the applicator interface 73 can be shorter than this average distance. In this way, the interface is placed on the abdomen of the subject with the wider extent sideways while pressing the interface 73 into the abdomen without pressing against or contacting the ribcage or the pelvis.

[0091] The applicator membrane 73 may be made of a softer, deformable material such that it may properly seal the applicator 68 against the skin of the patient. In some embodiments, the applicator membrane 73 may be replaceable, such that it may be changed for each treated patient. In some embodiments, the applicator frame 71 and/or the applicator membrane 73 may have a slight curve in its depth such as to better adapt to the body area over a patient’s intestines.

[0092] It will be appreciated that in some applications, the applicator membrane 73 can be round with no opposed lateral extensions, however, its coupling to the abdomen can be enhanced by providing the concave curve to the membrane 73. Alternatively, the applicator membrane 73 can be flat with no curve in its depth while making use of the opposed lateral extensions to enhance its coupling to the abdomen. These different shape properties can also be combined.

[0093] Now referring to Figure 4, which illustrates another embodiment of an exemplary internal structure of an exemplary gastrointestinal acoustic wave device in which the gastrointestinal applicator is connected to an acoustic wave generator through an acoustic waveguide. In this embodiment, the applicator may be connected to an acoustic wave generator through an acoustic waveguide 67. The acoustic waveguide 67 may be connected to the applicator though a coupler 77, such that the applicator may be used with different (e.g. diameter, material, etc.) acoustic waveguides 67. In some embodiments, the coupler 77 may alternatively allow the connection of different applicators to an acoustic waveguide 67. The coupler 77 may be attached to the applicator through a threaded opening 82. Someone skilled in the art will appreciate that any other mechanism for fixing the two ends may be used without departing from the teachings of this disclosure.

[0094] In the embodiment of Figures 4A, 4B and 4C, the applicator includes an anti bacterial filter 81 to prevent contamination. In some embodiments, the applicator may include an acoustic generator, such as a diaphragm. The acoustic generator may modify an input acoustic wave to an output acoustic wave (e.g. the diaphragm may change the amplitude of the acoustic wave being propagated to the applicator through the acoustic waveguide 67). In some embodiments, the applicator may further include an acoustic wave diffuser 83 which may amplify the received acoustic waves. In some embodiments, the wave diffuser 83 may attenuate the received acoustic waves. The generated acoustic waves may be optimized using conical elements and tubes of variable diameters.

[0095] In some embodiments, the applicator may include handles 75 to facilitate the application of the applicator to the patient’s target area. There may be two handles 75, generally placed towards the outer ends of the applicator opposing flaps, such that medical personnel, technician or other person performing the gastrointestinal treatment may use the device with both hands which may apply pressure on the device with increased uniformity. In some other embodiments, there may be a single handle or structure easing the gripping of the applicator. The single handle or structure may be generally placed over the central portion of the device, such that the applicator may be used with a single hand while still applying a relatively uniform pressure on the complete perimeter of the applicator’s contact area. In yet other embodiments, there may be more than two handles 75. For example, there may be two outer handles for when a treatment is done by a physician and there may also be a central handle either for a patient performing his own treatment, or for a physician who may perform the treatment with one hand.

[0096] The applicator may include a main body formed by a top and a bottom shell, the top shell defining handle portions 75 and the bottom shell having a wave diffuser 83, with an applicator membrane in the form of a pad for improved comfort and better conforming to the shape of the abdomen of a patient, for example a continuous positive airway pressure (CPAP) type interface, defining a curved applicator interface and covering most of the applicator interface. The top shell also includes a receiver opening having a support structure for receiving a filter and a connecting portion to secure the connector of the flexible tube 520. The wave diffuser receives acoustic signals from, for example, a transducer. In some embodiments, the wave diffuser can amplify the received acoustic signals. In some embodiments, the wave diffuser can attenuate the received acoustic signals. The generated acoustic waves are optimized using conical elements and tubes of variable diameters. The applicator membrane can be excited by acoustic signals to generate another set of acoustic signals. The applicator interface may apply the acoustic signal generated by the applicator membrane to a patient. The handle portions can facilitate handling of the applicator. For example, a practitioner can hold the handler portion during treatment. In one embodiment, the handle portions are be provided with a belt or strap in order to fix the applicator to the abdomen of a patient.

[0097] In some embodiments, the applicator membrane is recessed from the applicator interface. In this case, the applicator membrane can vibrate freely without touching the patient during treatment. In some embodiments, the distance between the applicator membrane and the applicator interface can be about 0.5 inch of diameter to about 5 inches, including all values and sub ranges in between. It is to be understood that the applicator may be of various dimensions and/or curvature in order to suit various sized patients.

[0098] In some embodiments, the applicator further includes an acoustic wave sensor allowing the system for gastroenterology treatment to identify areas of obstruction of the abdomen of a patient and determine the severity of the obstruction.

[0099] Although illustrated here as a threaded connection between the connecting portion of the receiver opening and the connector of the flexible tube 67, any other suitable connecting means can be employed such as, for example, luer locks, tight-fit, and/or the like.

[00100] Figure 5 is an illustration of an exemplary gastrointestinal acoustic wave device with the acoustic wave generator 86 shown. In such embodiment, the acoustic wave generator 86 may be any type of generator as is known in the prior art (e.g. electroacoustic transducer, rotary motor, piezoelectric, solenoid, etc.). In the embodiment of Figure 5, the acoustic wave generator 86 is in a separate housing and may be connected to the applicator 68 through an acoustic waveguide 67. The acoustic wave generated in the acoustic wave generator 86 may thus be propagated from the generator 86 to the applicator 68, such that it may be transferred to the patient.

[00101] The flexible tube 67 can include connectors at one or both ends so as to facilitate convenient removal or replacement of the applicator 68 and/or the tube 520. In one embodiment the flexible tube 67 is 84 inches or less. In some embodiments, the connectors include barbed connectors. In some embodiments, the connectors include threaded connectors. In some embodiments, the connectors include swivel connectors. In some embodiments, the connectors include any other connectors.

[00102] Someone skilled in the art will appreciate that the complete acoustic wave treatment device, while not shown, may further include electronic controls (e.g. computing device running software to control the frequency, intensity, duration and other parameters of the acoustic wave generator 86), a user interface, power connections and the likes. [00103] In some embodiments, the acoustic wave generator 86 may be directly mounted to the applicator. One such embodiment is illustrated in Figure 6. The acoustic wave generator 86 may include electronic controls directly on the unit or on a separate computing device which may be operatively connected through a wire or wirelessly (e.g. Wi-Fi, Bluetooth, etc.) to the acoustic wave generator 86. In some embodiments, the electronic controls may come from an application running on a mobile device or a tablet, such that the gastrointestinal acoustic wave treatment device may be easily used in a household setting. Similarly, electrical power may be supplied to the device through a wired connection or through a battery pack included inside the device.

[00104] The acoustic wave generator 86 may be fixed to the applicator through a coupler 77 that may be part of the applicator 68. The coupler 77 may thus be part of the applicator frame 71 which may further include an applicator membrane 73. In some embodiments, the acoustic wave generator 86 may be shaped as to be easily gripped by the hand of the person performing the treatment. In other embodiments, the applicator frame 71 may include handles to allow easier and more uniform pressure application on the entirety of the area circumscribed by the applicator membrane 73.

[00105] Figures 7A and 7B are drawings of a different exemplary gastrointestinal applicator which may be directly mounted to an acoustic wave generator, such as one that may be used in lieu of the applicator illustrated in Figure 6. As shown, the coupler 77 may be threaded for coupling to the acoustic wave generator. In some embodiments, the applicator frame 71 may be of a generally oval shape, such as it may be applied over the gut area without sinking too much into the soft tissues of the patient and without pressing against the patient’s ribcage and pelvis. The applicator may be easily replaced to use different sizes depending on the physiology of the patient.

[00106] More specifically, FIG. 7A shows a top perspective view of the applicator. FIG. 7B shows a long side view of the applicator. FIG. 7C shows a bottom perspective view of the applicator. FIG. 7D shows a bottom view of the applicator. FIG. 7E shows a short side view of the applicator. FIG. 7F shows a top view of the applicator. FIG. 7G shows a side perspective view of the applicator.

[00107] Figure 8 illustrates a system 900 for gastroenterology treatment, according to illustrative embodiments. The system 900 includes a transducer 910 to generate acoustic signals, a tube 920 to transmit the acoustic signals to an applicator 930 a, which can either apply the acoustic signals to a patient or generate another acoustic signal for treatment. The system 900 also includes a controller 940, which has a touch screen for the practitioner to conveniently control the treatment. In some embodiments, the controller 940 may include a frequency generator to generate the electrical signal for the transducer 910 to convert into acoustic signals. In some embodiments, the frequency generators can be coupled directly to the transducer 910.

[00108] The controller 940 and the transducer 910 are supported by a stand 950, which can have a swivel mechanism to permit convenient manipulation of the transducer 950 and/or the applicator 930. By placing the larger and usually bulkier components on the stand 950, the footprint and weight of the signal applicator 930 can be minimized, thereby providing for safe and convenient use on infants or aged group of people.

[00109] The stand 950 also includes a holder to hold additional applicators 930b and 930c. During treatment or to accommodate different treatments, these applicators 930b and 903c can be removed from the stand 910 and replace the applicator 930a.

[00110] In some embodiments, the controller 940 includes the signal generator and the electrical signal is transmitted to the transducer 910 via wires at least partially disposed within the stand 910. In some embodiments, the controller 940 includes the signal generator and the electrical signal is transmitted to the transducer 910 via wireless transmission. Examples of wireless transmission methods include, but not limited to, WiFi, 3G, 4G, Bluetooth, radio frequency (RF), or any other methods.

[00111] A separate gastroenterology treatment device 901 is illustrated in FIG. 8. The treatment device 901 includes a wheeled stand to hold other components, such as the transducer, the tube, the controller, and the applicator. In this manner, the device 901 can be highly transportable so as to allow convenient use at various locations.

[00112] Embodiments disclosed herein are also directed to minimizing and/or substantially eliminating performance variation in the systems and devices for gastroenterology treatment described above. In some embodiments, a calibration apparatus/method is provided. In some embodiments, the calibration apparatus/method encompasses adjustment of the output of the differential amplifier, and further encompasses standardizing all systems and devices for gastroenterology treatment to substantially the same final vibration and sound level. In some embodiments, the calibration apparatus/method disclosed herein includes addition of dynamic fan control to reduce background noise created by the cooling of the systems and devices for gastroenterology treatment. In some embodiments, the calibration apparatus/method disclosed herein includes entire respin of the differential amplifier to reduce electromagnetic noise. In some embodiments, the calibration apparatus/method disclosed herein includes use of a differential signal generator. In some embodiments, the calibration apparatus/method disclosed herein includes improvements on the signal generation aspects to avoid clipping.

[00113] In some embodiments, the calibration method/approach includes creating an airtight box with a passive speaker connected to an oscilloscope. By coupling the transducer (e.g., a vibrating membrane) to this calibration box containing the passive speaker, the transducer is set in motion, and the movement creates pressure that would make another speaker move, and transforms the air pressure difference back into an electrical signal that can be read, such as on an oscilloscope. In some embodiments, standardizing via the calibration method/approach disclosed herein includes comparing the systems and devices for gastroenterology treatment with a sample group of previous versions

[00114] FIG. 9 illustrates a system 1000 for calibration and noise reduction for gastroenterology treatment, according to illustrative embodiments. The system 1000 includes a signal generator 1010 to generate electrical signals, which are then amplified by an amplifier 1020. A transducer 1030 is included in the system 1000 to convert the electrical signals into acoustic signals. The system 1000 also includes a calibration box 1040 including a passive speaker coupled to the transducer 1030. As described above, the acoustic signal (and the air pressure associated with the acoustic signal) generated by the transducer 1030 can excite the passive speaker in the calibration box 1040, which can transform the air pressure difference back into an electrical signal. An oscilloscope 1050 is connected to the calibration box 1040 to read the electrical signals generated by the calibration box and generate control signal that can facilitate calibration of the system 1000. In some embodiments, other measuring equipment such as a voltmeter can also be used to read the electrical signal generated by the calibration box.

[00115] FIG. 10 illustrates a method 1100 for calibration and noise reduction for gastroenterology treatment, according to illustrative embodiments. At step 1110 of the method 1100, the system can be turned on. Then several initiation steps can be carried out, including initiation of the amplifier at step 1122, initiation of the user interface at step 1124, and initiation of overheat watchdog that can monitor the heat loading in the system, at step 1126. At step 1032, a user can select the signal frequency of electric signals generated by signal generators in the system. In addition, the signal waveform can be initialized at step 1134. For example, the desired waveform, such as sinusoidal wave or square wave, can also be set at this step.

[00116] At step 1142 in the method 1100, the user selects the desired amplitude of the acoustic signal. Alternatively, the user can select the desired power level of the acoustic signal. At step 1144, the signal amplitude can be initialized using calibration factors such as default calibration factors, or calibration factors as used in most recent treatment. [00117] The user starts the treatment at step 1152, followed by generation of signal waveform at step 1154. At step 1162, the user (or the system) determines whether to stop. In some embodiments, the user can decide to stop the treatment if a needed. In some embodiments, the user can decide to stop the treatment if it is the end of a predetermined treatment period. In some embodiments, the user can decide to stop the treatment for patient to change positions.

[00118] If the user decides to stop, the method 1100 proceeds to step 1172, where the treatment parameters, such as the frequency, amplitude, and duration, are written into a log file. The treatment can then end at step 1174.

[00119] Alternatively, if at step 1162, the treatment does not stop. The method 1100 proceeds to step 1164, where the user or the system determines whether a predetermined amount of time (e.g., 3 minutes or any other amount of time that is appropriate) has lapsed since the beginning of the treatment. If so, the method proceeds to step 1182, where the system generates a chopped signal to notify the user to change position of the transducer. If not, the method 1100 moves back to step 1162.

[00120] Where methods and/or schematics described above indicate certain events and/or flow patterns occurring in certain order, the ordering of certain events and/or flow patterns may be modified. Additionally, certain events may be performed concurrently in parallel processes when possible, as well as performed sequentially.

Claims

What is claimed is:

1. A gastrointestinal acoustic wave therapy device applicator configured to apply an acoustic wave to a patient, wherein an interface of said applicator with said patient is shaped to be at least one of wider in one lateral direction than an orthogonal lateral direction and concavely curved.

2. The gastrointestinal acoustic wave therapy device applicator as defined in claim 1 , wherein said interface of said applicator has an oval shape.

3. The gastrointestinal acoustic wave therapy device applicator as defined in claim 1 , wherein said interface of said applicator has a rounded rectangular shape.

4. The gastrointestinal acoustic wave therapy device applicator as defined in any of claims 1 to 3, wherein said applicator comprises a sealing membrane at said interface of said applicator with said patient.

5. The gastrointestinal acoustic wave therapy device applicator as defined in any of claims 1 to 4, wherein said interface is curved to adapt to a body area over intestines of said patient.

6. The gastrointestinal acoustic wave therapy device applicator as defined in any of claims 1 to 5, wherein said applicator comprises at least one handle part.

7. The gastrointestinal acoustic wave therapy device applicator as defined in any of claims 1 to 6, wherein said interface is longer than a distance from pelvis to ribcage of an average adult human subject, while the orthogonal dimension of said interface is shorter than said distance.

8. A gastrointestinal acoustic wave therapy device comprising: an acoustic wave generator operable to receive an input frequency, intensity and waveform and to generate an acoustic wave at said input frequency and intensity; and an applicator configured to apply said acoustic wave to a patient, wherein an interface of said applicator with said patient is shaped to be at least one of wider in one lateral direction than an orthogonal lateral direction and concavely curved.

9. The gastrointestinal acoustic wave therapy device as defined in claim 8, wherein said applicator is a gastrointestinal acoustic wave therapy device applicator as defined in any of claims 2 to 7.

10. The gastrointestinal acoustic wave therapy device as defined in claim 8 to 9, further comprising an acoustic waveguide operably connecting said acoustic wave generator to said applicator.

11 . The gastrointestinal acoustic wave therapy device as defined in any of claims 8 to 10, wherein said acoustic wave generator is directly mounted to said applicator.

12. The gastrointestinal acoustic wave therapy device as defined in any of claims 8 to 11 , wherein said applicator is replaceable.

13. A method for an acoustic therapy for treating a gastrointestinal condition, comprising the steps of: selecting at least one of a first frequency, a first intensity and a first waveform for said acoustic therapy; applying an acoustic wave device to an area over a patient’s intestines; and providing acoustic waves at said first frequency and said first intensity to said area for a treatment time.

14. The method as defined in claim 13, wherein said first frequency is between 20 Hz and 60 Hz.

15. The method as defined in claim 13 or 14, wherein said first frequency is 40 Hz.

16. The method as defined in any one of claims 13 to 15, further comprising adjusting at least one of said first frequency, said first intensity and said first waveform to at least one of a second frequency, a second intensity and a second waveform depending on a treatment response from said patient and providing acoustic waves at said adjusted frequency and intensity.

17. The method as defined in any one of claims 13 to 16, wherein said treatment time is between 2 to 30 minutes.

18. The method as defined in any one of claims 13 to 17, wherein said treatment time lasts until an activation of bowel movement.

19. The method as defined in any one of claims 13 to 18, further comprising repeating said applying said acoustic wave device and said providing acoustic waves for a second area over a patient’s intestines.

20. The method as defined in any one of claims 13 to 19, wherein said acoustic wave device is a gastrointestinal acoustic wave therapy device as defined in any one of claims 8 to 12.

21. A method for treating a post-operative patient, comprising the steps of: admitting a patient for a surgery; providing anesthesia to said patient; performing said surgery; providing a gastrointestinal acoustic therapy to said patient; and discharging said patient.