Systems and methods for treating obesity and other gastrointestinal conditions

Related application This application is a partial continuation of U.S. Patent Application No. 09 / 02,296 filed on February 19, 1998, each of which is incorporated herein by reference and is now U.S. Pat. No. 6,009,877. May 24, 2002, entitled "Systems and Methods for Forming Composite Lesions to Treat Dysfunctions in Sphincters and Adjoining Tissue," a continuation of US Patent Application No. 09 / 304,750 filed May 4, 1999. It claims the benefits of Simultaneous U.S. Patent Application No. 10 / 155,294 filed on the same day.

Field of invention In a general sense, the present invention relates to systems and methods for treating internal tissue areas of the body. More specifically, the present invention relates to systems and methods for treating tissues inside and around the stomach, including the cardia and pyloric sphincter.

Background of the invention A. Obesity It is estimated that there are over 300 million obese adults worldwide. Obesity is defined as having a weight that exceeds the recommended weight of each individual by 20 to 25 percent, taking into account their age, height, and gender. Obesity is usually caused by overeating and lack of exercise (in other words, consuming more calories than you burn). Only a small proportion of obese people are obese due to metabolic disorders.

Obesity affects virtually all age groups and socio-economic groups. Obesity has a number of physical and mental health consequences. Obese people include hypertension, type 2 (non-insulin dependent) diabetes, coronary heart disease, osteoarthritis, gout and other physical illnesses, as well as endometrial cancer, prostate cancer, colon cancer, and postmenopausal breast cancer. High risk of developing certain types of cancer. In addition to physical illness, in obese people, psychological disorders such as depression, decreased self-esteem, eating disorders, and distorted body image can occur.

The social consequences of being obese are significant. It is not uncommon for obese people to be discriminated against in the world of work, school, and social situations. Obesity exposes obese people to personal ridicule and may also limit recreational activities and clothing choices. Obesity is a serious problem for people suffering from obesity, from a high risk of premature death to a serious chronic condition that reduces overall quality of life.

A consistent and common feature of obesity is the recurring imbalance between the amount of calories ingested and the amount of energy consumed. A small percentage of obese people consume less energy and therefore maintain excess body mass despite consuming very few calories. However, more generally, obese people consume large amounts of calories, which maintain or increase body mass.

Why individuals overeat and become obese is a multifaceted issue. This issue involves psychological, social, and physical components. Some people may overeat in response to unwanted emotions such as boredom, sadness, or anger. Alternatively, one may not understand the implications of eating large amounts of high-energy foods for weight gain and obesity. More generally, people overeat in a Western way of life because of hunger, social conditions, and constant access to food sources.

The term hunger refers to the widespread perceptual effects of an individual's motives for obtaining and ingesting food sources. The components of hunger include psychological motives such as eating for fun and eating in social relationships. Physical motives include hypoglycemia, dehydration, or high levels of physical activity. The motivation for binge eating is closely related to self-management issues; anomalous signals telling individuals to eat; lack of a good understanding of the relationship between binge eating and obesity; and many other possible reasons. It is thought that it is doing.

The physical and psychological processes that lead to hunger and feeding are inextricably linked. The stomach and duodenum, further discussed herein, communicate with the brain via neural connections and also by hormones secreted into the bloodstream. Each structure promotes a signal that can lead to an individual's perception of the need to eat. An example of this is the "stomach rumbling" phase, which is a phase that indicates that a certain amount of time has passed since the last meal. One typically interprets this activity as hungry.

The opposite of feeling hungry is feeling full. A feeling of fullness is a feeling of fullness that occurs after eating a meal. People say they are full when they feel fully satisfied after eating.

Due to the serious medical and social complications caused by obesity, various treatments are commonly used. These treatments are based on a variety of factors, including the level of obesity, the individual's overall health, and the individual's motivation to lose weight.

Treatment may include dietary changes, exercise, behavioral changes, weight loss agents (eg, dexfenfluramine, sibutramine, orlistat). If obesity is severe and life-threatening, gastrointestinal surgery may be performed. Traditional surgical techniques typically focus on reducing the size of the stomach, such as gastric staple anastomosis, gastric bypass plasty, or implanting an inflatable band around the upper part of the stomach. More generally, a multifaceted method using a combination of these factors is used.

B. Gastroesophageal reflux disease Gastroesophageal reflux disease (GERD) is an inflammation of the esophagus caused by the backflow of gastric contents into the esophagus. In symptomatological patients, regurgitation is associated with insufficiency of the lower esophageal sphincter (LES), a band of muscle fibers that blocks the esophagus from gastric flow. Acidic or alkaline stomach contents return through the LES to the esophagus, causing symptoms.

GERD is believed to be caused by a combination of conditions that enhance the presence of acidic regurgitation in the esophagus. These conditions include transient LES relaxation, decreased resting tension in LES, abnormal esophageal clearance, delayed gastric emptying, decreased salivation, and abnormal tissue resistance. Because the resting tension of the lower esophageal sphincter is maintained by both myogenic (muscle) and neurogenic (nerve) mechanisms, some are called the lower esophageal sphincter or the peripheral region of the stomach (called the cardia). We believe that the abnormal electrical signal in) causes the spontaneous relaxation of this sphincter.

The most common symptom of GERD is heartburn. In addition to heartburn discomfort, regurgitation results in symptoms of esophageal inflammation such as odynophagia (pain when swallowing) and dysphagia (difficulty swallowing). Acid reflux also causes lung symptoms such as cough, asthma, asthma, aspiration pneumonia, and interstitial fibrosis; enamel caries, gingitis, halitosis, and gastric fluid reflux or heartburn Oral symptoms; sore throat symptoms such as tingling pain, laryngitis, crouching voice, and a feeling of suffocation with a ball in the throat; as well as ear pain.

Complications of GERD include esophageal erosion, esophageal ulcer, and esophageal stricture; replacement of normal esophageal epithelium with abnormal (Barrett) epithelium; and lung aspiration.

C. Barrett esophagus Barrett's esophagus is a disorder in which the lining of the esophagus undergoes cellular changes in response to stimuli caused by gastroesophageal reflux (GERD). Barrett's esophagus develops in a small proportion of GERD patients. The normal cells that form the lining of the esophagus, squamous epithelial cells, are transformed into specialized columnar cells, a type of cells not normally found in humans. Diagnosis of Barrett's esophagus is typically made by observing the esophagus with an endoscope and obtaining a sample of esophageal tissue (esophages with a biopsy).

Barrett's esophagus is believed to be caused by damage caused by GERD and / or bile reflux in which enzymes and bile are present in the stomach despite acid regulation. In some people, there is an abnormal reverse flow of bile into the stomach (regurgitation). Due to this sticky bile regurgitation, the stomach secretes large amounts of acid in an attempt to neutralize the alkaline bile. This excess acid causes increased pressure on flatulence and LES, often resulting in GERD. Therefore, the symptoms are similar to those of GERD, including heartburn and dysphagia.

There is increasing evidence that bile reflux plays a part in the etiology of Barrett's esophagus. Damage to the gastric mucosa by bile results in "chemical" gastritis with marked edema and intestinal dysplasia.

Serious complications are associated with Barrett's esophagus. These complications include increased risk of esophageal dysplasia and esophageal cancer.

Traditional treatments include general procedures to control GERD, drug application, and the aforementioned surgery. In more severe cases, such as when a biopsy indicates changes in dysplastic cells that are associated with an increased risk of cancer, surgical removal of part of the esophagus (resection of the esophagus) may be performed. ..

<p> Outline of the invention The present invention provides systems and methods for treating obesity and other conditions affecting the gastrointestinal tract.</p><p> One aspect of the present invention achieves tightening of the pyloric sphincter. Tightening of the pyloric sphincter can serve one or more physiological purposes. Tightening limits the outflow of substances from the stomach through the pyloric sphincter, for example, to prolong postprandial satiety and thereby reduce the incidence of binge eating, which can lead to obesity and other physiological conditions. Or it can be regulated. Tightening of the pyloric sphincter, for example, into the stomach of these substances through the pyloric sphincter to prevent or mediate the effects of contact of acids, enzymes, and bile, or other fluids with the stomach and / or esophagus. The reverse flow of can be restricted or regulated. The system and methods can be used as a mode of first-line treatment, or can be applied as replacement therapy before, during, or after the first-line intervention.</p><p> According to this aspect of the invention, the systems and methods can affect the tightening of the pyloric sphincter, for example by excising the tissue within the pyloric sphincter, the tissue at the pyloric sphincter, or the tissue near the pyloric sphincter. Surface tissue can be targeted for excision, or alternative, tissue below the surface can be targeted for excision, including submucosal tissue, the sphincter itself, or the area surrounding the sphincter. Resection elicits the desired tissue response, which, for example, initiates a localized healing process involving the influx of leukocytes and fibroblasts, followed by collagen deposition, and subsequent restoration and tightening of tissue compliance. Can be included. These effects will result in enhanced barrier function of the pyloric sphincter. Excision can be accomplished by exposing the tissue to conduction tissue heating, electrical resistance tissue heating, or excision agents, or a combination thereof.</p><p> According to this aspect of the invention, the systems and methods can also affect pyloric sphincter tightening, for example by injecting a therapeutic agent that elicits the desired tissue tightening response. Such therapeutic agents include, for example, at least one subtype of cytokine (which can initiate a localized healing process) and / or at least one subtype of vanilloid-containing compound (afferent, which affects the pyloric sphincter). Can cause interference with nerve impulses). The system and method can also affect the tightening of the pyloric sphincter, for example by injecting a therapeutic agent that may include a tissue filler. The presence of filler results in the restoration and tightening of additional tissue compliance, which enhances the barrier function of the sphincter.</p><p> According to this aspect of the invention, the systems and methods include tissue in or near the pyloric sphincter, for example by utilizing magnetic force or by surrounding the tissue with a contractile belt or band. It can also affect the tightening of the pyloric sphincter by physically driving towards a closely adjacent relationship.</p><p> According to this aspect of the invention, the systems and methods can affect pyloric sphincter tightening in combination or in a variety of different treatment modalities. For example, the systems and methods can, in cooperation with the application of therapeutic agents or physical tightening devices, apply energy to tissue areas to form at least one lesion.</p><p> Another aspect of the invention mediates the receptive relaxation of gastric muscles in response to afferent nerve signals induced by smooth muscle extension caused by the entry of food mass into the stomach. Mediation of this neurological event suppresses or reduces the increase in gastric volume during the diet and thus can suppress further relaxation and extension of the gastric muscles, especially in the fundus. Limiting gastric capacity during food intake prolongs the feeling of satiety during and after a meal. This, in turn, helps reduce or reduce the incidence of binge eating, which can lead to obesity and other physiological conditions. The system and methods can be used as a mode of first-line treatment, or can be applied as replacement therapy before, during, or after the first-line intervention.</p><p> According to this aspect of the invention, the systems and methods include, for example , tissues within the region of the stomach where afferent nerve receptors that induce receptive relaxation in the jet gate are present, regions of the stomach where afferent nerve receptors are present. Neurological activity is suppressed by excising the tissue in the stomach, or the tissue near the area of the stomach where afferent nerve receptors are located. These nerve receptors transmit nerve signals when stimulated by the preliminary stretching of the stomach muscles by ingestion of food, which interacts with the vagus nerve, eg, in the stomach, in the fundus. It commands further relaxation of the muscles, thereby conditioned the stomach to stretch and accept larger volumes of swallowing material (this process is called receptive relaxation). Resection of tissues within these nerve receptors, tissues at nerve receptors, or tissue near nerve receptors induces the formation of lesions that interfere with the transmission of nerve signals, thereby suppressing or alleviating receptive relaxation. To. In this way, further relaxation and extension of the gastric muscles is mediated.</p><p> Surface tissue can be targeted for excision, or, optionally, tissue below the surface, including submucosal tissue, can be targeted for excision. Excision can be accomplished by exposing the tissue to conduction tissue heating, electrical resistance tissue heating, or excision agents, or a combination thereof.</p><p> According to this aspect of the invention, the systems and methods are used in areas of the stomach where afferent nerve receptors such as jets are present, in areas of the stomach where afferent nerve receptors are present, or in afferent nerve receptors. By injecting a neurotherapeutic agent near the area of the stomach where the body is located, it can also affect the obstruction or reduction of the receptor relaxation response. This therapeutic agent results in the obstruction of afferent nerve impulses that affect receptive relaxation. Such neurotherapeutic agents can include, for example, at least one subtype of vanilloid-containing compound. Injection of the therapeutic agent may be done with or without tissue resection.</p><p> Yet another aspect of the invention provides systems and methods for treating obesity by reducing gastric distension during food intake. The system and method include a magnetic source attached to an area of the stomach. The magnetic source is sized and shaped to allow magnetic force to attract material attached to another area of the stomach. This magnetic attraction reduces gastric distension during food intake.<u style="single"> The present invention provides, for example:</u><u style="single">(Item 1)</u><u style="single"> A system for treating pyloric obesity by tightening the pyloric sphincter, which has been adopted to allow excision of tissue within the pyloric sphincter, tissue at the pyloric sphincter, or tissue near the pyloric sphincter. , A system that includes a configured actuator.</u><u style="single">(Item 2)</u><u style="single"> A method for treating obesity that includes the step of removing tissue within the pyloric sphincter, tissue at the pyloric sphincter, or tissue near the pyloric sphincter so as to affect pyloric sphincter tightening. ..</u><u style="single">(Item 3)</u><u style="single"> A system for treating pyloric reflux by tightening the pyloric sphincter, which has been adopted to allow excision of tissue within the pyloric sphincter, tissue at the pyloric sphincter, or tissue near the pyloric sphincter. , A system that includes a configured actuator.</u><u style="single">(Item 4)</u><u style="single"> A method for treating bile regurgitation, comprising excising the tissue within the pyloric sphincter, the tissue at the pyloric sphincter, or the tissue near the pyloric sphincter so as to affect the tightening of the pyloric sphincter. Method.</u><u style="single">(Item 5)</u><u style="single"> A system for treating obesity by tightening the pyloric sphincter, which, when used, has been adopted so that it can be deployed adjacent to the tissue area in the pyloric sphincter or in the vicinity of the pyloric sphincter. A system comprising an actuating device configured and a source of therapeutic agent coupled to the actuating element to apply the therapeutic agent in contact with the tissue area.</u><u style="single">(Item 6)</u><u style="single"> 5. The system of item 5, wherein the therapeutic agent comprises at least one cytokine and / or vanilloid compound and / or tissue filler.</u><u style="single">(Item 7)</u><u style="single"> A method for treating obesity by tightening the pyloric sphincter, the step of deploying an actuating element adjacent to or in contact with the tissue area in the pyloric sphincter or in the vicinity of the pyloric sphincter, and in contact with the tissue area. A method comprising the step of applying a therapeutic agent through the actuating element so as to.</u><u style="single">(Item 8)</u><u style="single"> 7. The method of item 7, wherein the therapeutic agent comprises at least one cytokine and / or vanilloid compound and / or tissue filler.</u><u style="single">(Item 9)</u><u style="single"> A system for treating pyloric reflux by tightening the pyloric sphincter, which, when used, has been adopted so that it can be deployed adjacent to the tissue area in the pyloric sphincter or in the vicinity of the pyloric sphincter. A system comprising an actuating device configured and a source of therapeutic agent coupled to the actuating element to apply the therapeutic agent in contact with the tissue area.</u><u style="single">(Item 10)</u><u style="single"> 7. The system of item 7, wherein the therapeutic agent comprises at least one cytokine and / or vanilloid compound and / or tissue filler.</u><u style="single">(Item 11)</u><u style="single"> A method for treating bile regurgitation by tightening the pyloric sphincter, a step of deploying an actuating element adjacent to or in contact with the tissue area in the pyloric sphincter or in the vicinity of the pyloric sphincter, and in contact with the tissue area. A method comprising the step of applying a therapeutic agent through the actuating element so as to.</u><u style="single">(Item 12)</u><u style="single"> 11. The method of item 11, wherein the therapeutic agent comprises at least one cytokine and / or vanilloid compound and / or tissue filler.</u><u style="single">(Item 13)</u><u style="single"> A system for treating obesity by tightening the pyloric sphincter, with a magnetic source attached within the area of the pyloric sphincter, in the area of the pyloric sphincter, or near the area of the pyloric sphincter. Large enough that the magnetic source can magnetically attract material that is attached within another region of the pyloric sphincter, to another region of the pyloric sphincter, or near another region of the pyloric sphincter. A system made up of sphincters and shapes.</u><u style="single">(Item 14)</u><u style="single"> A method for treating obesity, which comprises attaching a magnetic source within the area with the pyloric sphincter, in the area with the pyloric sphincter, or near the area with the pyloric sphincter, wherein the magnetic source is the pylorus. A method sized and shaped to allow magnetic force to attract material attached to another region of the pyloric sphincter, to another region of the pyloric sphincter, or near another region of the pyloric sphincter. ..</u><u style="single">(Item 15)</u><u style="single"> A system for treating pyloric reflux by tightening the pyloric sphincter, including a magnetic source attached within the area of the pyloric sphincter, in or near the area of the pyloric sphincter. The magnetic source is sized to magnetically attract material that is attached within another region of the pyloric sphincter, to another region of the pyloric sphincter, or near another region of the pyloric sphincter. And the system made in shape.</u><u style="single">(Item 16)</u><u style="single"> A method for treating bile reflux, comprising attaching a magnetic source within the area of the pyloric sphincter, to the area of the pyloric sphincter, or near the area of the pyloric sphincter, wherein the magnetic source is the pylorus. A method sized and shaped to allow magnetic force to attract material attached to another region of the pyloric sphincter, to another region of the pyloric sphincter, or near another region of the pyloric sphincter. ..</u><u style="single">(Item 17)</u><u style="single"> A system for treating obesity by tightening the pyloric sphincter, the system comprising a tissue contraction band deployed within the pyloric sphincter, in or near the pyloric sphincter.</u><u style="single">(Item 18)</u><u style="single"> A method for treating obesity that involves deploying a tissue contraction band within the pyloric sphincter, into the pyloric sphincter, or near the pyloric sphincter.</u><u style="single">(Item 19)</u><u style="single"> A system for treating pyloric reflux by tightening the pyloric sphincter, which comprises a tissue contraction band deployed within the pyloric sphincter, in or near the pyloric sphincter.</u><u style="single">(Item 20)</u><u style="single"> A method for treating bile reflux, comprising deploying a tissue contraction band within the pyloric sphincter, into the pyloric sphincter, or near the pyloric sphincter.</u><u style="single">(Item 21)</u><u style="single"> A system for treating obesity by mediating receptive relaxation of the muscles of the stomach, which removes tissue within a region of the stomach, tissue in the region of the stomach, or tissue near the region of the stomach. A system that includes an activator that has been adopted and configured to allow it.</u><u style="single">(Item 22)</u><u style="single"> A method for treating obesity, in which tissue within an area of the stomach, tissue in an area of the stomach, or tissue near the area of the stomach is excised to mediate receptive relaxation of the muscles of the stomach. A method that includes steps to do.</u><u style="single">(Item 23)</u><u style="single"> A system for treating obesity by mediating receptive relaxation of the muscles of the stomach, in use, tissue within, or near, the area of the stomach. Includes an actuating device that is employed and configured to be deployable adjacent to the tissue and a source of therapeutic agent that is coupled to the actuating element to apply the therapeutic agent in contact with the tissue. system.</u><u style="single">(Item 24)</u><u style="single"> 23. The system of item 23, wherein the therapeutic agent comprises at least a vanilloid compound.</u><u style="single">(Item 25)</u><u style="single"> A method for treating obesity, the step of deploying an actuating element adjacent to tissue within an area of the stomach, tissue in the area of the stomach, or tissue near the area of the stomach, and muscles of the stomach. A method comprising the step of applying a therapeutic agent through the actuating element to contact the tissue to mediate receptive relaxation of the tissue.</u><u style="single">(Item 26)</u><u style="single"> 25. The method of item 25, wherein the therapeutic agent comprises at least one vanilloid compound.</u><u style="single">(Item 27)</u><u style="single"> A system for treating obesity by reducing gastric distension during food intake, including a magnetic source attached to one area of the stomach, said magnetic source attached to another area of the stomach. A system that is sized and shaped so that it can be attracted by magnetic force, thereby reducing gastric distension during food intake.</u><u style="single">(Item 28)</u><u style="single"> 27. The system of item 27, wherein the magnetic source comprises an array of magnets.</u><u style="single">(Item 29)</u><u style="single"> 28. The system of item 28, wherein the array of magnets is supported by a biocompatible fabric.</u><u style="single">(Item 30)</u><u style="single"> A method for treating obesity, including the step of attaching a magnetic source to one area of the stomach, large enough that the magnetic source can magnetically attract material to be attached to another area of the stomach. A method of reducing gastric dilation during food intake, which is made into a magnet and shape.</u></p><p> The features and advantages of these and other aspects of the invention are set out in the "Descriptions and Drawings" below and the appended claims.</p>

<figref num="1">FIG. 1 is an anatomical chart of the human digestive system.</figref><figref num="2">FIG. 2 is an anatomical cross section of the human stomach.</figref><figref num="3">FIG. 3 is a schematic representation of a treatment delivery system for treating a tissue area of the stomach.</figref><figref num="4">4A and 4B are schematic views of a system for treating a tissue area of the stomach, including a treatment device with tissue penetrating members, and FIG. 4A shows a treatment device deployed in the pyloric sphincter tissue area. , FIG. 4B shows a therapeutic device penetrating the tissue area to inject a therapeutic agent into the sphincter and / or excise the tissue area for the purpose of enhancing the barrier function of the sphincter muscle.</figref><figref num="5">5A and 5B are schematic views of a system for treating a tissue area of the stomach, including a treatment device with a large number of tissue penetrating members, and FIG. 5A shows a treatment device deployed in the pyloric sphincter tissue area. FIG. 5B shows a treatment device penetrating the tissue area to inject a therapeutic agent into the sphincter and / or excise the tissue area for the purpose of enhancing the barrier function of the sphincter muscle.</figref><figref num="6">FIG. 6 is a schematic view of the type of tissue treatment device shown in FIG. 4A, deployed in the pyloric sphincter tissue area through an endoscope.</figref><figref num="7">Figure 7 shows the therapeutic agent infused and / or within the pyloric sphincter area with a basket element carried by the device shown in a deflated state to deploy to the target tissue area. And a perspective view of a therapeutic device for forming a lesion around the pyloric sphincter region.</figref><figref num="8">FIG. 8 shows the therapeutic device shown in FIG. 7 with a basket element supported by the device shown in an inflated state as when ready for use in the target tissue area. It is a perspective view.</figref><figref num="9">FIG. 9 is a side view of the distal end of the treatment device shown in FIG. 8 showing a guide wire passage that helps deploy the device to the target tissue area.</figref><figref num="10">Figures 10-19 show intragastric, especially pyloric sphincter tissue, for injecting therapeutic agents into the sphincter and / or excising the tissue area for the purpose of enhancing the barrier function of the sphincter. , Is a schematic diagram showing the development of the treatment apparatus shown in FIGS. 7 to 9.</figref><figref num="11">Figures 10-19 show intragastric, especially pyloric sphincter tissue, for injecting therapeutic agents into the sphincter and / or excising the tissue area for the purpose of enhancing the barrier function of the sphincter. , Is a schematic diagram showing the development of the treatment apparatus shown in FIGS. 7 to 9.</figref><figref num="12">Figures 10-19 show intragastric, especially pyloric sphincter tissue, for injecting therapeutic agents into the sphincter and / or excising the tissue area for the purpose of enhancing the barrier function of the sphincter. , Is a schematic diagram showing the development of the treatment apparatus shown in FIGS. 7 to 9.</figref><figref num="13">Figures 10-19 show intragastric, especially pyloric sphincter tissue, for injecting therapeutic agents into the sphincter and / or excising the tissue area for the purpose of enhancing the barrier function of the sphincter. , Is a schematic diagram showing the development of the treatment apparatus shown in FIGS. 7 to 9.</figref><figref num="14">Figures 10-19 show intragastric, especially pyloric sphincter tissue, for injecting therapeutic agents into the sphincter and / or excising the tissue area for the purpose of enhancing the barrier function of the sphincter. , Is a schematic diagram showing the development of the treatment apparatus shown in FIGS. 7 to 9.</figref><figref num="15">Figures 10-19 show intragastric, especially pyloric sphincter tissue, for injecting therapeutic agents into the sphincter and / or excising the tissue area for the purpose of enhancing the barrier function of the sphincter. , Is a schematic diagram showing the development of the treatment apparatus shown in FIGS. 7 to 9.</figref><figref num="16">Figures 10-19 show intragastric, especially pyloric sphincter tissue, for injecting therapeutic agents into the sphincter and / or excising the tissue area for the purpose of enhancing the barrier function of the sphincter. , Is a schematic diagram showing the development of the treatment apparatus shown in FIGS. 7 to 9.</figref><figref num="17">Figures 10-19 show intragastric, especially pyloric sphincter tissue, for injecting therapeutic agents into the sphincter and / or excising the tissue area for the purpose of enhancing the barrier function of the sphincter. , Is a schematic diagram showing the development of the treatment apparatus shown in FIGS. 7 to 9.</figref><figref num="18">Figures 10-19 show intragastric, especially pyloric sphincter tissue, for injecting therapeutic agents into the sphincter and / or excising the tissue area for the purpose of enhancing the barrier function of the sphincter. , Is a schematic diagram showing the development of the treatment apparatus shown in FIGS. 7 to 9.</figref><figref num="19">Figures 10-19 show intragastric, especially pyloric sphincter tissue, for injecting therapeutic agents into the sphincter and / or excising the tissue area for the purpose of enhancing the barrier function of the sphincter. , Is a schematic diagram showing the development of the treatment apparatus shown in FIGS. 7 to 9.</figref><figref num="20">Figures 20 and 21 are schematic anatomical views of the pyloric sphincter region showing a magnetic source embedded in the sphincter region, which magnetic source is located in another region of the pyloric sphincter for the purpose of enhancing the barrier function of the sphincter. It is sized and shaped so that the embedded material can be attracted by magnetic force.</figref><figref num="21">Figures 20 and 21 are schematic anatomical views of the pyloric sphincter region showing a magnetic source embedded in the sphincter region, which magnetic source is located in another region of the pyloric sphincter for the purpose of enhancing the barrier function of the sphincter. It is sized and shaped so that the embedded material can be attracted by magnetic force.</figref><figref num="22">Figures 22 and 23 are schematic anatomical views of the pyloric sphincter region showing a magnetic source attached around the outer surface of the sphincter region, which is intended to enhance the barrier function of the sphincter muscle. It is sized and shaped so that the material attached around the outer surface of another area can be attracted by magnetic force.</figref><figref num="23">Figures 22 and 23 are schematic anatomical views of the pyloric sphincter region showing a magnetic source attached around the outer surface of the sphincter region, which is intended to enhance the barrier function of the sphincter muscle. It is sized and shaped so that the material attached around the outer surface of another area can be attracted by magnetic force.</figref><figref num="24">Figures 24 and 25 are schematic anatomical views of the pyloric sphincter region showing a magnetic source attached around the inner surface of the sphincter region, which is intended to enhance the barrier function of the sphincter muscle. It is sized and shaped so that the material attached around the inner surface of another area can be attracted by magnetic force.</figref><figref num="25">Figures 24 and 25 are schematic anatomical views of the pyloric sphincter region showing a magnetic source attached around the inner surface of the sphincter region, which is intended to enhance the barrier function of the sphincter muscle. It is sized and shaped so that the material attached around the inner surface of another area can be attracted by magnetic force.</figref><figref num="26">FIG. 26 is a perspective view of one embodiment of a band sized and shaped so that it can be attached around the outer surface of the pyloric sphincter for the purpose of enhancing the barrier function of the sphincter.</figref><figref num="27">27 and 28 are anatomical perspective views showing how the band shown in FIG. 26 is attached around the pyloric sphincter.</figref><figref num="28">27 and 28 are anatomical perspective views showing how the band shown in FIG. 26 is attached around the pyloric sphincter.</figref><figref num="29">FIG. 29 is a perspective view of another embodiment of the band sized and shaped so that it can be attached around the outer surface of the pyloric sphincter for the purpose of enhancing the barrier function of the sphincter.</figref><figref num="30">30 and 31 are anatomical perspective views showing how the band shown in FIG. 29 is attached around the pyloric sphincter.</figref><figref num="31">30 and 31 are anatomical perspective views showing how the band shown in FIG. 29 is attached around the pyloric sphincter.</figref><figref num="32">FIG. 32 is a schematic anatomical view of a therapeutic device for treating a tissue region in the gastric jet, for injecting a therapeutic agent into the tissue region for the purpose of mediating responsive relaxation of gastric smooth muscle. And / or includes a therapeutic device with a tissue penetrating member for excision of the tissue area.</figref><figref num="33">FIG. 33A is a schematic anatomical side view of the stomach before responsive relaxation resulting from food intake. FIG. 33B is a schematic anatomical top view of the stomach shown in FIG. 33A prior to responsive relaxation.</figref><figref num="34">FIG. 34A is a schematic anatomical side view of the stomach after responsive relaxation and extension during food intake. FIG. 34B is a schematic anatomical top view of the stomach shown in FIG. 34A after responsive relaxation and extension during food intake.</figref><figref num="35">FIG. 35A is a schematic anatomical aspect of the stomach after responsive relaxation and extension during food intake, with the presence of a magnetic matrix to suppress or reduce the degree of extension and expansion during food intake. Is shown. FIG. 35B is a schematic anatomical top view of the stomach shown in FIG. 35A, which helps to suppress or reduce the degree of extension and dilation during food intake (compared to FIG. 34B). It shows the existence of a magnetic matrix.</figref>

Detailed explanation Although the disclosure herein is detailed and made accurately to allow those skilled in the art to practice the invention, the physical embodiments disclosed herein are also specific to other particular structures. It merely illustrates the present invention that can be made. Although preferred embodiments have been described, the details can be modified without departing from the invention as defined in the claims.

I. Anatomy of the digestive system Figures 1 and 2 show the human digestive system 10 in detail. The digestive system 10 consists of a series of hollow organs that connect from the mouth 12 to the anus 14 in the form of long, winding tubes. Digestion begins with mouth 12 where food is chewed and swallowed. In order to convert food and drink into nutrients available to the body, food must be converted into smaller molecules before they are absorbed into the bloodstream and transported to the cells of the body. When food is broken down into small pieces, the body can use these small parts to build new cells and even to supply energy.

Digestion involves mixing food, moving food through the gastrointestinal tract 10, and breaking down food from large fragments into small molecules. Food travels through the hollow organs of the digestive system 10 because they contain muscles and the walls are made movable by these muscles. The movement of the walls of the organ pushes food and liquid through the gastrointestinal tract 10. This movement of the esophagus 16, stomach 18, and small intestine 20 is called peristalsis. Peristalsis resembles a ring-shaped contraction wave.

Food enters the digestive system 10 through the mouth 12 and is swallowed. The swallowed food is pushed into the esophagus 16. The esophagus 16 is a muscular tube that extends from the throat 22 to the stomach 18. After this, food passes through the esophagus 16 and enters the stomach 18.

The stomach 18 is a generally J-shaped sac with a capacity of 1.5 liters in the average adult, but it swells and can withstand up to 4 liters. Food enters the stomach 18 from the proximal end of the stomach through an opening called the lower esophageal sphincter (LES) 24. LES24 closes the passage between esophagus 16 and stomach 18. However, as food approaches LES24, the surrounding muscles relax, allowing food to enter the stomach 18.

Stomach 18 has four parts. The first part, Cardia 26, surrounds LES24. The second part is the fundus 28, a small round area located above the level of LES24. Fundus 28 can be dilated by swallowing air, fluid, and / or food. The third part of the stomach 18, the body 30 of the stomach, is the large central part. The body 30 is located between the fundus 28 and the fourth portion of the stomach 18, which fourth portion is known as the pylorus or pyloric region 32.

In addition to these four parts of the stomach 18, there are also two bends. The smaller curved portion 34 of the stomach 18 forms a short concave boundary, while the larger curved portion 36 forms a long convex boundary of the stomach 18.

Thus, the stomach 18 has a proximal region that includes the cardia 26, the fundus 28, and the upper portion of the body 30. The role of this proximal region is to accept food and store it for subsequent digestion. The stomach 18 also has a distal region that includes the lower portion of the body 30 and the pylorus 32. The role of this distal region is to grind food.

There are three tasks that must be accomplished after food enters the stomach 18. The stomach 18 must store swallowed food and fluid until it can be released into the small intestine 20. As the food mass enters the stomach to allow storage, the smooth muscle of the fundus 28 of the stomach 18 stretches to accept a large volume of swallowing material without increasing pressure inside the stomach. Relax so that you can. This phenomenon is called receptive relaxation of the proximal stomach. FIG. 33A / B shows the stomach 18 before food intake, and FIG. 34A / B shows the stomach 18 after the receptive relaxation of the proximal stomach.

Receptive relaxation is mediated by the vagus nerve primarily by afferent stimulation of nerve receptors in gastric smooth muscle in the cardia. Gastric smooth muscle has the flexibility to maintain constant tension over a wide range of muscle lengths. However, above a certain extension level, nerve receptors depolarize and send vagus nerve signals to the vagus nerve, which then relaxes the smooth muscles in the fundus 28 and the proximal stomach. Sends an efferent nerve signal that leads to. This relaxation causes the fundus 28 to stretch and thereby condition it to accommodate a larger volume of food.

In the second task, the stomach 18 agitates the ingested nutrients. This agitation breaks the ingested nutrients into smaller particles. These small particles mix with gastric juice to form a liquid mixture called keems.

The third task of the stomach 18 is to slowly transfer the contents of the stomach to the small intestine 20, which can absorb nutrients.

As soon as food enters the stomach 18, peristalsis begins in the specialized cells of the fundus 28 and the body 30 of the stomach. These cells are known as smooth muscle pacemaker cells. Pacemaker cells provide a slow peristaltic wave that occurs 3 to 4 times per minute. This slow peristaltic wave mixes the contents of stomach 18. These rhythmic contractions are known as the basal electrical rhythm of the stomach 18, or BER. These peristaltic waves pass through the distal stomach and travel downward toward the pyloric sphincter 44.

The pyloric area 32 is funnel-shaped. A large area known as Pyloric Cave 38 leads to Pyloric Canal 40. The pyloric canal 40 is the narrowest part of the pyloric area 32. At the distal end of the pyloric region 32 is the pylorus 42. The pylorus 42 is thickened, forming the pyloric sphincter at its distal end, just as it forms the pyloric sphincter 44. The pyloric sphincter 44 regulates the release of the liquefied contents of the stomach 18 (ie, Keems) into the duodenum 46. The pyloric sphincter 44 is normally closed except when allowing fluid in the stomach to pass into the duodenum 46. Stomach 18 is connected to duodenum 46. The duodenum 46 is a C-shaped area at the proximal end of the small intestine 20.

As the pyloric area 32 begins to fill, a strong peristaltic wave chops the keems. Keems is pushed through the pyloric canal 40. For each wave, a small amount of Keems is pumped through the pyloric sphincter 44. Keems is pushed through the pyloric sphincter 44 by a mechanism known as the pyloric pump. The narrowness and strength of the pyloric sphincter 44 causes large amounts of keems to return to the pyloric region 32. The returned Keems are further chopped by the peristaltic waves.

The time that food is retained in the stomach 18 varies, but the stomach 18 is usually emptied in 3 to 5 hours. The stomach 18 gradually transfers the contents of the stomach to the duodenum 46. In the process of emptying the stomach, the peristaltic waves move the body 30 of the stomach 18 upwards. By doing so, the peristaltic wave ensures that all Keems are pushed into the pyloric region 32.

After the stomach 18 transfers a mixture of food and secretions to the small intestine 48, the other two digestive secretions mix with the food so that the process of digestion continues. One of these organs is the pancreas 50. The pancreas produces secretions that contain a wide range of enzymes to break down carbohydrates, fats, and proteins in food. Other enzymes that are active in the digestive process come from the glands in the wall of the intestine 20 and even from parts of this wall.

Liver 52 produces yet another digestive juice (called bile). Bile is stored in the gallbladder 54 between meals. Bile is secreted by the liver 52 and delivered from the liver to the gallbladder 54 via the cystic duct 56 and the hepatic duct 58 until needed by the digestive process. When functioning normally, the gallbladder 54 transfers bile through the bile duct 60 to the duodenum 46 to promote peristalsis and absorption, prevent putrefaction, and aid digestion by emulsifying fat. At mealtime, bile is squeezed from the gallbladder 54 into the bile duct 60, reaches the intestine 20, and mixes with the fat in the food. Bile acids dissolve fat in the watery contents of the intestine 20, much like a surfactant that dissolves oil from a frying pan. After being lysed, fat is digested by enzymes from the inner layers of pancreas 50 and intestine 20.

Digested molecules of food, as well as water and minerals from the diet, are absorbed through the cavity of the upper small intestine 20. Most absorbed substances cross the mucous membranes into the blood and are carried in the bloodstream to other parts of the body for storage or further chemical changes. The remaining food particles are advanced through the small intestine 20 into the large intestine 62 and finally sent to the rectum 64 for excretion through the anus 14.

II. Systems and methods for tightening the pyloric sphincter or the tissue area adjacent to the pyloric sphincter One aspect of the specification is for tightening tissues in the sphincter and tissue areas adjacent to the sphincter, tissues in the sphincter and tissue areas adjacent to the sphincter, or tissues near the sphincter and tissue areas adjacent to the sphincter. Disclose various systems and methods. The system and method are particularly well suited for tightening the pyloric sphincter 44. For this reason, the system and method are described in this context. However, the disclosed systems and methods are used to restore compliance or otherwise other sphincter areas (eg, lower esophageal sphincter or anal sphincter) and, in general, other internal tissues or muscle areas. It should be recognized that it is also applicable for tightening. These systems and methods that embody the features of the present invention are also applicable for use in systems and surgical techniques that are not necessarily catheter-based.

Tightening of the pyloric sphincter 44 delays or regulates the emptying of the stomach 18. Therefore, pyloric sphincter tightening provides a method for treating obesity. By delaying or regulating the emptying of the stomach 18, it is possible to prolong the feeling of fullness during and / or after a meal. Therefore, less food is consumed less frequently, resulting in long-term weight loss.

Tightening of the pyloric sphincter 44 can also reduce the incidence of bile regurgitation into the stomach 18 through the pylorus 42. Thus, pyloric sphincter tightening is a method of preventing or mediating the effects of bile contact with the tissues that form the lining of the stomach 18 and / or esophagus, such as heartburn, GERD, and Barrett's esophagus. provide.

Various treatment modalities can be used to affect the tightening of the pyloric sphincter 44. Some typical styles will be described.

A. Tissue treatment device A tissue treatment device 66 that is very suitable for tightening the pyloric sphincter 44 is shown in FIG. The device 66 includes, for example, a handle 68 made of molded plastic. The handle 68 carries a flexible catheter tube 70. The catheter tube 70 is a standard flexible medical grade plastic such as vinyl, nylon, poly (ethylene), ionomer, poly (urethane), poly (amide), and poly (ethylene terephthalate). It can be constructed using materials. The handle 68 is sized to be convenient for the physician to grasp so that the catheter tube 70 is introduced into the area of the pyloric sphincter 44. The catheter tube 70 may be deployed with or without the use of the guide wire 72 (see also FIG. 12).

The catheter tube 70 carries an actuating element 74 at its distal end.

The actuating element 74 includes one or more tissue penetrating members 76. As shown in FIG. 4A, a single tissue penetration member 76 may be used. Elongation of member 76 results in penetration of adjacent tissue by this member, as seen in Figure 4B. Alternatively, as shown in FIGS. 5A and 5B, the actuating element 74 can also carry a large number of tissue penetrating members 76 in various forms. Desirably, these numerous tissue-penetrating members 76 are spaced in an array, as described in more detail below.

In one mode of treatment, the actuating element 74 selectively applies excisional energy to the tissue in the pyloric sphincter 44, the tissue within the pyloric sphincter 44, or the tissue near the pyloric sphincter 44 through the tissue penetrating member 76. Fulfill. Application of excision energy creates one or more lesions below the mucosal surface, or a predetermined pattern of lesions. The formation of lesions by selective application of energy causes wound events. The natural healing of these lesions tightens the targeted adjacent tissue. The healing process results in contraction of the tissue surrounding the lesion, reducing the volume of the tissue surrounding the lesion, or otherwise altering the biomechanical properties of the tissue surrounding the lesion. The healing process naturally tightens the smooth muscle tissue within the pylorus 42. These effects will result in enhanced barrier function of the pyloric sphincter 44.

Lesion formation may be performed alone or in combination with the application of a therapeutic agent. The actuating element 74 can be configured to apply the therapeutic agent in a variety of ways. For example, the actuating element 74 can apply the therapeutic agent directly to the mucosal tissue covering the sphincter 44. Alternatively, the actuating element 74 can externally apply the therapeutic agent to the sphincter 44 through the mucosal tissue covering the sphincter 44. Alternatively, the actuating element 74 can also inject a therapeutic agent into the sphincter muscle 44 through the tissue penetration element 76, as indicated by the arrows in FIGS. 4B and 5A / B. The combined physiological effects of lesion formation and therapeutic agent application can interact to achieve the desired physiological results.

For example, the therapeutic agent can be selected from a group of substances that provide physical tightening of the pyloric sphincter 44, such as cytokine subtypes or tissue fillers.

As used herein, the term "cytokine subtype" means any polypeptide that affects the function of other cells and is a molecule that modulates cell-cell interactions in an immune or inflammatory response. is there. Cytokine subtypes include, but are not limited to, monokines and lymphokines, regardless of which cells produce them. The cytokine-containing therapeutic agent may be injected into the sphincter muscle or may be added externally to the outside of the sphincter muscle 44. Cytokines can play a role in initiating the healing process within a local area. This process is not limited to these, but is limited to leukocyte and macrophage influx, fibroblast stimulation and smooth muscle division and collagen secretion, new blood vessel growth, wound contraction and tightening, new collagen frames. Includes maturation of the work or existing collagen framework, and reduction of tissue compliance. These tissue effects could improve the barrier function of the pyloric sphincter 44. Examples of cytokine substances that can be used include the commercially available Regranex, which is recombinant human PDGF-BB. Cytokine-containing substances may be applied or infused as first-line therapy, or may be applied as replacement therapy before, during, or after first-line intervention. Excision energy may be used to induce the wound healing process, after which cytokines can be applied to promote more active wound healing.

Examples of tissue fillers that can be used include collagen, dermis, cadaveric allogeneic graft material, or ePTFE (foamed poly-tetrafluoroethylene) pellets. The tissue filling therapeutic material may be injected into the sphincter muscle or may be added externally to the outside of the sphincter muscle 44. Tissue filling therapeutics may be applied or infused as first-line therapy, or may be applied as replacement therapy before, during, or after first-line intervention. Cutting energy can be applied to the injected filler to alter the physical properties of the filler to achieve the desired effect, eg to expand or cure the filler.

As another example, the therapeutic agent can be selected from a group of substances that interfere with afferent nerve impulses that induce transient sphincter relaxation, such as vanilloid compounds. As used herein, the term "vanilloid compound" means a compound or mixture of compounds having a biologically active vanillyl group. Vanilloid compounds include both naturally occurring vanilloids and synthetic vanilloids, pharmacologically acceptable salts of vanilloid compounds (whether natural or synthetic), and these compounds (whether natural or synthetic). Also includes pharmaceutically acceptable derivatives and / or analogs of. Examples of natural vaniroid compounds are pepper, cayenne pepper, black pepper, paprika, cinnamon, chow, mace, mustard, ginger, turmeric, papaya seeds, and the cactus-like plant Euphorbia. Contains both crude and purified extracts of active vanilloid compounds from resininifera :. Synthetic vanilloid compounds, such as synthetic capsaicin, are disclosed in WO 96/40079, which is incorporated herein by reference. An example of a vanilloid material that can be used is manufactured by Afferon and is called RTX. The use of vanilloid-containing therapeutic agents can play a role in interfering with the afferent impulses that induce transient relaxation of the sphincter, which enhances the barrier function of the sphincter. The vanilloid-containing therapeutic agent can be added to the lining of the mucosa or externally to the outside of the sphincter 44. Vanilloid-containing therapeutic agents may be applied or infused as first-line therapy, or may be applied as replacement therapy before, during, or after first-line intervention. Excision energy may be used to induce the wound, after which active wound healing is promoted by applying a vanilloid-containing therapeutic agent.

Therefore, these treatment modalities, alone or in combination, can enhance the barrier function of the pyloric sphincter.

As shown in FIG. 3, the treatment device 66 can function as part of the system 78. System 78 includes an external therapeutic agent delivery device 80. A luer fitting 82 provided on the handle 68 connects the therapeutic device 66 to the therapeutic agent delivery device 80 so as to deliver the therapeutic agent for release to or near the actuating element 74. It is connected to the pipe 84. Alternatively or in combination, if lesion formation is desired, the system 78 may include a generator 86 to supply energy to the working element 74. A cable 88 connected to a handle 68 carries the generated energy to the working element 74.

In the illustrated embodiment, the generator 86 supplies radio frequency energy having frequencies ranging from, for example, about 400 kHz to about 10 mHz. Other forms of tissue excision energy, such as coherent or non-interfering light; heated or cooled fluids; resistance heating; microwaves; ultrasound; tissue excision fluids; or cold fluids, can of course be applied. it can.

System 78 also preferably includes control device 90. The control device 90 is connected to the generator 86 and the therapeutic drug delivery device 80. The control device 90, preferably including an on-board central processing unit, has a power level, cycle, and power level, cycle, and radio frequency energy distributed to the working element 74 to achieve and maintain a power level suitable for achieving the desired therapeutic objective. Manage duration. At the same time, the control device 90 can also manage the delivery of the therapeutic agent.

The control device 90 preferably includes an input / output (I / O) device 92. The I / O device 92 allows the physician to enter control and processing variables and also allows the control device 90 to generate the appropriate instruction signal.

Because the treatment site cannot be visualized directly, the treatment device 66 uses an endoscope 94 having a lumen 96 that passes through the mouth 12 and down the esophagus 16 as shown in FIG. Can be introduced. In the case of this embodiment, the catheter tube 70 is passed through the lumen 96 of the endoscope to the target site in the pyloric sphincter 44 or to the target site in the vicinity of the pyloric sphincter 44. If desired, a guide wire 72 can be used to facilitate deployment of the endoscope 94 and treatment device 66 to the target site.

As shown in FIG. 7, the actuating element 74 can include an inflatable structure 98. The inflatable structure 98 includes an array of tubular spine-like structures 100 that form a basket that can be selectively expanded and contracted. The inflatable structure 98 can further include an inflatable body 102 (eg, a balloon) in the basket. The purpose of the inflatable body 102 is to inflate and contract the basket within the pylorus 42. The inflated balloon structure 102 serves to temporarily expand the target tissue, thereby removing some or all of the folds normally present on the mucosal surface. FIG. 7 shows an inflatable structure 98 in a contracted or deflated state. FIG. 8 shows an inflatable structure 98 in an inflated state.

In this embodiment, the tissue penetration element 76 is carried within the spine-like structure 100 and can be stretched and retracted as in the previous case. Element 76 can be selectively moved between two positions. The first position is the retracted position depicted in FIG. 7, where the element 76 is retracted into the spine-like structure 100. The second position is the extended position depicted in FIG. 8, where the element 76 extends outward from the spine-like structure 100 through a hole in the spine-like structure 100. The tissue penetration element 76 serves as an electrode, which may be arranged in a bipolar pair or in a single spaced relationship suitable for unipolar manipulation.

One preferred embodiment is shown in FIG. Here, one of the spine-like structures 100 of the inflatable structure 98 provides a lumen 104 through which the guide wire 72 passes. This passage provides stability and support for the inflatable structure 98 as it passes over the guide wire 72. The lumen 104 has a distal opening 106 located beyond the distal end of the inflatable structure 98. The opening 106 serves as an outlet for the guide wire 72 passed through the guide assembly 108. The lumen 104 also has a proximal opening 110 that extends further proximal to the proximal end of the inflatable structure 98. The proximal opening 110 is provided on the outer surface of the catheter tube 70 to provide an unobstructed passage for the guide wire 72.

Explaining with reference to FIG. 10, in order to deploy the inflatable structure 98, the bite block 112 is placed in the patient's mouth and is properly placed when the patient is lying awake in the reclining or semi-reclining position. It is positioned in. The bite block 112 is used to keep the patient's mouth open while the device 66 is being inserted into the patient's mouth. Desirably, the bite block 112 carries the gripping tool 114. The gripping tool 114 is used to hold the device 66 in place. By contacting the outer surface of the device 66, the gripping tool 114 keeps the device 66 in a fixed position within the bite block 112. Both the bite block 112 and the gripping tool 114 are incorporated herein by reference in "Systems and Methods Employing a Guidewire for Positioning and Stabilizing External Instruments Deployed Within the". It is disclosed in Co-pending US Patent Application No. 10 / 017,906, filed December 14, 2001, entitled "Body".

After this, the doctor passes a small diameter guide wire 72 through the patient's mouth 12 and pharynx 116, as depicted in FIG. The guide wire 72 is directed into the patient's stomach 18 through the esophagus 16. The distal end of the guide wire 72 is located at the target site within the pylorus 42. If the goal is to treat obesity and GERD, the target site is the pyloric sphincter 44 and the area adjacent to the pyloric sphincter, as best shown in Figure 2.

Desirably, the physician uses the endoscope 94 in cooperation with the guide wire 72 to visualize the target area. The use of endoscope 94 is shown in FIG. However, it should be recognized that the physician may perform fluoroscopy instead to visualize the target area. The endoscope 94 may be used separately from the guide wire 72 in a side-by-side relationship, or the endoscope 94 may be introduced on the guide wire 72 itself, as shown in FIG. Good.

The body of the endoscope 94 includes a measured marking 118 along its length direction. The marking 118 indicates the distance between a given position along the body and the endoscope 94. By associating the marking 118 with the bite block 112, the physician can either relative or absolute, between the patient's mouth 12 and the endoscope 94 within the pyloric region 32. You can measure the distance. When the doctor visualizes the target site, eg, the pyloric sphincter 44, with an endoscope 94, the doctor records a marking 118 aligned with the bite block 112, leaving the guide wire 72 there, and the endoscope 96. Get rid of.

In the embodiment depicted, the catheter tube 70 comprises a measured marking 120 along its length direction. This measured marking 120 indicates the distance between a given position along the catheter tube 70 and the actuating element 74. The marking 120 provided on the catheter tube 70 is spaced and graduated in line with the marking 118 along the tubular body of the endoscope 94.

When treatment begins, the free proximal end of the guidewire 72 passes through the distal opening so that the guidewire 72 exits the lumen 104 through the proximal opening 110, as depicted in FIG. , Passed through the guide wire cavity 104 of the inflatable structure 98. The device 66 is then introduced over the guide wire 72 through the patient's mouth 12 and pharynx 116 to the desired location in the pyloric region 32, such as the pyloric sphincter 44. While the device 66 passes over the guide wire 72, the inflatable structure 98 is in a deflated state and the electrode 74 is in a retracted position. The position of device 66 within the pyloric sphincter 44 is shown in Figures 13A and 13B.

After this, tissue excision is performed. First, as shown in FIG. 14, the device 66 is held in a desired position by closing the gripping element of the gripping tool 114.

The inflatable structure 98 is then inflated by injecting fluid or air into the inflatable member 102, as depicted in FIG. 15, for example sterile water or air in device 66. It is injected into the balloon through a port provided on the handle 68, which inflates the balloon. The swelling of the inflatable member 102 causes the swelling of the inflatable structure 98, which results in close contact with the mucosal surface of the pyloric sphincter 44. The inflated structure 98 serves to temporarily dilate the pyloric sphincter 44 to remove some or all of the folds normally present on the mucosal surface. The inflated structure 98 also serves to place the spine-like structure 100 in close contact with the mucosal surface.

Next, for example, as depicted in FIG. 16, the electrode 76 is moved to the extended position by operating the push-pull lever provided on the handle 68 of the device 66. Electrodes 76 penetrate the mucosal tissue and enter the smooth muscle tissue of the pyloric sphincter 42.

The doctor then applies energy, such as radio frequency energy, for the desired time, eg, energy from about 400 kHz to about 10 mHz for about 90 seconds. If desired, a cooling liquid can also be introduced in this excision sequence (eg, each spine-like structure 100 carries a cooling liquid, such as sterile water, to contact the mucosal surface of the target tissue site. May include a lumen having a port for (not shown).

Radio frequency energy utilizes electrical resistance to heat smooth muscle tissue. The temperature is detected by the electrode 32 by a sensor 60 (not shown) carried in the electrode. Desirably, for the region of the pyloric sphincter 44, energy is applied to achieve tissue temperature in smooth muscle tissue ranging from 55 ° C to 95 ° C. In this way, lesions can typically be created at depths ranging from 1 mm to 4 mm below the mucosal surface.

Explaining with reference to FIG. 17, after applying a desired amount of radio frequency energy, the electrode 76 is retracted by, for example, operating a push-pull lever provided on the handle 68 of the device 66. The gripping tool 114 is moved to the open position, which allows the device 66 to be repositioned or removed, if desired.

In this way, a single series of lesions is formed depending on the number and location of electrodes 76 provided on the catheter. It is possible that excision affects nerves that weaken the muscles of the pyloric sphincter 44, resulting in physical contraction of the pyloric sphincter 44 and / or modulation of the neural conduction pathway. When it is desirable to create a large number of lesions in a pattern, for example, circular lesions along the target treatment site within the pyloric sphincter 44, in order to create higher density lesions within a given target tissue area. There is.

Various lesion patterns can be achieved within the pyloric sphincter 44. A large number of lesions in a pattern, created by repositioning and repositioning device 66 one or more times after performing the resection, may be spaced along the pyloric sphincter 44. For example, with reference to FIG. 18, the device 66 is rotated with the electrode 76 retracted and the inflatable structure 98 inflated, after which the electrode 76 is extended again and a second series. RF energy is applied to produce the lesions in.

Alternatively, with the electrode 76 retracted and the inflatable structure 98 inflated, the device 66 is moved axially (ie, traveling or retracting) as shown in FIG. After this, RF energy is applied so that the electrode 76 is stretched again and produces a second series of lesions. It should be understood that any number and combination of rotational and axial movements may be performed to produce the desired lesion pattern.

When all desired excision sequences have been completed, the electrode 76 is retracted. After this, the inflatable member 102 is deflated, and similarly the inflatable structure 98 is deflated. The gripping tool 114 is moved to the open position and the device 66 and bite block 112 are removed.

B. Complementary magnet system Figures 20-21 show an alternative system for using magnetism to tighten the pyloric sphincter 44. More specifically, the system uses complementary first and second magnets 122 and 124 that serve to provide and maintain a suitable position and shape of tissue in the pyloric sphincter 44. FIG. 20 shows a pair of first and second magnets 122 and 124 embedded in tissues on opposite sides of the pylorus 42. FIG. 21 shows the movement of tissue caused by the magnetic attraction between the embedded magnets 122 and 124. By moving and stabilizing the tissue in the desired position and shape, this system can tighten the pyloric sphincter 44 and thus help treat obesity, GERD, and / or Barrett's esophagus.

An object that exhibits magnetic properties (magnetism) is called a magnet. Magnetism is, after all, the attractive or repulsive force between various substances, especially those made of iron and certain other metals, due to the movement of electric charges. All magnets have a magnetic field, which is the area around the magnet where the magnetic effect is observed. In the illustrated embodiment, the magnets 122 and 124 are preferably permanent magnets, i.e., the magnets 122 and 124 maintain an essentially constant magnetic field over an extended period of time.

Magnets 122 and 124 have poles of opposite polarity. These poles are the central areas with the strongest magnetic attraction. If the magnet 122 or 124 is free to rotate, one pole points to the north side and is therefore called the north pole, and the other pole is also called the south pole. According to the laws of physics, poles of the same polarity (north-north or south-south) repel each other by magnetic force. Conversely, poles of different polarities (north-south or south-north) are magnetically attracted to each other. The magnetic attraction or repulsion depends on the strength of the magnets 122 and 124 and the distance between the two poles.

In the illustrated embodiment, the first magnet 122 and the second magnet 124 are oriented relative to each other so that the magnetic attraction attracts the first and second magnets 122 and 124 to each other. That is, the first magnet 122 has the opposite polarity to the second magnet 124, for example, the first magnet 122 has the north polarity and the second magnet 124 has the south polarity, or vice versa. As used herein, such orientation of the magnetic poles is referred to as "complementary".

It should be recognized that either magnet 122 or 124 can exert a magnetic force on unmagnetized material. Thus, one of the magnets 122 or 124 can be replaced with a material on which the remaining magnets 122 or 124 can exert a magnetic attraction, such as an iron plate.

When the magnets 122 and 124 are arranged in a complementary manner so that they are attracted to each other, the tissue of the pyloric sphincter 44 is also attracted, which tightens the sphincter 44 as indicated by the arrow in FIG.

As will be apparent to those skilled in the art, the first and second magnets 122 and 124 can be arranged in various sizes, configurations, and positions to achieve the desired position of the tissue.

In the illustrated embodiment, the magnets 122 and 124 are formed in a concave or fan shape to approach the contour of the surface of the pylorus 42.

In another embodiment depicted in FIGS. 22 and 23, magnets 122 and 124 are applied in a biocompatible cloth or other suitable matrix 130, followed by, as depicted in FIG. The aforementioned matrix 130 can be attached to the outer surfaces of the pylorus 42 on opposite sides using suture thread 131. FIG. 23 shows the movement of tissue caused by the magnetic attraction between the embedded magnets 122 and 124, as represented by the arrows.

Alternatively, magnets 122 and 124 are applied in a biocompatible cloth or other suitable matrix 130, followed by the movement of the tissue as shown by the arrows in FIG. As depicted in 24, the aforementioned matrix 130 can also be sutured to the opposite inner surfaces of the pylorus 42.

Both implantation and attachment can be accomplished by routine laparoscopy procedures. Desirably, the magnets 122 and 124 are embedded or attached in an inert form, i.e., in an unmagnetized form. The magnets 122 and 124 can then be activated after this procedure by exposing them to a magnetic field to impart the desired magnetism. When a substance with magnetic properties is placed in a magnetic field (the region surrounding the magnet), the strength of this magnetic field causes a magnetization force H in the substance, and the substance responds to this H and the magnetic susceptibility I / of this substance. Acquires a specific magnetization I depending on H.

If desired, magnets 122 and 124 can be removed by subsequent surgical procedures, such as laparoscopy procedures. In one preferred embodiment, the magnets 122 and 124 are configured to be capable of selectively inactivating, ie, demagnetizing, the magnets after embedding or mounting. Demagnetization results in the loss of magnetic properties.

In the inactive state, the magnets 122 and 124 can no longer perform the tightening of the pylorus 42. Such an embodiment eliminates the need for subsequent surgical procedures to remove magnets 122 and 124.

As will be apparent to those of skill in the art, the inactivated magnets 122 and 124 can be selectively reactivated, or "remagnetized", by exposure to a magnetic field as described above.

C. Pylorus band In yet another system for tightening the pylorus 42, a tightening member with a fastening mechanism can be wrapped around the circumference of the pylorus 42 to delay emptying the stomach and / or reduce bile reflux. .. In addition, this member prevents binge eating by reducing the maximum volume of the stomach. It should be understood that these tightening members and fastening mechanisms can be configured in various ways.

Figures 26-28 show one embodiment of such a system, in which the tightening member is a band 132 in the form of a cable tie, which allows the physician to see the individual anatomy of the patient. The diameter of the band 132 can be adjusted according to the above. The band 132 includes a head portion 134, a strap 136, and a tab 138.

The tab 138 is preferably serrated and configured to pass through a slot 140 provided in the head 134. The diameter of the band 132 is reduced by advancing the tab 138 through the slot 140 by pulling the tab 138. Conversely, moving the tab 138 in the opposite direction through the slot 140 increases the diameter of the band 132. The head 134 can include a locking / releasing claw 142 for fixing and stabilizing the band 132 at the desired diameter.

In one preferred embodiment, the strap portion 136 comprises a suture attachment site 144, such as a hole. These suture attachment sites 144 allow the suture 131 to pass through so as to secure the band 132 in the tissue.

Upon use, the physician will surgically implant the band 132 around the pylorus 42 by routine laparoscopy procedures. Tab 138 is threaded through slot 140 to obtain a diameter that provides the desired tightening of pylorus 42. This desired position is secured by activating the locking claws 142, for example by manipulating the tab 138 upwards. If desired, the suture attachment site 144 is utilized to sew the band 132 in place.

Figures 29-31 show another embodiment of such a system, in which the tightening member is a belt-like band 148, which allows the physician to see the individual anatomy of the patient. The diameter of the band 148 can be adjusted according to the structure. Band 148 includes body portion 150, tabs 152, and buckle 154.

The tab 152 is configured to pass through a slot 156 provided in the buckle 154. The tab 152 preferably includes a tapered end region 158 to allow easy passage through slot 156. The diameter of the band 148 is reduced by advancing the body portion 150 through slot 156 by pulling on the tab 152. Conversely, moving the body 150 in the opposite direction through the slot 156 increases the diameter of the band 148. The body 150 includes a series of holes 159 that engage the buckle 154 to secure the band 148 to the desired diameter.

In one preferred embodiment, the body portion 150 comprises a suture attachment site 160, such as a hole. These suture attachment sites allow the suture 131 to pass through so as to secure the band 148 in the tissue.

Upon use, the physician will surgically implant band 148 around the pylorus 42 by routine laparoscopy procedures. Tab 152 is threaded through slot 156 to obtain a diameter that provides the desired tightening of pylorus 42. By closing the buckle 154, this desired position is secured. If desired, the suture attachment site 160 is utilized to sew the band 148 in place.

In either embodiment, the band 132 or 148 can preferably be removed by a laparoscopy procedure, which avoids problems associated with long-term contraction of the pylorus 42. Since the bands 132 or 148 are removable, they are very suitable for temporary use, eg initial treatment of morbid obesity.

Regardless of the device used, tightening of the pyloric sphincter 44 limits or regulates the outflow of keems through the pyloric sphincter 44, thereby extending the retention time of the contents of the stomach 18. This not only creates a physical barrier to eating, but also induces a feeling of satiety that mediates against the urge to overeat. Also, restriction of the pyloric sphincter 44 reduces or prevents the occurrence of bile reflux, thereby preventing or mediating the effects of exposing bile to tissues within the stomach 18 or esophagus 16, which may include the Barrett's esophagus. Can also be fulfilled.

III. Systems and methods for suppressing receptive relaxation Another technical feature includes systems and methods for mediating receptive relaxation in the proximal gastric muscle. Mediation of this neurological event suppresses gastric muscle relaxation, especially in the fundus and proximal stomach, as it suppresses gastric expansion and associated increase in gastric volume. To do.

Limiting gastric capacity during food intake can prolong the feeling of satiety during and after a meal, thereby reducing the incidence of overeating, which can lead to obesity and other physiological conditions.

A. Tissue treatment device FIG. 32 shows a tissue therapy device 66 of the type shown in FIG. 3 deployed within the area of the stomach where nerve receptors are located, eg, cardia 26 (common reference numbers are used). .. The treatment device 66 includes an actuating element 74 supported at the end of the flexible catheter tube 70. Details regarding the deployment of therapeutic devices into the stomach have been previously described. The physician can introduce the catheter tube 70 and the actuating element 74 into the cardia 26 through the esophagus 16 with or without the use of a guide wire, as previously described.

The actuating element 74 of FIG. 32 includes one or more tissue penetrating members 76. As shown in FIG. 32, the working element carries a large number of tissue penetrating members 76.

In one mode of treatment, the actuating element 74 serves to selectively apply excisional energy through the tissue penetrating member 76 to the tissue at cardia 26, the tissue within cardia 26, or the tissue near cardia 26. Application of excision energy creates one or more lesions below the mucosal surface, or a predetermined pattern of lesions. These lesions create a neurological interaction between the afferent nerve receptors and the vagus nerve, the afferent nerves created when food entering the stomach stretches the smooth muscles innervated by these receptors. Suppress by interfering or mitigating the signal. Thereby, these lesions suppress or reduce the incidence of further muscle relaxation and extension in the stomach resulting from receptive relaxation. Surface tissue can be targeted for excision, or, optionally, tissue below the surface, including submucosal tissue, can be targeted for excision. Excision can be accomplished by exposing the tissue to conduction tissue heating, electrical resistance tissue heating, or excision agents, or a combination thereof.

In addition, this system and method can be used in the gastric region where afferent nerve receptors such as cardia are present, in the gastric region where afferent nerve receptors are present, or in the vicinity of the region where afferent nerve receptors are present. Injecting a neurotherapeutic agent through one or more tissue penetration elements 74 can also affect the inhibition or reduction of receptive relaxation. This neurological substance is selected to cause interference or reduction of afferent nerve impulses that affect receptive relaxation. Neurotherapeutic agents can include, for example, compounds containing at least one subtype of vanilloid, as described above. Injection of the therapeutic agent may be done with or without tissue resection. The vanilloid-containing therapeutic agent can be added to the inner layer of the mucosa or externally to the outside of the cardia 26. Vanilloid-containing therapeutic agents may be applied or infused as first-line therapy, or may be applied as replacement therapy before, during, or after first-line intervention. Excision energy may be used to induce the wound, after which active wound healing is promoted by applying a vanilloid-containing therapeutic agent.

Thus, these treatment modalities, alone or in combination, can mediate the receptive relaxation response to prevent or reduce the occurrence of binge eating that can lead to obesity.

B. Complementary magnetic matrix Figures 35A and 35B depict an alternative system 500 for alleviating the consequences of receptive relaxation. System 500 includes first and second matrices 502 and 504 attached to the anterior and posterior walls of the proximal stomach 506, respectively. The first and second matrices each carry an array of magnets, 508 and 510, respectively. The magnet 508 of the first matrix 502 and the magnet 510 of the second matrix 504 have poles of different polarities (ie, north-south or south-north). Therefore, these array-shaped magnets 508 and 510 attract each other as shown by the arrows in FIG. 35B. The principles of magnetic action and magnetic attraction have been previously investigated.

The magnetic attraction between the two matrices 502 and 504 suppresses or reduces the distant expansion or extension of the anterior and posterior walls of the proximal stomach 506. As a result, the magnetic attraction generated by the matrices 502 and 504 physically suppresses dilation, even if the proximal gastric smooth muscle is conditioned to dilate and stretch to accept food by receptive relaxation. Or reduce. As a result, these matrices suppress or reduce the incidence of further muscle relaxation and extension in the proximal stomach that results from receptive relaxation. Figures 34A and 34B show the degree of normal extension resulting from receptive relaxation and food intake. Figures 35A and 35B show the degree of reduced extension as a result of magnetic attraction. Matrix 502 and 504 serve to reduce gastric volume despite receptive relaxation.

Limiting gastric capacity during food intake can prolong the feeling of satiety during and after a meal, thereby reducing the incidence of overeating, which can lead to obesity and other physiological conditions.

Matrix 502 and 504 can include elastic biocompatible cloth or other suitable material that can be attached to the anterior and posterior walls of the proximal stomach, for example by suture 512. ..

It should be recognized that either magnet array 508 or 510 can exert a magnetic force on the unmagnetized material. Thus, one of the magnet arrays 508 or 510 can be replaced with a material on which the remaining magnet array can exert a magnetic attraction, such as an iron plate.

Both implantation and attachment can be accomplished by routine laparoscopy procedures. The magnet arrays 508 and 510 may be mounted in an inert form, i.e., in an unmagnetized form. The magnet arrays 508 and 510 can then be activated after this procedure by exposing them to a magnetic field to impart the desired magnetism.

If desired, the magnet arrays 508 and 510 can be removed by subsequent surgical procedures, such as laparoscopy procedures.

The preceding description is only considered to illustrate the principles of the present invention. Moreover, it is not desirable to limit the invention to the structures and operations themselves shown and described herein, as those skilled in the art can readily make numerous modifications and modifications. Although preferred embodiments have been described, the details can be modified without departing from the invention as defined in the claims.