WO2011004335A2

WO2011004335A2 - Duodenal liner device and methods and devices for restricting the passage of chyme from the stomach

Info

Publication number: WO2011004335A2
Application number: PCT/IB2010/053117
Authority: WO
Inventors: Elad Magal
Original assignee: Duocure, Inc.
Priority date: 2009-07-09
Filing date: 2010-07-07
Publication date: 2011-01-13
Also published as: WO2011004335A3

Abstract

Disclosed are duodenal liner devices including a liner tube and a bore-changing component configured to reversibly change the size of the bore of a portion of the liner lumen of the liner tube. Disclosed are also restriction devices configured for deployment in a duodenum to restrict the passage of chyme from the stomach to the downstream portions of the digestive tract.

Description

DUODENAL LINER DEVICE AND METHODS AND DEVICES FOR RESTRICTING THE PASSAGE OF CHYME FROM THE STOMACH

RELATED APPLICATIONS

The present application gains priority from U.S. Provisional Patent Application Nos.

61/224,077 filed 9 July 2009 and 61/232,940 filed 11 August 2009, both which are included by reference as if fully set forth herein.

FIELD AND BACKGROUND OF THE INVENTION

The invention, in some embodiments thereof, relates to the fields of bariatrics and/or diabetes, and generally to gastrointestinal and/or eating disorders. Some embodiments relate to methods and devices useful for providing a beneficial effect, in some embodiments, related to treating a condition related to an eating disorder.

The gastrointestinal tract of placental mammals such as humans is a tube passing from the mouth to the anus, having various physically different regions, each having different functions and corresponding structures. Food passing through the lumen of the gastrointestinal tract is processed at the different regions to be digested, allowing nutrients and energy to be absorbed while expelling waste.

The upper portion of a gastrointestinal tract 10 of a human, schematically depicted in cross section in Figure 1 as viewed from the front, includes an esophagus 12, a stomach 14 and a duodenum 16.

Stomach 14 is a hollow J-shaped organ having muscular gastric walls defining a gastric cavity 18. A lower esophageal sphincter 20 opens into the large cardiac portion of stomach 14 defined between a lesser curvature 22 on the right and a greater curvature 24 to the left. Above the cardiac portion is fundus 26. Below the cardiac portion, is a pyloric portion 28 of stomach 14, including a pyloric antrum 30 and terminating with a pyloric sphincter 32.

Pylorus 34, the distal aperture of stomach 14, is defined by pyloric sphincter 32 and leads to the lumen of duodenum 16. Pylorus 34 is ordinarily tightly closed by pyloric sphincter 32 to prevent reflux from duodenum 16 to the stomach 14.

Duodenum 16, the most proximal part of the small intestine, is approximately 24 cm long. In an adult the course of the duodenum describes an almost 270° imperfect circle divided into four roughly linear portions: the first (superior) portion; the second (descending) portion; the third (transverse) portion; and the fourth (ascending) portion. The superior portion of duodenum 16 is about 5 cm long commencing at pyloric sphincter 32 and passing backwards, upwards, and rightwards to the neck of the gall-bladder, varying slightly in direction according to the degree of distension of the stomach. Unlike the other portions of duodenum 16, pyloric sphincter 32 and pyloric portion 28 of stomach 14, the superior portion of duodenum 16 is relatively immotile. The part of the superior portion of duodenum 16 that abuts pyloric sphincter 32 has a larger diameter than other portions of duodenum 16 defining a slightly bulging cavity termed a duodenal bulb 36.

In a stomach 14, ingested food is liquefied into chyme by the contractions of the gastric walls that churn the food in the presence of hydrochloric acid and digestive enzymes. When the ingested food is sufficiently processed in stomach 14, pyloric sphincter 32 opens and the chyme is expelled through pylorus 34 into the duodenum 16. In duodenum 16, the acidic chyme is neutralized and digested by bile and enzymes.

Obesity is a result, a symptom and/or a cause of many pathological conditions still unexplained in several respects.

One concept for the treatment of obesity and related conditions is to reduce the efficiency of digestion of ingested food, for example by reducing absorption of fat and carbohydrates. An accepted method for reducing the efficiency of digestion of ingested food is by deploying a gastrointestinal liner in the gastrointestinal tract.

Common gastrointestinal liners include a tubular sleeve deployed inside a portion of the gastrointestinal tract to function as an intraluminal gastrointestinal bypass device. Duodenal liner devices (i.e., gastrointestinal liners deployed at least partially in the duodenum) are suggested to act analogously to, and provide at least some of the advantages of a Roux-en-Y gastric bypass, including weight loss and control of type-2 diabetes.

A typical duodenal liner device is described in US 7,267,694 to Levine et al, where the proximal end of a flexible, floppy liner tube of impermeable material defining a liner lumen is endoscopically deployed and anchored with the help of a barbed stent in the pylorus or in the superior section of the duodenum, the stent also ensuring that the proximal lumen opening of the liner tube remains dilated. Chyme from the stomach enters the dilated proximal lumen opening of the liner tube and passes through the liner lumen to the distal lumen opening. Digestive enzymes secreted in the duodenum pass through the duodenum on the outside of the liner tube. The enzymes and the chyme do not mix until the chyme exits from the distal lumen opening of the liner tube. In such a way, the efficiency of digestion of the chyme is diminished, reducing the amount of energy absorbed from the food. GI Dynamics, Inc., (Watertown, MA, USA) produces the Endobarrier® device that is substantially a duodenal liner device configured so that the proximal end of the device is anchored inside the duodenal bulb with the help of a barbed anchoring stent that also keeps the proximal lumen opening dilated.

An additional concept for the treatment of obesity and related conditions is induction of a feeling of satiety. The induced feeling of satiety causes a treated subject to eat less, reducing the amount of calories consumed.

In PCT patent publication WO 2008/096362 of the Inventor, which is included by reference as if fully set forth herein, is described a method of inducing a feeling of satiety by deploying a duodenum obstructing device. Such devices partially obstruct the lumen of a duodenum in which deployed, in some cases reducing the rate of passage of chyme through the duodenum and in some cases, thereby reducing the rate of chyme exiting the stomach. As a result in some instances a given volume of consumed food produces a perception of satiety more quickly, for a longer duration and/or more intensely than without the deployed duodenum obstructing device, apparently due to a more intense and longer lasting stimulation of duodenal and/or gastric satiety mechanoreceptors.

In PCT patent publication WO 2008/104968 of the Inventor, which is include by reference as if fully set forth herein, is described a method of inducing a feeling of satiety by spray administration of a composition at the luminal walls of a duodenum.

SUMMARY OF THE INVENTION

Some embodiments of the invention relate to duodenal liner devices having advantages over known duodenal liner devices. Specifically, some embodiments of the invention relate to duodenal liner devices where the size of the bore of a portion of the liner tube is reversibly changeable.

Some embodiments of the invention relate to methods and restriction devices suitable for deployment in the gastrointestinal tract that restrict the passage of chyme from the stomach to the downstream portions of the digestive tract, in some embodiments together with a duodenal liner and in some embodiments devoid of a duodenal liner.

According to an aspect of some embodiments of the invention, there is provided a duodenal liner device, comprising:

a) a liner tube configured for deployment inside a duodenum of a mammalian subject, the liner tube having walls of a flexible material defining a liner lumen, a proximal end defining a proximal lumen opening, and a distal end defining a distal lumen opening;

b) an expandable centering component configured for deployment in a duodenal bulb functionally associated with the proximal end of the liner tube, radially expandable from a collapsed configuration to an expanded configuration; and

c) a bore-changing component functionally associated with the liner tube configured to reversibly change a size of a bore of a portion of the liner lumen while the liner tube is deployed in a duodenum.

In some embodiments, the duodenal liner device further comprises a bore-size controller configured to control the bore-changing component. In some such embodiments, the duodenal liner device further comprises an event-detector functionally associated with the bore-size controller, the bore-size controller configured to activate the bore-changing component to change the size of the bore as a consequence of detection of an event of significance for changing the size of the bore by the event- detector.

In some embodiments, the bore-changing component comprises a bore-changing balloon with an internal bore-changing volume, and the changing of the size of the bore of the portion of the liner tube comprises introduction of inflation fluid into the bore-changing volume or withdrawal of inflation fluid from the bore-changing volume.

In an exemplary embodiment, the duodenal liner device further comprises, a centering component controller configured to control a configuration of the centering component. Optionally, the duodenal liner device further comprises an event-detector functionally associated with the centering component controller, the centering component controller configured to control a configuration of the centering component as a consequence of detection of an event of significance for changing the configuration of the centering component.

In some embodiments, the centering component comprises a centering balloon with an internal centering- component volume, and changing the configuration of the centering component comprises introduction of inflation fluid into the centering- component volume or withdrawal of inflation fluid from the centering-component volume.

In another embodiment of the present invention, there is provided a duodenal liner device, comprising:

a) a closed channel readily deployable in a portion of a gastrointestinal canal of a mammalian subject, the channel having walls defining a lumen, a proximal end defining a proximal lumen opening, and a distal end defining a distal lumen opening; and

b) a dual-compartment member having an inner inward-expandable compartment concentrically connected to an outer outward-expandable compartment, the dual- compartment member is affiliated to a portion of the channel walls and configured for deployment in a duodenal bulb;

wherein the inner compartment is capable of narrowing at least part of the channel lumen while expanded, and the outer compartment is capable of expanding to mount the duodenal liner device to the duodenal bulb walls.

In an exemplary embodiment, the dual-compartment member further comprises hooking and/or roughened means peripherally coupled to the outer compartment, whereby facilitating an improved mounting to the duodenal bulb walls.

In an exemplary embodiment, at least one of the compartments is a stent or an inflatable compartment (e.g., a balloon). Optionally, at least one of the compartments is self expandable. Alternatively, at least one of the compartments is expanded by auxiliary means and/or may be balloon expandable.

Optionally, the dual- compartment member is releasably connected to the channel walls. Optionally, the gastrointestinal canal portion is at least part of a duodenum.

Optionally, the duodenal bulb is a pylorus, optionally a pyloric canal, optionally a pyloric antrum, optionally a pyloro duodenal opening. Optionally, at least part of the device mounting is supported by the pyloric sphincter.

In an exemplary embodiment, at least part of the device is biodegradable, optionally the channel walls and/or any or both of the compartments walls. Optionally, at least part of the device is provided as drug eluting.

According to an aspect of some embodiments of the invention, there is also provided a restriction device for deployment in a mammalian duodenum, comprising:

an inflatable annular balloon configured for deployment in a duodenal bulb, the annular balloon having a collapsed configuration and an inflated configuration, wherein when the annular balloon is deployed in a duodenal bulb in the inflated configuration, the device had an outer diameter and a restriction section having a fixed bore-size to restrict the passage of chyme from the stomach through the restriction section.

According to an aspect of some embodiments of the invention, there is also provided a device for deployment in the digestive tract of a human subject, comprising: a duodenal liner tube configured to reside inside the duodenum of the human subject, wherein the liner tube comprises walls of a flexible material defining a liner lumen, a proximal end defining a proximal lumen opening, and a distal end defining a distal lumen opening; and

an expandable balloon component, wherein the expandable balloon component is functionally associated with the proximal end of the liner tube; and

a tether comprising an elongated flexible material, having a proximal and a distal end, wherein the distal end of the tether engages at least one of the liner tube or the expandable balloon component.

In some embodiments, the tether comprises one or more lumens, wherein one lumen of the tether is in fluid communication with the expandable balloon component.

In some embodiments, the proximal end of the tether is configured to engage an anchor, and configured, when secured to a surface of the human subject, to secure the liner tube inside the duodenum. In some embodiments, the anchor is a tether anchor. In some embodiments, the anchor is a percutaneous endoscopic gastrostomy anchor.

In some embodiments, the distal end of the tether engages the liner tube, in some embodiments at multiple locations. In some embodiments, the distal end of the tether engages the expandable balloon component. In some embodiments, the distal end of the tether engages the liner tube and the expandable balloon component.

In some embodiments, the proximal end of the tether is configured to pass through a gastric wall of a human subject, and the anchor is configured to be secured to an outer surface of the gastric wall. In some embodiments, proximal end of the tether is configured to pass through a gastric wall as well as other tissue of the human subject, and the anchor is configured to be secured to the surface of a muscle layer. In some embodiments, the proximal end of the tether is configured to pass through a gastric wall as well as other tissue to emerge through skin of the human subject, and the anchor is configured to be secured to an outer surface of the skin.

According to an aspect of some embodiments of the invention, there is also provided a device for deployment in the digestive tract of a human subject, comprising:

a duodenal liner tube configured to reside inside the duodenum of the human subject, wherein the liner tube comprises walls of a flexible material defining a liner lumen, a proximal end defining a proximal lumen opening, and a distal end defining a distal lumen opening; an expandable balloon component, wherein the expandable balloon component is functionally associated with the proximal end of the liner tube, wherein the expandable balloon component has a collapsed configuration and an expanded deployed configuration, and wherein the expandable balloon component is configured to reside completely in a duodenal bulb of the human subject;

a percutaneous endoscopic gastrostomy tube, wherein the percutaneous endoscopic gastrostomy tube comprises a channel- defining component and a percutaneous endoscopic gastrostomy anchor; and

a tether, wherein the tether comprises an elongated flexible material having one or more lumina, a proximal end, and a distal end, wherein one lumen of the tether is in fluid communication with the expandable balloon component, wherein at least a portion of the tether passes through the channel- defining component of the percutaneous endoscopic gastrostomy tube, wherein the proximal end of the tether engages the percutaneous endoscopic gastrostomy anchor, and wherein the distal end of the tether engages at least one of the liner tube or the expandable balloon component,

wherein the percutaneous endoscopic gastrostomy anchor is configured, when secured to an outer skin surface of the human subject, to secure the liner tube inside the duodenum.

In some embodiments, the proximal end of the tether is configured to pass through a gastric wall of the human subject, and the percutaneous endoscopic gastrostomy anchor is configured to be secured to an outer surface of the gastric wall. In some embodiments, the proximal end of the tether is configured to pass through a gastric wall as well as other tissue of the human subject, and the percutaneous endoscopic gastrostomy anchor is configured to be secured to the surface of a muscle layer. In some embodiments, the proximal end of the tether is configured to pass through a gastric wall as well as other tissue to emerge through skin of the human subject, and the percutaneous endoscopic gastrostomy anchor is configured to be secured to an outer surface of the skin.

According to an aspect of some embodiments of the present invention there is also provided a device for deployment in the digestive tract of a human subject, comprising:

a duodenal liner tube, configured to reside inside a duodenum of a human subject, wherein the liner tube comprises walls of a flexible material defining a liner lumen, a proximal end defining a proximal lumen opening, and a distal end defining a distal lumen opening; and

an expandable balloon component configured to reside completely in a duodenal bulb of a human subject, wherein the expandable balloon component is functionally associated with the proximal end of the liner tube, wherein the expandable balloon component has a collapsed configuration and an expanded deployed configuration, wherein a smooth outer surface of the expandable balloon component is configured, when deployed in the duodenal bulb, to sufficiently contact luminal walls of the duodenal bulb to anchor the liner tube inside the duodenum.

In some embodiments, the device further comprises a tether, wherein the distal end of the tether engages at least one of the liner tube or the expandable balloon component.

In some embodiments of the devices for deployment in the digestive tract of a human subject described above, the device comprises a restriction section to restrict the flow of chyme from the stomach of the subject to downstream portions of the digestive tract through the proximal lumen opening. In some embodiments, the restriction section is configured to reside completely in the duodenal bulb when deployed.

In some embodiments, the restriction section has a substantially fixed bore-size when deployed in a duodenum that substantially slows down the entry of chyme from a stomach of the human subject through the proximal lumen opening.

In some embodiments, the fixed bore-size of the restriction section is defined at least partially by at least a portion of the expandable balloon.

In some such embodiments, the fixed bore-size of the restriction section is defined at least partially by a restriction component that is distinct from the expandable balloon.

In some embodiments of the devices for deployment in the digestive tract of a human subject, the restriction component of the device comprises:

a bore-changing component, wherein the bore-changing component is functionally associated with the proximal end of the liner tube;

wherein the bore-changing component is configured to reside completely in a duodenal bulb of the human subject; and

wherein the bore-changing component is configured, when residing in the duodenal bulb of the human subject, to dilate and constrict when inflation fluid is introduced into the bore- changing component to reversibly change a dimension of a portion of the proximal lumen opening of the liner tube residing in the duodenal bulb. In some such embodiments, the the change in dimension of the portion of the proximal lumen opening residing in the duodenal bulb slows down the entry of chyme from a stomach of the human subject through the proximal lumen opening.

Unless otherwise defined, all medical, technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention pertains. In case of conflict, the patent specification, including definitions, will control.

As used herein, the indefinite articles "a" and "an" mean "at least one" or "one or more" unless the context clearly dictates otherwise.

BRIEF DESCRIPTION OF THE FIGURES

Some embodiments of the invention are herein described, by way of example only, with reference to the accompanying figures. The description, together with the figures, makes apparent how embodiments of the invention may be practiced to a person having ordinary skill in the art. The figures are for the purpose of illustrative discussion of embodiments of the invention and no attempt is made to show structural details of an embodiment in more detail than is necessary for a fundamental understanding of the invention. For the sake of clarity, some objects depicted in the figures are not to scale.

In the Figures:

FIG. 1 (prior art) is a schematic depiction of part of a human gastrointestinal tract including the stomach and duodenum, in cross section view from the front;

FIGS. 2A-2D schematically depict an embodiment of a duodenal liner device, comprising a centering component including a stent and a bore-changing component including a bore-changing balloon;

FIG. 3 schematically depicts an embodiment of a duodenal liner device, comprising a centering component including a stent and a bore-changing component including a bore- changing balloon and a detachable inflation fluid conduit;

FIG. 4 schematically depicts an embodiment of a duodenal liner device, comprising a centering component including a stent and a bore-changing component including a bore- changing balloon and a device controller configured to function as a bore-size controller;

FIGS. 5A-5C schematically depict an embodiment of a duodenal liner device, comprising an internal volume that constitutes both a centering- component volume of a centering component and a bore-changing volume of a bore-changing component; FIGS. 6A-6G schematically depict an embodiment of a duodenal liner device, comprising a centering component including a centering balloon and a bore-changing component including a bore-changing balloon;

FIG. 7 schematically depicts an embodiment of a duodenal liner device, comprising a centering component including a centering balloon and a bore-changing component including a bore-changing balloon and a device controller configured to function as a bore-size controller and as a centering component controller;

FIG. 8 schematically depicts an embodiment of restriction device including half- toroidal proximal and distal annular balloon sections;

FIGS. 9A-9J schematically depict an embodiments of restriction device including substantially flat proximal and distal annular balloon sections;

FIGS. 10A- 1OB schematically depict an embodiments of restriction device including a substantially planar restriction component;

FIGS. HA- HD schematically depict an embodiments of restriction device including a funnel-shaped restriction component;

FIGS. 12A-12C schematically depict embodiments of restriction devices devoid of a liner tube;

FIGS. 13 A and 13B schematically depict an embodiment of a restriction device, comprising an expansion restrictor encircling an annular balloon; and

FIGS. 14A and 14B schematically depict an embodiment of a restriction device, comprising an expansion restrictor inside an annular balloon.

DESCRIPTION OF SOME EMBODIMENTS OF THE INVENTION

Some embodiments of the invention relate to methods and devices useful for providing a beneficial effect for treating conditions relating to eating disorders. Some embodiments of the invention relate to duodenal liner devices, for example duodenal liner devices including a reversibly changeable liner lumen bore. Some embodiments of the invention relate to methods and restriction devices suitable for deployment in the gastrointestinal tract that restrict the passage of chyme from the stomach into the duodenum.

Some embodiments of the present invention have at least one beneficial effect.

Beneficial effects include effects such as curing a condition, treating a condition, preventing a condition, treating symptoms of a condition, curing symptoms of a condition, ameliorating symptoms of a condition, treating effects of a condition, ameliorating effects of a condition, and preventing results of a condition. For example, in some embodiments some of the beneficial effects are similar to or the same as beneficial effects of prior art duodenal liner devices including reducing the amount of energy absorbed from an ingested amount of food and thus have a beneficial effect for persons suffering from overweight and obesity or control of Type II diabetes.

For example, in some embodiments, some of the beneficial effects arise from the delay of gastric emptying related to the restriction of the passage of chyme from the stomach into the duodenum, thereby reducing the rate of chyme exiting the stomach. As a result in some instances a given volume of consumed food produces a perception of satiety more quickly, for a longer duration and/or more intensely, apparently due to a more intense and longer lasting stimulation of duodenal and/or gastric satiety mechanoreceptors.

The principles, uses and implementations of the teachings of the invention may be better understood with reference to the accompanying description and figures. Upon perusal of the description and figures present herein, one skilled in the art is able to implement the teachings of the invention without undue effort or experimentation. In the figures, like reference numerals refer to like parts throughout.

Before explaining at least one embodiment of the invention in detail, it is to be understood that the invention is not limited in its application to the details set forth herein. The invention can be implemented with other embodiments and can be practiced or carried out in various ways. It is also understood that the phraseology and terminology employed herein is for descriptive purpose and should not be regarded as limiting.

As is well-known, duodenal liner devices generally include a liner tube having walls of material defining a liner lumen. A duodenal liner device is deployed inside at least part of the duodenum so that the liner tube constitutes an intraluminal bypass of at least part of the duodenum. At least some chyme from the stomach enters a proximal lumen opening of the liner tube and passes through the liner lumen and therefore does not interact with the luminal walls of the duodenum. As a result, the chyme is less efficiently digested and/or absorbed, leading to a reduced caloric uptake and various beneficial effects for persons suffering from overweight and obesity or control of Type II diabetes.

Herein is disclosed that in some embodiments a duodenal liner device including a liner tube together with a bore-changing component to reversibly change the size of the bore of a portion of the liner lumen while the liner tube is deployed in a duodenum, provides advantages over known duodenal liner devices. Specifically, in some embodiments when a duodenal liner device is deployed in the gastrointestinal tract of a subject and the bore- changing component is set so that the size of the bore of the portion of the liner lumen is sufficiently small, the portion of the liner lumen functions as a bottleneck, reducing the rate of passage of chyme from the stomach into the liner lumen. Since the rate of stomach emptying is reduced, a relatively small volume of consumed food fills the stomach more completely and/or more quickly and/or for a longer period of time. In some such embodiments, the relatively small volume of consumed food stimulates gastric mechanoreceptors to produce a perception of satiety that is more intense and/or earlier onset and/or lasts longer.

In some embodiments, the effect of the duodenal liner (e.g., reduced caloric absorption) with the bottleneck effect of the reduced bore-size of a portion of the liner lumen (e.g., more effective induction of a perception of satiety by only a small amount of consumed food) act together to produce an exceptional beneficial effect.

Thus, according to an aspect of some embodiments, there is provided a duodenal liner device, comprising:

a) a liner tube configured for deployment inside a duodenum of a mammalian (human or non-human) subject, the liner tube having walls of a flexible material defining a liner lumen, a proximal end defining a proximal lumen opening, and a distal end defining a distal lumen opening;

b) an expandable centering component configured for deployment in a duodenal bulb functionally associated with the proximal end of the liner tube, having a collapsed configuration and an expanded configuration; and

c) a bore-changing component functionally associated with the liner tube configured to reversibly change the size of the bore (the cross sectional size) of a portion of the liner lumen near the proximal lumen opening of the liner tube while the liner tube is deployed in a duodenum.

Liner tube

Some embodiments of a duodenal liner device include a liner tube of a material defining a liner lumen, a proximal end defining a proximal lumen opening and a distal end defining a distal lumen opening. Like liner tubes known in the art, a liner tube used in implementing embodiments of the invention is configured for deployment inside a duodenum of a mammal, such as a human.

Generally, the liner tube is sufficiently flexible to follow the curvature of the duodenum. Further, in some embodiments the walls of the liner tube may be sufficiently flexible and/or collapsible to allow duodenal peristalsis to drive chyme through the lumen of the liner tube. Sufficient collapsibility of the walls of the liner tube can prevent continuous intimate contact of the outer surface of the liner tube with the duodenal mucosa, avoiding damage to the duodenal mucosa and allowing digestive secretions as well as chyme not collected into the liner lumen to pass through the duodenal lumen outside the liner lumen.

In some embodiments, at least a portion of the wall of a liner tube is porous or semipermeable to allow entry of digestive secretions into the liner lumen and/or to allow the flow of fluids and digested matter out of the liner lumen.

In some embodiments, at least a portion of the wall of a liner tube is impermeable (analogous to the Endobarrier® by GI Dynamics Inc, Watertown, MA, USA and as described in US 7,267,694 which is included by reference as if fully set forth herein).

In some embodiments, the diameter of the liner lumen is substantially constant along the entire length of the liner tube. Although any suitable luminal diameter may be used the luminal diameter is optionally not more than about 35 mm, optionally not more than about 30 mm or optionally not more than about 25 mm. That said, the proximal end of the liner tube of material is of a size to match the centering component, in embodiments having a smooth and continuous transition from a wider diameter near the centering component to a smaller distal diameter. Consequently, in some embodiments, the proximal end of the liner tube is flared and in some embodiments, the centering component and the proximal end of the liner tube together define a funnel-like structure.

The length of the liner tube is any suitable length, optionally predetermined, and may be selected in accordance with clinical decisions made by the treating physician, optionally in situ. That said, a typical liner tube may be between about 25 cm and about 160 cm long. Generally, the liner tube is selected so that when the duodenal liner device is deployed, the distal lumen opening of the liner tube is located distal to the duodenal-jejunal flexure and empties out into the jejunum. In some embodiments, the liner tube is even longer.

Any suitable material may be used in fashioning a liner tube as described herein, In some embodiments, the material is elastic. Suitable materials from which embodiments of a liner tube for implementing a duodenal liner device are fashioned include silicone, polyurethane, polyethylene (e.g., low density polyethylene films) and fluoropolymers (e.g., expanded polytetrafluoroethylene). In some embodiments, a liner tube is fashioned from fluoropolymer or polyethylene film impregnated with polyurethane or silicone to reduce permeability, as taught in US 7,267,694. One particularly useful material is elastomeric polyurethane as is discussed below.

Methods useful for the manufacture of thin walled polyurethane articles such as a liner tube are well-known to one skilled in the art and are described, for example, in PCT patent publications WO/1995/005097 and WO/2003/103741 and in US Patent Nos. 5,679,423 and US 6,523,540.

Another particularly useful material is silicone rubber as is discussed below. Methods useful for the manufacture of thin walled polyurethane articles such as a liner tube are well- known to one skilled in the art.

In some embodiments, a liner tube comprises an anti-buckling or anti-twisting component to reduce the chance of buckling and/or twisting, as taught in US 7,267,694.

In some embodiments, some or the entire liner tube is configured to be visible using a medical imaging modality, for example is made of a material or includes features that are detectable with the help of an imaging modality, for example include radio-opaque portions detectable with X-ray imaging modalities or sono-opaque portions detectable with ultrasonic imaging modalities. In some embodiments, markers visible in an imaging modality are arranged along the length of the liner tube, for example in a line, to allow medical personnel to determine if the liner tube is twisted. If the liner tube is twisted when deployed, untwisting can be performed as described in US 7,267,694.

A liner tube used in implementing a duodenal liner device as described herein may be or may resemble a liner tube used in implementing duodenal liner devices known in the art. The type and properties of a liner tube used is dependent on medical criteria including the condition treated, the severity of the condition and decisions made by the treating physician. A person having ordinary skill in the art is familiar with various duodenal liner devices, for example duodenal liner devices described in US 2004/148034 and US 7,267,694.

Bore-changing component

Some embodiments of a duodenal liner device include a bore-changing component functionally associated with the liner tube, the bore-changing component configured to reversibly change the size of the bore (the cross sectional size) of a portion of the liner lumen while the liner tube is deployed in a duodenum.

In some embodiments, a bore-changing component is configured to reversibly change the size of the bore of a portion of the liner lumen near the proximal lumen opening of the liner tube. In some embodiments, the bore-changing component is configured to reversibly change the size of the bore of a portion of the liner lumen that is to be deployed in the superior portion of the duodenum. In some embodiments, the bore-changing component is configured to reversibly change the size of the bore of a portion of the liner lumen that is to be deployed in the duodenal bulb of the duodenum, that is to say close to or at the location of the expandable centering component.

In some embodiments, a bore-changing component is configured to reversibly change the size of the bore of a portion of the liner lumen from a dilated state to a reduced size state. In some embodiments, the bore-changing component is configured to reduce the size of the bore substantially continuously from a dilated state to any size down to a minimal size. In some embodiments, the bore-changing component is configured to reduce the size of the bore incrementally from a dilated state to at least one reduced size.

In an exemplary embodiment, when the bore-changing component is expanded, a bore portion is changed from a first configuration to a second configuration. Optionally, the first and second bore portion configurations are differentiated by angle of convergence/divergence (e.g., bore portion may have substantially constant diameter throughout its length and may be, optionally reversibly, altered to a curving and/or inclining diameter). Optionally, the bore portion, in any of the configuration, may be non-constant in diameter.

In some embodiments, the bore-changing component is configured to reduce the size of the bore from a dilated state to a minimal size of not more than about 38 mm² (corresponding to a radius of about 3.5 mm of a round bore), to a minimal size of not more than about 28 mm² (corresponding to a radius of about 3 mm of a round bore), to a minimal size of not more than about 19 mm² (corresponding to a radius of about 2.5 mm of a round bore), to a minimal size of not more than about 12 mm² (corresponding to a radius of about 2 mm of a round bore), to a minimal size of not more than about 7 mm² (corresponding to a radius of about 1.5 mm of a round bore) and in some embodiments to a minimal size of not more than about 3 mm² (corresponding to a radius of about 1 mm of a round bore). In some embodiments, the bore-changing component is configured to reduce the size of the bore from a dilated state to a substantially entirely shut state where passage of chyme therethrough is substantially entirely blocked.

As noted above, in some embodiments the bore-changing component may be configured to, optionally reversibly, change the size of the bore of a portion of the liner lumen while the liner tube is deployed in a duodenum.

In some embodiments, when deployed the size of the bore is usually constant, but the size of the bore is adjustable by manipulation of the bore-changing component. In some such embodiments, a person such as a treating physician optionally periodically manipulates (e.g., once a week, once a month) the bore-changing component to change the size of the bore, e.g., increasing the size of the bore to allow faster entry of chyme into the liner lumen or decreasing the size of the bore to reduce the rate of entry of chyme into the liner lumen.

In some embodiments, the bore-changing component may be used to adjust the size of the bore as required to achieve a maximal beneficial effect with reduced negative side-effects (e.g., reflux, nausea). The ability to change the size of the bore allows gradual adjustment of the bore-size as needed, that in some embodiments increases patient acceptance and compliance, as well as in some embodiments allowing gradual, and therefore more effective, behavioral modification, for example voluntary reduced food consumption supported by more effective induction of a feeling of satiety.

In some embodiments, a duodenal liner device further comprises a bore-size controller configured to control the bore-changing component, for example, with respect to the size to which the bore is set, when the bore-size is reduced, when the bore-size is increased, the rate of bore-size increase and decrease, and the like. In some embodiments, a bore-size controller includes a timer. Suitable bore- size controllers are similar to controllers known for use with gastrointestinal devices known in the art, for example in PCT publications WO 2006/035446 (of the Applicant) and WO 2008/104968 and WO 2008/096362 (of the Inventor), all three which are included by reference as if fully set forth herein.

In some embodiments, a duodenal liner device further comprises an event-detector functionally associated with the bore-size controller, the bore-size controller configured to activate and/or control and/or monitor the bore-changing component to change the size of the bore of the of the liner lumen as a consequence of detection of an event of significance for changing the size of the bore by the event-detector. In some such embodiments, the bore- changing component is configured to change the size of the bore from a first size to a second size, and to maintain the second size for a specified period of time subsequent to detection of such an event.

Some such or similar optional embodiments allow reduction in size or even complete closure of the bore of a portion of the liner lumen for, in some embodiments, a stronger effect (e.g., quick onset of an intense feeling of satiety after consumption of a relatively small portion of food) followed by a controlled, in some embodiments gradual, increase of the size of the bore to reduce undesired side-effects (e.g., reflux, nausea) and increase desired effects (longer lasting feeling of satiety caused by longer stimulation of gastric mechanoreceptors). For example, in some embodiments, subsequent to detection of such an event, the bore-size controller controls the bore-changing component to reduce the size of the bore from a dilated state to a predetermined smaller size (e.g., entirely shut, 12 mm² cross section) so that ingested food does not leave the stomach, but rather relatively quickly induces a relatively intense feeling of satiety. After a predetermined period of time, the bore-size controller controls the bore-changing component to gradually increase the size of the bore-size (to less than full dilation) to allow chyme to leave the stomach slowly, on the one hand to avoid reflux or a feeling of nausea, but at the same time to avoid rapid emptying of the stomach which might lead to a sudden feeling of hunger. After an additional predetermined period of time, the bore-size controller controls the bore-changing component to increase the bore-size to a maximum- sized dilated state.

In some embodiments, the event-detector comprises a manually- operated switch and the detected event comprises manual operation of the switch. For example, in some embodiments, the bore-changing component of a duodenal liner device deployed in the gastrointestinal tract of a subject is set so that the bore of the liner lumen is ordinarily in a dilated state. When intending to consume food, the subject activates the event-detector manually. As a result, the bore-size controller controls the bore-changing component to temporarily reduce the bore-size according to a pre-planned schedule.

In some embodiments, the event-detector is configured to detect physiological events occurring in the body of the subject in which the duodenal liner device is deployed, for example, physiological changes (e.g., increased gastrointestinal tract activity, gastric contraction) indicative of an event such as food ingestion or hunger. Suitable event detectors include electrodes configured for implantation or deployment in the body if the subject. Suitable event detectors are known in the art, for example in PCT publications WO 2006/035446 (of the Applicant) and WO 2008/104968 and WO 2008/096362 (of the Inventor), US Patent Publication 2003/0167024 as well as other commercially- available gastric- activity detectors such as delivered with devices produced by Betastim Ltd. (Caesarea, Israel).

A duodenal liner device may include any suitable bore-changing component. In some embodiments, the luminal surface of the liner tube defining the liner lumen is substantially smooth, substantially continuous and substantially uninterrupted by parts of the bore- changing component. In some embodiments, the luminal surface of the liner tube defining the liner lumen is substantially smooth and/or substantially continuous and/or substantially uninterrupted by parts of the bore-changing component including from the proximal lumen opening. In some embodiments, a portion of the bore-changing component comprises a portion of the liner lumen.

In some embodiments, a portion of the bore-changing component is contained within the liner lumen.

In some embodiments, the bore-changing component comprises a bore-changing balloon with an internal bore-changing volume, and the changing of the size of the bore of the portion of the liner tube comprises introduction of inflation fluid into the bore-changing volume or withdrawal of inflation fluid from the bore-changing volume of the bore-changing balloon. In some such embodiments, introduction of inflation fluid to the bore-changing volume of the bore-changing balloon reduces the size of the bore while withdrawal of inflation fluid from the bore-changing volume of the bore-changing balloon increases the size of the bore.

In some embodiments, the bore-changing volume of the bore-changing balloon encircles a portion of the liner tube.

In some embodiments, the bore-changing volume of the bore-changing balloon is located, at least partially, inside the liner lumen.

In some embodiments, a wall of the bore-changing balloon constitutes a part of the liner lumen.

In some embodiments, the bore-changing component further comprises a pressure generator configured to introduce inflation fluid into and withdraw inflation fluid from the bore-changing volume through an inflation fluid conduit, thereby changing the size of the bore of the portion of the liner lumen. In some embodiments of a duodenal liner device that includes a bore-size controller, the bore-size controller configured to activate a pressure- generator to introduce inflation fluid into or withdraw inflation fluid from the bore-changing volume.

In some embodiments, the pressure generator is configured to move inflation fluid between a reservoir and the bore-changing volume, e.g., a liquid such as water or saline or a gas such as air or nitrogen. In some embodiments, the pressure generator is configured to introduce inflation fluid from the surroundings into the bore-changing volume, for example gastric juices from the stomach or air from the surroundings. Suitable pressure generators are known to a person having ordinary skill in the art, for example in the field of gastric balloons as taught for example in US Patent 5,259,399.

The pressure generator and the associated inflation fluid conduit may be located in any suitable location. Suitable locations and implementations thereof are known to a person having ordinary skill, for example, analogous to devices discussed in PCT publications WO 2008/104968 and WO 2008/096362 of the Inventor.

In some embodiments, at least part of the pressure generator is configured for extracorporeal deployment, and in some such embodiments the inflation fluid conduit is configured to pass through the pylorus.

In some embodiments, the pressure generator is configured for intragastric deployment and the inflation fluid conduit is configured to pass through the pylorus.

In some embodiments, the inflation fluid conduit is configured to pass through a gastric wall. In some such embodiments, a portion of the pressure generator is configured for extracorporeal deployment. In some such embodiments, the pressure generator is configured for intracorporeal implantation, e.g., subcutaneous, intramuscular or submuscular.

Expandable centering component

In some embodiments, an expandable centering component of a duodenal liner device is configured for deployment in a duodenal bulb and is functionally associated with the proximal end of the liner tube. Generally, a centering component has at least two configurations: a collapsed (smaller radial dimension) configuration and an expanded (larger radial dimension) configuration. Alternatively or additionally, the centering component includes a first non-protruded and a second protruded configurations, with respect to the average outer diameter of the duodenal liner device. It is generally preferred that in a collapsed configuration the centering component be as small as possible, allowing deployment with minimal trauma.

In some embodiments, when the duodenal liner device is deployed in the duodenal bulb and the centering component is in an expanded configuration, the centering component maintains the proximal lumen opening of the liner tube substantially centered with the duodenal lumen and the pylorus, so that chyme passing the pylorus enters the proximal lumen opening of the liner tube.

In some embodiments, when the duodenal liner device is deployed in the duodenal bulb and the centering component is in an expanded configuration, the centering component helps maintain the proximal lumen opening of the liner tube dilated so that chyme passing the pylorus enters the proximal lumen opening of the liner tube.

In some embodiments, when the duodenal liner device is deployed and the centering component is in an expanded configuration, the centering component acts as an anchoring component, helping to preventing excessive distal migration of the liner tube into the gastrointestinal tract.

In some embodiments, when the duodenal liner device is deployed and the centering component is in an expanded configuration, the centering component presses against the luminal walls of the duodenal bulb to stimulate duodenal mechanoreceptors and thereby induce a feeling of satiety.

In some embodiments, the centering component is reversibly expandable from the expanded configuration to the collapsed configuration, allowing simple removal, repositioning or adjustment of the duodenal liner device, for example for clinical considerations.

In some embodiments, a centering component is self-expanding, that is to say, has an inherent tendency to adopt an expanded configuration when free of constraints. In some such embodiments, the self-expanding force is relatively weak so that when deployed inside a duodenal bulb, the force applied by the centering component does not press into and damage the gastrointestinal intima. In some embodiments, the size of the centering component in the expanded configuration is similar to or somewhat smaller than that of the duodenal bulb in which deployed. In some such embodiments, the centering component comprises a self- expanding stent or similar component.

In some embodiments, a centering component is controllably expandable, that is to say, is configured to be controllably changed from a collapsed configuration to an expanded configuration. Controllable expansion allows selection of the radial size of the centering component in an expanded configuration to be selected during deployment.

In some embodiments, the centering component is expandable by application of an outwards radial force to an inner surface of the centering component. In some such embodiments, during the deployment process, the centering component is brought to the duodenal bulb in the collapsed configuration. A deployment device comprising an expansion component such as an endoscopically-mounted balloon may be used to apply a required outwards radial force to an inner surface of the centering component to bring the centering component to an expanded configuration. In some such embodiments, the centering component comprises a balloon-expandable stent or similar component.

In some embodiments, the duodenal liner device is configured so that the expandable centering component is reversibly and controllably changeable from the collapsed configuration to an expanded configuration. In some embodiments, the expandable centering component is configured to substantially continuously increase in size from the collapsed configuration to substantially any of a continuum of expanded configurations up to a maximal size. In some embodiments, the centering component is configured to increase in size incrementally from the collapsed configuration to at least one expanded configuration.

In some embodiments, the duodenal liner device is configured so that the expandable centering component is in a collapsed configuration substantially only for deployment, removal, maintenance and adjustment of the position of the duodenal liner device. In some such embodiments, the expandable centering component acts as an important or exclusive anchoring component to maintain proper positioning of the duodenal liner device in the gastrointestinal tract.

In some embodiments, when the duodenal liner device is deployed, the radial size of the centering component in the expanded configuration may be optionally adjusted. For example, in some embodiments where the centering component function to apply pressure to the luminal walls, a person such as a treating physician optionally periodically manipulates (e.g., once a week, once a month) the size of the centering component, increasing the size in order to increase the pressure applied and decreasing the size of the centering component in order to decrease the pressure applied.

In some embodiments, a duodenal liner device further comprises a centering component controller configured to control the configuration of the centering component, for example, with respect to when the centering component is in a collapsed configuration, when the centering component is in an expanded configuration, the size of the expanded configuration, when the configuration is changed, the rate of change and the like. In some embodiments, a centering component controller includes a timer. Suitable centering component controllers are similar to the optional bore-size controllers described above. In some embodiments, a duodenal liner device includes only a centering component controller. In some embodiments, a duodenal liner device includes two distinct controllers: a centering component controller and a bore-size controller. In some embodiments, a duodenal liner device includes a single controller that functions as both as centering component controller and as a bore-size controller.

In some embodiments, a duodenal liner device further comprises an event-detector functionally associated with the centering component controller, the centering component controller configured to control the configuration of the centering component as a consequence of detection of an event of significance for changing the configuration of the centering component. In some embodiments, a duodenal liner device is provided with at least two separate event detectors, a first of two event detectors functionally associated with the centering component controller and a second of two event detectors functionally associated with a bore-size controller. In some embodiments, a duodenal liner device includes a bore- size controller and a centering component controller, both controllers functionally associated with the same event-detector.

In some such embodiments, the centering component controller is configured to change the configuration of the centering component and to maintain the configuration for a specified period of time subsequent to detection of such an event. For example, in some embodiments, a centering component is ordinarily in a collapsed configuration so as to minimize interference natural processes of the body of the subject. Substantially no pressure is applied to the luminal walls of the duodenal bulb and fluid from the stomach passes through the pyloric sphincter into the duodenum to contact the duodenal intima. Subsequent to detection of such an event (e.g., corresponding to the beginning of consumption of food), the centering component controller controls the centering component to increase in radial size from the collapsed configuration to a predetermined expanded size. In the expanded state, the centering component maintains the proximal lumen opening of the liner tube dilated and substantially centered with the duodenal lumen and the pylorus, so that fluid such as chyme passing the pylorus enters the proximal lumen opening of the liner tube. Optionally, the radial size of the centering component is such that the centering component presses against the luminal walls of the duodenal bulb to stimulate duodenal mechanoreceptors and thereby induce a feeling of satiety. The chyme that enters the proximal lumen opening of the liner tube passes through the liner lumen in the usual way. After a predetermined period of time, the centering component controller controls the centering component to change to a collapsed configuration. Such embodiments, allow the gastrointestinal tract to function in a substantially natural manner by applying the full effect of the liner tube only when food is being consumed while minimizing the influence of the deployed liner tube when food is not being consumed.

In some embodiments, the event-detector functionally associated with the centering component controller comprises a manually- operated switch and the detected event comprises manual operation of the switch. For example, in some embodiments, the centering component of a duodenal liner device deployed in the gastrointestinal tract of a subject is set so that the centering component is ordinarily in a collapsed state. When intending to consume food, the subject activates the event-detector manually. As a result, the centering component controller controls the centering component to temporarily increase in size to an expanded state according to a pre-planned schedule. In some embodiments, the event-detector functionally associated with the centering component is configured to detect physiological events occurring in the body of the subject in which the duodenal liner device is deployed, for example, physiological changes as described above with reference to an event detector functionally associated with a bore-size controller.

A duodenal liner device may include any suitable centering component. In some embodiments, a portion of the centering component comprises a portion of the liner lumen.

In some embodiments, the centering component comprises a centering balloon with a centering- component volume, and the changing of the configuration of the centering component comprises introduction of inflation fluid into the centering- component volume or withdrawal of inflation fluid from the centering- component volume. In some such embodiments, introduction of inflation fluid to the centering-component volume increase the radial size of the centering component while withdrawal of inflation fluid from the centering- component volume decreases the radial size of the centering. In some embodiments, when the centering- component volume is substantially empty of inflation fluid, the centering balloon is in a collapsed configuration.

In some embodiments, the centering balloon comprises an annular balloon encircling a portion of the liner tube.

In some embodiments, the duodenal liner device further comprises a pressure generator configured to introduce inflation fluid into and withdraw inflation fluid from the centering- component volume of the centering balloon through an inflation fluid conduit, thereby changing the configuration of the centering balloon. In some embodiments including a centering- component controller, the centering component controller is configured to activate the pressure-generator to introduce inflation fluid into or withdraw inflation fluid out of the centering-component volume of the centering balloon.

In some embodiments, a duodenal liner device is provided with at least two separate pressure generators, a first of two pressure generators functionally associated with the centering component and a second of two pressure generators functionally associated with a bore-changing component. In some embodiments, a duodenal liner device includes a bore- size controller and a centering component controller, both controllers functionally associated with the same pressure generator.

Analogously to and as discussed with reference to a bore-changing balloon, in some embodiments, the pressure generator is configured to move inflation fluid between a reservoir or from the surroundings and the centering- component volume of the centering balloon. Analogously to and as discussed with reference to a bore-changing balloon, the pressure generator and the associated inflation fluid conduit may be located in any suitable location, e.g., intragastric deployment, extracorporeal deployment or intracorporeal implantation of the pressure generator.

In some embodiments, both the expandable centering component and the bore- changing component of a duodenal liner device are inflatable balloons, a centering balloon and a bore-changing balloon, respectively. In some such embodiments, the centering component volume and the bore-changing volume balloon are in fluid communication so that fluid is introduced into both internal volumes at the same time. In some such embodiments, the centering component volume and the bore-changing volume are substantially the same. In some embodiments, the internal volume of the centering balloon and the bore-changing balloon are mutually isolated and devoid of fluid communication.

In some embodiments, a duodenal liner device further comprises an expansion restrictor functionally associated with the centering component. Generally, an expansion restrictor is configured to substantially limit the radial expansion of the expandable centering component to a defined maximal diameter and/or to change the shape of the centering component, for example to give the centering component a more elongate shape when inflated, for example to better fit in a duodenal bulb and to ensure orientation of the proximal opening of the device across a pylorus when deployed.

In some embodiments, the expansion restrictor is configured to substantially limit the radial expansion of the expandable centering component to a single defined maximal diameter.

In some embodiments, the expansion restrictor is adjustable and is configured to allow a user to set the defined maximal diameter from a choice of at least two potential diameters.

Elongated tether

As noted above, in some embodiments, the centering component also functions as an anchoring component to prevent excessive distal migration of the duodenal liner device into the gastrointestinal tract. In some optional embodiments, the centering component does not effectively act as an anchoring component.

Some embodiments of a duodenal liner device include a tether that passes through a gastric wall of a subject when deployed that substantially anchors (alone or together with other components) a duodenal liner device in place. In some embodiments, the tether defines and passes through a channel in the body of the subject. In some embodiments, the channel is substantially straight. Duodenal liner devices including suitable tethers have been described in the co-pending PCT patent application PCT/IB2009/050253 of the Inventor, which is included by reference as if fully set-forth herein.

In addition to an anchoring/restraining function, the use of a tether as described in PCT/IB2009/050253 and herein allows for simple and efficient deployment, association with extracorporeally deployed components such as device controllers and pressure generators. Further, the use of the tether as described in PCT/IB2009/050253 and herein allows for simple and efficient maintenance and relocation of a duodenal liner device, defining a straight channel through the body of the subject and acting as a guide for a removal or maintenance tool.

Thus, in some embodiments, a duodenal liner device further comprises an elongated tether having a proximal tether end and a distal tether end, the distal tether end functionally associated with the proximal end of the liner tube, the tether configured to pass through a gastric wall of a subject in which deployed. In some embodiments, when deployed the tether passes from the duodenum through the pylorus, pyloric antrum and into the pyloric portion of the stomach of a subject in which deployed. In some embodiments, the tether passes into the gastric wall near a pyloric portion of the stomach of the subject. In some embodiments, the tether passes into the gastric wall at the greater curvature of the stomach of the subject. In some embodiments, the channel enters the body from the left side of the body of the subject. In to some embodiments, the channel is transcutaneous and enters the body at a point located no higher than the top of the twelfth thoracic vertebra T 12 and no lower than the bottom of the second lumbar vertebra L2.

In some embodiments, a tether is substantially an elongated, flexible component part of which function is to prevent release of a deployed duodenal liner device into the gastrointestinal tract with concomitant gastrointestinal blockage. When a duodenal liner device is deployed, a distal end of the tether is functionally associated with the proximal end of the liner tube while the proximal end passes through at least the gastric wall and is anchored in place. In a preferred embodiment, a tether is sufficiently strong not to break under the pulling force applied by peristalsis to the liner tube. Preferred tethers are sutures, wires, tubes and like components.

In typical embodiments, the outer surface of a tether is of a material such as used in the manufacture of percutaneous endoscopic gastrostomy tubes, such as polyethylene, polypropylene, polyethylene terephthalate (Dacron®), fluorinated hydrocarbons (e.g., polytetrafluoroethylene), silicone, polyvinylchloride, latex, polyurethane, silicone polyurethane copolymers, synthetic polyisoprene and other materials. In some embodiments, a tether comprises one or more strands of one or more materials, e.g., polyethylene (e.g., UHMWPE such as Dyneema® (Koninklijk DSM, Heerlen, The Netherlands) or Spectra® (Honeywell, Morris Township, NJ, USA)).

In some embodiments, a tether is a hollow tube and comprises one or more lumina. In some such embodiments, the tether is configured to function as a fluid conduit. In some embodiments, at least one lumen of the tether functions as an inflation fluid conduit providing fluid communication between a pressure generator and a bore-changing volume of a bore-changing balloon. In some embodiments, at least one lumen of the tether functions as an inflation fluid conduit providing fluid communication between a pressure generator and a centering component volume of a centering balloon.

It is generally preferred that the outer diameter of a tether be as small as possible to be as unobtrusive as possible, to cause as little tissue trauma as possible and to avoid substantial leakage of gastric fluids. Thus, although tethers of any suitable size may be used, in some embodiments the outer diameter of a tether is not more than about 5 mm, not more than about 3 mm, not more than about 2 mm and even not more than about 1 mm.

Passage through layers of tissue

In some embodiments, when a duodenal liner device is deployed, a tether of the duodenal liner device passes through a gastric wall and, in some embodiments, other layers of tissues.

In some embodiments, a tether passes directly through layers of tissue, that is to say, the outer surface of the tether contacts the tissue. In such embodiments, the tether may be considered as defining a channel through the body of the subject in which deployed.

In some embodiments, a tether does not pass directly through layers of tissue, but rather through a passage defined by an implanted channel- defining component. For example, in some embodiments a PEG device (e.g., a commercially- available PEG device such as a MIC™ gastrostomy feeding tube (Ballard Medical Products, Draper, Utah, USA) defines a channel through the body of the subject through which a tether passes. In some such embodiments, the tether does not necessarily contact tissue during passage in the channel, but rather contacts portions of the passage defined by of the channel-defining component. Generally, the luminal size of the passage defined by the channel- defining component is close to the external diameter of the tether to reduce or eliminate the chance of leakage. Anchor

In some embodiments, when a duodenal liner device is deployed, a proximal end of a tether of the duodenal liner device passes through at least the gastric wall and is anchored in place. Generally an anchor is a solid object. In some embodiments, an anchor comprises a pad that distributes pulling forces applied by the tether on a surface. A person having ordinary skill in the art is acquainted with suitable anchors, for example anchors similar to (although in some embodiments different in shape and/or dimensions) to anchors used in implementing the Coapsys® device commercially available from Myocor, Inc. (Maple Grove, MN, USA).

In some embodiments where the tether passes through a channel- defining component, the tether is functionally associated with a dedicated anchor that is not a component of the channel- defining component. In some such embodiments, the tether is functionally associated with an anchor that is a component of the channel- defining component, such as the external anchoring button of a PEG device.

In some embodiments, the tether passes only through the gastric wall and is secured to an anchor located on and contacting an outer surface of the stomach, in some embodiments the peritoneum. In some such embodiments, an anchor distributes forces over the outer surface of the stomach.

In some embodiments, the tether passes through the gastric wall as well as other tissue to an anchor that contacts a muscle layer, for example an abdominal muscle layer. In some such embodiments, an anchor distributes forces over the outer surface of the muscle layer. An advantage of some such embodiments is that the anchor and proximal tip of the tether are hidden under the skin, reducing the chance of infection and providing a more esthetic appearance, yet are readily accessible by cutting through the skin.

In some embodiments, the tether passes through the gastric wall as well as other tissue to emerge through the skin, to be secured to an anchor that contacts the outer skin surface. A person having ordinary skill in the art is acquainted with suitable such anchors, for examples extracutaneous anchors used with commercially available PEG devices, e.g., a MIC™ gastrostomy feeding tube (Ballard Medical Products, Draper, Utah, USA).

Composition Administration

In some embodiments, a duodenal liner device as described herein is configured to facilitate administration of a composition, e.g., a pharmaceutical composition to a gastrointestinal tract in which deployed. In such embodiments, a duodenal liner device includes additional components necessary for administration of a pharmaceutical composition. Such components are described in PCT patent publications WO 2008/096362 and WO 2008/104968 and PCT patent application PCT/IB2009/050253 of the Inventor, all three which are included by reference.

Gastric balloon

A duodenal liner device as described herein may, in some instances, be used with a gastric balloon to have an additional or increased beneficial effect. In some embodiments, a duodenal liner device as described herein is deployed together with a known gastric balloon. In some embodiments, a duodenal liner device as described herein includes a functionally- associated gastric balloon, substantially as described in PCT patent publication WO 2008/104968 and PCT patent application PCT/IB2009/050253 of the Inventor.

Stimulating electrodes

In some embodiments, a duodenal liner device as described herein is configured to allow electrical stimulation of the gastrointestinal tract. In such embodiments, a duodenal liner device includes additional components necessary for electrical stimulation of the gastrointestinal tract. Such components are described in PCT patent publications WO 2008/096362 and WO 2008/104968.

An embodiment of a duodenal liner device, duodenal liner device 38 is schematically depicted in cross section in Figures 2A and 2B and in cross section deployed in a human gastrointestinal tract in Figures 2C and 2D.

Duodenal liner device 38 comprises a 50 cm long tube 40 of elastomeric polyurethane having 0.1 mm thick (in some embodiments between 0.05 and 0.2 mm thick) walls and a 35 mm inner diameter. About 4 cm of the proximal end of tube 40 are folded over and secured to the outer wall of tube 40 using a polyurethane adhesive at seam 42 to define a 3 cm long tubular centering- component volume 44 in which a self-expanding stent 46 of shape-memory Nitinol is contained. The fold defines a proximal end 48 of device 38.

In Figures 2, five stent struts are seen in cross section. As known for self-expanding stents, stent 46 may be constrained to a small radius collapsed configuration by application of an inwards radial force. When the constraint is released, stent 46 radially expands to an expanded configuration. In Figures 2 A and 2B, stent 46 is depicted unconstrained in a fully expanded configuration. A 5 cm wide inner balloon-defining tube 50 of 0.03 mm thick (in some embodiments between 0.02 and 0.1 mm thick) elastomeric polyurethane is secured to the inner walls of tube 40 with a circular proximal seam 52a near proximal end 48 and a circular distal seam 52b defining a tubular bore-changing volume 54.

Defining inflation fluid conduit 56 is a 100 cm long 1.5 mm outer diameter polyurethane tube having a 1 mm diameter lumen secured with polyurethane adhesive to the luminal wall of tube 40 in parallel to the axis of tube 40 from a distal end 58 of tube 40 (and also device 38) and to the luminal surface of inner balloon-defining tube 50 until about 1 cm from proximal end 48 of device 38. A distal end 60 of inflation fluid conduit 56 is sealed with a plug of silicone adhesive. A 1 mm bore-changing perforation 62 through a wall of inflation fluid conduit 56 and inner balloon-defining tube 50 provides fluid communication between the lumen of inflation fluid conduit 56 and bore-changing volume 54.

At a proximal end 64 of inflation fluid conduit 56 is a bore-size inlet valve 66 such as known in the art of gastrostomy feeding tubes (e.g., the MIC Gastrostomy Feeding Tube by Kimberly-Clark N.V., Zaventem, Belgium). When engaged with a standard syringe, bore-size inlet valve 66 opens, allowing inflation fluid (a liquid or gas) to be introduced into or withdrawn from the lumen of inflation fluid conduit 56 and, through bore-changing perforation 62, also into bore-changing volume 54. When the syringe is disengaged, bore-size inlet valve 66 closes.

A liner tube 67 of device 38 comprises tube 40 including a proximal lumen opening 68 defined by proximal end 48 and a distal lumen opening 70 defined by distal end 58 of tube 40. A portion 76 of the lumen of liner tube 67 is surround by and defined by inner balloon- defining tube 50.

An expandable centering component 72 of device 38 comprises centering-component volume 44 and stent 46. As is known in the art, when constrained inside a tubular delivery device, expandable centering component 72 has a small- diameter collapsed configuration. When released from the constraints, expandable centering component 72 expands outwards to an expanded configuration.

A bore-changing component 74 of device 38 comprises inner balloon-defining tube 50, bore-changing volume 54, inflation fluid conduit 56 and bore-changing perforation 62. As the walls of inner balloon-defining tube 50 are significantly thinner and more compliant than the walls of tube 40, when inflation fluid is introduced into bore-changing volume 54 through conduit 56, inner balloon-defining tube 50 expands, reducing the size of the bore of a portion 76 of liner tube 67, Figure 2A. When inflation fluid is withdrawn from bore-changing volume 54 through conduit 56, elasticity draws inner balloon-defining tube 50 towards the inner surface of tube 40 between seams 52a and 52b, increasing the size of the bore of portion 76 of the lumen of liner tube 67, Figure 2B. When bore-changing volume 54 is empty of inflation fluid, the bore of the lumen of liner tube 67 is completely dilated.

Device 38 is depicted deployed in a human gastrointestinal tract in Figures 2C and 2D, where expandable centering component 72 is deployed in duodenal bulb 36, liner tube 67 trails distally into duodenum 16 and proximal end 64 of inflation fluid conduit 56 passes through a passage defined by a PEG (percutaneous gastrostomy) device 78.

In both Figures 2C and 2D, centering component 72 is in an expanded state, pressing lightly against, constrained by and following the contours of the intima of duodenal bulb 36. Centering component 72 anchors duodenal liner device 38 in place, preventing excessive distal migration of duodenal liner device 38 into the gastrointestinal tract. In some embodiments, the outer surface of centering component 72 includes features such as roughness, spikes, barbs, chevrons and the like to increase resistance to possible distal migration.

Importantly, centering component 72 maintains proximal lumen opening 68 dilated and substantially centered with the lumen of duodenum 16 and pylorus 34 so that chyme exiting gastric cavity 18 substantially entirely enters the lumen of liner tube 67 through proximal lumen opening 68. As the luminal surface of liner tube 67 is substantially uninterrupted by components of bore-changing component 74, the chyme flows smoothly into and through the lumen of liner tube 67.

In some embodiments, deployment of a duodenal liner device such as device 38 is performed with the help of percutaneous gastrostomy. A PEG device 72 (e.g., defining a 20 French passage from BARD, Billerica, Massachusetts, USA or Boston Scientific, Boston, Massachusetts, USA or a 24 French passage e.g. from Wilson Cook, Winston- Salem, North Carolina, USA) is deployed in the usual way, for example using the Ponsky-Gauderer pull method, defining a passage from the surroundings into gastric cavity 18 through the abdominal wall 73 and the wall of stomach 14.

Duodenal liner device 38 is advanced through PEG device 72 inside a delivery device and released inside duodenum 16 so that stent 46 expands inside and conforms to the luminal surface of duodenal bulb 36 so that expandable centering component 72 is deployed inside duodenal bulb 36, analogous to the described in US 7,267,694 for esophageal deployment of a liner device. Liner tube 67 is unfurled inside the duodenum in the usual way so that the lumen of liner tube 67 is open from proximal lumen opening 68 to distal lumen opening 70 (e.g., with the help of a liquid such as water or a solid unfurling device. Once unfurled, the distal portion of inflation fluid conduit 56 that is secured to the luminal surface of liner tube 67 functions as an anti-buckling component, reducing the chance of twisting and buckling of liner tube 67.

As noted above, proximal end 64 of inflation fluid conduit 56 and bore-size inlet valve 66 remain outside the body of the subject and is optionally secured to the proximal portion of PEG device 72.

While duodenal liner device 38 is deployed, the size of the bore of portion 76 of the lumen of liner tube 67 is adjustable by manipulation of bore-changing component 74 by introduction or withdrawal of inflation fluid (e.g., a liquid such as saline or water, a gas such as air) from bore-changing volume 54 of bore-changing component 74. The desired size of the bore of portion 76 of the lumen of liner tube 67 and therefore the amount of inflation fluid introduced into bore-changing volume 54 is determined in accordance with clinical considerations, for example, by a treating physician based on medical criteria.

Inflation fluid is introduced through bore-size inlet valve 66 into bore-changing volume 54 through fluid conduit 56 and bore-changing perforation 62, reducing the size of the bore of a portion 76 of the lumen of liner tube 67.

In Figure 2C where bore-changing volume 54 is relatively empty, the size of the bore of portion 76 of the lumen of liner tube 67 is relatively large, allowing unhindered passage of chyme from stomach 14, through pylorus 34 into and through the liner lumen.

In contrast, in Figure 2D where bore-changing volume 54 is relatively full, the size of the bore of portion 76 of the lumen of liner tube 67 is relatively small, reducing the rate of passage of chyme from stomach 14, through pylorus 34 into the liner lumen.

In a typical course of treatment using a duodenal liner device such as 38, the device is initially deployed where the amount of inflation fluid in bore-changing volume 54 is such that the size of the bore of portion 76 of the lumen of liner tube 67 is close to fully dilated, e.g., Figure 2C. The condition of the subject is monitored, especially tolerance to deployed duodenal liner device 38. Periodically, e.g. once a week, once every two weeks, at the discretion of the handling physician, bore-changing component 74 is manipulated by adding inflation fluid into bore-changing volume 54 through bore-size inlet valve 66 to decrease the size of the bore of portion 76 of the lumen of liner tube 67. The decrease in size increases the resistance to and therefore the rate of passage of chyme from gastric cavity 18 through pylorus 34. As a result, a given, relatively small, amount of food may induce a quicker and/or more intense and/or longer lasting feeling of satiety through quicker and/or greater and/or more sustained stimulation of gastric mechanoreceptors. The subject thus becomes used to consuming less food. As a result, in addition to the beneficial effects of liner tube 67, in some embodiments the subject also potentially adopts long-term modified behavior.

If the subject suffers from the side-effects of intestinal blockage such as nausea or esophageal reflux, the handling physician may choose to increase the size of the bore of portion 76 of the lumen of liner tube 67 by withdrawing inflation fluid from bore-changing volume 54 through bore-size inlet valve 66 to provide immediate relief.

If desired or required for medical reasons, duodenal liner device 38 may be removed or repositioned in any suitable way. The fact that proximal end 64 of inflation fluid conduit 56 and bore-size inlet valve 66 remain outside the body of the subject and passing through a PEG device 78 provide a number of advantages. Maintenance, removal and repositioning, if needed, are simple and performed through the passage already defined by PEG device 78. In some embodiments, inflation fluid conduit 56 is used as a guide along which devices such as tools for removal of device 38 are optionally guided.

An additional embodiment of a duodenal liner device, device 80 is schematically depicted in Figure 3 in cross section deployed in a human gastrointestinal tract. Duodenal liner device 80 is substantially the same as duodenal liner device 38 but is provided with a detachable inflation fluid conduit 56.

Specifically, as seen in Figure 3, bore-size inlet valve 66 of fluid conduit 56 is close to inner balloon-defining tube 50. At the distal end of inflation fluid conduit 56 is a coupling portion 86.

When it is desired to change the size of the bore of portion 76 of the lumen of liner tube 67, inflation fluid conduit 56 is passed through the passage defined by PEG device 78 and coupling portion 86 is contacted with bore-size inlet valve 66 of bore-changing component 74. Inflation fluid conduit 56 is rotated so that threads of coupling portion 86 engage threads of bore-size inlet valve 66, coupling inflation fluid conduit 56 to valve 66. When fully coupled, valve 66 is open and inflation fluid is optionally introduced into or withdrawn from bore-changing volume 54 to change the size of the bore of portion 76 of the lumen of liner tube 67.

An additional embodiment of a duodenal liner device, device 88 is schematically depicted in Figure 4 in cross section. Duodenal liner device 88 is substantially the same as duodenal liner device 38 discussed with reference to Figures 2 but is configured for automatic control of the size of the bore of portion 76 of the lumen of liner tube 67. Automatic control of the size of the bore of portion 76 of the lumen of liner tube 67 is effected with the help of an externally- carried unit superficially similar to known medical device controllers (e.g., the external unit of a Minimed Paradigm® insulin pump by Medtronics, Minneapolis, Minnesota, USA) including a casing 90 having the size and shape of a mobile phone and provided with a connector 92 for reversible connection to bore-size inlet valve 66 at proximal end 64 of inflation fluid conduit 56. Inside casing 90 are contained a pressure generator 94, a power storage unit 96, a device controller 98 and a manual activation switch 100. Device controller 98 is configured for wireless communication with an event-detector 102.

Device controller 98, power-storage unit 96, event-detector 102, pressure generator 94 are all similar to and function analogously to like components described in PCT patent publications WO 2008/096362 and WO 2008/104968 of the Inventor.

Pressure generator 94 is configured, under control of device controller 98, to draw air from the surroundings and introduce the air as inflation fluid into bore-changing volume 54 or to withdraw air therefrom and expel the air to the surroundings, through bore-size inlet valve 66, inflation fluid conduit 56 and bore-changing perforation 62.

Event-detector 102 is configured for implantation in a gastric wall (for example as described in US 2003/0167024), detection of electrical activity in the gastric wall indicative of food consumption, and wireless transmission of detected gastric activity to device controller 98 in a manner analogous to wireless-event detectors known in the art (e.g., as used with a Minimed Paradigm® insulin pump by Medtronics, Minneapolis, Minnesota, USA).

Device controller 98 is configured to function as a bore-size controller. Specifically, device controller 98 is configured to monitor electrical activity of the walls of a stomach through event-detector 102 and to control the size of the bore of portion 76 of the lumen of liner tube 67. Upon detection of a relevant event (e.g., electrical activity indicative of food being consumed), as detected by event-detector 102, device controller 98 activates pressure generator 94 to introduce an amount of inflation fluid into bore-changing volume 54 as described above to reduce the size of the bore of portion 76 of liner tube 67 to a predetermined smaller size. After a predetermined period of time, device controller 98 activates pressure generator 94 to withdraw inflation fluid from bore-changing volume 54 to increase the size of the bore of portion 76 of the lumen of liner tube 67, for example to a dilated state.

Deployment of duodenal liner device 88 is substantially as described above for device 38. During use, the subject in which device 88 is deployed may choose to detach and attach the external unit including device controller 98 as desired through connector 92. For example, the subject detaches the external unit for sleep and bathing, and attaches the external unit when needed.

During use, bore-changing volume 54 is ordinarily substantially empty so that the size of the bore of portion 76 of the lumen of liner tube 67 is substantially dilated.

When the subject begins to eat, event-detector 102 detects electrical activity indicative thereof. As described above, in response device controller 98 activates pressure generator 94 to introduce a predetermined amount of inflation fluid into bore-changing volume 54 to reduce the size of the bore of portion 76 of the lumen of liner tube 67 to a predetermined smaller size, e.g. 10 mm² cross section.

As discussed above with reference to device 38, due to the small size of the bore of portion 76 of the lumen of liner tube 67, a given, relatively small, amount of food may induce a quicker and/or more intense and/or longer lasting feeling of satiety through quicker and/or greater and/or more sustained stimulation of gastric mechanoreceptors.

After a predetermined period of time, device controller 98 activates pressure generator 94 to withdraw fluid from internal bore-changing volume 54 to increase the size of the bore of portion 76 to the ordinary dilated state. Subsequently, device controller 98 resumes monitoring relevant events detected by event-detector 102.

Due to the automatic event-reactive reduction of size of the bore of portion 76 of the lumen of liner tube 67, the subject gains the combined beneficial effects of a duodenal liner continuously with the additional beneficial effect of reduced rate of transfer of chyme from the stomach only when food is actually consumed, providing a more naturally functioning gastrointestinal system.

Manual activation switch 100 may be used in two ways. The subject may choose to initiate the decrease the size of the bore of portion 76 of the lumen of liner tube 67 manually by activating manual activation switch 100. Alternatively, the subject may choose to increase the size of the bore of portion 76 of the lumen of liner tube 67 manually by activating manual activation switch 100, for example due to the onset of nausea.

In some embodiments, various operating parameters of device controller 98 may be changed or modified while duodenal liner device 88 is deployed. Typical parameters that may be changed include the exact nature of event that is considered significant, the period of time after detection of a significant event when device controller 98 activates pressure generator 94, the rate of decreasing the size of the bore of portion 76, the ultimate size at which the size of the bore of portion 76 is maintained, the period of time for which the size of the bore of portion 76 is maintained in a smaller state, and the rate by which the size of the bore of portion 76 is increased. Generally operating parameters are changed at the discretion and in accordance with the decisions of a treating physician, to allow tailoring of the operating parameters to a specific subject for increased beneficial effects and reduced undesired negative side effects, as well as changing the operating parameters as the medical condition of the subject changes. The changes may be effected, for example, on a touch-screen or other interface in casing 90 (analogous, e.g., to the Minimed Paradigm® insulin pump by Medtronics, Minneapolis, Minnesota, USA).

An additional embodiment of a duodenal liner device, device 104 is schematically depicted in Figures 5A-5C in cross section and is similar in some aspects to device 38.

Like device 38, duodenal liner device 104 comprises a 50 cm long tube 40 of elastomeric polyurethane having 0.1 mm thick walls and a 35 mm inner diameter. About 5 cm of the proximal end of tube 40 are folded over and secured to the outer wall of tube 40 using a polyurethane adhesive at seam 42 to define a 4 cm long centering-component and a volume 105 that constitutes both a centering- component volume and a bore-changing volume. The fold defines a proximal end 48 of device 104.

Encircling volume 105, midway between proximal end 48 and seam 42, is expansion restrictor 106, a 3 cm wide ring of 0.2 mm thick elastomeric polyurethane with a certain diameter, typically in the range of about 50 mm to about 60 mm (the range of typical diameters of a human duodenal bulb lumen). Expansion restrictor 106 is secured to the outer surface of sleeve 40 at two points with polyurethane adhesive.

Like device 38, duodenal liner device 104 comprises inflation fluid conduit 56 with a plugged distal end 60 and including a bore-size inlet valve 66 at proximal end 64. Inflation fluid conduit 56 includes a perforation 62 allowing fluid communication between the lumen of inflation fluid conduit 56 and volume 105.

A liner tube 67 of device 104 comprises tube 40 including a proximal lumen opening 68 defined by proximal end 48 and a distal lumen opening 70 defined by distal end 58 of tube 40.

Both an expandable centering component 72 and a bore-changing component 74 of device 104 comprise volume 105, inflation fluid conduit 56, perforation 62 and expansion restrictor 106. Thus, the volume of expandable centering component 72 and bore-changing component 74 may be considered as being in fluid communication. As discussed below, expansion restrictor 106 is configured to substantially limit the radial expansion of expandable centering component 72 to a defined maximal diameter when inflation fluid is introduced into volume 105 as well as to change the shape of centering component 72, for example to give centering component 72 a more elongate shape when inflated, for example to better fit in a duodenal bulb and/or to ensure orientation of proximal opening 68 of device 104 across a pylorus when deployed.

Deployment and use of duodenal liner device 104 is analogous to the described above.

During deployment, the performing physician is provided with a variety of different duodenal liner devices 104 having different sized expansion restrictors 106. The physician determines the diameter of the duodenal bulb lumen of the subject, e.g., by ultrasound imaging, and selects a specific device 104 having an expansion restrictor 106 similar in size to the diameter of the duodenal bulb lumen of the subject.

The selected device 104 is deployed as described above so that expansion restrictor 106 is located inside the duodenal bulb, for example through a PEG device 78, where centering component 72 is in a collapsed state where volume 105 is substantially empty of inflation fluid, see Figure 5 A.

The performing physician introduces inflation fluid into volume 105 through inflation fluid conduit 56 using bore-size inlet valve 66. Volume 105 expands substantially equally inwards and outwards until volume 105 reaches an outer diameter substantially equal to the diameter of expansion restrictor 106, Figure 5B. Duodenal liner device 104 is thereby anchored in the gastrointestinal tract of the subject but the size of the bore of a portion 76 of the lumen of liner tube 67 is still large enough to provide no substantial effect.

When it is desired to reduce the size of the bore of portion 76 of the lumen of liner tube 67 in accordance with the teachings herein, additional inflation fluid is introduced into volume 105. Since expansion restrictor 106 is significantly less compliant than the walls of liner tube 67 the luminal walls defining volume 105 expand inwards, reducing the size of the bore of portion 76 of the lumen of liner tube 67, Figure 5C, in accordance with the decision of the performing physician.

In duodenal liner device 104, expansion restrictor 106 is a ring of polyurethane that encircles volume 105. Expansion restrictors for embodiments of duodenal liner devices may be of any suitable material and of any suitable structure.

In duodenal liner device 104, expansion restrictor 106 is connected to centering component 72. In some embodiments, an expansion restrictor is a separate component.

In some embodiments, an expansion restrictor is adjustable. In some such embodiments, the expansion restrictor is configured to allow a user to set the defined maximal diameter from a choice of at least two potential diameters. For example, during deployment the diameter of the duodenal bulb lumen of the subject is determined, the treating physician adjusts the expansion restrictor to limit the radial size of the centering component to a suitable diameter and then deploys the device substantially as described above. In some embodiments, a suitable diameter is generally a diameter that is approximately the diameter of the duodenal bulb lumen (generally between about 50 mm and about 60 mm). In some embodiments, a suitable diameter is somewhat smaller that the diameter of the duodenal bulb lumen.

For example, in some embodiments having an adjustable expansion restrictor, an expansion restrictor has a structure analogous to a cable tie. For example, in some such embodiments, an expansion restrictor has a structure analogous to a belt. In some such embodiments, the expansion restrictor is a separate component that engages loops on a surface of the centering component.

An additional embodiment of a duodenal liner device, device 108 is schematically depicted in Figures 6A-6C in cross section and is similar in some aspects to device 38.

Duodenal liner device 108 comprises a 50 cm long tube 40 of elastomeric polyurethane having 0.2 mm thick walls and a 35 mm inner diameter, Figure 6 A.

Secured to the lumen of tube 40 is a polyurethane conduit tube 110, depicted in cross section in Figure 6B, having a 2 mm outer diameter and 0.2 mm thick walls, with four lumens defined by a cross-shaped partition having 0.3 mm wide arms: a drawstring lumen 112a, 112b, 112c and 112d

Secured to the outer surface of the proximal end of tube 40 with polyurethane adhesive at distal outer seam 114a (about 5.5 cm from the proximal end of tube 40) and proximal outer seam 114b (at the proximal end of tube 40) is outer balloon-defining tube 116, a 6 cm long tube of elastomeric polyurethane having 0.1 mm thick walls and a 35 mm inner diameter. Between distal outer seam 114a and proximal outer seam 114b, the inner surface of outer balloon-defining tube 116 and the outer surface of tube 40 define centering-component volume 44. A centering component perforation 120 penetrates through a wall of conduit tube 100 to provide fluid communication between centering-inflation lumen 112a and centering- component volume 44. Approximately 0.5 cm of outer balloon-defining tube 116 extends beyond the proximal end of tube 40.

Secured to the inner surface of the proximal end of tube 40 and a portion of conduit tube 110 with polyurethane adhesive at distal inner seam 122a (about 5.5 cm from the proximal end of tube 40) and proximal inner seam 122b (at the proximal end of tube 40) is inner balloon-defining tube 50, a 6 cm long tube of elastomeric polyurethane having 0.1 mm thick walls and a 35 mm inner diameter. Between distal inner seam 122a and proximal inner seam 122b, the outer surface of inner balloon-defining tube 50 and the inner surface of tube 40 define a bore-changing volume 54. A bore-changing perforation 62 penetrates through a wall of conduit tube 110 to provide fluid communication between bore-changing inflation lumen 112b and bore-changing volume 54. Approximately 0.5 cm of inner balloon-defining tube 50 extends beyond proximal end of tube 40.

The portions of outer balloon-defining tube 116 and inner balloon-defining tube 50 that extend beyond the proximal end of tube 40 are welded together to define a ring-shaped drawstring volume 128 at the proximal end of tube 40 defining a proximal end 48 of device 108.

As depicted in Figure 6D, a portion of the material defining drawstring volume 128 is cut away around conduit tube 110. A drawstring perforation 130 penetrates through a wall of conduit tube 110 to provide fluid communication with drawstring lumen 112c at the level of drawstring volume 128. A length of expanded polytetrafluoroethylene suture 132 loops through drawstring volume 128. Both ends of suture 132 enter drawstring perforation 130, passing through drawstring lumen 112c to the proximal end of conduit tube 110.

Distally to distal outer seam 114a, four composition perforations 134 pass through tube 40, penetrating through a wall of conduit tube 110 to provide fluid communication with composition lumen 112d of conduit tube 110.

Secured to proximal end 64 of conduit tube 110 is an adaptor 136. Adaptor 136 includes a free opening 118 in communication with drawstring lumen 112, through which the ends of suture 132 emerge.

Adaptor 136 also includes a bore-size inlet valve 66 in fluid communication with bore- changing inflation lumen 112b, a centering fluid inlet valve 138 in fluid communication with centering inflation lumen 112a, and a composition inlet valve 140 in fluid communication with composition lumen 112d, valves 66, 138 and 140 similar to bore-size inlet valve 66 described above.

A liner tube 67 of device 108 comprises tube 40 including a proximal lumen opening

68 defined by proximal end 48 and a distal lumen opening 70 defined by distal end 58 of tube 40. A portion 76 of the lumen of liner tube 67 is defined by inner balloon defining tube 50.

An expandable centering component 72 of device 108 comprises centering-component volume 44, centering inflation lumen 112a and centering component perforation 120. A bore-changing component 74 of device 108 comprises volume 54, bore-changing inflation lumen 112b and bore-changing perforation 62.

A composition-administration component of device 108 comprises composition lumen 112d, composition inlet valve 140, and composition perforations 134.

Deployment and use of duodenal liner device 108 is analogous to the described above.

Device 108 is deployed in a collapsed state as described above where both centering- component volume 44 of expandable centering component 72 and bore-changing volume 54 of bore-changing component 74 are substantially empty of inflation fluid.

When expandable centering component 72 is located in duodenal bulb 36, inflation fluid is introduced into centering- component volume 44 through centering inflation lumen 112a using centering fluid inlet valve 138. Centering-component volume 44 expands radially outwards until expandable centering component 72 reaches an outer diameter substantially equal to that of duodenal bulb 36, Figure 6F. Duodenal liner device 108 is thereby anchored in the gastrointestinal tract of the subject.

When it is desired to reduce the size of the bore of portion 76 of the lumen of liner tube 67, inflation fluid is introduced into bore-changing volume 54, in a manner analogous to device 38 discussed above, Figure 6G.

When device 108 is deployed, a composition is optionally administered to the subject through the duodenum, for example, in accordance with the teachings of PCT publication WO2008/104968 of the Inventor. Specifically, a composition is forced through composition inlet valve 140, into composition lumen 112d and out through composition perforations 134 into duodenum 16.

When it is desired to remove device 108, substantially all inflation fluid is withdrawn from centering-component volume 44 and bore-changing volume 54 through centering fluid inlet valve 138 and bore-size inlet valve 66 and the associated lumens, respectively. The ends of suture 132 are pulled out through free-opening 118 in adaptor 136, acting as a drawstring collapsing proximal end 48 of device 108 and pulling device 108 out of duodenum 14, through PEG device 78 and out of the body of the subject.

An additional embodiment of a duodenal liner device, device 142 is schematically depicted in Figure 7 in cross section. Duodenal liner device 142 is substantially the same as duodenal liner device 108 discussed with reference to Figures 6 but includes a device controller 98 that is configured to function as a bore-size controller and as a centering- component controller for automatic control of the size of the bore of portion 76 of the lumen of liner tube 67, analogously to device 88 discussed with reference to Figure 4 and also, in some embodiments, for automatic control of the configuration of centering component 72.

Similarly to device 88, device 142 comprises an externally- carried unit including a casing 90 in which are contained a pressure generator 94, a power storage unit 96, a device controller 98 and a manual activation switch 100. Device controller 98 is configured for wireless communication with an event-detector 102. Additionally, contained within casing 90 are a composition pressure generator 144, a composition reservoir 146 and a selection valve 148. Apparent on the outside of casing 90 is connector 150 configured to reversibly connect to adaptor 136 at proximal end 64 of conduit tube 110.

When connector 150 is properly connected to adaptor 136, composition pressure generator 144 is functionally associated with composition inlet valve 140 and pressure generator 94 is functionally associated with centering fluid valve inlet 138 and bore-size inlet valve 66 through selection valve 148.

Deployment of device 142 is analogous to the described above.

In some embodiments, during deployment, expandable centering component 72 is expanded manually as described above.

In some embodiments, during deployment, selection valve 148 is set by device controller 98 to provide fluid communication between pressure generator 94 and centering- component volume 44. Subsequently, device controller 98 activates pressure generator 94 to introduce ambient air as inflation fluid through selection valve 148, centering fluid inlet valve 138, centering inflation lumen 112a and centering component perforation 120, increasing the size of centering component 72.

Use of device 142 is analogous to the described above.

In some embodiments, in parallel with the automatic changing of the size of the bore of portion 76 of the lumen of liner tube 67 under control of device controller 98 (analogously to device 88 discussed with reference to Figure 4), device controller 98 activates composition pressure generator 144 to administer a composition contained in composition reservoir 146 to the gastrointestinal tract, for example in accordance with the teachings of PCT patent publication WO 2008/104968 of the Inventor. Specifically, based on detection of an event, e.g., periodically or a physiological event detected by an event detector 102, device controller 98 activates composition pressure generator 144 to draw composition contained in composition reservoir 146 and force the composition through composition inlet valve 140, composition lumen 112d, to emerge through composition perforations 134. In some embodiments, the small size of the bore of portion 76 of the lumen of liner tube 67 together with the administration of a composition, for example as taught in PCT patent publication WO 2008/104968, means that a given, relatively small, amount of food may induce a quicker and/or more intense and/or longer lasting feeling of satiety through quicker and/or greater and/or more sustained stimulation of gastric mechanoreceptors coupled with the effect of the composition.

In some embodiments, in parallel with the automatic changing of the size of the bore of portion 76 of the lumen of liner tube 67 under control of device controller 98, device controller 98 activates pressure generator 94 and selection valve 148 to automatically vary the size of centering component 72. Specifically, based on detection of an event, e.g., periodically or a physiological event detected by an event detector 102, device controller 98 sets selection valve 148 to provide fluid communication between pressure generator 94 and centering- component volume 44 through centering inflation lumen 112a. Device controller 98 then activates pressure generator 94 to introduce or withdraw inflation fluid (air) through selection valve 148, centering fluid inlet valve 138, centering inflation lumen 112a and centering component perforation 120, increasing or decreasing the size of centering component 72.

For example, in some such embodiments, the radial size of centering component 72 is slightly reduced at some predetermined rest configuration, having a size sufficient to maintain device 142 properly positions in the gastrointestinal tract without applying excessive pressure to the luminal walls of duodenal bulb 36 so as to avoid an undesirable side-effect, for example, adhesion of centering component 72 to the duodenal bulb intima, blocking and necrosis of duodenal bulb intima, extensive distension of duodenal bulb 36 and/or desensitization of duodenal bulb mechanoreceptors.

Automatically, e.g., upon detection of event such as consumption of food by event detector 102 or triggering by manual activation switch 100 (in some embodiments subsequent to reduction of the size of the bore of portion 76 of the lumen of liner tube 67), device controller 98 activates pressure generator 94 to increase the size of centering component 72 to a predetermined stimulating configuration.

In some embodiments, the increased size of the stimulating configuration of centering component 72 assists in preventing distal migration of device 142 due to the intestinal peristalsis which in some embodiments increases concomitantly with a detected event or in some embodiments comprises a detected event that triggers automatic increase of size of centering component 72. After a predetermined period of time, device controller 98 activates pressure generator 94 to withdraw inflation fluid from bore-changing volume 54 to decrease the size of centering component 72, for example, to the predetermined rest configuration. Decreasing of the size of centering component 72 is optionally earlier, later or substantially at the same time, as withdrawing of inflation fluid from bore-changing volume 54 to increase the size of the bore of portion 76 of the lumen of liner tube 67. In some embodiments, inflation fluid is withdraw from bore-changing volume 54 in a first step, allowing emptying of stomach 14, and inflation fluid is withdraw from centering-component volume 44 after a certain period of time, so that centering component 72 is reduced in size only after the intensity of duodenal peristalsis is reduced.

In some embodiments, the increased size of the stimulating configuration of centering component 72 leads to stimulation of duodenal mechanoreceptors of duodenal bulb 36 to induce a feeling of satiety. In some embodiments, the combined beneficial effects of the small size of the bore of portion 76 of the lumen of liner tube 67 together with the stimulation of duodenal mechanoreceptors means that a given, relatively small, amount of food may induce a quicker and/or more intense and/or longer lasting feeling of satiety through quicker and/or greater and/or more sustained stimulation of gastric mechanoreceptors and duodenal mechanoreceptors. Due to the automatic event-reactive reduction of size of the bore of portion 76 of the lumen of liner tube 67 and event-reactive stimulation of duodenal satiety mechanoreceptors, in some embodiments the subject gains the combined beneficial effects of a duodenal liner continuously with the additional beneficial effect of stimulated duodenal satiety mechanoreceptors and a reduced rate of transfer of fluids from the stomach only when food is actually consumed, providing a more naturally functioning gastrointestinal system.

In some embodiments, the diameter of the centering component 72 in the rest configuration is only slightly smaller than the diameter in the stimulating configuration. For example, in some embodiments, the diameter in the rest configuration is no less than about 90% of the diameter in the stimulating configuration, e.g., 50 mm vs. 55 mm. For example, in some embodiments, the diameter in the rest configuration is no less than about 95% of the diameter in the stimulating configuration, e.g., 52.5 mm vs. 55 mm.

In some embodiments, similar to device 142, a corresponding device controller 98 is not configured to control the configuration of a centering component 72. Rather, in some such embodiments, controlling the configuration of centering component 72 is performed manually, analogously to device 108 discussed with reference to Figures 6. In the embodiments described above, duodenal liner devices are provided comprising a bore-changing component that allows changing the size of a bore of a portion of a liner lumen of the device when deployed in a duodenum. For example, in devices 38, 80, 88, 104, 108 or

142 the size of a portion of the bore can be changed by introduction or removal of a fluid from a bore-changing volume 54.

Some embodiments of the invention relate to restriction devices configured for deployment in a mammalian duodenum to restrict the passage of chyme from the stomach to the downstream portions of the digestive tract, to achieve an effect similar to the bore- changing component of the duodenal liner devices described above or some embodiments of the devices described in the PCT published as WO 2008/096362 of the Inventor. Such restriction devices have a restriction section to restrict the passage of chyme from the stomach passing therethrough, the restricting section having a pre-determined fixed deployed bore-size. Specifically, when properly deployed in a duodenal bulb, such restriction devices have a restriction section having a fixed bore size that acts as a bottleneck to the passage of chyme from the stomach to the downstream portion of the intestinal tact.

Thus according to an aspect of some embodiments there is also provided a restriction device for deployment in a mammalian (human or non-human) duodenum, comprising: an inflatable annular (ring-shaped) balloon configured for deployment in a duodenal bulb, the annular balloon having a collapsed configuration and an inflated configuration, wherein when the annular balloon is deployed in a duodenal bulb in the inflated configuration the device has an outer diameter and a restriction section having a fixed bore-size to restrict the passage of chyme from the stomach through the restriction section.

In some embodiments, the fixed bore-size of the restriction section is defined by the size of the hole of the annular balloon.

In some embodiments, the fixed bore-size of the restriction section is defined by a restriction component distinct from the annular balloon. In such embodiments, the restriction component can be of any suitable shape, material and construction. In some embodiments, the restriction component has a funnel-shape secured to the annular balloon allowing passage of chyme through the missing apex of the funnel-shape that constitutes the restriction section. In some embodiments, the restriction component is substantially a planar ring-shaped sheet of material secured to the annular balloon, where the hole of the ring constitutes the restriction section.

The annular balloon is of any suitable dimensions. Suitable dimensions are typically dependent on the intended use of the device. Devices intended for deployment in younger human subjects typically comprise an annular balloon having an outer diameter of between about 10 and 60 mm, in some embodiments between about 15 and 50 mm, and in some embodiments between about 20 and 40 mm. Devices intended for deployment in adult human subjects typically comprise an annular balloon having an outer diameter of between about 20 to 80 mm, in some embodiments between about 25 to 70 mm, and in some embodiments between about 30 and 60 mm. The inflated axial length of an annular balloon is typically between about 5 and 100 mm, in some embodiments between about 10-70 mm, and in some embodiments between about 30 and 50 mm.

In some embodiments, the fϊxed-bore-size of the restriction section is not more than about 38 mm² (corresponding to a radius of about 3.5 mm of a round bore), not more than about 28 mm² (corresponding to a radius of about 3 mm of a round bore), not more than about 19 mm² (corresponding to a radius of about 2.5 mm of a round bore), not more than about 12 mm² (corresponding to a radius of about 2 mm of a round bore), not more than about 7 mm² (corresponding to a radius of about 1.5 mm of a round bore) and in some embodiments not more than about 3 mm² (corresponding to a radius of about 1 mm of a round bore).

Generally, the inflatable annular balloon of the restriction device is similar in function, operation and construction to inflatable annular balloons used as expandable centering components of embodiments of duodenal liner devices described hereinabove. Generally, the annular balloon functions as a centering component to maintain the proximal opening of the restriction section across the pylorus. In some embodiments, the annular balloon comprises a centering- component volume, and the changing of the configuration of the annular balloon comprises introduction of inflation fluid into the centering-component volume or withdrawal of inflation fluid from the centering- component volume. Introduction of a sufficient amount of inflation fluid to the centering- component volume so that the annular balloon is inflated brings the device to a deployed configuration. When the centering-component volume is substantially empty of inflation fluid so that the annular balloon is substantially entirely deflated and in a collapsed configuration, the device has small- dimensions allowing simple deployment.

In some embodiments, the annular balloon has a substantially fixed inner diameter.

In some embodiments, the annular balloon has a substantially fixed outer diameter when fully inflated. In some embodiments, the outer diameter of the annular balloon is not fixed, and substantially increases with the introduction of additional inflation fluid. In some embodiments the annular balloon is substantially made of two parts: a distal balloon part and a proximal balloon part.

In some embodiments, the restriction device further comprises a liner tube configured for deployment inside the duodenum having walls of a flexible material defining a liner lumen, a proximal end defining a proximal lumen opening, and a distal end defining a distal lumen opening, substantially as described above with reference to duodenal liner devices. In such embodiments, the liner tube is configured so that chyme passing through the restriction section enters the liner lumen. In some embodiments, the restriction device is devoid of a liner tube.

In some embodiments, the restriction device further comprises a tether, substantially as described above with reference to the duodenal liner device. In some such embodiments, the restriction device further comprises an anchor, substantially as described above with reference to duodenal liner devices.

In some embodiments, the restriction device is further configured for administration of a composition, for example in the gastrointestinal tract, substantially as described above with reference to duodenal liner devices.

In some embodiments, the restriction device further comprises a gastric balloon, substantially as described above with reference to duodenal liner device.

In some embodiments, the restriction device comprises stimulating electrodes, substantially as described above with reference to duodenal liner devices.

In some embodiments, the restriction device further comprises an expansion restrictor functionally associated with the annular balloon, substantially as described above with reference to the duodenal liner device, for example expansion restrictor 62 of device 104 depicted in Figures 5. Such an expansion restrictor is generally configured to substantially limit the radial expansion of the annular balloon to a defined maximal outer diameter when inflation fluid is introduced into the internal volume of the annular balloon as well as to change the shape of the annular balloon, for example to give the annular balloon a more elongate shape when inflated, for example to better fit in a duodenal bulb and/or to ensure orientation of a proximal opening of the device across a pylorus when deployed. In some embodiments, the expansion restrictor is configured to substantially limit the radial expansion of the annular balloon to a single defined maximal outer diameter. In some embodiments, the expansion restrictor is adjustable and is configured to allow a user to set the defined maximal outer diameter from a choice of at least two potential outer diameters. A challenge encountered when implementing methods of treatment with the help of a restriction device as described herein including a restriction section having a fixed bore-size for restricting the passage of chyme from the stomach to the duodenum is adjustment of the size of the restriction, that is to say, to increase or to decrease the restricting effect when desired.

An aspect of some embodiments of a method of treatment described herein is the use of a relatively cheap restriction device that is simple to deploy and to remove.

Preferably, restriction devices such as described herein are deployed through a transcutaneous passage (PEG) into the gastrointestinal tract, for example as described hereinabove, preferably with a line (e.g., tether) secured between the device and accessible proximity of the transcutaneous passage. In some embodiments the line provides a device- anchoring function. In some embodiments, the line provides a fluid transport function. Additionally, for removal of the restriction device, the line can be used as a convenient guide along which a removal tool can be manoeuvred for simple and safe removal of the device.

After a first already-deployed restriction device is removed from the body of a subject, a replacement restriction device is deployed, in some embodiments having a different restriction section bore-size. As a restriction device as described above is simple to deploy, simple to remove, causes little if any damage to the duodenal intima and is cheap, the method is advantageous to known methods.

Method of making a restriction device

It is desirable to have a restriction device having a defined restriction section bore-size that is safe and robust when deployed in a subject. It is also desirable that the device be cheap and simple to manufacture to allow the periodic replacement of a device for safety or for adjusting the bore-size of the restriction section.

In some embodiments, the annular balloon of a device that is configured for deployment in the duodenal bulb (e.g., a restriction device as described herein) must have limited inward expansion, that is to say, over-inflation does not cause substantial inwards expansion of the annular balloon to undesirably close and even block the hole through the balloon.

In some embodiments, the annular balloon of a device that is configured for deployment in the duodenal bulb (e.g., a restriction device or a duodenal liner device as described herein) must have limited outwards expansion, that is to say, over-inflation does not cause substantial expansion of the annular balloon outwards to increase the balloon outer diameter and potentially damage the duodenal bulb in which deployed.

Herein is taught a method of manufacture of a restriction device for deployment in a mammalian duodenum as described above, the device including an inflatable annular balloon configured for deployment in a duodenal bulb, the method comprising:

a) providing a proximal balloon part, made of a sheet of flexible material, having a substantially circular periphery and a distal balloon part made of a sheet of flexible material having a substantially circular periphery;

b) sealingly attaching the periphery of the proximal balloon part to the periphery distal balloon part to make an outer balloon seam; and

c) sealingly attaching an inner area of the proximal balloon part to an inner area of the distal balloon part to make a luminal balloon seam having a closed-curve shape defining a bore of the annular balloon;

thereby making an annular balloon with an internal volume between the proximal balloon part, the distal balloon part, the outer balloon seam and the luminal balloon seam, the annular balloon having an outer diameter defined by the outer balloon seam; and the size of the bore of the annular balloon defined by the luminal balloon seam.

The closed-curve shape of the luminal balloon seam is any suitable shape, typically round, but in some embodiments, square, rectangular, triangular, or oval.

In some embodiments, the distal and proximal balloon parts are provided having a hole or the like around which the luminal balloon seam is made.

In some embodiments, the distal and proximal balloon parts are provided as solid sheets of materials and after or during when the luminal balloon seam is made, excess material is removed from inside the luminal balloon seam to clear the bore of the annular balloon.

The materials from which the proximal and distal balloon parts are made are any suitable material such as polyurethane and elastomeric silicone.

An embodiment of a restriction device, device 152 is schematically depicted in Figure 8 in cross section and is similar in some aspects to duodenal liner device 104 discussed with reference to Figures 5.

Like duodenal liner device 104, device 152 includes a liner tube 67 that comprises a 50 cm long tube 40 of elastomeric polyurethane having 0.1 mm thick walls and a 35 mm inner diameter. However, a 3 cm section of the proximal end of tube 40 is tapered so that the proximal lumen opening of tube 40, is 5 mm in diameter.

Secured to the proximal end of tube 40 is an inflatable annular balloon 154 having a toroidal inner volume 105. Annular balloon 154 comprises a distal balloon part 156 and a proximal balloon part 158 .

Distal balloon part 156 (a half torus, corresponding to a torus "sliced" in a plane perpendicular to the torus axis) of elastomeric polyurethane is secured with polyurethane adhesive along and conforming to an outer surface of the tapered proximal end of tube 40 to define a distal balloon part / tube seam 160.

Proximal balloon part 158, also a half torus, matching distal balloon part 156 is attached (e.g., by welding or adhesive) to distal balloon part 156 at an outer balloon seam 162 and a luminal balloon seam 164 so that distal balloon part 156 and proximal balloon part 158 together define inflatable annular balloon 154 with inner volume 105.

Like device 104, device 152 comprises inflation fluid conduit 56 with a plugged distal end 60 and including an inlet valve at a proximal end (not depicted in Figure 8). Inflation fluid conduit 56 includes a perforation 62 allowing fluid communication between the lumen of inflation fluid conduit 56 and inner volume 105 of annular balloon 154.

When inner volume 105 is substantially empty of fluid, annular balloon 154 is in a small- dimensioned collapsed configuration suitable for deployment.

When inner volume 105 is filled with fluid, annular balloon 154 is in an inflated configuration, having a size and shape suitable for deployment in a human duodenal bulb. Outer balloon seam 162 defines a 50 mm fixed outer diameter of annular balloon 154. Due to the presence of outer balloon seam 162, over-inflation of annular balloon 154 does not substantially increase the outer diameter but leads to axial stretching of balloon 154. Luminal balloon seam 164 substantially defines a 5 mm diameter bore-size of a restriction section 166. Due to the presence of luminal balloon seam 164, over-inflation of annular balloon 154 does not substantially decrease the bore-size of restriction section 166.

Deployment and use of device 152 is similar to the described above with reference to duodenal liner devices.

During deployment, the performing physician is provided with a variety of different devices 152 having annular balloons 154 with different sized outer diameters and different restriction section 166 bore-sizes (in some embodiments, the different devices are provided together as components of a kit comprising at least two such devices). Analogously to the described above for device 104, the physician determines the diameter of the duodenal bulb lumen of the subject, e.g., by ultrasound imaging, and selects a group of devices 152 having an annular balloon 154 with an outer diameter similar in size to the diameter of the duodenal bulb lumen of the subject.

From the variety of devices 152, the performing physician, based on medical criteria, a calculated prognosis or trial-and error, then selects a specific device 152 having a certain restriction section 166 bore-size, where a smaller bore-size leads to a comparatively greater restriction of the passage of chyme from the stomach through the restriction section (in some embodiments leading to a greater gastric- evacuation delaying effect) and where a larger bore- size leads to a comparatively lesser restriction of the passage of chyme from the stomach through the restriction section (in some embodiments leading to a lesser gastric- evacuation delaying effect).

The selected device 152 with annular balloon 154 in a collapsed configuration is deployed substantially as described above (for example through a PEG device 78) so that annular balloon 154 is located inside the duodenal bulb. In some embodiments, a restriction device such as 152 is provided packaged in a tubular delivery device. In some such embodiments, the distal end of the tubular delivery device is passed through a transcutaneous passage (e.g., of PEG device 78), through the pylorus into the duodenal bulb. The restriction device is pushed out of the delivery device while the delivery device is drawn outwards so that annular balloon 154 remains inside the duodenal bulb with inflation fluid conduit 56 trailing from the delivery device. The delivery device is withdrawn so that a proximal end of the inflation fluid conduit 56 is accessible. Inflation fluid is introduced into the volume 105 of annular balloon 154 through inflation fluid conduit 56 until volume 105 is sufficiently filled so that annular balloon 154 is in an inflated configuration having an outer diameter determined by outer balloon seam 162 and a fixed restriction section 166 bore-size determined by luminal balloon seam 164. Device 152 is this properly deployed with annular balloon 154 seated inside the duodenal bulb. The proximal end of inflation fluid conduit 56 is secured to the outer part of the transcutaneous passage substantially as described above.

Device 152 is thereby deployed in the duodenum where annular balloon 154 maintains proximal lumen opening 68 of liner tube 67 across the pylorus. Chyme from the stomach passes through the pylorus and into proximal lumen opening 68. The rate of passage of chyme into the distal portions of liner tube 67 and the downstream portions of the digestive tract is restricted by the limited size of restriction section 166.

If after some time the physician decides that the bore-size of the deployed restriction section 166 is not suitable, the deployed device 152 is removed and a different device 152 having a restriction section 166 with a desired bore-size is deployed instead. For example, a physician decides to replace an already- deployed device 152 having a restriction section 166 with a 5mm diameter round bore-size with a device 152 having a restriction section 166 with a 3 mm diameter round bore-size.

An additional embodiment of a restriction device, device 168 is schematically depicted in Figures 9A through 9J. Device 168 is substantially entirely fashioned of elastomeric polyurethane.

Device 168 is similar in some aspects to restriction device 152. One notable difference is that in device 168, an annular balloon 154 comprises a proximal balloon part 158 and a distal balloon part 156 that are disks of material and not than half tori as in device

168, both disks having a 71 mm outer diameter and a 8 mm diameter central hole 174 that helps define the bore-size of a restriction section 166 of device 168. Assembly of annular balloon 154 of device 168 is analogous to the described with reference to device 152 and comprises attaching the outer periphery of balloon parts 156 and 158 (e.g., by welding or adhesive) making an outer balloon seam 162 that defines the outer diameter of annular balloon 154 and attaching the periphery of central holes 174 making a luminal balloon seam

164 that defines the bore size of a restriction section 166.

The fact that the proximal and distal parts of annular balloon 154 of device 168 are substantially planar disks and not half tori makes manufacture and assembly of device 168 relatively simple.

In Figure 9A, components of device 168 are depicted separated in a perspective view and include a liner tube 40 (tapered so that the proximal lumen opening of tube 40 is 10 mm in diameter), distal balloon part 156 and proximal balloon part 158 to which an inflation fluid conduit 56 is secured.

In Figure 9B, components of device 168 are depicted separated in side view.

In Figure 9C, the inner face of proximal balloon part 158 is depicted.

In Figure 9D, device 168 is depicted in cross section, assembled with annular balloon 154 in an inflated configuration.

In Figure 9E, the area encircled in Figure 9D is magnified to show annular balloon 154 of device 168 in greater detail.

In Figure 9F, the area encircled in Figure 9E is magnified to show the connection between inflation fluid conduit 56 and proximal balloon part 158 in greater detail, including perforation 62 providing fluid communication between the lumen of inflation fluid conduit 56 and volume 105 of annular balloon 154. In Figure 9G, a detailed side-view of proximal balloon part 158 is depicted, showing attachment of inflation fluid conduit 56 thereto.

In Figure 9H, a detailed view of the inner face of proximal balloon part 158 and inflation fluid conduit 56 is depicted.

In Figure 91, a detailed perspective view of the outer face of proximal balloon part

158 and inflation fluid conduit 56 is depicted where annular balloon 154 is in the inflated configuration. Analogously to device 152, a luminal seam 162 that secures distal balloon part 156 and proximal balloon part 158 to the proximal end of tube 40 defines fixed bore-size restriction section 166 of device 168 and an outer balloon seam 162 defines a fixed-size outer diameter of annular balloon 154.

In Figure 9J, a detailed side view of proximal balloon part 158 and inflation fluid conduit 56 is depicted where annular balloon 154 is in the inflated configuration.

Deployment and use of device 168 is analogous to the described above for device 152.

In restriction devices 152 and 168, described with reference to Figure 8 and Figures 9 respectively, the fixed bore-size of restriction section 166 is defined by the size of the hole of annular balloon 154 that depends on the size of luminal seam 164. As noted above, in some embodiments, a restriction device comprises a separate restriction component that defines the fixed bore-size of restriction section 166.

The proximal end of an additional embodiment of a restriction device, device 176 is schematically depicted in Figures 1OA and 1OB. Device 176 is substantially similar to restriction devices 152 and 168 and includes an inflatable annular balloon 154 configured for deployment in a duodenal bulb of a human but comprises a restriction component 178 distinct from annular balloon 154, a planar ring-shaped sheet of material which outer periphery is secured to annular balloon 154 so that the hole 180 in the ring constitutes a restriction section 166 of device 176.

In Figure 1OA, components of device 176 are depicted separated in a perspective view and include a liner tube 40 (a not-tapered parallel-walled 50 cm long tube of elastomeric polyurethane having 0.1 mm thick walls and a 35 mm inner diameter), a distal balloon part 156 and a proximal balloon part 158 (substantially disks of 0.1 mm thick elastomeric polyurethane having an outer diameter of 71 mm and a 34 mm diameter central hole 174), an inflation fluid conduit 56 as described above attached to proximal disk 72 as described above, and a restriction component 178, substantially a ring of 0.1 mm thick elastomeric polyurethane having a 36mm outer diameter and a 5 mm central hole 180. For assembly, the outer periphery of restriction component 178, the peripheries of central holes 174 of distal balloon part 156 and proximal balloon part 158 and the proximal end of tube 40 are secured together (e.g., by welding or adhesive) to form a luminal seam 164 (see Figure 10B) and the outer peripheries of distal balloon part 156 and proximal balloon part 158 are secured together (e.g., by welding or adhesive) to form an outer balloon seam 162.

In Figure 1OB, device 176 is depicted assembled in side cross section where annular balloon 154 is in an inflated configuration. As discussed above with reference to devices 152 and 168, distal balloon part 156 and proximal balloon part 158 together constitute annular balloon 154 where outer balloon seam 162 defines a fixed outer diameter of annular balloon 154. However, unlike devices 152 and 168, in device 176, the size of the bore of restriction section 166 is defined by the size of hole 180 in restriction component 178.

Deployment of device 176 is substantially as described above for devices 152 and 168. Once device 176 is properly deployed, the passage of chyme from the stomach is restricted by hole 180 that constitutes the restriction section 166 of device 176.

The proximal end of an additional embodiment of a restriction device, a device 182 is schematically depicted in Figures HA- HD, in cross section. Device 182 includes a funnel- shaped restriction component 178 distinct from an annular balloon 154. For use, the funnel- shaped restriction component 178 of device 182 is provided with an intact apex.

In Figure HA, a tube 40 (that partially constitutes a liner tube 67) of device 182 is depicted prior to assembly. Tube 40 is open at distal end 58 and tapers to a closed proximal end 184 with a closed tip 186, similar to a pointed condom. As is explained in more detail below, proximal end 184 of tube 40 constitutes a restriction component 178 of device 182. On proximal end 184 is a series of markings 188, each marking indicating the location of a specific inner diameter of proximal end 184. In some embodiments, on a respective proximal end is found a series of markings that indicate something else, for example each marking indicating a specific length from some point, e.g., a tip 186 of tube 40.

In Figure HB, device 182 is depicted assembled in a schematic cross section, including an annular balloon 154 (in a collapsed configuration) comprising a distal balloon part 156 and a proximal balloon part 158 mutually secured with outer balloon seam 162, and secured to tube 40 with luminal balloon seam 164. In device 182, the length of proximal end

184 from luminal balloon seam 164 to tip 186 is 5 cm.

Deployment and use of device 182 is substantially analogous to the described hereinabove. Device 182 is provided for use substantially as depicted in Figure HB where tip 186 of proximal end 184 of tube 40 is intact. Typically, device 182 is provided packaged in a delivery device with tip 186 being accessible.

Prior to actual deployment of device 182, the treating physician decides on a desired bore-size of restriction section 166 when deployed. The physician trims proximal tip 186 of proximal end 184, for example by cutting with scissors with reference to markings 188, making a truncated open proximal tip thereby defining the bore-size of restriction section 166 of device 182, as depicted in Figure 11C.

Device 182 is then deployed for example substantially as described above, including introducing inflation fluid through conduit 46 into volume 105 so that annular balloon 154 is in an inflated configuration inside the duodenal bulb of a subject. Subsequently, truncated proximal end 184 of tube 40 is inwardly everted from luminal seam 164 into the bore of tube

40 as depicted in Figure 1 ID.

Once device 182 is deployed, the passage of chyme from the stomach is restricted by restriction section 166, through the fixed-bore size defined by the hole made by trimming tip 186.

In some embodiments of restriction devices having a funnel-shaped restriction component similar to device 182, the funnel-shaped restriction component 178 is provided without a complete sealed apex, but is provided with an opening that defines a predetermined restriction section bore-size.

Restriction devices having a funnel-shaped restriction component such as device 182 have a funnel-shaped restriction section of any suitable size. That said, in some embodiments, the total length of the funnel-shaped restriction is relatively short, in some embodiments, not more than about 10 cm long, not more than about 7 cm and even not more than about 5 cm.

The embodiments of the restriction devices discussed above include a duodenal liner to provide a beneficial effect in addition to the beneficial effect provided by the restriction itself. Additionally, in some embodiments a duodenal liner trailing distally from the centering component into the duodenum functions as a trailing orientation component, assisting in maintaining the proximal opening of the device properly directed in relation to the pylorus.

In some embodiments, a restriction device is provided with a short duodenal liner tube

(typically not more than about 20 cm, not more than about 15 cm, and even not more than about 10 cm) which functions primarily as an orientation component and barely, if at all, as a duodenal liner tube. In some embodiments, a restriction device as described herein is substantially devoid of a duodenal liner tube. In some such embodiments, a restriction device comprises a trailing orientation component such as a ribbon. In some such embodiments, a centering component is substantially devoid of a trailing orientation component. In some such embodiments, a centering component is elongated to assist in preventing misorientation of the centering component when deployed.

Some embodiments of restriction devices devoid of a duodenal liner tube include restriction devices that are substantially identical to device 152, 168, 176 or 182 but are devoid of liner tube 67. Embodiments of such devices are schematically depicted in cross section in Figures 12: device 190 depicted in Figure 12A substantially identical to device 152 depicted in Figure 8, device 192 depicted in Figure 12B substantially identical to device 176 depicted in Figure 10, and device 194 depicted in Figure 12C substantially identical to device 182 depicted in Figures 11.

As described above, when deployed devices 104, 152, 168, 176, 182, 190, 192 and 194 remain connected to inflation fluid conduit 56 when deployed in the body of a subject, substantially as discussed above. In some embodiments, an inflation fluid conduit 56 is detachable, similarly to the duodenal liner device 80 discussed with reference to Figure 3.

The restriction devices described above (152, 168, 176, 182, 190, 192 and 194) as well as some embodiments of the duodenal liner device (devices 104, 108, 142) comprise an inflatable balloon as a centering component configured for deployment in a duodenal bulb and not some other component such as a stent (e.g., 38, 80 or 88). As noted above, in some embodiments a centering component also functions as an anchoring component. It has been surprisingly found that in some embodiments an inflatable balloon as a part of a centering component is superior and has unexpected advantages when functioning as anchoring component. This is despite a reasonable expectation that an inflatable balloon centering component provides insufficient anchoring to counter the distally- pulling peristaltic forces applied by the duodenum and small intestine to a liner tube, such as of a duodenal liner device.

In some embodiments of the duodenal liner devices described above, a component such as a self- expanding stent applies a continuous outwards pressure to the duodenal bulb luminal walls. As the duodenal bulb accommodates the force by growing outwards, the stent continues expanding and applying the outwards radial force. This may lead to a permanent or semi-permanent distension of the duodenal bulb that may have undesirable side effects. In contrast, since an inflatable balloon has a fixed volume once inflated with a given amount of non-volatile inflation fluid, in some embodiments a balloon as a part of a centering component applies a lower pressure as the duodenal bulb accommodates to the applied pressure. As a result, in some such embodiments the extent of duodenal bulb distension is negligible or even non-existent.

In some embodiments of the duodenal liner device, a component such as a stent applies a significant outwards force where the stent-struts contact the duodenal luminal wall. As a result, in some embodiments the stent-struts are driven into the duodenal bulb luminal walls that may have undesirable side effects, including difficult in removing a duodenal liner device anchored in the duodenal bulb by an in-grown stent. In contrast, in some embodiments a balloon as a part of a centering component conforms to adopt the contours of the duodenal bulb luminal walls. As a result, in some embodiments a balloon as a part of a centering component applies less pressure over a much greater surface area of a duodenal bulb luminal wall than an equivalent stent, providing similar centering and anchoring with fewer negative side effects.

Additionally, in some embodiments the reduced pressure applied by a balloon as a part of a centering component leads to less interference with secretion of fluids from a contacted duodenal luminal surface.

Additionally, in some embodiments the reduced pressure applied by a balloon as a part of a centering component leads to less adhesion of the centering component to a contacted duodenal luminal surface.

Additionally, in some embodiments the fluid- filled nature of a balloon together with the reduced pressure applied by a balloon as a part of a centering component allows the balloon some limited deformation to match duodenal bulb movement. In some embodiments, deformation to match duodenal bulb movement allows the duodenal bulb to function more naturally.

In some embodiments, removing a device including an inflatable balloon as a part of a centering component is simple as once the inflation fluid is removed from the centering component volume, the device collapses to small dimensions.

As discussed above, in some embodiments it is desirable to restrict the extent of outwards expansion and to modify the shape of an annular balloon such as of a duodenal liner device, including a device comprising a centering component volume distinct from a bore- changing volume. Thus, in some embodiments, a duodenal liner device (e.g., comprising a centering component volume distinct from a bore changing volume such as devices such as 38, 80 or 88 but especially such as 108 and 142) as well as restriction devices (e.g., 152, 168, 176, 182, 190, 192 and 194) comprise an expansion restrictor, for example to limit the outwards expansion of an annular balloon and/or to change the shape of the annular balloon, for example to give the annular balloon a more elongate shape when inflated, for example to better fit in a duodenal bulb and to ensure orientation of the proximal opening of the device across a pylorus when deployed.

Duodenal liner device 104 described above with reference to Figures 5 comprises an expansion restrictor 106, substantially a relatively thick ring of material encircling a portion of the annular balloon centering component of device 104 for substantially limiting the outer diameter and shaping the centering component of device 104, an annular balloon.

Analogously, some embodiments of a restriction device comprising an annular balloon, for example fashioned of a distal balloon part 156 and a proximal balloon part 158, comprise an expansion restrictor that is substantially a relatively thick ring encircling a portion of the annular balloon. In some embodiments, the expansion restrictor is secured to the annular balloon at or near an outer balloon seam.

The proximal end of an exemplary such embodiment, a restriction device 196 is schematically depicted in Figures 13A and 13B. Device 196 is substantially the same as device 182 depicted in Figures 11 but also includes an expansion restrictor 106 similar to that of device 104, comprising a ring preferably of substantially the same material as a distal balloon part 156 and a proximal balloon part 158 that encircles and is connected to an outer balloon seam 162, Figures 13 A (annular balloon 154 in a collapsed configuration with volume 105 empty of inflation fluid) and 13B (annular balloon in an inflated configuration with a volume 105 filled with inflation fluid, for example when device 196 is deployed). As annular balloon 154 is overinflated, expansion restrictor 106 forces annular balloon 154 to adopt a predetermined size and shape and to expand axially to an elongate shape, for example to better fit a duodenal bulb and/or to maintain the proximal opening of the device across from a pylorus when deployed.

An additional embodiment of a restriction device including an expansion restrictor, device 198, is schematically depicted in Figures 14A (perspective partial cross section of separated components of the device) and 14B (side cross section). Device 198 is substantially similar to device 176 depicted in Figures 10 but comprises a perforated expansion restrictor disk 200 disposed between a distal balloon part 156 and a proximal balloon part 158 as an expansion restrictor and as a restriction component (analogously to restriction component 180 in device 176). Disk 200, optionally of substantially the same material as balloon parts 156 and 158, includes fluid flow perforations 202 and a central hole 180 and is optionally more resistant to stretching, for example is fashioned of a thicker material, than balloon parts 156 and 158. The size of central hole 180 of expansion restrictor disk 200 determines the bore- size of restriction section 166 of device 200 when fully assembled.

Addition of a expansion restrictor disk 200 during the manufacturing process is quick and easy, substantially comprising appropriate stacking and securing (e.g., by welding or use of adhesive) expansion restrictor disk 200 together with balloon parts 156 and 158.

When an annular balloon 154 of a restriction device including an expansion restrictor such as disk 200 as depicted in Figures 14 is inflated, the maximal extent of outwards radial expansion of annular balloon 154 is substantially limited by disk 200 so that over-inflation forces annular balloon 154 to expand axially to an elongated shape, for example to better fit a duodenal bulb and/or to maintain the proximal opening of the device across from a pylorus when deployed.

As seen from the figures above, in some embodiments a restriction device or a duodenal liner device as disclosed herein is configured so that when deployed the bore- changing volume (e.g., 54) or restriction section 166 is located (at least partially, in some embodiments substantially entirely) inside a duodenal bulb 36 and therefore close to a pylorus 34. In some embodiments, such configuration has been found to provide a number of advantages.

In some embodiments, such positioning assists in directing the flow of chyme smoothly into the lumen of a liner tube 67 of a device.

In some embodiments, the location of the bore-changing volume (e.g., 54) or restriction section 166 in the duodenal bulb 36 as opposed to distally therefrom prevents the bore changing volume (e.g., 54) or the restriction section 166 from interfering with natural duodenal or intestinal peristalsis.

In some embodiments, the location of the bore-changing volume (e.g., 54) or restriction section 166 in the duodenal bulb 36 as opposed to distally therefrom reduces stretching of the liner tube (e.g., 67) which would potentially be caused when intestinal peristalsis would push the bore-changing volume or the restriction section 166 distally. Such stretching could potentially weaken, and even tear, a liner tube (e.g., 67).

As seen from the figures above, in some embodiments a portion of a bore-changing component (e.g., 74, 152) or restriction section 166 of a device defines, at least partially, a proximal end (e.g., 48) of a respective device. Duodenal liner and restriction devices as described herein may be deployed using any suitable method including surgically and endoscopically through the esophagus. That said, deployment through a percutaneous gastrostomy as described in the specific embodiments described above allows simple adjusting of the degree of expansion of the expandable centering component and/or bore-changing component, maintenance and retrieval, and avoids trauma and unpleasantness associated with other deployment methods. Further, embodiments including a deployed inflation fluid conduit that passes through the PEG such as devices 38, 88, 104, 108, 142, 152, 168, 176, 182, 190, 192, 194, 196 and 198 are provided with an added level of safety, in some embodiments limiting the extent to which the device is distally drawn into the gastrointestinal tract if an anchoring component (e.g., the expandable centering component or annular balloon) fails in maintaining the device in place.

In some of the embodiments depicted above, the side of a plugged-end inflation fluid conduit 56 is secured to a side of an annular balloon 154, and a perforation 62 made to allow fluid communication between the conduit and volume 105 of the annular balloon 154. In some embodiments, a distal end of a fluid conduit passes through a wall of the balloon allowing fluid communication to volume 105 through the distal end of the conduit lumen.

In the embodiments of the devices discussed in detail above, various components are made of elastomeric polyurethane Embodiments of the devices described herein may fashioned of any suitable material or combination of materials. For example, in some embodiments, various components of a device are made of silicone rubber. Generally such embodiments, the silicone rubber components are thicker than the corresponding polyurethane components described above. For example in some embodiments a tube analogous to tube 40 is made of silicone rubber between about 0.15 mm and about 0.3 mm thick and a balloon-defining tube analogous to balloon-defining tube 50 is made of silicone rubber between 0.1 mm and about 0.2 mm thick. Other suitable materials may be used, for example Nylon.

Various components of the embodiments of the devices discussed in detail above are secured together with the use of adhesive. Generally, the various components of duodenal liner devices as disclosed herein are secured together using any suitable method, for example welding or adhesive.

In some embodiments, one or more surfaces of a device as disclosed herein are treated, for example, to increase impermeability, chemical resistance and/or smoothness. For example, in some embodiments, one or more surfaces such as the luminal surface of a liner tube 67 undergo plasma treatment or parylene coating, for example commercially available from Para Tech Coating, Inc. (Aliso Viejo, California, USA)

In embodiments of the devices discussed in detail above, air from the surroundings is used as inflation fluid for expanding a bore-changing component and/or an expandable centering component. In some embodiments of duodenal liner devices as disclosed herein, a different inflation fluid is used. For example, in some embodiments, gastric juices are pumped from the stomach into one or more of the volumes by a pressure generator such as a pump. For example, in some embodiments, inflation fluid (e.g. a liquid such as saline or water, or a gas, such as air or nitrogen) is contained in a fluid reservoir functionally associated with a pressure generator.

In the embodiments of the duodenal liner device discussed in detail above, bore- changing component 74 the size of the bore of a portion of the liner tube is changed by withdrawal of fluid from or introduction of fluid into a bore-changing volume 54 of a bore- changing balloon. In some embodiments of the duodenal liner disclosed herein, a bore- changing component comprises a different component configured to reversibly change a size of a bore of a portion of the liner tube, for example, a mechanical valve.

In some embodiments of the duodenal liner device discussed in detail above, a device controller such as 98 is configured for extracorporeal deployment. In general, a device controller is deployed in any suitable location. In some embodiments of the duodenal liner disclosed herein, a device controller is configured for intracorporeal implantation, such as subcutaneous implantation. In some embodiments of the duodenal liner disclosed herein, a device controller is configured for intracorporeal deployment, such as intragastric deployment.

In some embodiments, the teachings herein are combined with or used together with other treatments or devices. For example, in some embodiments, the volume of the stomach of a subject is reduced for example, by one or more techniques such as suturing, stapling, lap- band deployment and deployment of a separate gastric balloon together with deployment of a duodenal liner device as disclosed herein.

Embodiments of the invention have been described herein primarily with reference to treatment of living human subjects. It is understood, however, that embodiments of the invention are performed for the veterinary treatment of a non-human mammal, especially a pig or other swine as well as horses, cats and dogs.

Embodiments of the invention have been described herein primarily with reference to treatment of living subjects. It is understood that application of the invention for training and educational purposes (as opposed to treating a condition) falls within the scope of some of the claims, whether on a living non-human subject or on a dead subject, whether on a simulated human body, a human cadaver or on a non-human body, whether on part or an entire gastrointestinal tract isolated (at least partially) from a body, or on a body.

It is appreciated that certain features of the invention, which are, for clarity, described in the context of separate embodiments, may also be provided in combination in a single embodiment. Conversely, various features of the invention, which are, for brevity, described in the context of a single embodiment, may also be provided separately or in any suitable subcombination or as suitable in any other described embodiment of the invention. Certain features described in the context of various embodiments are not to be considered essential features of those embodiments, unless the embodiment is inoperative without those elements.

Although the invention has been described in conjunction with specific embodiments thereof, it is evident that many alternatives, modifications and variations will be apparent to those skilled in the art. Accordingly, it is intended to embrace all such alternatives, modifications and variations that fall within the spirit and broad scope of the appended claims.

Citation or identification of any reference in this application shall not be construed as an admission that such reference is available as prior art to the invention.

Section headings are used herein to ease understanding of the specification and should not be construed as necessarily limiting.

Claims

WHAT IS CLAIMED IS:

1. A duodenal liner device, comprising:

a) a liner tube configured for deployment inside a duodenum of a mammalian subject, said liner tube having walls of a flexible material defining a liner lumen, a proximal end defining a proximal lumen opening, and a distal end defining a distal lumen opening;

b) an expandable centering component configured for deployment in a duodenal bulb functionally associated with said proximal end of said liner tube, radially expandable from a collapsed configuration to an expanded configuration; and

c) a bore-changing component functionally associated with said liner tube configured to reversibly change a size of a bore of a portion of said liner lumen while said liner tube is deployed in a duodenum.

2. The device of claim 1, wherein said portion of said liner lumen is a portion of said liner lumen to be deployed in a superior portion of a duodenum.

3. The device of any of claims 1 to 2, wherein said portion of said liner lumen is a portion of said liner lumen to be deployed in a duodenal bulb.

4. The device of any of claims 1 to 3, wherein said bore-changing component is configured to reduce the size of said bore from a dilated state to a minimal size of not more than about 38 mm².

5. The device of any of claims 1 to 4, wherein the size of said bore is adjustable by manipulation of said bore-changing component.

6. The device of any of claims 1 to 5, wherein a luminal surface of said liner tube defining said liner lumen is substantially uninterrupted by parts of said bore-changing component.

7. The device of any of claims 1 to 6, wherein a portion of said bore-changing component comprises a portion of said liner lumen.

8. The device of any of claims 1 to 7, wherein a portion of said bore-changing component is contained within said liner lumen.

9. The device of any of claims 1 to 8, wherein said bore-changing component comprises a bore-changing balloon with an internal bore-changing volume, and said changing of the size of said bore of said portion of said liner tube comprises introduction of inflation fluid into said bore-changing volume or withdrawal of inflation fluid from said bore-changing volume.

10. The device of claim 9, wherein said bore-changing volume of said bore-changing balloon encircles a portion of said liner tube.

11. The device of claim 9, wherein said bore-changing volume of said bore-changing balloon is located inside said liner lumen.

12. The device of any of claims 9 to 11, wherein a wall of said bore-changing balloon constitutes a part of said liner lumen.

13. The device of any of claims 1 to 12, wherein said centering component is configured to maintain said proximal lumen opening of said liner tube substantially centered with a duodenal lumen when deployed in said expanded configuration.

14. The device of any of claims 1 to 13, wherein said centering component is configured to maintain said proximal lumen opening of said liner tube dilated when in said expanded configuration.

15. The device of claim 1 to 14, wherein said centering component is configured to assist in preventing excessive distal migration of said liner tube into a gastrointestinal tract when in said expanded configuration.

16. The device of any of claims 1 to 15, wherein said centering component is reversibly expandable, from said expanded configuration to said collapsed configuration.

17. The device of any of claims 1 to 16, wherein said centering component is controllably expandable.

18. The device of any of claims 1 to 17, wherein a radial size of said centering component in said expanded state is adjustable.

19. The device of any of claims 1 to 18, wherein a portion of said centering component comprises a portion of said liner lumen.

20. The device of any of claims 1 to 19, wherein said centering component comprises a centering balloon with a centering- component volume, and changing said configuration of said centering component comprises introduction of inflation fluid into said centering- component volume or withdrawal of inflation fluid from said centering-component volume.

21. The device claim 20, wherein said centering balloon is a substantially annular balloon encircling a portion of said liner lumen.

22. The device of any of claims 20 to 21, wherein said bore-changing component comprises a bore-changing balloon with an internal bore-changing volume, and said changing of the size of said bore of said portion of said liner tube comprises introduction of inflation fluid into said bore-changing volume of said bore-changing balloon or withdrawal of inflation fluid from said bore-changing volume of said bore-changing balloon.

23. The device of claim 22, wherein said centering-component volume and said bore- changing volume are in fluid communication.

24. The device of claim 22, wherein said centering-component volume and said bore- changing volume are mutually isolated.

25. The device of any of claims 1 to 24, further comprising an expansion restrictor functionally associated with said centering component, configured to substantially limit the radial expansion of said centering component to a defined maximal diameter.

26. The device of claim 25, wherein said expansion restrictor is configured to substantially limit the radial expansion of said centering component to a single defined maximal diameter.

27. The device of claim 25, wherein said expansion restrictor is adjustable and is configured to allow a user to set a defined maximal diameter from a choice of at least two potential diameters.

28. A restriction device for deployment in a mammalian duodenum, comprising:

an inflatable annular balloon configured for deployment in a duodenal bulb, said annular balloon having a collapsed configuration and an inflated configuration, wherein when said annular balloon is deployed in a duodenal bulb in said inflated configuration the device had an outer diameter and a restriction section having a fixed bore- size to restrict the passage of chyme from the stomach through said restriction section.