Gastrointestinal implant with duodenal bulb anchor

Abstract

A gastrointestinal implant adapted to be implanted in a gastrointestinal structure such as a duodenum, a jejunum, and / or an ileum comprises a plurality of adjacent layers bonded to one another. One of more of the layers comprises at least one of a selected pore size and interpore distance, and at least one medicament is coupled to at least one medial surface of one or more layers to achieve one or more treatment goals selected from minimizing or alleviating trauma associated with implantation of the gastrointestinal sleeve, preventing or treating infection, treating eating disorders or conditions of the patient, treating one or more gastrointestinal tract structures exterior to or distal to at least a portion of the sleeve, or treating the patient's microbiome.

Description

PATENTATTORNEY DOCKET NO.: 51148-049WO2GASTROINTESTINAL IMPLANT WITH DUODENAL BULB ANCHORBackground of the Invention

[0001] Obesity is a significant and worsening health problem. Over thirty percent of the United States adult population is overweight (body mass index between 25 and 29.9), a group exceeding 100 million adults. An additional 42 percent, over 140 million, are obese (body mass index of 30 or higher), with a further nine percent (over 30 million) considered severely obese.

[0002] Excess body weight places strain on bones and joints, and adversely impacts major body organs and the nervous and circulatory systems. The World Health Organization estimates that about 2.8 millions deaths per year are directly related to obesity, and the US Centers for Disease Control and Prevention (CDC) estimates that 300,000 such deaths occur in the United States. Annual obesity healthcare costs in the US exceed $50 billion. Despite the toll in health suffering and financial cost associated with obesity, the prevalence of continues to increase not on the in the US but worldwide.

[0003] Co-morbidities associated with obesity is one of the principal costs to the healthcare system stems from co-morbidities associated with obesity. This includes Type- 2 diabetes, which recent data shows afflicts about 12% of the adult US population, as almost half of this group are clinically obese. Related co-morbidities of obesity include hypertension, coronary artery disease, hypercholesteremia, sleep apnea and pulmonary hypertension.

[0004] While the cause of obesity — an excess intake of calories relative to energy expended — is simple, the physiology and psychology of obesity are complex, and a reliable cure for obesity has proven elusive despite significant public and private investments. Once an individual’s BMI exceeds 30, significant lifestyle changes are usually required to meaningfully improve health status.

[0005] Surgical methods to address obesity have been explored in a variety of procedures to modify the anatomy to reduce food consumption. These include stapling of the stomach, or gastroplasty, which were widely performed in the 1980s and early 1990s to reduce the volume of the stomach and achieve a faster sensation of satiety. Although many patients achieved initial weight loss, obtaining sustained weight reduction remained elusive. Although the reasons are not fully known, one cause involved the stretching of surgically-reduced stomach over time. In addition, the psychological desire for food among some patients led many to regain weight despite the smaller pouch.PATENTATTORNEY DOCKET NO.: 51148-049WO2

[0006] More recent surgical procedures with greater success in achieving long-term weight loss include Roux-en-Y gastric bypass and the biliopancreatic diversion with duodenal switch (BPD). Both Roux-en-Y and BPD procedures reduce the size of the stomach and shorten the effective-length of intestine available for nutrient absorption. By reducing the stomach size, both procedures limit the ability of the patient to take in food. In addition, both are malabsorptive in that bypassing the duodenum makes it more difficult to digest fats, high sugar and carbohydrate rich foods, thereby inducing weight loss. Both surgeries provide feedback to the patient by producing a dumping syndrome if they do eat high fat or carbohydrate food sources. Dumping occurs when carbohydrates directly enter the jejunum without being first conditioned in the duodenum, resulting in a significant discharge of fluid from the intestinal lining into the partially digested food, which can leave the patient light-headed and with severe diarrhea. For reasons that have not been determined, the procedures have immediate therapeutic effect on diabetes.

[0007] Though well-established surgically, the exact mechanism of action in these procedures is poorly understood. Current theory is that negative feedback is provided from both regurgitation into the esophagus and dumping when large volumes of certain foods are eaten. Eventually, patients learn that to avoid both these issues they must be compliant with the dietary restrictions imposed by the modified anatomy. In the BPD procedure, the stomach is not reduced in size as much as in Roux-en-Y procedures, so the patient is able to consume sufficient quantities of food to compensate for the reduced absorption. However, because more of the upper intestinal tract is bypassed, BPD can have serious side effects because of the significant malabsorption, and is reserved for the most morbidly obese patients.

[0008] Surgical treatments for obesity have significant risks of complications, with ten percent or more of patients requiring surgical intervention after the initial surgery. Early small bowel obstruction occurs in 2-6% in these surgeries, and mortality rates are reported to be approximately 0.5-1 .5%. While many patients successfully lose weight and maintain at least some of the weight loss over time, there is a need for less invasive procedures with lower rates of complications. Laparoscopic techniques in these surgeries provide some reduction in complications, but they continue to have relatively high rates of complications and demand a high level of surgical skill.

[0009] Devices to reduce absorption in the small intestines have been proposed (See U.S. Pat. No. 5,820,584 (Crabb), U.S. Pat. No. 5,306,300 (Berry) and U.S. Pat. No. 4,315,509 (Smit)). However, these devices have not been successfully implemented.PATENTATTORNEY DOCKET NO.: 51148-049WO2

[0010] There is a need for improved devices and procedures for improved treatment of obesity which are less invasive than existing surgeries, provide a reduced risk profile, and are reversible.Summary of the Invention

[0011] The present invention provides an apparatus and method to limit absorption of food in specific parts of the gastrointestinal system of a patient using a stent and a flexible, multi-layer sleeve barrier having one or more elutable medicaments within the layers, and a pore size selected to modulate a rate of elution of the one or more elutable medicaments from the exterior and / or inner surfaces of the sleeve. In one embodiment, at least a portion of the sleeve is adapted to be positioned within a superior duodenum of the patient.

[0012] In one embodiment, the invention provides gastrointestinal implant system comprising: a) a collapsible stent adapted to contact a portion of a gastrointestinal system of a patient in an expanded position, the stent having a proximal stent end adapted to contact a first patient gastrointestinal structure, a distal stent end adapted to contact a second patient gastrointestinal structure distal to the first patient gastrointestinal structure, and a stent body defining a stent lumen; and b) a flexible sleeve having a sleeve lumen extending at least partially through the stent lumen, a proximal sleeve end adapted to be coupled to the collapsible stent, a distal sleeve end extending a selected length into at least one of a duodenum, a jejunum, and an ileum of the patient, an exterior sleeve surface facing toward the gastrointestinal system of the patient, and an interior sleeve surface defining the sleeve lumen, wherein the flexible sleeve is adapted to receive chyme into the sleeve lumen at the proximal sleeve and allow it to exit the distal sleeve end, the sleeve comprising: 1 ) a sleeve wall comprising a plurality of polymer layers each having first and second polymer layer sides, each polymer layer being bonded to at least one adjacent polymer layer on at least one of the first polymer layer side and the second polymer layer side, wherein one of said first and second polymer layer sides comprises the exterior sleeve surface, a second of said first and second polymer layer sides comprises the interior sleeve surface, and the remaining first and second polymer layer sides comprise medial sleeve layer sides, wherein at least one of said plurality of polymer layers comprises at least a first pore size; and 2) at least one elutable medicament coupled to one of said medial sleeve layer sides, wherein the at least one pore size is selected to modulate a rate of elution of the elutable medicament from at least one of the exterior sleeve surface and the interior sleeve surface.PATENTATTORNEY DOCKET NO.: 51148-049WO2

[0013] In one embodiment, the invention provides a gastrointestinal implant system comprising: a) a collapsible stent adapted to be positioned in an expanded position in at least a portion of a superior duodenum of a patient, comprising: 1 ) a proximal stent end adapted to contact a first patient gastrointestinal structure in the superior duodenum; 2) a distal stent end adapted to contact a second patient gastrointestinal structure distal to the first patient gastrointestinal structure; and 3) a stent body defining a stent lumen; and b) a flexible sleeve having an exterior sleeve surface adapted to face toward the gastrointestinal system and an interior sleeve surface defining a sleeve lumen, comprising: 1 ) a proximal sleeve end adapted to be coupled to the collapsible stent; 2) a distal sleeve end adapted to extend a selected length into one of a duodenum, a jejunum, and an ileum of the patient; 3) a sleeve wall comprising a plurality of polymer layers each bonded to at least one adjacent polymer layer, each polymer layer comprising a first polymer layer side and a second polymer layer side, wherein one of the first and second polymer layer sides comprises the exterior sleeve surface, a second of the first and second polymer layer sides comprises the interior sleeve surface, and the remaining first and second polymer sides each comprise medial sleeve layer sides, at least one of said plurality of polymer layers comprising a first pore size; and 4) at least one elutable medicament coupled to at least one of the medial sleeve layer sides, wherein the first pore size is selected to modulate a rate of elution of the elutable medicament from at least one of the exterior sleeve surface and the interior sleeve surface.

[0014] In a further embodiment, the invention provides a method of treating an eating condition of a patient comprising: a) implanting a gastrointestinal device in portion of a gastrointestinal system of a patient, the gastrointestinal device comprising 1 ) a collapsible stent adapted for implantation in a portion of a gastrointestinal system of a patient in an expanded condition and comprising a proximal stent end, a distal stent end, and a stent body defining a stent lumen ;2) a flexible sleeve having an exterior sleeve surface, an interior sleeve surface defining a sleeve lumen, the flexible sleeve comprising: A) a proximal sleeve end coupled to the collapsible stent; B) a distal sleeve end adapted to extend a selected length into one of a duodenum, a jejunum, and an ileum of the patient; and C) a sleeve wall comprising a plurality of polymer layers each bonded to at least one adjacent polymer layer, each polymer layer comprising a first layer side and a second layer side, wherein one of the first and second layer sides comprises the exterior sleeve surface, a second of the first and second polymer layer sides comprises the interior sleeve surface, and the remaining first and second polymer sides each comprise medial sleevePATENTATTORNEY DOCKET NO.: 51148-049WO2 layer sides, at least one of said plurality of polymer layers comprising a first pore size; and D) at least one elutable medicament coupled to one of the medial sleeve layer sides, wherein the first pore size is selected to modulate a rate of elution of the elutable medicament from at least one of the exterior sleeve surface and the interior sleeve surface; b) receiving chyme into the proximal sleeve; c) allowing the chyme to pass through the sleeve lumen and exit through the distal sleeve end; and d) eluting the at least one elutable medicament from at least one of the exterior sleeve surface and the interior sleeve surface.

[0015] In an additional embodiment, the invention provides a method of making a gastrointestinal implant sleeve: a) providing a mandrel form for the gastrointestinal sleeve shape; b) providing a biocompatible polymer ribbon adapted for winding around a mandrel, the ribbon comprising a spool source; c) winding the ribbon around the mandrel form to provide a layer of the gastrointestinal sleeve having an inside surface facing the mandrel and an outside surface oppose to the inside surface; d) coating the outside surface with a first medicament; e) repeating steps (c) and (d) one or more times to provide one or more additional layers of the gastrointestinal sleeve, wherein each of the one or more additional layers is adjacent to a prior gastrointestinal sleeve layer; f) after each repetition of steps (c) and (d), bonding the additional layer to the prior gastrointestinal sleeve layer; g) removing the gastrointestinal sleeve from the mandrel form, the gastrointestinal sleeve having at least a first dimension; and h) expanding the gastrointestinal sleeve from a first dimension to a second dimension adapted for implant into a location in at least a part of a duodenum of a patient.

[0016] The flexible sleeve is open at both ends and adapted to limit absorption of nutrients in the gastrointestinal tract. The sleeve may be impregnated with an antihunger hormone such as peptide-YY, or with one or more medicaments (e.g., heparin, rifampin, minocycline, or a GLP-1 agonist) to reduce inflammation, risk of infection, or to treat an eating condition of the patient. In some embodiments, the sleeve comprises low friction materials such as polytetrafluoroethylene (PTFE) including cast PTFE and expanded PTFE, cast fluorinated ethylene propylene with polytetrafluoroethylene coating, extruded fluorinated ethylene propylene and extruded perfluoroalkoxy.Brief Description of the Drawings

[0017] The foregoing and other objects, features and advantages of the invention will be apparent from the following more particular description of preferred embodiments of the invention, as illustrated in the accompanying drawings in which like reference charactersPATENTATTORNEY DOCKET NO.: 51148-049WO2 refer to the same parts throughout the different views. The drawings are not necessarily to scale; emphasis instead is placed upon illustrating the principles of the invention.

[0018] As used herein, the term “non-penetrating stent” refers to a stent that is capable of contacting the body of a patient without causing entry of any portion of the stent beyond the surface of the body portion being contacted. The term precludes not only having a portion passing completely through a wall of a body portion, such as a wall of a superior duodenum, but also causing a partial entry into the body portion without completely penetrating or piercing the same. Accordingly, a “non-penetrating” stent lacks any barb, point, or sharp edge intended to penetrate the contacted body portion partially or completely. The term does not preclude a roughened, non-penetrating surface capable of allowing ingrowth of tissue (e.g., epithelial cells) into the outer surface of the stent.

[0019] As used herein, the term “multi-layer” as applied to an implantable sleeve refers to a flexible sleeve comprising a series of thin-walled concentric layers bonded to one or more adjacent layers. The layers are located radially outward of one another and comprise at least a first sleeve layer having a first inner surface that comprises the inner surface of the sleeve, and a first outer surface that is bonded to an inner surface of at least a second sleeve, which also comprises an outer surface that may either be bonded to an inner surface of a third sleeve, or may comprise the outer surface of the sleeve. All sleeve layer sides except the inner sleeve surface (which is adapted to receive chyme in a proximal end thereof) or the outer sleeve surface (which is adapted to be adjacent to aa gastrointestinal system surface of the patient) are referred to as “medial” sleeve surfaces because they are between (i.e., medial to) the inner surface and outer surface of the sleeve as a whole.

[0020] As used herein, an “elutable” medicament is one that is bonded to a medial surface of a sleeve layer, and which must diffuse through the pores of at least one layer of the sleeve to reach the sleeve lumen or the sleeve outer surface. An elutable medicament does not include a medicament directly coated onto the interior surface of the sleeve or to the outer surface of the sleeve. A “rate of elution” refers to a rate at which a medicament diffuses from an inner or outer surface of a sleeve, and may be given as an absolute or molar amount over a rate of time following implant (e.g., 100 micrograms per day for 3 days following implant, 2 millimoles per day for 1 week following implant). In some instances, two different rates may be provided based on different elution profiles from multiple layers (e.g., 200 micrograms / day for 2 days after implant followed by 50 micrograms / day for 5 days), or from specific portion(s) of the sleeve (e.g., 5 millimoles / dayPATENTATTORNEY DOCKET NO.: 51148-049WO2 of rifampin from a first proximal portion of the sleeve adjacent to a stent, and 30 micrograms / day of heparin from a second proximal portion of the sleeve distal to the sent and adjacent to the descending, horizontal, and ascending duodenum).

[0021] A rate of elution may be controlled by several variables, including the relative concentration per area of the medicament on a sleeve surface (e.g., 2 micrograms per square centimeter), the pore size of the pores of one or more layers (e.g., 10 micrometers, 50 nanometers, etc.), and the pore density on a layer (e.g., 500 pores / cm2).

[0022] FIG. 1 is a sectional view of a portion of a portion of the digestive tract of a human patient, showing the stomach, duodenum, and jejunum.

[0023] FIGS. 2A and 2B are perspective views of an embodiment of a non-penetrating stent for securing a gastrointestinal implant in a gastrointestinal structure of a human patient, in an expanded configuration (FIG. 2A) and a collapsed configuration (FIG. 2B).

[0024] FIG. 2C illustrates a gastric sleeve during a procedure coupling the sleeve to the stent of FIGS. 2A and 2B.

[0025] FIG. 2D shows the gastric sleeve of FIG. 2C after coupling to the stent of FIGS. 2A and 2B.

[0026] FIG. 2E and 2F are perspective views of further embodiments of a non-penetrating stent for securing a gastrointestinal implant in a gastrointestinal structure of a human patient.

[0027] FIGS. 3A-3E are perspective views showing steps for creating layers of a multilayer implantable sleeve adapted for elution of one or more medicaments into a gastrointestinal system of a patient, during a manufacturing procedure according to one embodiment of the invention.

[0028] FIG. 4A is a perspective view of an alternative embodiment of providing an elutable coating on one or more medial layers of an elutable sleeve suitable for implantation in a Gl system of a patient.

[0029] FIG. 4B is a perspective view of an elutable coating on a layer of an elutable sleeve.

[0030] FIG. 5A is a perspective view showing the layer structure of a multi-layer sleeve adapted for elution of one or more medicaments located between adjacent medial layers of the sleeve, before removing from a mandrel on which the sleeve layers have been created.

[0031] FIG. 5B is a perspective of the layer structure of the multi-layer sleeve of FIG. 5A after removal of the sleeve from the mandrel.PATENTATTORNEY DOCKET NO.: 51148-049WO2Detailed Description of the Invention

[0032] Exemplary embodiments of the present disclosure are illustrated in the drawings, which are illustrative rather than restrictive. No limitation on the scope of the technology or on the claims that follow is to be implied or inferred from the examples shown in the drawings and discussed here.

[0033] In some embodiments, the gastrointestinal sleeve includes an anchor portion and a floppy, flexible, thin, conformable, and / or collapsible sleeve portion. FIG. 1A is a sectional view of a portion of the digestive tract in a human patient. Food to be digested is introduced to the stomach 102 by through the cardiac orifice 110 from the esophagus by the dilation of the cardiac sphincter 111. The stomach 102 acts to partially digest food to produce chyme, a semi-fluid, homogeneous, gruel-like material produced by gastric digestion in the stomach 102. Chyme exits the stomach through the pyloric orifice 108, which is a distal aperture of the stomach 102 surrounded by a strong band of circular muscle forming the pyloric sphincter 109. Chyme exits the stomach 102 via dilation of the pyloric sphincter 109, and passes into the duodenum, which is the first part of the small intestine. The small intestine is about 15-20 feet in length and comprises a convoluted tube extending from the pyloric orifice 108 to the ileocecal valve where it terminates in the large intestine. The small intestine has three sections, the duodenum, the jejunum 106, and the ileum (not shown in FIG. 1 ). The duodenum makes up the first 10- 12 inch section of the small intestine and tends to be the shortest, widest, and most fixed part of the small intestine.

[0034] The duodenum has four sections which typically form a U shape: the superior duodenum 119, the descending duodenum 132, the horizontal duodenum 136, and ascending duodenum 126. The superior duodenum 119 is about two inches long and ends at the superior duodenal flexure 128. The superior duodenum 119 also defines a feature referred to as the duodenal bulb, which begins just distal to the pyloric sphincter 109 and has a length of about 1 to 1.5 inches in an adult human. While the duodenal bulb is sometimes described as comprising only a proximal, dilated portion of the superior duodenum 119, in the present disclosure the term “duodenal bulb” is used synonymously as the entire superior duodenum from immediately distal to the pyloric sphincter 109 to the superior duodenal flexure 128. The superior duodenum 119 defines a lumen therein that is slightly larger than the remaining portions of the duodenum, and has less motion than the pyloric sphincter 109 and the distal portions of the duodenum 132,136, 126. Notably, the motion of the superior duodenum 119 is substantially limited to radialPATENTATTORNEY DOCKET NO.: 51148-049WO2 contractions without having a significant linear component (i.e., no movement along the central axis of the intestine). The tissue of the intestinal wall of the pyloric sphincter 109 and the superior duodenum tends to be thicker than that of the remaining portions of the duodenum and other parts of the small of the small intestine.

[0035] The descending duodenum 132 is about three to four inches long and introduces includes circular tissue folds 138 also known as the valves of Kerckring, which are not present in the superior duodenum 1 19 but are found in the horizontal duodenum 136 and ascending duodenum 126. The descending duodenum 132 also includes a nipple-shaped structure, the papilla of Vater 114, through which pancreatic juice from the pancreas and bile (produced by the liver and stored by the gall bladder) enter the duodenum from the pancreatic and bile ducts. The pancreatic juice contains enzymes for protein digestion, and bile dissolves the products of fat digestion. The ascending section is about two inches long and ends at the duodenojejunal flexure 116 where it joins the jejunum 106, the next section of the small intestine. The duodenoejunal flexure 116 is fixed to the ligament of Treitz 118 (not shown in FIG. 1 ). The juices secreted into the duodenum break the partially digested food down into particles small enough to be absorbed by the body. Additional details are provided in Gray's Anatomy (“Anatomy of the Human Body,” by Henry Gray) and “Human Physiology,” Vander, 3rd ed, McGraw Hill, 1980.

[0036] This invention includes methods and devices for placing or implanting a gastrointestinal implant device in a mammal. For example, this invention includes methods and devices for implanting a gastrointestinal sleeve. In some embodiments, the gastrointestinal sleeve includes an anchor portion and a floppy, flexible, thin, conformable, and / or collapsible sleeve portion.

[0037] FIG. 2A is a perspective view of one embodiment of a Gl implant device 200 including a collapsible stent 210 adapted to non-penetratingly secure the gastrointestinal implant in a portion of a gastrointestinal system (e.g., a superior duodenum 119) of a patient. The collapsible stent 210, shown in an expanded configuration in FIG. 2A, comprises a stent body 212 having a plurality of struts 218 defining a stent lumen, with a shape adapted to fit within a desired portion of the Gl tract. In one embodiment, the stent body 212 is generally tubular or cylindroid in shape and defines a stent lumen having a central axis 211. In the embodiment of FIG. 2A, the stent 210 is generally barrel or fusiform in shape, while in other embodiments the stent may have a right cylindrical shape, a tapering cylindrical shape, or other tubular shapes (e.g., a corrugated tubular shape). The stent 210 includes a proximal end 214 adapted to be located in the superiorPATENTATTORNEY DOCKET NO.: 51148-049WO2 duodenum 119 at a location near but distal to the pyloric sphincter 109, and a distal end 216 adapted to be located in the superior duodenum near but proximal to the superior duodenal flexure 128. In an alternative embodiment (not shown), distal end 216 may extend beyond the superior duodenal flexure 128 and into the descending duodenum 132. In a still further embodiment, proximal end 214 may be adapted for implantation into a portion of the Gl tract of the patient distal to the superior duodenum, such as the descending duodenum, the horizontal duodenum, the ascending duodenum, or the jejunum of the patient.

[0038] The stent 210 further comprises a plurality of non-penetrating anchors 220, 222, 224, adapted to contact an interior wall of the superior duodenum 119. As used herein, “non-penetrating” refers to structures lacking barbs, spikes, prongs, or other sharp or pointed structures adapted to provide contact to puncture or penetrate tissue. Instead, non-penetrating structures are those which provide a contact surface that is not adapted to penetrate tissue. A first anchor 220 is located nearer to the proximal end 214 of stent 210 than to the distal end 216. A second anchor 222 is located distal to the first anchor 220 near the middle of the stent body, and a third anchor 224 is located distal to the second anchor 222 and near the distal end 216. In the embodiment of FIGS. 3A-3D, the anchors 220, 222, 224 each comprise a series of individual wire or wire-line spring elements that together comprise a ring structure positioned generally transverse to the axis 211 of the stent body 212, and each of the individual wire or wireline portions extend radially outward from the stent body and has a curved or rolled shape adapted to non- penetratingly engage a portion of the wall of the superior duodenum at selected locations between the pyloric sphincter 109 and the superior duodenal flexure 128. Each spring element of anchors 220, 222, 224 is adapted to exert a radial force on the outer duodenal wall when the stent 210 is positioned in the superior duodenum 119, and comprises a spiral cross-section with an opening 221 , 223, 225 (FIG. 2C) facing toward the distal end 216 of the stent.

[0039] Because the openings 221 , 223, 225 of each wire element of anchors 220, 222, 224 face toward the distal end 216 of the stent 210, movement of the gastrointestinal implant in a distal direction of the patient’s Gl tract will result in a proximally directed force F of the Gl tissue on the outer edges of each wire element, as shown in FIG. 2C. Proximally-directed force F will tend to unfurl or open the spiral shape of each wire element of anchors 220, 222, 224, which will in turn cause an opposing resistive force on the tissue as each wire element of anchors 220, 222, 224 resists force F. Conversely,PATENTATTORNEY DOCKET NO.: 51148-049WO2 proximal movement of the implant will result in a force G acting distally (i.e., opposite to force F) that will tend to compress or close the spirally shaped spring wire elements, which will also generate an opposing proximal spring force on the Gl tissue by the spring wire elements, but less than the force resisting force F acting in the opposite direction to the spiral openings. Accordingly, the distally-opening wire elements of anchors 220, 222, 224 shown in FIGS. 2A-2D will resist distal movement and migration more than proximal movement.

[0040] In an alternative embodiment, shown if FIG. 2E, the wire spring elements of one of the anchors 222 may comprise proximally-facing spiral openings, which will resist proximal movement more than distal movement. In a still further alternative embodiment shown in FIG. 2F, the spring wire elements of anchors 220, 222, 224 may comprise a mixture of both proximally-facing openings and distally-facing openings, each providing greater resistance to distal movement (in the case of distally-facing openings) or proximal movement (in the case of proximally-facing spiral openings). As shown in FIGS. 2A-2F and 2B, three distinct ring anchors 220, 222, and 224 (each comprising a plurality of wire elements) are provided. In alternative embodiments, two, four, or more anchor elements may be provided, and each anchor element may have a circumference or diameter selected to securely position the Gl device in the superior duodenum with no or minimal migration.

[0041] FIG. 2B shows the stent 210 of FIG. 2A in a collapsed configuration. The stent body 212 is shown collapsed into a smaller radial diameter than in FIG. 2B, and the spring wire anchors 220, 222, and 224 may be folded partially downward against the stent body 212. In the collapsed configuration, the stent 210 (and sleeve 250, FIGS. 2C and 2D) may be coupled to a catheter or other delivery system for delivering the gastrointestinal implant to a deployment location distal to the pyloric sphincter 109.

[0042] FIG. 2C illustrates a gastrointestinal implant 200 comprising the stent 210 of FIGS. 2A and 2B and a flexible sleeve 250. The implant 200 is shown prior to the coupling of the sleeve 250 to the stent 210. The sleeve 250 includes a proximal portion 252 adapted to fold down to cover at least a portion of the stent body 210. The sleeve proximal portion 252 includes a proximal end 254 and slits or apertures 256 adapted to allow the wire spring elements of anchors 220, 222, and 224 to extend through the slits to engage the wall surfaces of the superior duodenum 119. Sleeve 250 also includes a distal portion 258 and a distal end 260. Distal portion 258 extends into at least one of the duodenum, jejunum and / or ileum to prevent the absorption of food in the Gl tract until it exits thePATENTATTORNEY DOCKET NO.: 51148-049WO2 sleeve lower in the Gl tract. A tapered or narrowing section 262 is shown as the diameter of sleeve 250 narrows to accommodate a narrowing of the anatomy from the superior duodenum 119 into more distal portions of the Gl tract. In alternative embodiments, a constant diameter may be used.

[0043] FIG. 2D illustrates the gastrointestinal implant 200 after the coupling procedure shown in FIG. 2C is completed. In the embodiment shown, proximal portion 252 has been folded down over stent body 212 and sealed to a portion of the sleeve 250 distal to the distal end 216 of stent 210. As shown, proximal portion 252 covers substantially all of the stent body 212 while slits 256 allow the wire spring elements of anchors 220, 222, and 224 to extend radially outward from the stent body to engage a wall of the superior duodenum 119. Although FIG. 2D is shown with the stent body 212 substantially completely covered by the proximal portion 252 of sleeve 250, in alternative embodiments some or all of the stent body may remain exposed or uncovered by the sleeve.

[0044] The sleeve material is preferably thin and conformable to the Gl tract so that it may collapse to a small volume to minimize tissue irritation. In addition, is preferably has a low coefficient of friction so that chyme easily passes through without adhesion or holdup, and has a low permeability to fluids so that chyme does not pass through the sleeve way to contact tissue adjacent to the sleeve. One suitable material is expanded polytetrafluoroethylene (PTFE) tape having a wall thickness of about 0.0004”. This material is hydrophobic but slightly porous, although the pores may close over time following implantation in the Gl tract. Porosity may be reduced by using ePTFE tape having a smaller pore size and / or a reduced interpore dimension, coating the inside or outside of the sleeve with materials such as silicone or polyurethane, or by using other polymers that are essentially non-porous, such as cast PTFE, PTFE with fluorinated ethylene propylene (FEP) or perfluoroalkoxy coatings, extruded FEP and extruded PFA. Rubber-like materials typically have significantly higher coefficients of friction and are not preferred by may be used in some embodiments. Suitable materials may have a density within a range of 0.22 - 1 .5 g / cm2.

[0045] The sleeve material may have a pore size and pore density selected to achieve a desired elution rate of the one or more medicaments to be delivered. For expanded polymers such as PTFE, pores may comprise small elliptical or elongated apertures. In one embodiment, the pores comprise ellipses having a uniform orientation, generally parallel major axes, a minor axis dimension within a range of 0.1 -100 microns, and a mean separation distance with a range of 1 -100 microns between major axes of adjacentPATENTATTORNEY DOCKET NO.: 51148-049WO2 pores. In another embodiment, the pores may have a major axis dimension within a range of 1 -10 microns and a mean separation distance between major axes of adjacent pores within a range of 10-80 microns. In some embodiments, the pores may comprise generally circular, elliptical, or other (e.g., parallelogram) shapes with a mean separation distance between geographical centers of each pore of from 0.1 -20 microns, and a mean separation distance between geographical centers of 0.1 -100 microns.

[0046] FIGS. 3A-3E illustrate certain aspects of a method of manufacturing a multi-layer gastrointestinal implant sleeve having an elutable medicament therein, according to one Suitable multi-layer sleeves may be manufactured by building up a plurality of layers on a mandrel 310, with each layer created by wrapping a polymer tape 320 around the mandrel in a series of partially overlapping turns. FIG. 3A illustrates the creation of a first layer portion 340 by wrapping a polymer tape 320 around mandrel 310 a mandrel in a first direction designated by arrow 312, at a first angle 0 (314) to the axis of the mandrel. Beginning at a proximal end 325, the polymer tape 320 is wrapped in series of partially overlapping spiral turns, designated generally by 342 and 344, around mandrel 310, and terminates at a distal end 330. In one embodiment, ePTFE tape having a thickness of approximately 0.0004” may be used to create first layer portion 340, although other polymer tapes may be used. Although FIG. 3A is shown with the tape wound from the proximal to the distal end, in alternative embodiments, first layer 340 may begin at the distal end and terminate at proximal end 325. In one embodiment (not shown), first layer portion 340 may be heated to bond the overlapping turns together to create a first sleeve layer.

[0047] FIG. 3B illustrates the creation of a second layer portion 350 over (i.e., radially outside of) first layer portion 340 by wrapping the polymer tape 320 over first layer portion 340 in another series of partially overlapping spiral turns designated generally by 352 and 354. Second layer portion 350 starts generally at the distal end 330 of the first layer portion 340, and is wrapped at a second angle 4> (316) to the mandrel axis. Angles 0 (314) and 4> (316) preferably have opposing or crossing orientations, which adds strength to the final sleeve after heat bonding the first layer portion 340 and second layer portion 350 together. Although second layer portion 350 is shown wrapped around mandrel 310 in the same direction 312 as first layer portion 340, in different embodiments second layer portion 350 may be wrapped round the mandrel in the opposite direction to first layer portion 340. In a still further embodiment (not shown), second layer portion 350 may start at the proximal end 325 and be wrapped toward the distal end 330. In the embodimentPATENTATTORNEY DOCKET NO.: 51148-049WO2 shown in FIG. 3B, second layer portion 350 is terminated at proximal end 325 of first layer portion 340.

[0048] After second layer portion is completed, a first heat-bonded layer 360 may be created by heat bonding first layer portion 340 and second layer portion 350, as shown in FIG. 3C, to provide a single layer having a controlled pore size and interpore distance. The opposing angles of tape 320 in the turns of the second layer portion 350 relative to first layer portion provides improved strength in heat-bonded layer 360.

[0049] FIG. 3D illustrates a medicament 375 being applied to heat-bonded layer 360 using a spray nozzle 370, either as the mandrel 310 rotates or by moving the spray nozzle relative to the mandrel to produce a medicament coating 380 on the heat-bonded layer. In various embodiments, one or more medicaments may be applied to heat-bonded layer 360 to achieve one or more treatment goals such as minimizing or alleviating trauma associated with implantation of the gastrointestinal sleeve, preventing or treating infection, treating eating disorders or conditions of the patient, treating one or more gastrointestinal tract structures exterior to at least a portion of the sleeve, treating one or more Gl tract structures distal to the sleeve, or treating the patient’s microbiome. As used herein, the term medicament may comprise any substance to produce a biological effect in the body, and includes chemicals, drugs, proteins, amino acids, antibiotics, probiotics, prebiotics, and other biologically active compounds. Medicament 375 may be applied to heat-bonded layer 360 using a carrier such as an aqueous or organic chemical, excipient, solvent, or mixtures thereof, which may be removed by natural or augmented evaporation (e.g., blown air across the rotating mandrel).

[0050] FIG. 3E shows a first portion 390 of a second layer being applied over the medicament coating on heat-bonded layer 360, similar to first layer portion 340 in FIG. 3A. Preferably, a second portion would thereafter be applied over first layer portion 390, similarly to second portion 350 of FIG. 3B, followed by heat-bonding to create a second heat-bonded layer similar to layer 360 in FIG. 3C. The second heat-bonded layer may be coated with a medicament in some embodiments, or may remain uncoated. Additional heat-bonded layers may be created by repeating the processes shown in FIGS. 3A-3E, Some layers may be coated with the same or different medicaments to achieve one or more treatment objectives, while other layers may remain uncoated.

[0051] FIGS. 4A and 4B illustrate an alternative embodiment of a method of providing an elutable coating on a medial surface layer of an implantable sleeve. FIG. 4A is similar to FIG. 3B, except that a spray nozzle 470 (similar to spray nozzle 370 of FIG. 3D) is usedPATENTATTORNEY DOCKET NO.: 51148-049WO2 to spray an elutable medicament 475 on an upper surface 422 of polymer tape 420 before the tape is wound in overlapping layers on mandrel 410 to create a second layer portion 450 above (i.e., radially exterior to) a first layer portion 440. Second layer portion 450 is wrapped from distal end 430 of the first layer portion 440 at a second angle 4> (416) to the mandrel axis, which has an opposing orientation to angle 0 (414) of first layer portion 440. Adjacent turns designated generally as 452, 454 in second layer portion 450 and 442, 444 in first layer portion 440, partially overlap to provide a continuous structure with no apertures (other than the pores in polymer tape 450). In an alternative embodiment (not shown), the elutable medicament 475 may be applied to a lower surface 421 of polymer tape 420 instead of, or in addition to, coating applied to upper surface 422.

[0052] FIG. 4B illustrates a coated and heat bonded layer of an implantable sleeve, which is then coating with one or more additional polymer layers using one of the methods shown in FIG. 4A or FIG. 3B. As previously noted, if the coating shown in FIG. 4B comprises the outer layer of the sleeve, the coating is not considered an “elutable” medicament coating because an elutable coating diffuses from a medial surface of a sleeve layer, which does not include either the innermost or outermost surface of the sleeve.

[0053] FIG. 5A provides a cutaway view of an embodiment of a multi-layer gastrointestinal implant sleeve 500 on a mandrel 510, illustrating that the sleeve comprises a plurality of layers built radially exterior to one another. Although different embodiments may have more or few layers, the multi-layer sleeve 500 of FIG. 5A includes 4 layers: a first, inner layer 520, a second layer 530 surrounding first layer 520, a third layer 540 surround second layer 530, and a fourth, outer layer 550 surrounding third layer 540. Adjacent layers are bonded together by known means such as heating the mandrel 510, laser welding portions of adjacent layers during fabrication (e.g., as shown in FIGS. 3A-E and 4A-B), or methods. One or more outer surfaces of the inner layers (e.g., first layer 520, second layer 530, third layer 540) may be coated with one or more medicaments as previously described. In the embodiment of FIG. 5A, second layer 530 and third layer 540 are shown coated in medicaments 535 and 545.

[0054] FIG. 5B shows a cutaway, exploded view of the gastrointestinal implant sleeve 500 after removal from mandrel 510 and radial and longitudinal expansion. The Gl implant sleeve 500 comprises an inner lumen 522, and includes a first layer 524 having an inside surface 522 that also comprises the inside surface of the sleeve. First layer 524 further includes an outside surface 425 bonded to an inside surface 532 of second layer 530.PATENTATTORNEY DOCKET NO.: 51148-049WO2Second layer 530 also includes an outside surface 534 that is bonded to an inside surface 542 of third layer 540. Similarly, third layer 540 has an outside surface 544 bonded to an inside surface 552 of fourth layer 550. Fourth layer 550 also includes an outside surface 554 that is also the outer surface of the sleeve 500. Because surfaces 524, 532, 534, 542, 544, and 552 are surfaces between the inside sleeve surface 522 and outside sleeve surface 544, and are bonded to one or more other surfaces of the sleeve layers, they are medial surfaces which may be coated with an elutable medicament to be released or eluted from the inside or outside surface of the sleeve 500 to treat the patient to achieve one or more treatment goals for the patient. Treatment goals may include, without limitation, minimizing or alleviating trauma resulting from implantation of the Gl sleeve 500, preventing or treating infection, treating eating disorders or conditions, treating one or more Gl structures exterior to or distal to the sleeve, or treating the patient’s microbiome.

[0055] The particular embodiments disclosed above are illustrative only, as the invention may be modified and practiced in different but equivalent manners apparent to those skilled in the art having the benefit of the teachings herein. Embodiments of the present invention disclosed and claimed herein may be made and executed without undue experimentation with the benefit of the present disclosure. While the invention has been described in terms of particular embodiments, it will be apparent to those of skill in the art that variations may be applied to systems and apparatus described herein without departing from the concept, spirit and scope of the invention. Examples are all intended to be non-limiting. It is therefore evident that the particular embodiments disclosed above may be altered or modified and all such variations are considered within the scope and spirit of the invention, which are limited only by the scope of the claims.

Claims

PATENTATTORNEY DOCKET NO.: 51148-049WO2CLAIMS1 . A gastrointestinal implant system comprising: a) a collapsible stent adapted to contact a portion of a gastrointestinal system of a patient in an expanded position, the stent having a proximal stent end adapted to contact a first patient gastrointestinal structure, a distal stent end adapted to contact a second patient gastrointestinal structure distal to the first patient gastrointestinal structure, and a stent body defining a stent lumen; and b) a flexible sleeve having a sleeve lumen extending at least partially through the stent lumen, a proximal sleeve end adapted to be coupled to the collapsible stent, a distal sleeve end extending a selected length into at least one of a duodenum, a jejunum, and an ileum of the patient, an exterior sleeve surface facing toward the gastrointestinal system of the patient, and an interior sleeve surface defining the sleeve lumen, wherein the flexible sleeve is adapted to receive chyme into the sleeve lumen at the proximal sleeve and allow it to exit the distal sleeve end, the sleeve comprising:1 ) a sleeve wall comprising a plurality of polymer layers each having first and second polymer layer sides, each polymer layer being bonded to at least one adjacent polymer layer on at least one of the first polymer layer side and the second polymer layer side, wherein one of said first and second polymer layer sides comprises the exterior sleeve surface, a second of said first and second polymer layer sides comprises the interior sleeve surface, and the remaining first and second polymer layer sides comprise medial sleeve layer sides, wherein at least one of said plurality of polymer layers comprises at least a first pore size; and2) at least one elutable medicament coupled to one of said medial sleeve layer sides, wherein the at least one pore size is selected to modulate a rate of elution of the elutable medicament from at least one of the exterior sleeve surface and the interior sleeve surface.

2. The gastrointestinal implant system of claim 1 , wherein the sleeve wall comprises at least a first polymer layer having a first pore size and at least a second polymer layer having a second pore size, wherein both the first pore size and the second pore size are selected to selected to modulate a rate of elution of the at least one elutable medicament.PATENTATTORNEY DOCKET NO.: 51148-049WO23. The gastrointestinal implant system of claim 2, wherein the first pore size and the second pore size are different, the first pore size is selected to provide a first rate of elution for the at least one medicament, and the second pore size is selected to provide a second rate of elution of the at least one medicament that is different from the first rate of elution.

4. The gastrointestinal implant system of claim 1 , wherein the sleeve wall comprises at least an outer polymer layer comprising the exterior sleeve surface and having a first pore size selected for eluting a first elutable medicament from the exterior sleeve surface toward the gastrointestinal system, and at least an inner polymer layer comprising the interior sleeve having a second pore size selected for eluting a second elutable medicament into the sleeve lumen.

5. The gastrointestinal implant system of claim 1 , wherein the at least one medicament is selected from a medicament to alleviate trauma associated with implantation of the gastrointestinal implant system, a medicament adapted to treat or prevent infection, a medicament adapted to treat obesity, a medicament adapted to treat one or more gastrointestinal tract structures, a medicament to treat gastrointestinal tissue exterior to at least a portion of the flexible sleeve, and a medicament adapted to treat one or more gastrointestinal tract structures distal to the distal sleeve end.

6. The gastrointestinal implant system of claim 1 , wherein the sleeve wall comprises at least one non-elutable polymer layer selected to prevent elution of the at least one medicament through the non-elutable polymer layer.

7. The gastrointestinal implant system of claim 6, wherein the at least one non-elutable polymer layer is selected from a polymer layer having no pores and a polymer layer having a pore size too small to permit elution of the at least one medicament.

8. The gastrointestinal implant system of claim 1 , wherein the sleeve wall comprises a polymer layer having a proximal portion having a first pore size selected to provide a first rate of elution of the at least one elutable medicament from the proximal portion and a distal portion having a second pore size selected to provide a second rate of elution ofPATENTATTORNEY DOCKET NO.: 51148-049WO2 the at least one elutable medicament, different from the first rate of elution, from the distal portion.

9. A gastrointestinal implant system comprising: a) a collapsible stent adapted to be positioned in an expanded position in at least a portion of a superior duodenum of a patient, comprising:1 ) a proximal stent end adapted to contact a first patient gastrointestinal structure in the superior duodenum;2) a distal stent end adapted to contact a second patient gastrointestinal structure distal to the first patient gastrointestinal structure; and3) a stent body defining a stent lumen; and b) a flexible sleeve having an exterior sleeve surface adapted to face toward the gastrointestinal system and an interior sleeve surface defining a sleeve lumen, comprising:1 ) a proximal sleeve end adapted to be coupled to the collapsible stent;2) a distal sleeve end adapted to extend a selected length into one of a duodenum, a jejunum, and an ileum of the patient;3) a sleeve wall comprising a plurality of polymer layers each bonded to at least one adjacent polymer layer, each polymer layer comprising a first polymer layer side and a second polymer layer side, wherein one of the first and second polymer layer sides comprises the exterior sleeve surface, a second of the first and second polymer layer sides comprises the interior sleeve surface, and the remaining first and second polymer sides each comprise medial sleeve layer sides, at least one of said plurality of polymer layers comprising a first pore size; and4) at least one elutable medicament coupled to at least one of the medial sleeve layer sides, wherein the first pore size is selected to modulate a rate of elution of the elutable medicament from at least one of the exterior sleeve surface and the interior sleeve surface.

10. The gastrointestinal implant system of claim 9, wherein the proximal sleeve end is adapted to be coupled to the proximal stent end, and the flexible sleeve is adapted to extend at least partially through the stent lumen.PATENTATTORNEY DOCKET NO.: 51148-049WO211 . The gastrointestinal implant system of claim 9, wherein the sleeve wall comprises:A) a first polymer layer having a first pore size, a first polymer layer side that comprises the exterior sleeve surface, and a second polymer layer side comprising a medial sleeve layer side;B) a second polymer layer adjacent to said first polymer layer and having a second pore size different from the first pore size, a first polymer layer side bonded to the second polymer layer side of the first polymer layer, and a second polymer layer side;C) a third polymer layer having a first polymer layer side bonded to the second polymer layer side of the second polymer layer, and a second polymer layer side opposite to the first polymer layer side; wherein the at least one elutable medicament comprises:A) a first reservoir of the at least one medicament coupled to at least one of the second polymer layer side of the first polymer layer and the first polymer side of the second polymer layer; andB) a second reservoir of the at least one medicament coupled to at least one of the second polymer layer side of the second polymer layer and the first polymer layer side of the third polymer layer; and wherein the first pore size is selected to provide a first elution rate of the at least one elutable medicament from the first reservoir, and the second pore size is selected to provide a second elution rate of the at least one elutable medicament from the second reservoir.

12. The gastrointestinal implant system of claim 11 , wherein the third polymer layer is a non-elutable polymer layer selected to prevent elution of the at least one medicament from the second polymer layer side of the third polymer layer.

13. The gastrointestinal implant system of claim 9, wherein the sleeve wall comprises:A) a first polymer layer having a first pore size, a first polymer layer side that comprises the exterior sleeve surface, and a second polymer layer side comprising a medial sleeve layer side;B) a second polymer layer having a second pore size, a first polymer layer side that comprises the interior sleeve surface, and a second polymer layer side comprising a medial sleeve layer size;PATENTATTORNEY DOCKET NO.: 51148-049WO2C) at least one third polymer layer, wherein a first side of the at least one third polymer is bonded to the second polymer layer side of the first polymer layer, and a second side of the at least one third polymer layer is bonded to the second polymer layer side of the second polymer layer; wherein the at least one elutable medicament comprises:A) a first reservoir coupled to at least one of the second polymer layer side of the first polymer layer and the first side of the at least one third polymer layer; andB) a second reservoir coupled to at least one of the second polymer layer side of the second polymer layer and the second side of the at least one third polymer layer; and wherein the first pore size is selected to provide a first elution rate of the at least one elutable medicament from first reservoir and the exterior sleeve surface, and the second pore size is selected to provide a second elution rate of the at least one elutable medicament from second reservoir and the interior sleeve surface.

14. The gastrointestinal implant system of claim 13, wherein the at least one medicament comprises a first elutable medicament in the first reservoir selected for treating gastrointestinal tissue exterior to at least a portion of the flexible sleeve, and a second elutable medicament in the second reservoir selected to treat one of an eating disorder and gastrointestinal tract tissue distal to the distal sleeve end.

15. The gastrointestinal implant system of claim 9, wherein the sleeve wall comprises at least one non-elutable polymer layer selected to prevent elution of the at least one medicament through the non-elutable polymer layer.

16. The gastrointestinal implant system of claim 9, wherein the sleeve wall comprises a polymer layer having a proximal portion having a first pore size selected to provide a first rate of elution of the at least one elutable medicament from the proximal portion and a distal portion having a second pore size selected to provide a second rate of elution of the at least one elutable medicament, different from the first rate of elution, from the distal portion.

17. A method of treating an eating condition of a patient comprising:PATENTATTORNEY DOCKET NO.: 51148-049WO2 a) implanting a gastrointestinal device in a portion of a gastrointestinal system of a patient, the gastrointestinal device comprising1 ) a collapsible stent adapted for implantation in a portion of a gastrointestinal system of a patient in an expanded condition and comprising a proximal stent end, a distal stent end, and a stent body defining a stent lumen;2) a flexible sleeve having an exterior sleeve surface, an interior sleeve surface defining a sleeve lumen, the flexible sleeve comprising:A) a proximal sleeve end coupled to the collapsible stent;B) a distal sleeve end adapted to extend a selected length into one of a duodenum, a jejunum, and an ileum of the patient; andC) a sleeve wall comprising a plurality of polymer layers each bonded to at least one adjacent polymer layer, each polymer layer comprising a first layer side and a second layer side, wherein one of the first and second layer sides comprises the exterior sleeve surface, a second of the first and second polymer layer sides comprises the interior sleeve surface, and the remaining first and second polymer sides each comprise medial sleeve layer sides, at least one of said plurality of polymer layers comprising a first pore size; andD) at least one elutable medicament coupled to one of the medial sleeve layer sides, wherein the first pore size is selected to modulate a rate of elution of the elutable medicament from at least one of the exterior sleeve surface and the interior sleeve surface; b) receiving chyme into the proximal sleeve; c) allowing the chyme to pass through the sleeve lumen and exit through the distal sleeve end; and d) eluting the at least one elutable medicament from at least one of the exterior sleeve surface and the interior sleeve surface.

18. The method of claim 17, wherein the sleeve wall comprises a first polymer layer having a first pore size and a second polymer layer having a second pore size different from the first pore size, and wherein eluting the at least one elutable medicament comprises eluting the medicament at a first rate of elution and a second rate of elution different from the first rate of elution.PATENTATTORNEY DOCKET NO.: 51148-049WO219. A method of making a gastrointestinal implant sleeve: a) providing a mandrel form for the gastrointestinal sleeve shape; b) providing a biocompatible polymer ribbon adapted for winding around a mandrel, the ribbon comprising a spool source; c) winding the ribbon around the mandrel form to provide a layer of the gastrointestinal sleeve having an inside surface facing the mandrel and an outside surface oppose to the inside surface; d) coating the outside surface with a first medicament; e) repeating steps (c) and (d) one or more times to provide one or more additional layers of the gastrointestinal sleeve, wherein each of the one or more additional layers is adjacent to a prior gastrointestinal sleeve layer; f) after each repetition of steps (c) and (d), bonding the additional layer to the prior gastrointestinal sleeve layer; g) removing the gastrointestinal sleeve from the mandrel form, the gastrointestinal sleeve having at least a first dimension; and h) expanding the gastrointestinal sleeve from a first dimension to a second dimension adapted for implant into a location in at least a part of a duodenum of a patient.

20. The method of claim 19, wherein the gastrointestinal sleeve comprises at least a first length and a first diameter after the removal of the gastrointestinal sleeve from the mandrel, and at least a second length and a second diameter after the expanding of the gastrointestinal sleeve from a first dimension to a second dimension.

Images