Abstract:
Methods and devices create an intestinal braking effect, are non-invasive or minimally invasive, and may be reversible. These methods and devices may be accomplished via stabilized implantable systems and ingestible pills. In one aspect, a method of inducing satiety includes implanting an implant within a lumen of a gastrointestinal tract and retaining a portion of chyme that flows by the implant within a body of the implant. The method further involves re-releasing the retained chyme from the implant into the gastrointestinal tract at a predetermined rate slower than a rate caused by natural peristalsis.

Description:
PRIORITY 
       [0001]    This application claims priority to U.S. Provisional Patent Application Ser. No. 61/348,270, entitled “Intestinal Brake Inducing Intraluminal Therapeutic Substance Dosing Devices and Methods,” filed May 26, 2010, the disclosure of which is incorporated by reference herein. 
     
    
     FIELD OF INVENTION 
       [0002]    The present invention relates to methods and devices that elute a therapeutic substance which aid in inducing an intestinal braking effect. 
       BACKGROUND OF THE INVENTION 
       [0003]    When food content enters the intestines, an intestinal braking effect occurs which helps to slow the passage of this food content therethrough in order to aid in the absorption of nutrients to in the body. Intestinal brake has been shown to initiate satiation more quickly and is theorized to play an important role in the effectiveness (both Excess Weight Loss (EWL) and co-morbidity resolution) of Roux-En-Y Gastric Bypass (RYGB) surgery. Procedures such as ileal transposition have been developed based on the concept of delivery of substances with rich nutrient/caloric content to the ileum and have been shown to be effective in numerous animal models. However, known methods tend to be overly invasive and often require a permanent perforation in the intestinal lumen. Accordingly, there is a need for creating an intestinal braking effect which is non-invasive or minimally invasive, and which may be reversible. 
     
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
         [0004]    The invention will be more fully understood from the following detailed description taken in conjunction with the accompanying drawings, in which: 
           [0005]      FIG. 1  is a schematic partially transparent view of an intra-intestinal therapeutic substance eluting implant. 
           [0006]      FIG. 2  is schematic partially transparent view of an intra-intestinal therapeutic substance eluting implant with a rechargeable drug-eluting reservoir. 
           [0007]      FIG. 3  is a schematic partially transparent view of an intra-intestinal therapeutic substance eluting implant with a rechargeable drug-eluting reservoir comprising a fill port attached therewith. 
           [0008]      FIG. 4  is a schematic partially transparent view of an intra-intestinal therapeutic substance eluting implant with a rechargeable drug-eluting reservoir comprising a fill port and a pressure sensing system attached therewith. 
           [0009]      FIG. 5  is a schematic partially transparent view of delivery system for nutrient binding material. 
           [0010]      FIG. 6  is a graph representing chyme levels in the body for a patient with and without a chyme holding stent. 
           [0011]      FIG. 7  is a schematic partially transparent view of a collapsible implant with a conical chyme pouch. 
           [0012]      FIG. 8  is a schematic partially transparent view of a chyme holding implant and details thereof. 
           [0013]      FIG. 9  is a schematic partially transparent view of a collapsible implant with absorbent material. 
           [0014]      FIG. 10  is a schematic partially transparent view of an implant including an extra-luminal choke ring. 
           [0015]      FIG. 11  is a schematic partially transparent view of an implant including a wide band choke ring. 
           [0016]      FIG. 12  is a schematic view of an inflatable delivery mechanism. 
           [0017]      FIG. 13  is schematic partially transparent view of artificially formed dead end branches for stabilizing an implant. 
           [0018]      FIG. 14  is a schematic partially transparent view of a procedure for forming an artificial dead end branch. 
           [0019]      FIG. 15  is a schematic view of an artificially formed T-branch dead end for stabilizing an implant. 
           [0020]      FIG. 16  is a schematic partially transparent view illustrating the steps for creating a dead end branch using proven laparoscopic stapler techniques. 
           [0021]      FIG. 17  is a schematic partially transparent view illustrating the steps for creating a dead end and holding an implant within the dead end using a linear stapler, circular stapler and an extra-luminal band. 
           [0022]      FIG. 18  is a schematic partially transparent view of a loop anastomosis for stabilizing an implant. 
           [0023]      FIG. 19  is a schematic partially transparent view of a minimal segment loop for stabilizing an implant. 
           [0024]      FIG. 20  is a schematic partially transparent view of an excised portion of intestine reattached to the intestine via side-to-side anastomosis thereby creating a flow through chyme pouch having an implant therein. 
           [0025]      FIG. 21  is a schematic partially transparent view of an ingestible eluting device in its collapsed form. 
           [0026]      FIG. 22  is a schematic partially transparent view of an ingestible eluting device in its expanded form. 
           [0027]      FIG. 23  is a schematic partially transparent view of a therapeutic substance pill with nanochannels and details thereof. 
           [0028]      FIG. 24  is a schematic partially transparent view of a pressure wave pill and details thereof. 
           [0029]      FIG. 25  is a graph representing pH changes in a patient&#39;s stomach throughout the day. 
           [0030]      FIG. 26  is a schematic partially transparent view of a pill to increase peristalsis as it passes through he stomach and intestines of a patient. 
       
    
    
     DETAILED DESCRIPTION OF THE INVENTION 
       [0031]    Certain exemplary embodiments will now be described to provide an overall understanding of the principles of the structure, function, manufacture, and use of the devices and methods disclosed herein. One or more examples of these embodiments are illustrated in the accompanying drawings. Those skilled in the art will understand that the devices and methods specifically described herein and illustrated in the accompanying drawings are non-limiting exemplary embodiments and that the scope of the present invention is defined solely by the claims. For example, the features illustrated or described in connection with one exemplary embodiment may be combined with the features of other embodiments. Such modifications and variations are intended to be included within the scope of the present invention. 
         [0032]      FIG. 1  is a schematic partially transparent view of an intra-intestinal therapeutic substance eluting implant  100 . In this particular embodiment, implant  100  is shown as a degradable intestinal stent positioned in intestine  8 , just past the ileocecal valve (see reference indicia  10  in  FIG. 4 ). Alternatively, implant  100  may be non-degradable. Implant  100  allows for the addition of nutrients and bio-active substances to the intestines, thereby inducing satiety through an intestinal braking effect. In certain embodiments, implant  100  may be deployed during a standard colonoscopy procedure using a deployment device attached to a flexible endoscope. This device and method would have the benefits of inducing satiety through a non-invasive procedure, and is combinable with the single yearly recommended colonoscopy, thus permitting monitoring of colon health and enabling weight loss in a patient. In one embodiment, implant  100  may be constructed from a degradable polymer having therapeutic substances therein. Non-limiting examples of such therapeutic substances include nutrients and specific satiety inducing bio-active substances such as pancreatic polypeptides (PPY), free fatty acids (FFA) and cholecystokinin (CCK). In alternative embodiments, implant  100  may be coated with bioactive substances such as amino acids, glutamine, or lipids. These substances may elute over time. Implant  100  may be formed from a number of materials including coated string, mesh, fabric, buttons, tube, or any other suitable material. Implant  100  may further be rigid or flexible and may optionally be anchored to the wall of intestine  8  to secure its position. As may be appreciated, implant  100  may be of any desirable shape and size. In certain embodiments, implant  100  may be helically shaped in order to allow flexibility along with intestine  8 . Due to the stent shape illustrated in  FIG. 1 , intestine  8  will begin to grow over implant  100  in time, thereby encapsulating implant  100  in the intestinal wall, thus providing the benefit of direct tissue for the therapeutic substances which would aid in transfer of the therapeutic substances to the bloodstream. In another embodiment, implant  100  may be designed not to adhere to intestine  8 . This may be accomplished, for example, by adding a lubricating means to the external surfaces of implant  100 . In this manner, implant  100  would be more easily removed from the body should the patient so desire. In the case of implant  100  being a degradable intestinal stent, it may be desirable to construct implant  100  from a polymer or other substance having a full degradation period of a year or so in order to coordinate the full degradation of implant  100  with a yearly colonoscopy, during which a replacement implant  100  may be installed. 
         [0033]    In regard to  FIG. 1 , numerous alternatives are envisioned. For example, in one embodiment, implant  100  may include means to create “pulsations” of therapeutic substances rather than simply providing a constant release of these therapeutic substances. Accordingly, implant  100  may be constructed in a manner which provides alternating layers of therapeutic substance containing polymers and non-therapeutic substance containing polymers. Similarly, the alternating layers may comprise layers containing different dosing or concentrations of the therapeutic substances or different therapeutic substances from the surrounding layers. This may for example create a feeling of satiety, then a reduction in that feeling, or may help maintain the effectiveness of implant  100  through time. Further, the therapeutic substance utilized in implant  100  can be tailored to suit the intended location of the stent, taking into account factors such pH level exposure which may alter the life span of implant  100 . Additionally, implant  100  may be configured to deliver an electrical stimulation to the GI tract at a location such as the ileum, and further may elute linoleic acid amongst its therapeutic substances. Non-limiting disclosure of the benefits of electrical stimulation of the ileum in the presence of linoleic acid in order to increase glucagon-like peptide 1 (GLP-1) expression an example of this is disclosed in US2005/0131386A1, Jun. 16, 2005 “METHOD AND DEVICE FOR MINIMALLY INVASIVE IMPLANTATION OF BIOMATERIAL”, which is hereby incorporated herein by reference. In yet another embodiment, implant  100  may comprise an intestinal stent containing an active substance such as PPY or GLP-1 andoxytomodulin placed at the ileum. Further, the stent may be in the form of a metal (e.g., cobalt chromium, stainless steel, Nitinol, etc.) or absorbable polymer ring or mesh affixed to the gastrointestinal (GI) tract by sutures. The active substance may be a synthetic which is analogous to a human hormone or animal derived hormone. 
         [0034]    The device and procedure outlined herein with respect to  FIG. 1  is intended to induce satiety by introducing a therapeutic substance to activate an intestinal braking effect via a therapeutic substance eluting implant  100 . The procedure has the further benefit of being non-invasive or minimally invasive, as well as being a reversible procedure should the patient or physician so desire. There are no anatomical changes to the GI tract, and placement of implant  100  may be realized endoluminally via a flexible endoscope or flexible endoscopic platform. Implant  100  may be delivered through a working channel or over the outside of the flexible endoscopic platform. Implant  100  may be delivered in collapsed or expanded state and delivered to the desired location within the GI tract either transorally or transanally. Further, the dosing and concentrations of the therapeutic substance(s) eluted by implant  100  may be tailored to meet the individual needs of the patient and may further be enhanced to vary over time and may be localized to control the delivery of hormone triggers to the desired receptors. 
         [0035]      FIG. 2  is schematic partially transparent view of an intra-intestinal therapeutic substance eluting implant  200  with a rechargeable drug-eluting reservoir  202 . In this particular embodiment, therapeutic substance eluting implant  200  is shown as a degradable intestinal stent positioned in intestine  8 , just past the ileocecal valve (see reference indicia  10  in  FIG. 4 ), which acts to trap rechargeable drug-eluting reservoir  202  thereon. As with the embodiments disclosed in  FIG. 1 , this allows for the addition of therapeutic substances such as nutrients and bio-active substances to intestines  8  to induce satiety through an intestinal braking effect. Reservoir  202  may be recharged via an external source, such as through a port fixated to the patient&#39;s fascia as is discussed later herein with respect to  FIGS. 4 &amp; 5 . 
         [0036]      FIG. 3  is a schematic partially transparent view of an intra-intestinal therapeutic substance eluting implant  200  with a rechargeable drug-eluting reservoir  202  comprising a fill port  300  attached therewith. In this embodiment, fill port  300  is connected to reservoir  202  via tube  302 . In certain embodiments, a valve  304  may be included at the connection point between reservoir  202  and tube  302 , or at any other desirable location, in order to maintain a desired fill level of therapeutic substance within reservoir  202 . When reservoir  202  falls below the desired fill level, a surgeon may inject additional therapeutic substance into fill port  300  by means such as a Huber needle. Alternatively, a transhepatic catheter may be inserted through hepatic duct  14  ( FIG. 4 ) and pass through liver  2  ( FIG. 4 ), connecting to a subcutaneous fill port  300  for refilling reservoir  202 . 
         [0037]      FIG. 4  is a schematic partially transparent view of an intra-intestinal therapeutic substance eluting implant  200  with a rechargeable drug-eluting reservoir  202  comprising a fill port  300  and a pressure sensing system  400  attached therewith. In this particular embodiment, the locations of the various components of the system are shown within the body of a patient. Following the natural path through the GI tract, food content enters through esophagus  1  and passes through cardia  4  into stomach  3 . After some time, the food content is partially digested and becomes chyme. This chyme exits stomach  3  through pylorus  5  into duodenum  6 . Duodenum  6 , jejunum  7  and ileum  9  make up the three sections of small intestine  8 . At the end of small intestine  8  in the ileum  9  is ileocecal valve  10  which serves to connect small intestine  8  to large intestine  11 . Large intestine  11  is the final section of the GI tract and terminates at anus  12  through which solid waste may be expelled from the body. Aiding in the entire digestion process are liver  2  and gall bladder  13  which act to provide bile and other biochemicals necessary for digestion to duodenum  6  through hepatic duct  14 . In  FIG. 4 , a pressure sensing system  400  is positioned at cardia  4  to provide a signal to rechargeable drug-eluting reservoir  202  of intra-intestinal therapeutic substance eluting implant  200  when food is consumed. The signal sent initiates activation of a pump (not shown in  FIG. 4 ) which delivers a therapeutic substance through reservoir  202  to induce an intestinal braking effect which would help to create or maintain a sensation of satiety. As has been shown and described previously herein, fill port  300  has been provided to enable the system to be refilled with therapeutic substance when necessary, and may be of the subcutaneous type. 
         [0038]    In regard to  FIG. 4 , numerous alternatives are envisioned. For example, in one embodiment, reservoir  202  may be attached to a micro-pump which would release therapeutic substance automatically at predetermined points during the day in order to induce an intestinal braking effect which would help to create or maintain a sensation of satiety These smaller doses are distributed along a more continuous schedule and serve to maintain the feeling of satiety longer through prolonged addition of nutrients to the lower GI tract. As may be appreciated, additional reservoirs and pumps may be added to the system described above to deliver the desired therapeutic substance. In another embodiment, reservoir  202  may be a degradable therapeutic substance infused foam material that may be injected behind implant  200  to fill the gap created by the shape of implant  200 . Over time, the foam material would release the therapeutic substance to induce an intestinal braking effect. This foam material could be re-injected via a flexible member during an annual colonoscopy. In yet another embodiment, reservoir  202  may be constructed from a semi-permeable membrane that would leach out a therapeutic substance over time. Similar to the previous embodiment disclosed, this reservoir could be refilled by means of a flexible member inserted during an annual colonoscopy procedure. For example, the flexible member may comprise a Huber needle at one end which may be attached via tubing to a secondary reservoir, such as a saline bag, external to the patient during the colonoscopy. In still another embodiment, reservoir  202  may comprise a swallowable reservoir that is captured by implant  200 . In one embodiment, implant  200  may be in the form of a stent having tines that protrude into intestine  8  and capture reservoir  202  as it is brought into position by the natural peristalsis of the digestive cycle. Reservoir  202  may be in the form of a hollow cylinder which allows chyme to pass therethrough, but contain a therapeutic substance in the reservoir body. The therapeutic substance may then be released via slow perfusion, a small leak or a self-contained pump system. As the therapeutic substance is released, the diameter of reservoir  202  may decrease enough to allow it to pass through implant  200 . A replacement reservoir could then be swallowed and the process would repeat. 
         [0039]      FIG. 5  is a schematic partially transparent view of delivery system for nutrient binding material. As was described previously herein, food content  500  enters the GI tract through esophagus  1  into stomach  3 . In this particular embodiment, implant  502  resides within stomach  3 . Implant  502  generally comprises a balloon implant that is tacked to the stomach as a long term implant. In one embodiment, implant  502  is divided into two compartments separated by an intermediary wall  512 , where one compartment contains a pH sensitive hydrogel  506  and the other compartment contains a non-digestible fatty acid or high soluble fiber liquid  510 . Hydrogels are cross-linked hydrophilic polymers that can contain a large amount of water. By incorporating functional groups, a hydrogel can be made stimulus-sensitive, such that they undergo volume changes in response to certain stimuli. Examples of such stimuli include pH changes, temperature changes, light, ion concentrations and electrical fields. In one embodiment where the stimuli is pH change, as a pH level becomes acidic, hydrogel  506  becomes hydrophilic and attracts water through a pH sensitive membrane  504  and begins to expand. As a pH level becomes neutral or basic, hydrogel  506  becomes hydrophobic and contracts, expelling any bound up water through porous membrane  508 . When hydrogel  506  is in an expansion mode, not only does membrane  508  allow the entire implant to grow and take up space in the stomach to create a satiety sensation, it also places pressure on the second compartment of implant  502  which contains non-digestible fatty acid or high soluble fiber liquid  510 . As the second compartment of implant  502  which contains non-digestible fatty acid or high soluble fiber liquid  510  is placed under pressure by the expansion of hydrogel  506 , membrane  508  releases a small amount of the non-digestible fatty acid or high soluble fiber liquid  510  contained therein, which then attaches to food content  500  thereby slowing their absorption into the body as they pass through the remainder of the GI tract. This in turn induces an intestinal brake as undigested nutrients and fatty acids enter ileum  9 . Intermediary wall  512  may be constructed of a flexible elastomeric material such as silicone in order to allow a transfer of force from one compartment to the other. In regard to  FIG. 5 , numerous alternatives are envisioned. For example, in one embodiment, the first compartment may be constructed of a fine mesh or a highly permeable expansible membrane containing hydrogel. Examples of suitable hydrogels include chitosan, polyacrylamide (PAAM), and poly(2-Hydroxyethyl Methacrylate) (pHEMA)). 
         [0040]    In another embodiment a chyme holding implant is provided.  FIG. 6  is a graph representing chyme levels in the body for a patient with and without a chyme holding implant. The graph on the left of  FIG. 6  illustrates typical chyme levels in the body during the day without a chyme holding stent. As may be appreciated, chyme levels are highest shortly after a meal and decrease over time, eventually crossing the hunger threshold which induces a sensation of hunger in the patient. A more desirable graph is illustrated on the right of  FIG. 6  where the chyme levels are maintained above the hunger threshold, thereby maintaining a sensation of satiety in the patient throughout the day. One means for creating such a graph is through the implantation of a chyme holding implant within the intestine which would act to hold a portion of chyme therein to prevent its movement through the intestines, such that chyme is in chemical and/or biological contact with the intestinal cells responsible for intestinal brake, thereby inducing an intestinal braking effect. In one embodiment, chyme would be held long enough so that chyme from one meal would remain into the next. Alternatively, chyme may be held for longer periods of time if so desired. In another embodiment, the implant protects the chyme therein from further digestion through the use of chemical or mechanical means. By holding chyme from one meal to the next, the GI tract would be tricked to behave as if food had just been ingested due to the chyme&#39;s tendency to induce the intestinal brake. This would allow the patient to eat less and achieve a desired weight loss. 
         [0041]      FIG. 7  is a schematic partially transparent view of a collapsible implant  700  with a conical, flexible chyme pouch  702  positioned within intestine  8 . Implant  700  has an inlet  704  and an outlet  706 . Peristalsis forces chyme in the direction indicated by arrow  708  due to narrow exit  706  from pouch  702 . Therefore, a select amount of chyme is delayed from movement, which creates a semi-constant stream of chyme between meals, as was discussed previously herein with respect to  FIG. 6 . 
         [0042]      FIG. 8  is a schematic partially transparent view of a chyme holding implant  800  and details thereof. In the embodiment illustrated in detail (A) of  FIG. 8 , chyme  802  may be funneled into an expansible slow leak reservoir  804  to achieve the desired effect of time released chyme. In one embodiment, implant  800  may be suspended by wire elements  806  in intestine  8  which are centered on stent  814  in a configuration that allows some chyme to bypass the reservoir via bypass channels  808  and some to be trapped within reservoir  804 . As chyme is accumulated, reservoir  804  would expand. The limited size of slow leak catheter  810  of reservoir  804  would allow the accumulated chyme impelled by the pressure of reservoir  804  returning to its unexpanded state to slowly drip therefrom long after a meal was over. In this manner, chyme may further be prevented from retrograde motion by a one-way valve means at outlet  812 , such as a duck bill valve, located between implant  800  and reservoir  804 . This increases the capacity of the implant to hold and release chyme, thereby extending the sensation of satiety in the patient. The entire assembly may be located within a stent  814  positioned at a target location within intestine  8 . A cross-sectional view of the arrangement and interactions of implant  800 , reservoir  804 , slow leak catheter  810  and one-way valve  812  are shown in detail (B) of  FIG. 8 . 
         [0043]      FIG. 9  is a schematic partially transparent view of a collapsible implant  900  with absorbent material  902 . In this particular embodiment, collapsible implant  900  is shown with a piece of absorbent material  902  affixed thereto, and is affixed within intestine  8  at a target location. In one embodiment, material  902  comprises a hollow cylindrical sponge. As peristalsis moves chyme through the GI tract, some chyme contained within material  902  is pushed out, and flows in a direction indicated by arrow  904 . Subsequent peristaltic motions repeat this effect. Therefore, some amount of chyme is delayed from movement through the GI tract, thereby creating a prolonged sensation of satiation in a patient. 
         [0044]      FIG. 10  is a schematic partially transparent view of an implant  1000  including extra-luminal choke ring  1002 . In the embodiment illustrated in detail (A) of  FIG. 10 , implant  1000  is implanted at a target location within intestine  8  and a choke ring  1002  is positioned extraluminally proximate a groove  1004 . In detail (B) of  FIG. 10 , choke ring  1002  is crimped such that it fits within groove  1004  in a manner that secures implant  1000  in place within intestine  8 , yet prevents necrosis. Although illustrated as a round wire, it is contemplated that choke ring  1002  may be formed in different configurations to include features such as flat or undulating cross-sections, locking features, and the like, without departing from the scope of the present invention. Further, it is contemplated that this system may be implanted using non-invasive or minimally invasive methods such as single site laparoscopy. 
         [0045]      FIG. 11  is a schematic partially transparent view of an implant  1100  including a wide band choke ring  1102 . In this particular embodiment, implant  1100  is positioned within intestine  8  in a similar manner to that of the embodiment described above in  FIG. 8 . However, in this particular embodiment the external surface  1104  of implant  1100  does not include a groove and is formed of a mesh material. The mesh material comprising external surface  1104  causes numerous contact points between wide band choke ring  1102  and implant  1100  through intestine  8 , thereby securing implant  1100  within intestine  8 . 
         [0046]      FIG. 12  is a schematic view of an inflatable delivery mechanism  1200 . Mechanism  1200  is an exemplary means for delivering an implantable device such as stent  1202  into the GI tract as is detailed in previous embodiments of the present invention. In one embodiment, mechanism  1200  attaches to a flexible endoscope  1204  and mechanism  1200  is inflated to secure stent  1202  externally thereon. When stent  1202  is delivered to the desired location, mechanism  1200  is deflated thereby releasing stent  1202 . At that point, mechanism  1200  and endoscope  1204  can be removed from the patient&#39;s body and mechanism  1200  can be removed from endoscope  1204 . In an alternative embodiment, mechanism  1200  may stay in place with stent  1202  to serve as a reservoir of therapeutic substance. This would obviate the need to perform a separate fill procedure in situ upon deployment. It should be noted that implantation of a device within the GI tract may necessitate a guide wire extending means in order to reach the target area within the GI tract, since such locations typically fall beyond the ileocecal valve and thus may be out of reach for known colonoscopes. 
         [0047]      FIG. 13  is schematic partially transparent view of artificially formed dead end branches for stabilizing an implant  1300 . As is shown in details (A) and (B) of  FIG. 13 , intestine  8  is transected at a location  1302 , and an end-to-side anastomosis is performed in order to reconnect proximal portion  1306  and distal portion  1308  of intestine  8 , thus leaving a branch portion  1310  in place with an implant  1300  therein. Branch  1310  and implant  1300  together serve as a retrograde dead end within intestine  8 . Alternatively, a side-to-side anastomosis may be performed in place of the end-to-side anastomosis disclosed, so long as care is taken to prevent formation of a second blind pouch which may collect chyme. In either procedure, intestine  8  remains vascularized and connected to mesentery. Thus, implant  1300  may continue to have an impact on hormonal activities of intestine  8 . Certain embodiments of implant  1300  may include an occluded end portion  1312  in order to prevent any chyme passage. As may be appreciated, implant  1300  may be of the drug eluting type disclosed previously herein. As yet another alternative, intestine  8  may undergo an end-to-end anastomosis in order to form a continuous section. Details of the end-to-end anastomosis are given in  FIG. 15 . 
         [0048]      FIG. 14  is a schematic partially transparent view of a procedure for forming an artificial dead end branch. Details (A), (B) and (C) of  FIG. 14  outline the procedural steps for forming an artificial dead end branch as described in  FIG. 13 . Detail (A) of  FIG. 14  illustrates intestine  8  prior to end-to-side anastomosis. Detail (B) of  FIG. 14  illustrates intestine  8  transected into proximal portion  1306  and distal portion  1308  by means of a linear cutting device (not shown). Detail (C) of  FIG. 14  illustrates the formation of a dead end branch via implantation of implant  1300  and end-to-side anastomosis at junction  1400 . 
         [0049]      FIG. 15  is a schematic view of an artificially formed T-branch dead end for stabilizing an implant. Details (A), (B) and (C) of  FIG. 15  outline the procedural steps for forming an artificially formed T-branch dead end for stabilizing an implant via an end-to-end anastomosis as was briefly mentioned in the description of alternative embodiments of  FIG. 13 . Detail (A) of  FIG. 15  illustrates intestine  8  having cut lines  1502  and  1504  shown therein. Together, cut lines  1502  and  1504  serve to create portion  1506  of intestine  8 , which is shown to be excised in detail (B) of  FIG. 15 . Detail (C) of  FIG. 15  illustrates the formation of an artificially formed T-branch dead end for stabilizing an implant (not shown) where excised portion  1506  is reattached to intestine  8  at junction  1510  and stapled at its opposing end to create a dead end branch  1508 . Further, cut lines  1502  and  1504  are connected to form an end-to-end anastomosis  1512 . 
         [0050]      FIG. 16  is a schematic partially transparent view illustrating the steps for creating a dead end branch using laparoscopic stapler techniques. A first step (A), illustrates intestine  8  in an unaffected state. In a second step (B), intestine  8  is folded to create an overlap  1600 . In a third step (C), access is gained via aperture  1602  which is formed by cutting tool  1604 . In a forth step (D), stapler  1606  is inserted into folded intestine  8  through aperture  1602 . In a fifth step (E), stapler  1606  secures overlap  1600  together with staples  1608 . In a sixth step (F), stapler  1606  is removed through aperture  1602  and staples  1608  hold overlap  1600  together. In a seventh step (G), a therapeutic substance reservoir  1610  with a slow drip catheter portion  1612  is inserted into intestine  8  through aperture  1602 . In an eighth and final step (H), aperture  1602  is closed and an external ring clamp  1614  is applied between the tissue surrounding reservoir  1610  and the remainder of intestine  8  such that reservoir  1610  is maintained within the dead end branch portion formed and catheter  1612  is positioned in the flow path of intestine  8  in order to provide a slow drip therapeutic substance which will initiate an intestinal braking effect and thereby create or maintain a sensation of satiety in the patient. 
         [0051]      FIG. 17  is a schematic partially transparent view illustrating the steps for creating a dead end and holding an implant  1610  within the dead end using a linear stapler, circular stapler and an extra-luminal band. Steps (A) and (B) illustrate intestine  8  being transected into proximal portion  1306  and distal portion  1308  by means of a linear cutting device  1700 . In a third step (C), proximal portion  1306  of intestine  8  is stapled at its transected end to create a dead end, and a side-to-side anastomosis  1706  is performed to reconnect proximal portion  1306  and distal portion  1308 . In a fourth and final step (D), a therapeutic substance reservoir  1610  with a slow drip catheter portion  1612  is inserted into intestine  8  through open transected end  1704  of distal portion  1308  of intestine  8 , which is then stapled closed and an external ring clamp  1708  is applied between the tissue surrounding reservoir  1610  and the remainder of intestine  8  such that reservoir  1610  is maintained within the dead end branch portion formed and catheter  1612  is positioned in the flow path of intestine  8  in order to provide a slow drip therapeutic substance which will initiate an intestinal braking effect and thereby create or maintain a sensation of satiety in the patient. 
         [0052]      FIG. 18  is a schematic partially transparent view of a loop anastomosis for stabilizing an implant  1804 . Detail (A) of  FIG. 18  illustrates intestine  8  prior to loop anastomosis. Detail (B) of  FIG. 18  illustrates wherein a loop  1800  is formed by bringing two distal points of intestine  8  together with a side-to-side anastomosis  1802  having flow channels therethrough though which chyme  1806  passes. In this manner, loop  1800  houses implant  1804  thereby keeping it from the chyme path, yet allowing it to initiate an intestinal braking effect in intestine  8  as with previously disclosed embodiments of the present invention. In some embodiments, occluded implants may be further provided to prevent chyme  1806  from entering loop  1800  which may cause blockage or infection. 
         [0053]      FIG. 19  is a schematic partially transparent view of a minimal segment loop for stabilizing an implant  1900 . Detail (A) of  FIG. 19  illustrates intestine  8  having implant  1900  positioned therein and cut lines  1502  and  1504  thereon, prior to loop anastomosis. Together, cut lines  1502  and  1504  serve to define proximal portion  1306  and distal portion  1308  and further to create portion  1506  of intestine  8 , which is shown to be excised and reattached via loop anastomosis in detail (B) of  FIG. 19 . Detail (B) of FIG.  19  illustrates the completed loop anastomosis procedure wherein excised intestine portion  1506  serves as a loop which is attached to intestine  8  at end  1908  and end  1910  via end-to-side anastomosis. Further, cut lines  1502  and  1504  are brought together at junction  1906  via end-to-end anastomosis. In this manner, the loop formed by portion  1506  houses implant  1900  thereby keeping it from the chyme path, yet allowing it to initiate an intestinal braking effect in intestine  8  as with previously disclosed embodiments of the present invention. In some embodiments, occluded implants may be further provided to prevent chyme  1912  from entering the loop formed by portion  1506  which may cause blockage or infection. 
         [0054]      FIG. 20  is a schematic partially transparent view of an excised portion  1506  of intestine  8  reattached to the intestine via side-to-side anastomosis thereby creating a flow through chyme pouch  2000  having an implant  2002  therein. As was disclosed previously herein with respect to other embodiments, implant  2002  may be of the flow through and/or slow drip type and may further have therapeutic substance eluting properties in order to initiate a desired intestinal braking effect. As an alternative, implant may be of the sponge type as was discussed previously herein in regard to  FIG. 9 , wherein peristalsis moves chyme through the GI tract, such that some chyme contained within the sponge material of implant  2002  is pushed out, and flows in a direction indicated by arrow  2004 . Subsequent peristaltic motions repeat this effect. Therefore, some amount of chyme is delayed from movement through the GI tract, thereby creating a prolonged sensation of satiation in a patient. 
         [0055]      FIG. 21  is a schematic partially transparent view of an ingestible eluting device  2100  in its collapsed form. In one embodiment, device  2100  has a short term degradable exterior coating  2102  which contains three collapsed pill sections  2104 ,  2106  and  2108 , as well as an axle  2110  therein. In one embodiment, axle  2110  is formed of a bioabsorbable polymer. Further, pill sections  2104 ,  2106  and  2108  may be formed of one or more types of therapeutic substance. In another embodiment, device  2100  may contain apertures which allow passage of chyme and the like therethrough. As may be appreciated, device  2100  may take on any number of sizes and shapes, but in certain embodiments device  2100  is sized and shaped such that it cannot pass through the ileocecal valve without undergoing degradation of its degradable components. 
         [0056]      FIG. 22  is a schematic partially transparent view of the ingestible eluting device  2100  in its expanded form. In this particular embodiment, pill sections  2104  and  2106 , and axle  2110  are shown expanded radially from a center point at angles of roughly 120° from one another, although other angles are anticipated depending upon factors such as the number of pill layers in device  2100 . As may be seen in  FIG. 22 , none of the components of device  2100  are permitted to block passage of chyme and other substances through ileocecal valve  10  due to their radially expanded configuration. As was discussed previously herein, device  2100  is sized and shaped such that it cannot pass from ileum  9  to large intestine  11  through ileocecal valve  10  without undergoing degradation of its degradable components. However, once the degradable components of device  2100  have become depleted, the remaining components may then pass through ileocecal valve  10  and through the remainder of the GI tract naturally. 
         [0057]      FIG. 23  is a schematic partially transparent view of a therapeutic substance pill  2300  with nanochannels  2308  and details thereof. Detail (A) of  FIG. 23  illustrates a cross-sectional view of pill  2300  having sidewall  2302  and end caps  2306  containing a therapeutic substance  2304  therein. In this particular embodiment, therapeutic substance  2304  comprises fat or glucose, although numerous other therapeutic substances may be utilized in addition to or in place of fat or glucose. In certain embodiments, therapeutic substance  2304  acts to stimulate GLP-1 over a short period of time as it passes by K-cells within the duodenum and then again stimulating GLP-1 through the L-cells within the ileum in order to induce an intestinal braking effect. The principle being triggering the signaling pathway for GLP-1 stimulation without the negative effects associated with ingesting additional fat or glucose. As can be seen in details (B) and (C), sidewall  2302  has a thickness T through which nanochannels  2308  pass. Nanochannels  2308  may be patterned and sized as desired to enable the desired amount of fluid communication therethrough, and may further serve as an enzyme barrier to prevent digestion of therapeutic substance  2304  contained within pill  2300 , but still allow for the passage of GLP-1 which would allow the body&#39;s signaling pathway to identify the presence of therapeutic substance  2304  in the GI tract in order to stimulate GLP-1. In certain embodiments, sidewall  2302  may be constructed of polymeric material or of silicon. In certain other embodiments, an adhesive may coat a portion of pill  2300  thereby allowing it to be easily secured in a desired location within the GI tract. 
         [0058]      FIG. 24  is a schematic partially transparent view of a pressure wave pill  2400  and details thereof. Detail (A) of  FIG. 24  illustrates a cross-sectional view of pill  2400  having sidewall  2402  and end caps  2406  containing therein an electromechanical system  2404  for creating pulse waves  2408 . In this particular embodiment, sidewall  2402  is formed of a semi-flexible material that allows outward expansion, as is shown in detail (B) of  FIG. 24 , which aids in the production of pulse waves  2408 . The creation of pulse waves  2408  may be done for example by generating a low frequency pressure wave using electromechanical system  2404  which, if done in the ileum, would stimulate the interaction of chyme with the villi and microvilli, and thus with the L-cells of the ileum. Such stimulation would in turn initiate an intestinal braking effect creating a sensation of satiation in the patient. In certain embodiments, electromechanical system  2404  may consist of a MEMS transducer that would be capable of creating an abrupt expansion of sidewall  2402  which would in turn propagate pulse waves  2408  through the chyme within the immediate proximity of pill  2400 . As may be appreciated, pill  2400  may contain its own power source and be activated in the stool, or may be a passive type device. Further, additional coatings and barrier layers that may affect the travel rate and/or chemical/hormonal characteristics of pill  2400  are also contemplated. As with previous embodiments of the present invention, pill  2400  may also deliver a therapeutic substance if so desired. 
         [0059]      FIG. 25  is a graph representing pH changes in a patient&#39;s stomach throughout the day, as taken from Simonian, H. P., Vo, L., Doma, S., Fisher, R. S., Parkman, H. P., “Regional Postprandial Differences in pH within the Stomach and Gastroesophageal Junction”, Digestive Diseases and Sciences, pgs. 2276-2285; 50(12) 2005. As may be seen from this graph, physiological changes of the digestive system between fasting and consumption may be described in terms of changes in gastric acidity as measured using pH (the log concentration of hydronium ion concentration, or log [H+]). The pH scale spans from 1 (acidic) to 14 (basic), with 7.0 being neutral. During the fasting state, the stomach pH is low (acidic). With meal ingestion, there is buffering of intragastric acidity with an elevation of gastric pH. The change in pH occurs rapidly with the initiation of consumption as food enters into the stomach. This change also occurs even in light of the secretion of gastric acids continuously during consumption. The buffering capacity of foods, including acidic or “spicy” foods is sufficient to provide a significant change in gastric pH. 
         [0060]    In regards to the information disclosed in the graph of  FIG. 25 , it is desirable to treat a patient with a pill which creates a coating within the stomach that helps to induce an intestinal braking effect. In one embodiment, such a pill would accelerate the delivery of fatty acid compounds and/or other therapeutic substances to the body to enable a reduction in food consumption or the sensation of hunger in a patient. In one embodiment, when such a pill is ingested, chemical compounds which terminate in long chain fatty acids are contained within the pill and act to bind to the interior walls of the stomach at acidic pH levels. Upon initial consumption of a meal, compounds release which act to neutralize the pH levels in the stomach. The bound chemical compounds are then released from the stomach walls into the stomach in high concentrations at the start of the meal, thus allowing for a more rapid stimulation of the ileum to initiate an intestinal braking effect. It may be desirable to include longer chained fatty acids such as palmitic, lignoceric acid, and hexacosanic acid in order to decrease the digestibility of the substance, thereby increasing the likelihood that the substance reaches the ileum. 
         [0061]      FIG. 26  is a schematic partially transparent view of a pill  2600  to increase peristalsis as it passes through stomach  3  and intestines  8  of a patient. Detail (A) of  FIG. 26  illustrates the second pill  2600  of a two pill system. In one embodiment, a first pill  2604  comprising a nutrient pill having a degradable outer layer is ingested orally by a patient. A short time later, second pill  2600  is ingested orally. In certain embodiments, pill  2600  is an electronic pill having low voltage electrodes  2602  thereon. In such embodiments, electrodes  2602  are pulsed to create an increase in the peristaltic rate of the GI tract. Details (B), (C), (D) and (E) show the progression of nutrient pill  2604  and electronic pill  2600  through the GI tract utilizing the increased peristalsis created by electronic pill  2600  as a means to speed delivery of the pills to the target location. As may be appreciated, alternative embodiments may comprise a combined electronic and nutrient pill, or may utilize other known means for increasing peristalsis. 
         [0062]    One skilled in the art will appreciate further features and advantages of the invention based on the above-described embodiments. Accordingly, the invention is not to be limited by what has been particularly shown and described, except as indicated by the appended claims. All publications and references cited herein are expressly incorporated herein by reference in their entirety.