Abstract:
Devices and methods for substantially reducing the caloric efficiency of the digestive tract by capturing food being digested in the stomach  10  and/or anywhere else in the gastrointestinal (GI) tract, absorbing or encapsulating the captured food into multiple capturing members and moving such multiple capturing members containing the ingestible encapsulated food down the GI tract, practically out of reach of the GI absorption organs, thus excluding the entrapped ingredients from being involved in the digestion and\or absorption process. The device is designed for oral delivery. The system can be comprised of liquid, food bars or a capsule system. The capsule system is comprised of an external capsule that dissolves in accordance with a temporal or ph dependent preset, which allows the food intake to be at least partially fluidic. The capsule system is further comprised of a mechanism designed to capture and isolate a portion of the food being digested.

Description:
RELATED APPLICATIONS 
       [0001]    The present application claims the benefit under 35 USC 119(e) of U.S. provisional application 60/542,843 filed on Feb. 10 th , 2004, and PCT application PCT/IL05/00154 also known as WO2005/074378, the disclosure of which are incorporated herein by reference. 
     
     FIELD OF THE INVENTION 
       [0002]    The present invention relates in general to a device and method for substantially reducing the caloric efficiency of the digestive tract by capturing food being digested in the stomach and/or anywhere else in the GI tract, into entrapping members; moving the entrapping member containing said food down the GI tract, thus excluding at least part of the food intake from being absorbed in the small intestine and further down the GI tract. 
       BACKGROUND OF THE INVENTION AND RELATED ART 
       [0003]    Obesity is a chronic disease due to excess fat storage, a genetic predisposition, and strong environmental contributions. This problem is worldwide, and the incidence is increasing daily. There are medical, physical, social, economic, and psychological comorbid conditions associated with obesity. There is no cure for obesity except possibly prevention. Non-surgical treatment has been inadequate in providing sustained weight loss. Currently, surgery offers the only viable treatment option with long-term weight loss and maintenance for the morbidly obese. Surgeries for weight loss are called bariatric surgeries. There is no one operation that is effective for all patients. Gastric bypass operations are the most common operations currently used. Because there are inherent complications from surgeries, bariatric surgeries should be performed in a multidisciplinary setting. The laparoscopic approach is being used by some surgeons in performing the various operations. The success rate—usually defined as &gt;50% excess weight loss that is maintained for at least five years from bariatric surgery—ranges from 40% in the simple to &gt;70% in the complex operations. The weight loss from surgical treatment results in significant improvements and, in some cases, complete resolution of comorbid conditions associated with obesity. Patients undergoing surgery for obesity need lifelong nutritional supplements and medical monitoring. 
         [0004]    It is accepted that patients suffering from obesity are at a substantially increased risk of medical ailments and a range of diseases, including: Type II diabetes, heart disease, stroke, high blood pressure, high cholesterol, certain cancers, and other disorders. Furthermore, patients suffering morbid obesity have life expectancy that is significantly reduced, by at least ten to fifteen years. 
         [0005]    For patients suffering from extremely severe obesity (morbid obesity), i.e. for patients whose weight exceeds the ideal weight by at least 50 kilograms, for example, it is absolutely essential to operate surgically on such patients in order to avoid not only a series of health problems that stem from such obesity, but also to avoid certain and imminent death of such patients. 
         [0006]    It has also been observed that treatment based on a severe diet combined with a series of physical exercises associated with a change in behavior, in particular eating behavior, are relatively ineffective in such cases of morbid obesity, even though such methods of treatment are the most healthy. 
         [0007]    Methods that have been used in the prior art to treat obesity include gastric bypasses and small-bowel bypasses such as described in U.S. Pat. No. 6,558,400 and U.S. Pat. No. 6,543,456. The number of these bariatric surgeries has skyrocketed from 40,000 per year back then to 120,000 in 2002. Many complications are associated with these procedures. Many patients have suffered serious side effects and regret having had it. 
         [0008]    Other methods aim at reducing the effective volume of the stomach to induce a satiety feeling by the patient and hence reducing the calorie intake per meal. 
         [0009]    One such method is the stapling of portions of the stomach has also been used to treat obesity, such as described in U.S. Pat. No. 5,345,949. This includes both vertical and horizontal stapling and other variations trying to reduce the size of the stomach or make a small stoma opening. Many problems have been associated with the use of staples. First, staples are undependable; second, they may cause perforations; and the pouch or stoma opening formed by the staples becomes enlarged over time making the procedure useless. 
         [0010]    Another method that has been developed is the placement of an inflatable bag or balloon into the stomach causing the recipient to feel “full”. Such a procedure has been described in the patent to Garren et al U.S. Pat. No. 4,416,267. The balloon is inflated to approximately 80% of the stomach volume and remains in the stomach for a period of about three months or more. This procedure, although simple, has resulted in intestinal blockage, gastric ulcers, and even in one instance, death and fails to address the problems of potentially deleterious contact with the gastric mucosa which can result from leaving an inflated bag in the stomach for an extended period of time. Moreover, it also failed to produce significant weight loss for long periods of time. 
         [0011]    Yet another method employs the placement of a band around a portion of the stomach thereby compressing the stomach and creating a stoma opening that is less than the normal interior diameter of the stomach for restricting food intake into the lower digestive portion of the stomach. Kuzmak et al in U.S. Pat have described such a band. U.S. Pat. No. 4,592,339. It comprises a substantially non-extensible belt-like strap, which constrictively encircles the outside of the stomach thereby preventing the stoma opening from expanding. Kuzmak et al also describe bands, which include a balloon-like section that is expandable and deflatable through a remote injection site. The balloon-like expandable section is used to adjust the size of the stoma opening both intra-operatively and post-operatively. 
         [0012]    Complications have been observed with both inflatable and non-inflatable gastric bands. In particular, obstruction of the stoma from edema and migration of the band has been observed. Such edema-caused obstruction of the stoma may be due to excessive vomiting. In these cases, the stoma must be enlarged either by deflating the expandable portion of a band or by removing the band altogether. 
         [0013]    Yet another method is to impose satiety. U.S. Pat. No. 6,677,318, describing a swellable sponge-like structure. These structures are swallowed by the patient being collapsed inside a capsule. The capsule dissolves in the stomach and the polymer structure with super absorbing characteristics; absorb the gastric juices, which cause the structure to swell considerably. This patent aims to reduce food intake by causing the recipient to feel “full”, yet the absorbed content of the sponge is finally digested. 
         [0014]    Lipase inhibition as a mean for reducing lipid intake is well known in the art, the major draw back is the oily stool as a side effect. To overcome this side effect, polymers capable of absorbing lipids where introduce, as in U.S. Pat. No. 4,432,968, but as the absorption is reversible and shifted backwards as a result of bile salt emulsifier, the overall entrapment was quite poor. 
         [0015]    In order to overcome the a forth mentioned drawbacks, the present invention relates on a lipid absorption polymer having an prolonged equilibrium period in the range of 4-8 hours so as to keep the absorption step active during the relevant period in the digestion tract. 
         [0016]    It is then the object of this invention to overcome these and other deficiencies described above. 
       SUMMARY OF THE INVENTION 
       [0017]    The invention seeks to provide a successful and non-invasive alternative to existing approaches for controlling obesity. 
         [0018]    The invention objective is to substantially reduce the caloric efficiency of the digestive tract by capturing food being digested in the stomach and/or anywhere else in the GI tract into entrapping members; moving the entrapping member containing the entrapped food ingredients down the gastrointestinal tract, thus excluding at least part of the entrapped food from being absorbed in the small intestine. 
         [0019]    Another objective of this invention is to introduce a lipid absorption polymer having an prolonged equilibrium period in the range of 4-8 hours so as to keep the absorption step active during the relevant period in the digestion tract. 
         [0020]    Another objective of this invention is to interfere with the micelles formation and capture the free lipids contained within 
         [0021]    Another objective of this invention is to provide a delivery system of the material via means of compressing the material so that it takes less space in the intake, and when the capsule, for example, opens up or dissolves, the individual particles of the material expand to accommodate the captured liquids. 
         [0022]    In one embodiment, the device is comprised of a capsule system for oral delivery. The capsule system is comprised of an external capsule made of gelatin—as an example that dissolves in accordance with a temporal preset, which allows the food intake to be at least partially fluidic. The capsule system is further comprised of an internal permeable bag having a structure such as meshed, woven or fibers, made of disintegrable material such as gelatin for example, which bag contain expandable, super absorbent beads, which dry beads are larger than the pores of the bag, which bag is inflatable. When the bag comes in contact with the fluidic content of the stomach, fluids penetrate into the bag. The fluids are absorbed by the expandable, hydrogel beads enclosed. These beads expand partially or until they reach the absorption capacity limit. Optionally, the internal bag further contains a coating capsule, which dissolves at this time and coats the expandable beads, to seals and protects them from disintegration or prevent leakage of entrapped liquid, throughout their journey out of the GI tract. 
         [0023]    For the sake of clarity, a capsule is a sealed container and a bag is a permeable containers. 
         [0024]    In other embodiments, the external capsule contains folded mechanical structures, which open up to captures some of the stomach content and protects them from disintegration throughout their journey through and out of the GI tract. 
         [0025]    Further scope of applicability of the present invention will become apparent from the detailed description given hereinafter. However, it should be understood that the detailed description and specific examples, while indicating preferred embodiments of the invention, are given by way of illustration only, since various changes and modifications within the spirit and scope of the invention will become apparent to those skilled in the art from this detailed description. 
     
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
         [0026]    The present invention will become more fully understood from the detailed description given herein below and the accompanying drawings, which are given by way of illustration only and thus not limitative of the present invention. 
           [0027]      FIG. 1  is a view of the assembled device. 
           [0028]      FIG. 2   a  is a view of the external capsule. 
           [0029]      FIG. 2   b  is a view of the internal bag. 
           [0030]      FIG. 2   c  is a view of an expandable bead. 
           [0031]      FIG. 2   d  is a view of a coating capsule. 
           [0032]      FIG. 3  illustrates a basic embodiment of this invention depicting an outer capsule containing super absorbent expandable beads. 
           [0033]      FIG. 4   a  illustrates of the capsule system entering the stomach at t 1 . 
           [0034]      FIG. 4   b  illustrates the external capsule dissolving at t 2 . 
           [0035]      FIG. 4   c  illustrates the expandable beads expanding as they absorb stomach fluids. 
           [0036]      FIG. 4   d  illustrates the expandable beads reaching the size limits of the internal bag at t 4 . 
           [0037]      FIG. 4   e  illustrates the rupture of the coating capsule at t 4 . 
           [0038]      FIG. 4   f  illustrates the internal capsule dissolving at t 5 . 
           [0039]      FIG. 4   g  and  FIG. 3   h  illustrate the draining stage of the coated at t 6 . 
           [0040]      FIG. 5  is a temporal illustration of a full cycle of the process. 
           [0041]      FIGS. 6   a - d  illustrates another embodiment of the invention. 
           [0042]      FIGS. 7   a - c  illustrates another embodiment of the invention. 
           [0043]      FIGS. 8   a - c  illustrates yet another embodiment of the invention. 
           [0044]      FIG. 9  illustrates an embodiment for loading the force into the small structures. 
       
    
    
     DETAILED DESCRIPTION OF PREFERRED EMBODIMENTS 
       [0045]    Before explaining embodiments of the invention in detail, it is to be understood that the invention is not limited in its application to the details of construction and the arrangement of the components set forth in the following description or illustrated in the drawings. 
         [0046]    Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. The materials, methods, and examples provided herein are illustrative only and not intended to be limiting. 
         [0047]    In accordance with one basic embodiment of the present invention, illustrated in  FIG. 3 , the device is in a form of a pill comprises an outer capsule  200  made of Gelatin for example, which capsule  200  is at least partly filled with cross-linked polymer beads, such as Hydrogels, supper absorbent polymers, cross-linked polymers, known in the art, which beads having a diameter in the range of microns to few mm and are made of non toxic and non digestible polymer and are capable of absorbing fluids at a ratio of at least 5:1 (W/W), (liquid\bead) by diffusion, osmotic force, ionic interaction, and\or capillary force, and\or magnetic force, or other physic-chemical mechanism, such as polyacryl amid derivatives, which absorbing beads may also act as ion exchanger, exclusion gel such as a cross-linked polydextran (or possibly Cellulose Ethers like material), which beads optionally may also contain functional groups that improves permeability when the ambient is acidic (low pH—at the stomach), yet the permeability is reduced when the ambient pH is neutral or basic (small intestine). 
         [0048]    In practice, the pill is ingested, and the capsule  100  dissolves at a temporal preset, beads  300  which are now in contact with the content of the food being digested, absorbs caloric enriched liquid and swells. Next the beads along with content of the stomach  10  are moved into the small intestine, where the entrapped content of the beads are practically not involved in the digestion and absorbing steps in the intestine. It is plausible to design the beads such that they will continue to absorb digested food in the small intestine and further down the GI tract. 
         [0049]    In another embodiment, similar to the first embodiment, the beads are pre coated or pre absorbed by a composition capable of forming at least a partial nutrient barrier on small intestine. The composition helps further to reduce the absorption of food in case of leaking from the bead. 
         [0050]      FIG. 1  is a view of the assembled capsule system. It comprises an external capsule  100  which can be made of a biocompatible material such as gelatin, an internal bag  200  which can be made from gelatin with a net like structure, absorbing beads  300  which can be made from Hydrogels and coating capsule(s)  400 . 
         [0051]      FIG. 2   a  illustrates the opened external capsule, which opens into two halves  201  and  202  at time t 2  (see  FIG. 5 ). It cans also dissolve with control thickness or any other known technique. 
         [0052]      FIG. 4   a  illustrates the assembled capsule being swallowed by the patient at time t 1  (see  FIG. 5 ) which is a while after he started his meal at time t 0  (see  FIG. 5 ).  FIG. 2   b  is a view of the internal bag  200 ,  FIG. 2   c  is a view of an expandable bead  301  and  FIG. 2   d  is a view of a coating capsule  400 . 
         [0053]      FIG. 4   b  illustrates the dissolution of the external capsule in the stomach  10  at time t 2 . At this time the super absorbing expandable beads  300  are exposed to the stomach  10  fluids and start absorbing them, as illustrated in  FIG. 4   c  and continue at time period t 3  (see  FIG. 5 ). 
         [0054]    Optionally, after the expandable beads  300  fill out the space allowed by the internal bag  200 , as illustrated in  FIG. 4   d , they press against the coating capsule(s)  400 . This triggers at time t 4  (see  FIG. 5 ) the rupture, as illustrated in  FIG. 4   e , or dissolution of the coating capsule(s)  400 , which contains an agent that coats and seals (see  FIG. 4   f ) all the expandable beads such that they and their content remains untouched throughout their migration down the GI tract. 
         [0055]    Once all the expandable beads  300  are coated, at time t 5  (see  FIG. 5 ), the internal bag dissolves, all the expandable beads are free to move about the GI tract, at time period t 6  (see  FIG. 5 ), and they are drained untouched through and out of the GI tract, as illustrated in  FIGS. 4   g  and  4   h . The expandable beads  300  dissolve after a preset number of days, in case they were not able to clear out of the GI tract. In another option, the patient drinks a liquid that dissolves expandable beads  300 . 
         [0056]    Thus the content of the expandable beads  300  which contains ingested food remains untouched, is not digested and absorbed by the body and hence reduces the calorie efficiency of the meal. 
         [0057]    In another embodiment of this invention, time t 5  (see  FIG. 5 ), when the internal bag  200  dissolves and the expandable beads  300  are free to move about the GI tract, occurs only after the fed mode of the stomach  10  is finished, and the stomach  10  goes into its maintenance mode. 
         [0058]    I another embodiment (not shown) the fluids pass on their way to the super absorbable beads through a filter which is wide on the outer side and narrow in the inner side. This makes it easy for the fluids the flow inward the beads and hard to flow back. 
         [0059]    In yet another embodiment of this invention, a polymer capable of absorbing lipid having an prolonged equilibrium period in the range of 4-8 hours so as to keep the absorption step active during the relevant period in the digestion tract, is provided. One such polymer for example is Polypore, having high absorption ratio of 13 gr lipid to 1 gr polymer 
         [0060]    Another embodiment of the present invention is to interfere with the micelles which are necessary for the lipid digestion activity. The purpose of the polymer is to disassemble the micelles and extract the lipids. Such a polymer is, for example, isss Gantrez® series, especially Gantrez 225 and Gantrez 425. 
         [0061]    So when a mixture of Polypore and Gantrez are introduced to the small intestine, the Gantrez will interfere with the micelle formation equilibrium, and the polypore will absorb the free lipids without the highly competitive back extraction mechanism. 
         [0062]    Another embodiment of this invention is illustrated in  FIGS. 6   a - 6   d  in this embodiment the inner bag is in the form of a folded basket  202  which contains a stack of spheres  500  each of which is split into to halves  501  and  502  which are connected by a spring like connection  503  that the force embedded in it will close up the spheres to the poison  504  in a relaxed mode. When the external capsule  100  dissolves, the force embedded in the stacked up halve spheres  500  will cause the optional basket  202  to open up optionally locked into the position illustrated in  FIG. 6   d . This allows the half spheres to close up to position  504  which scoops up the food being digested while closing up. The sphere  504  is now small enough to leave the basket  202  through the opening  203 , being pushed by the next pair of half spheres. The last pair of half spheres in the stack may remain in the basket  202 , which dissolves after a preset time and clears out down the GI tract. The optional basket  202  is designed to avoid the possibility that the closing sphere will harm the stomach  10  inner walls. The spheres  500  are of a size appropriate to be able to travel through the GI tract. The closed spheres are made of a substantially ingestible biocompatible material and remain closed and untouched through the journey down and out of the GI tract. The spheres  500  dissolve after a preset number of days, in case they were not able to clear out of the GI tract. In another option, the patient drinks a liquid that dissolves spheres  500 . 
         [0063]    Another embodiment of this invention is illustrated in  FIGS. 7   a - 7   c . In this embodiment, the capsule is filled up with number of folded stent like structures  600 . When the external capsule  100  dissolves, a force will cause the stents  600  to open up and lock into the position illustrated in  FIG. 7   c . The force can be embedded in the structures  600 , apply via external or internal spring (not shown) or generated internally or externally via chemical reaction with the stomach  10  content. While stents  600  open up inside the stomach  10  they will suck up some of the content into the stents. The stents  600  are built such that they have entry holes  604  through which the content is sucked up. Optionally, entry holes  604  are equipped with a directional valve such that the stomach  10  content can only enter into the stents but can not escape. The size of the opened stents  600  is designed to be able to travel through the GI tract. The stents are made of a substantially ingestible material and remain closed and untouched throughout their journey down and out of the GI tract. The folded structures  601 ,  602 ,  603  can also be polymer beads and the force applied to them before delivery to compress the beads substantially so that they open inside the GI tract to capture various liquids. One such polymer, for example, is Polypore, having high absorption ratio of 13 gr lipid to 1 gr polymer and high ratio of its free form volume to its compressed form volume. 
         [0064]    In another embodiment the force (such as spring force or elastic force) is being loaded into the small structures  700  before using the capsule.  FIG. 9  shows a device  800  for compressing the small structures  700  and encapsulating them to form the pill to be swallowed. Turning the handle  802  in direction  806  moves the bar  804  in direction  808 . The capsule half  101  is pushed towards the second half  102  and the small structures  700  are compressed. This will overcome the possibility that the force will deteriorate over time. 
         [0065]    Another embodiment of this invention is illustrated in  FIGS. 8   a - 8   c . In this embodiment, the capsule is filled up with a number of folded structures  700 . When the external capsule  100  dissolves, the force embedded within the structures will cause the structures  700  to open up into the position  702  illustrated in  FIG. 8   c . The force can be embedded in the structures  700 , in the manufacturing process by taking a semi rigid structure and forcing it into a collapsed form by applying pressure. The kinetic energy stored in the structures  700  will be used to restore the structures into their natural form once the capsule  100  has opened up. This force is designed so that it can over come the pressure inside the stomach  10 . While structures  700  open up inside the stomach  10  they will suck up some of the content into the structures  700 . The structures  700  are made up such that they have entry holes  703  through which the content is sucked up. Optionally, entry holes  703  are equipped with a directional valve such that the stomach  10  content can only enter into the structures  700  but cannot escape. The size of the opened stents  700  is designed to be able to travel through the GI tract. The full structures  700  are made of a substantially ingestible material and remain closed and untouched throughout the journey down and out of the GI tract. 
         [0066]    In another embodiment the folded structures are polymer beads and the force applied to them before delivery to compress the beads substantially so that they take less space on the intake but open inside the GI tract to capture various liquids. One such polymer, for example, is Polypore, having high absorption ratio of 13 gr lipid to 1 gr polymer and high ratio of its free form volume to its compressed form. 
         [0067]    The invention being thus described in terms of several examples and embodiments, it will be obvious that the same may be varied in many ways. Such variations are not to be regarded as a departure from the spirit and scope of the invention, and all such modifications as would be obvious to one skilled in the art are intended to be included within the scope of the following claims.