JP2015515308A - Highly porous cellulose sponge - Google Patents

Abstract

The present invention provides, inter alia, compositions, devices and methods for influencing weight loss and / or weight management by sequestering other compounds such as nutrients or toxins from absorption in the gastrointestinal tract. The compositions, devices, and methods use one or more members made from a compressible absorbent matrix material. In various embodiments, the matrix material is suitable for daily use. The compressible absorbent matrix material is configured to be efficiently packed in a small space and / or configured to absorb and substantially retain digestive material in the stomach, And / or having a surface shape. The devices and compositions may further comprise one or more hydrogels, soluble or insoluble fibers, waxes, and / or gums to provide the desired mechanical properties and / or absorption or shielding properties.

Description

Cross-reference of related applications

  This application has priority over US patent application Ser. No. 13 / 841,138 filed Mar. 15, 2013 and US Provisional Application No. 61 / 616,037 filed Mar. 27, 2012. And the disclosures of which are incorporated by reference.

  The present invention relates to devices, compositions and methods for reducing the amount of nutrients or other compounds absorbed into the GI tract from ingested food, among other uses.

The term “overweight” refers to body weight above the normal range. Overweight and obesity are determined by calculating body mass index (BMI), the weight in kilograms divided by the height squared in meters. Overweight is generally defined as a BMI of 25 to 29.9 kg / m ² , and obesity is generally defined as a BMI of 30 kg / m ² or greater, and severe obesity Disease is generally defined as a BMI of 40 kg / m ² or greater (or a BMI of 35 kg / m ² or greater in the presence of other medical comorbidities). A BMI of less than about 22.0 kg / m ² is ideal, but this is difficult and may be an unrealistic target for many individuals.

  Overweight and obesity are global health plagues with an increasing prevalence. In the United States, over two-thirds of Americans are overweight and 26-55% are obese, based on data collected by the Centers for Disease Control and the National Institutes of Health in 2007. Globally, overweight and obesity affect both developed and developing countries. For example, about 23% of the UK population is obese, compared to about 11-23% in Mexico, about 30-40% in South Africa, and about 10% in Pakistan.

Overweight and obesity are associated with numerous health risks, including type 2 diabetes, hypertension, dyslipidemia, coronary heart disease, cancer and stroke, and early death, among others. Compared to normal weight individuals, a BMI of 26.5 to 29.9 kg / m ² is associated with a 1.5-fold increased risk of death. Those with a BMI of 30 kg / m ² or more have a 2- to 3-fold increase in all-cause mortality. The economic impact is significant, and the Brookings Institute publication states that the cost of overweight and obesity to the United States will be at least $ 147 billion annually. The rationale for weight loss is clear from both medical and economic aspects.

  Currently available methods for weight loss include behavior modification (dietary change and exercise therapy), medication, and bariatric surgery. Drug treatment is needed for patients who have not reached weight loss goals with dietary habits and exercise alone. The FDA has explicitly approved two classes of drugs for use in weight loss. Sympathomimetics (eg, phendimetrazine, diethylpropion, phentermine) stimulate the release of norepinephrine and / or inhibit its reuptake into nerve endings. To put it simply, this effect is similar to that produced by caffeine, but is much stronger. Sympathomimetics cause appetite suppression but can also cause hypertension, potentially myocardial infarction, and as a result are limited to use by the FDA for less than 12 weeks. Ephedrine is one of this class that has recently been removed from the market due to these harmful side effects.

  The malabsorption drugs are from other drug classes approved by the FDA for use in obesity. Orlistat is the only representative of this group. Orlistat alters fat digestion by inhibiting pancreatic lipase, resulting in malabsorption of 30% of ingested fat. Instead of being taken up by the body, this fat is excreted by the stool. Orlistat is the only FDA approved drug for obesity that is acceptable for long-term use (up to 4 years).

  For patients with severe obesity, the only proven mechanism of long-term weight loss is bariatric surgery. Bariatric surgery results in weight loss due to malabsorption and / or restriction. Absorption (similar to orlistat above) means incomplete absorption of ingested food. The body does not absorb all of the calories present in a meal or a given food product. Restriction means producing an early feeling of fullness as a result of reducing the size of the stomach and reducing food consumption.

  Overweight and obese patients who do not meet the BMI criteria for severe obesity do not have surgery as an available option for weight loss, as this is usually covered by insurance coverage for these treatments This is because it is limited to severe obesity. Thus, overweight and obese patients have access to only one FDA approved drug for weight loss. Thus, there is a great need for alternatives for weight loss and weight management.

  The present invention provides compositions, devices, and methods for affecting weight loss and / or weight management (among others) by sequestering nutrients or other compounds (eg, alcohol or toxins) from absorption in the gastrointestinal tract. provide. In various embodiments, compositions, devices, and methods that use compressible absorbent matrix materials are suitable for routine use.

  In one aspect, the present invention is a compressible absorbent matrix material designed to absorb and substantially retain nutrient material in the gastrointestinal tract, such as nutrient material present in the stomach after a meal. Alternatively, an apparatus or composition comprising a plurality of members is provided. The device or composition further uses one or more hydrogels, soluble or insoluble fibers, waxes, and / or gums to achieve the desired mechanical properties, as described in detail herein, And / or may provide absorption or shielding properties. In some embodiments, the device is in the form of a capsule that includes a matrix material member that may be in the form of a tube. Alternatively, the device or composition may be a food additive.

  In another aspect, the present invention provides a method for absorbing and retaining (eg, shielding) nutrients or other compounds from the absorption action of the gastrointestinal tract. The method includes providing a device or capsule for ingestion before, during, or after a meal. The subject may be an overweight or obese subject, and the composition or device may be used routinely to affect weight loss. Alternatively, the subject may be a person who has normal weight but needs weight management, for example, due to an overweight pattern or history.

  In various embodiments, an orally ingested device or composition contains one or more “sponges” or “sponge tubes” in a compressed or dense state that expands upon entering the GI tract. To do. The sponge matrix or skeleton is displaced by expansion of the sponge, and the volume is greatly expanded. For example, in certain embodiments, the sponge material may itself absorb more than 10 times its weight in the fluid, which helps shape the material as in the case of the skeleton. When the sponge expands, it not only absorbs 10 times its volume, but also sucks in all the fluid contained within the skeletal void space. That is, the sponge “chamber” or “hole” dramatically expands the volume of fluid absorbed. These fluids will then be trapped inside the sponge skeleton by the hydrogel in the sponge cell walls sealing each chamber.

  More specifically, sponges absorb portions of the stomach suspension in the stomach, reducing the amount of food that can be absorbed in the small intestine. In this way, the calories are “isolated” from the body and promote weight loss. The device or composition design maximizes the ability and / or efficiency of nutrient absorption (and nutrient sequestration) and avoids the side effects associated with drug-based therapies for obesity. For example, the material and / or surface shape of the matrix material, together with one or more hydrogels, soluble and / or insoluble fibers, waxes, and gums, provides efficient packing of the matrix material and the desired elasticity and / or expansion. It provides not only the desired mechanical properties, but also the desired properties for nutrient absorption and subsequent sequestration and shielding from digestive action.

  In various embodiments, the present invention helps to reverse the trend in the food industry that gradually reduces fiber from food and replaces it with sugar. Thus, the present invention also provides fiber to eating habits while eliminating sugar absorption.

  In various embodiments, the present invention absorbs sugar and / or alcohol rich fluids that are generally soluble, and as a result can be absorbed by the GI more than other less soluble nutrients. In addition, sugar and / or alcohol may not be beneficial to health. Such fluids may then be sequestered in their original state and / or in the gel or mucus state by the composition and device. For example, the fluid may be sequestered by the absorption, reaction with, or association with other compounds such as soluble fiber. Therefore, the body “meets” less nutrients (such as sugar, carbohydrates, fats, alcohol, and spirits) (eg, becomes able to absorb during digestion), and conversely, is more beneficial "Meet" the fiber.

  In various embodiments, the present invention sequesters compounds, liquids (eg, alcohols), drugs, or other dangerous or toxic substances taken actively or unintentionally in the stomach or in the gastrointestinal tract. Bring things. The composition or device has the potential to absorb and inhale the ingested material, gel it, and remove it safely and naturally from the body.

  In various embodiments, the present invention provides nutrient sequestration without significantly altering the individual's normal eating habits, normal taste, and normal amount of food consumed by the average consumer.

  The devices and compositions of the present invention may be used routinely or chronically by overweight and obese individuals for the duration of weight loss or by normal weight individuals for weight management. For example, the device may be used from 1 to 20 times per week for a year or years (eg, 1 year, 2 years, 3 years or more). The device may be used from 1 to 3 times a day (eg, every meal) for 1 year, 2 years, 3 years or more. Alternatively, it may be used for a short period of time by normal weight individuals who may overeat and desire a reduction in long-term calorie “damage”. Thus, the device and method provides an inexpensive and safe solution for obesity and overweight worldwide with corresponding benefits in associated medical comorbidities, longevity, care costs, and global economic burden. Can serve hundreds of millions of people.

  The device and composition may be used to absorb toxins or alcohol taken actively or unintentionally and prevent its digestion or biological effects. In these embodiments, the device or composition need not be used on a daily basis, but may be taken with food that is at risk of containing toxins or when intake of toxins is found or alcohol May be used to avoid or reduce the effects of excessive consumption of

FIG. 6 shows an exemplary design of an absorbent material. FIG. 6 illustrates an exemplary absorbent material. FIG. 6 shows another exemplary design of the device of the present invention.

  The present invention provides, inter alia, compositions, devices and methods for influencing weight loss and / or weight management by sequestering other compounds such as nutrients or toxins from absorption in the gastrointestinal tract. The compositions, devices, and methods use one or more members made from a compressible absorbent matrix material. In various embodiments, the matrix material is suitable for daily use. The compressible absorbent matrix material is configured to be efficiently packed in a small space and / or configured to absorb and substantially retain digestive material in the stomach, And / or having a surface shape. The devices and compositions may further comprise one or more hydrogels, soluble or insoluble fibers, waxes, and / or gums to provide the desired mechanical properties and / or absorption or shielding properties.

  The compositions and devices reduce caloric absorption by the body of ingested nutrients. The method of operation of the device may be referred to as “absorption”, whereby nutrients are absorbed by the matrix material (eg, sponge material) and sequestered within the GI tract. Thus, sequestered nutrients are not metabolized or absorbed by the gut and are secreted with the matrix material. The device is inert, operates in a passive manner and does not substantially interfere with the body's metabolism, basically the device takes ingested nutrients, intestinal villi and other digestive activities “Shield” from the absorption of water.

  The compressible absorbent matrix material may in some embodiments be a sponge material and may be in the form of a “sponge tube” and / or “sponge drop”. The tube may be the simplest and most straightforward shape of the matrix material, but the matrix material may or may not be tubular. This is because other surface shapes may be suitable and / or advantageous in certain embodiments. For example, pieces of sponge irregularly shaped pieces that do not have any definitive shape and are unique to each other can be produced by mechanically breaking the sponge into small pieces, In embodiments, it may be suitable and / or advantageous. It is more important that a volume is contained within the sponge than its apparent shape.

  The sponge material may be a naturally occurring material, or may be a number of openings, spaces, eg, irregular or shaped shapes, and continuous or independent “cells” that may be defined by a sponge matrix “cell wall”. May be an artificially foamed type of sponge. Sponge materials can also have a defined surface or amorphous shape, alternating alternating shaped or amorphous empty spaces and closed spaces, or a mixture of defined and amorphous or amorphous spaces It may be a material having In some embodiments, the sponge material has a geometrically manipulated structure that can be collapsed under mechanical action, chemical action, or thermal action, or a combination thereof, and then expanded. The shape can be taken and the expanded shape may be the original shape (before compression) or another intended shape. The expanded shape typically responds to removal of mechanical, chemical, or thermal effects upon interaction with the stomach contents or / and chemical interaction with suitable additives present in the device. Happens.

  The matrix material is subjected to mechanical compression, thermal and / or chemical treatment (eg, by chemically modifying the material, by crosslinking, by compounding, or by covalent compounding, etc.). The size and / or volume can be reduced to a much smaller size and / or volume than the original uncompressed size and / or expanded volume. The compressible property allows multiple matrix material members to be efficiently packed into a small space such as a capsule or other delivery vehicle. For example, the compressed size or volume may be less than about 50% of the expanded size, or in other embodiments, less than about 40%, less than about 30%, about 25% of the expanded size or volume. Less than about 20%, less than about 15%, less than about 10%, less than about 5%, less than about 1%, less than about 0.5%, or less than about 0.1%. Typically, after release of applied mechanical compression or chemical constraints (e.g., by chemical reaction, fracture, cross-linking, etc.), or both, the material can assume its original larger shape.

  The mechanism of expansion of the matrix material may also be an elastic return, in which case the material is not itself an elastomeric material, but the material at least partially assumes its original shape after a period of compression and / or stress. Can be sufficiently robust to still be possible (eg, molecular creep time is long enough).

  The matrix material can be mechanically flattened and stacked, or simply compressed and then encapsulated, for example, in a conventional pharmaceutical capsule for ingestion. The matrix material is usually made of an elastic and / or elastic material that can be compressed and can absorb liquids and / or materials in the gastrointestinal tract. The matrix material usually has an internal porosity like a natural sponge. The bubbles in the sponge or sponge-like material may be irregular and / or amorphous (eg, like a normal commercially available artificial or natural sponge). Alternatively, in some embodiments, the sponge material bubbles may be more regular and / or geometric, such as honeycomb or other geometric and / or capacitive arrangements. It may be arranged scientifically.

  The geometry of the matrix material also expands and / or increases in the expansion of the device, their digestive fluid absorption and / or retention capacity compared to amorphous and / or non-geometric devices containing natural fibers. An effect may be brought about. This expansion and / or augmentation effect may be at least 2 times, at least 5 times, at least 10 times, at least 50 times, or at least 100 times compared to an amorphous device (eg, a device having an amorphous shape). it can. Accordingly, much smaller quantities, masses, volumes, doses, or quantities of the device (s) or composition are required in these embodiments. For example, in some embodiments, the user only needs to take a small pill or capsule (eg, a conventional size pill or capsule). Due to the augmentation and / or expansion effects described herein, such small pills or capsules have a greater ability to absorb digestive fluid and, consequently, its isolation or shielding from absorption by the body. Can be effectively brought.

  In some embodiments, the sponge material may be a conventional or natural sponge made by conventional methods. In other embodiments, sponge-type materials may be manufactured from, for example, foaming agents, reactants, penetrants, etc., such as extrusion, blow molding, injection molding, thermoforming, mechanical or chemical engraving and molding, etc. May be formed. Alternatively, the sponge material may be made by assembling smaller segments and / or geometrically and / or irregularly shaped units into larger units, thereby careful selection of the sponge form Enable. For example, the sponge material may be made by an extrusion process, a blow molding process, an injection or thermoforming molding process, or may be mechanically and / or chemically printed, or mechanically engraved or formed. Good. The sponge material may or may not be partly or wholly elastic, elastomeric, elastic material, recoiled, or partly rigid or semi-rigid and / or flexible material. May be. Figures 17-20 illustrate certain exemplary sponge materials suitable for use in the present invention.

  Sponge materials are usually designed so that the cell walls have a “shape memory”, i.e. the cells are totally removed after the applied mechanical and / or chemical compressive forces have been released. Selected to at least partially return or expand to the size and / or shape of the. In some embodiments, the sponge material is only by water absorption that causes the matrix material to expand, similar to the expansion caused by air being compressed within an expandable plastic matrix (eg, an expandable bounce house). It may expand and contract.

  The mechanism of expansion of the released sponge material is, for example, due to the return of the shape memory material such that the material at least partially assumes its original shape at physiological conditions in the stomach (eg 37 ° C.). May be. Elastomeric or elastic materials may be used for the sponge material, for example, elastomeric materials such as latex, guayule rubber, polyurethane rubber, silicone rubber, cellulose, nanocellulose, nitrile rubber, or elastin, collagen and / or other A biological material such as a natural protein, or any other suitable material that can retain and preserve its original shape after a long time under compression, or return to a memory shape or take a different shape. May be. Alternatively, the expansion mechanism may be primarily due to the fluid absorption of the sponge when it includes a material such as hemicellulose with high absorption strength, creating hydrodynamic forces to expand the sponge skeleton. be able to.

  The sponge matrix can be made from a material that is safe for human consumption. Examples of suitable materials include polyurethane, nylon, polyethylene, polypropylene, polyacrylate, EVA, natural rubber, silicone, silicone rubber, latex, epdm rubber, butyl rubber, nitrile rubber, PVA, PLA polymer or copolymer. Suitable elastomeric biomaterials include silicones, thermoplastic elastomers, polyolefin and polydiene elastomers, polyvinyl chloride, natural rubber, guayule rubber, heparinized polymers, hydrogels, polypeptides, and elastomers, which may be other polymers, or It may be blended with natural or artificial elastomers and / or fillers such as clay, starch, elastic fibers, elastic microfibers, elastic nanofibers, such as cellulose and its derivatives, elastic and inelastic fillers and powders, etc. Further inert and / or natural compounds may be blended.

  Other suitable materials for the matrix include cellulose, nanocellulose, bacterial cellulose, cellulose fibers, microfibers and nanofibers, natural polymers such as methylcellulose, ethylcellulose, ethylmethylcellulose, other cellulose derivatives, natural or synthetic or artificial elastomers and / or Or cellulose blended with chitosan, optia, and other disaccharides, and fillers such as natural clays (eg montmorillonite) and natural hydrogels.

  In certain embodiments, substantially all of the desired properties, such as swelling, absorption, inhalation, shielding, retention, disintegration, etc., are provided, and may be biocompatible, biodegradable, only natural materials Sponge materials that may be included may be used.

  In certain embodiments, suitable sponges are carboxylated specially sized porous cellulose sponges and high on the surface such as COONa and COOK with a degree of substitution between 0.2 and 0.3. It may be produced by adding a hydrophilic functional group.

  In embodiments where disintegration of the matrix material within the GI tract is appropriate or required, biodegradable fillers, compounds, or fibers can be used. Partial or total disintegration of these compounds, fillers, or fibers in the gastrointestinal tract may induce partial or total collapse of the sponge material. Thus, the average disintegration time of the material may be brought about by adjusting the proportion of such additives. Exemplary fillers may include starch and / or other polysaccharides.

  The size of the sponge matrix may range, for example, from a diameter of about 1 nm to about 25 mm, or about 1 μm to about 100 μm. The length of the sponge tube may be, for example, in the range of about 1 μm to about 3 inches. Thus, the surface shape of the present “tube” may vary depending on the width and length selected. Also, different sizes and shapes of sponges may be used to selectively capture different particle sizes and / or suspensions and / or colloids. Thus, the capsule may contain a series of sponges having various external surface shapes, sponge materials, sponge forms, and the like.

  In addition, the sponge surface shape maximizes the nutrient sequestration capacity of each capsule by maximizing packing or stacking efficiency or maximizing the number of sponges that can be compressed into the capsule. May be selected.

  The compositions and devices may further include other natural or synthetic materials to provide desired mechanical properties or desired absorption and / or shielding properties.

  After being absorbed, the fluid should be kept inside or isolated within the matrix material so that the fluid absorbed by the device is not subsequently released. In addition, the absorbed fluid or material should be shielded from exposure to digestive enzymes. Thus, the absorbed fluid may be gelled or made more viscous. Nutrients thus captured may be sealed or sequestered inside the tube by one or more hydrogels, fibers, and / or gums. Such hydrogel (s), fiber (s) and / or gum (s) are incorporated directly into the sponge material, formulated into the sponge wall matrix, contained inside the sponge cell and It may be / or distributed or located in a particular region of the tube, such as the inlet or opening of the tube described herein.

  While not being bound by any particular theory or explanation of the mode of action or mechanism, the device is partially dependent on the behavior of dietary fibers (eg, soluble and / or insoluble fibers) within the digestive system. It may act in a similar manner. That is, the compositions and devices may reduce and / or delay nutrient absorption and / or accelerate the passage of nutrients in the gastrointestinal tract. Thus, in certain embodiments, the compositions and devices may contain as much natural fiber as possible, soluble or insoluble, or a combination of both. In certain embodiments, a combination of soluble and insoluble fibers is used. Insoluble fibers may be included to provide the desired mechanical properties described herein, including expansion and shielding, among others. Insoluble fibers may also be included due to their mucus properties that gel the fluid and / or increase the viscosity of the encapsulated, constrained, encapsulated, or entrained fluid.

  Non-limiting examples of suitable hydrogels include polyvinyl alcohol, poly (ethyl oxazoline), polyvinyl acetate-polyvinyl alcohol copolymer, poly (2-hydroxyethyl acrylate, poly (2-hydroxyethyl methacrylate), carboxymethyl cellulose, Polyacrylic acid and copolymers thereof, disaccharides, polysaccharides, chitosan, alginate, water-soluble proteins, and polynucleic acids, natural clays (eg montmorillonite), sodium bentonite, absorbent fibers, superabsorbent fibers, micro and nano fibers, Includes micro and nano powders, and combinations thereof.

  As a result of the mixing of the hydrogel and / or mucus and / or gum that forms the compound within the sponge material, the bubbles, pores, or walls of the sponge may be less permeable and thus the first absorption of digestive fluid or After the separation, the fluid entry and exit may be inhibited. There are a number of different artificial and / or natural compounds that can achieve this effect. Exemplary natural compounds may include soluble fibers, gums and the like as described herein above. Individual hydrogels, gums, or fiber materials, or mixtures thereof, may be selected to provide a desired absorption profile and / or other desired properties (eg, expansion properties, absorption capacity, mechanical properties, etc.) Good.

  The hydrogel (s), fiber (s) and / or gum (s) dispersed in or added to the sponge matrix and mechanically contained within the tube or tube bubble seal the bubble. Multiple sealed or partially sealed compartments may be created. In this compartment, fluid movement may be partially or fully restricted to prevent leakage of absorbed nutrients or penetration by digestive enzymes as the sponge progresses through the GI tract before excretion. . The hydrogel (s), fiber (s) and / or gum (s) in the sponge ceiling wall expand with fluid until the expansion of the sponge bubbles completely or partially seals the axial hole. . Another effect of hydrogel (s), fiber (s), and / or gum (s) is to better resist the final passage in the colon when the tube is about to be drained naturally by the body In addition, the sponge tube may be made more mechanically stable or robust.

  In some embodiments, nutrients are confined within the sponge by hydrogel (s), fiber (s), and / or gum (s), which then passes through the upper GI tract, Collapse. For example, these compartments may collapse after the portion of the GI tract where nutrient absorption occurs most, so that mechanical stability may not be necessary. In this case, the sponge material is used in the lower GI tract to ensure safety in facilitating over-consumption of the tube, or clinically slow draining intestines (eg to avoid bowel obstruction). Can be selected to collapse at least partially or completely within.

  In some embodiments, the compositions and devices comprise insoluble and soluble dietary fibers such as resistant starch, non-digestible starch, and non-starch polysaccharides. Examples include arabinoxylan, cellulose, dextrin, insulin, lignin, wax, chitin, pectin, beta-glucan, and oligosaccharides including galacto and fructooligosaccharides. Other exemplary polysaccharides include etheropolysaccharides such as pectin. The compositions and devices may use a mixture of different insoluble fibers, a mixture of different soluble fibers, and / or one or more mixtures of each of the insoluble or soluble fiber (s). In certain embodiments, a mixture of two types of fibers (eg, insoluble and soluble) may be used. The insoluble fiber (s) may provide a “sponge” framework and / or provide a shielding function.

  In certain embodiments, the composition or device comprises one or more soluble fibers selected from exopolysaccharide mucus. The exopolysaccharide mucus contains aloe, tsurmuraki (malabar spinach), cactus, yahuzunomata (irish moss), yam (long but Japanese yam), drossera (mousenoke), fenugreek, flax seeds, kombu, licorice, usbenitachaoi, It may be from velvet squid, okra, parthenium, musstri violet (Panthus), psyllium seed bark, salvia hispanica (Chia) seeds, red crab bark (slippery elm, or any suitable plant.

  In these and other embodiments, the compositions and devices may comprise cellulose or a derivative of cellulose such as cellulose-like methylcellulose, ethylcellulose and / or methylethylcellulose.

  In these and other embodiments, the compositions and devices may include natural gums such as those obtainable from seaweed and other sources. Such compounds include polyelectrolytes: agar (E406), alginic acid (E400), and sodium alginate (E401), and carrageenan (E407). Natural gums obtained from non-marine plant sources include polyelectrolytes: gum arabic from sap of acacia trees (E414), gati gum from sap of anogeese trees, gum tragacanth from the sap of forsythia shrub (E4I3), and Contains Karaya gum (E416) from the sap of Sterculia tree. Other natural gums are guar gum from guar beans (E412), locust bean gum from carob tree seeds (E410), beta-glucan from oats or bran, chickle gum obtained from chickle trees, sap of dipterocarpaceae trees Damar gum, glucomannan (E425) from konjac plant, mastic gum obtained from mastic tree, chewing gum. In certain embodiments, the mucus material comprises psyllium seed peel from plantain plants, spruce gum from spruce trees, tara gum from cod seeds (E417), and / or natural gums produced by bacterial fermentation, such as , Polyelectrolytes: including gellan gum (E418) and xanthan gum (E415). Fibers of animal origin such as keratin (such as silk), elastin and / or collagen may also be used. These natural rubbers or fibers may be obtained from commercial sources.

  The hydrogel (s), fiber (s), wax, and / or gum (s) may be added for matrix material expansion, for example by providing chemical expansion by absorption of water and other fluids. A mechanism (or force) may be provided. For example, the hydrogel (s), fiber (s) and / or gum (s), which may be present in the matrix material expand or within the sponge cell wall, absorb water and fluid and cure the cell wall The sponge tube may be at least partially returned to its original size and / or shape prior to compression and / or stacking.

  In some embodiments, the device or composition comprises hemicellulose or xylan, alone or chemically and mechanically formulated. This short-chain polysaccharide (hemicellulose) is inexpensive and has an excellent ability to absorb fluid. For example, the device or composition may include hemicellulose-citrate-chitosan, airgel foam, both of which are elastic and highly absorbent. In these or other embodiments, the device or composition includes one or more fillers such as crystalline and / or amorphous cellulose, lignin, or other curable compounds. In such embodiments, the matrix expansion mechanism is partly the result of fluid absorption, which may cure the sponge skeletal material and increase the total expansion.

  In some embodiments, the composition or device comprises an ester of hemicellulose with an organic acid (eg, having a carboxyl group). Examples include hemicellulose citrate, hemicellulose acetate, and other organic acids that make foams with the desired flexibility and elastic recoil. In other embodiments, the composition or device comprises hemicellulose alone or with chitosan. In yet another embodiment of the device or composition, starch-citrate-chitosan, starch-chitosan, or starch-hemicellulose-chitosan may be used.

  Additional compounds may be included in the presence or absence of hemicellulose-citrate-chitosan to obtain the desired gelling action. Such compounds include various types of cellulose or other artificial and synthetic compounds such as bovine serum albumin pectinate, pectin-ethylcellulose, calcium and chitosan pectates, naproxen pectin, deesterified pectin, zinc pectate Including one or more of gels, amylose, chondroitin sulfate (cross-linked or non-cross-linked), cyclodextrin, dextran, calcium and alginates, locust bean gum, guar gum, glutaraldehyde, and epichlorohydrin. For example, in certain embodiments, guar gum may be used that may be formulated or only dispersed within a hemicellulose matrix foam sponge.

  Another mechanism for expansion of the matrix material may include a combination of compounds and / or proteinaceous materials or structures arranged in a manner similar to muscle structure, in which case another configuration of one component Shrinkage, expansion, and / or twisting of the element may cause rolling and / or twisting or expanding action, resulting in material expansion.

Yet another mechanism for releasing the compressed matrix material may include a blowing agent and / or a gas releasing agent that is activated by the gastric heat and / or acid environment, which includes gas and / or foaming. To expand the material (eg, NaHCO ₃ ). Thus, if the sponge material reacts to the acid environment of the stomach, all or part of the sponge material may react with the stomach acid to at least partially increase the volume and return the sponge to its original shape. . After dissolution of the capsule containing the compressed material (such as a gelatin capsule), the matrix material normally released into the stomach usually expands inside the stomach and absorbs the fluid therein.

  Yet another mechanism of expansion is included in the electrostatic and / or magnetic repulsion and / or attraction between some parts of the sponge and other parts of the sponge, or contained within a tube or pill separate from the tube, or It may also include electrostatic interactions with similar entities independently introduced into the stomach. In yet another embodiment, the matrix material may be introduced as a twisted shape by the elastic expansion mechanism described above, which can then be untwisted and expanded.

  In certain embodiments, nutrient capture may also be caused by twisting of the matrix material (such as caramel wrapping) or rolling, in which case the matrix material has a flat geometric configuration. However, such a mechanism may be possible in other shapes and may comprise an absorbent mechanism associated with the sponge material. Such twisting and / or rolling may be caused or induced by one or a combination of the mechanisms mentioned above.

  The matrix material may be cylindrical and may have an elliptical, oval, square, rectangular, triangular, or polygonal, or trapezoidal cross-section or shape. In addition, various regular or irregular shapes or cross sections may be used in forming the compositions and devices, and a given “tube” is one of the more discrete regions of a particular shape or cross section. May be included. The surface shape and cross-section may support, for example, efficient packing into the capsule, so that a sufficient amount of “tube” may be delivered in a small space. The surface shape, cross section, and aperture configuration may further allow efficient absorption of gastric digestion products. Mixed surface shapes or shapes are also possible. Figures 1 to 16 show several exemplary shapes and cross-sectional surface shapes. Further, as shown, the matrix material typically has one or more axial openings or holes along its longest axis, but two or more holes are along essentially any axis. May be present. Figures 1-16 show some possible hole configurations.

  The hole (s) may be aligned with the center of the tube's major axis (eg, along the longest side) or may be off-center. The hole (s) can have a circular, star, cross or other segmented surface shape (see FIGS. 1-16). The purpose of this hole is to facilitate the quick absorption of nutrients in the stomach. The sponge structure with holes is designed to facilitate entrapment and capture of larger sized particulate material that can otherwise be absorbed inside the sponge. In addition, the hole (s) usually reduce the volume of the compressed tube inside the capsule gradually, so that more tubes can be accommodated in a single capsule and a larger amount of nutrients Can be isolated by a single pill.

  In some embodiments, the device or composition may include one or more release agents within the sponge cavity or cavities, or within the foam, to avoid adhesion between the walls of the foam. . Such release agents can be natural or artificial waxes, wax compounds with gums for elasticity, or simply a small layer of a polymer such as a polyethylene compound or polyethylene glycol or simply polyethylene. In certain embodiments, the release agent dissolves in the stomach or is a natural blowing agent (eg, baking soda).

  The outer skin of the matrix material can be essentially intact, smooth and free of perforations or holes, or it may have a number of holes, which are some implementations. It may be small in form. Such completely or partially intact skin may avoid the loss of absorbed nutrients from the matrix material due to the mechanical and enzymatic action of digestion. However, in some embodiments, the exterior of the matrix material is essentially the same as the interior, and may be perforated or the like.

  Nutrients to be absorbed usually enter the matrix material through openings that may be present at the end if no skin is present, or from the open end of the hole through the tube. The surface shape of the sponge, as well as the number and placement of tubes within the sponge, accommodate as many tubes as possible inside a certain capsule volume to ensure the best shape memory return after the tubes are released from the capsule. Can be selected to maximize the absorption of each tube, or a combination of these or other factors.

  The matrix material may be manufactured by normal extrusion or by foaming blocks of material after mechanical cutting of the desired shape. Alternatively, the matrix material can be punched from a rapidly moving strip. The matrix material may be encapsulated by nip-rolling a sheet of sponge material. The roll may be a continuous film of packing or protective compound, as often used in the pharmaceutical industry. For example, the material may be PLA or other natural or artificial material. The nip roll simultaneously compresses and cuts the matrix material, prints the film in an ether roll and seals it around the sponge. A plurality of these printed sponges surrounded by a double film are placed in a normal gel cap capsule or other similar container. A similar but smaller process can be used to make a food-based sponge. A “sponge” matrix, skeleton, alternatively folded mechanically punched holes in the main skeleton material (eg foam) and folded, cored, bubble-containing material Later, it can be manufactured by rolling or folding, gluing or mechanically fastening the strip with holes to retain the three-dimensional structure, and then compressing and encapsulating it. The roll can be designed not only to flatten the sponge, but also to provide lateral compression.

  Depending on size, the present invention may use matrix material encapsulation, microencapsulation, or nanoencapsulation. Such known encapsulation techniques are used, for example, for the delivery of micronutrients or drugs. In some embodiments, the devices and compositions are encapsulated with casein. Techniques for micro or nano encapsulation include pan coating, air suspension coating, spray drying, ion channel gelling, coacervation, in situ polymerization. In other embodiments, the sponge is encapsulated by freezing in a compressed state. After being compressed and frozen with a small amount of water, the sponge matrix remains compressed, thereby allowing easy encapsulation.

  When the treated sponge is in an expanded form, the sponge can be recompressed, for example, mixed with flavored fat and formed into coated granules ready for human consumption.

  For weight loss or weight control, a composition or device as described is taken before, during, or after a meal or any other food intake such as breakfast, snacks, etc. Capsules can be specially adapted to large or small human bodies and / or to light or heavy meals by adjusting the capsule size and thus the number of tubes and the capsule's total absorption capacity. For example, a “sponge tube” is ingested and in the stomach or intestine, the capsule dissolves and releases the tubes simultaneously or in groups (eg, with delayed release). The released tube, which is no longer mechanically or chemically constrained by the capsule, is then expanded to absorb, capture, enclose, and inhale some of the stomach or intestinal contents that are present when the tube is released .

  In some embodiments, the composition or device may be used directly in a food product (eg, mixed with it) to reduce the caloric content of the food containing the device. For example, the apparatus can be dispersed, added and / or mixed in food or served in a packaged food for addition to food (eg, in pre-packaged food, served in a restaurant). May be included as a separate component (e.g., with food, household food, or in drinking water). In one embodiment, the device (s) (eg, capsules, etc.) may be sized or sized so that they can be mixed with or added to the prepared food. For example, less than about 500 μm, less than about 250 μm, less than about 100 μm, less than about 50 μm, less than about 40 μm, less than about 30 μm, less than about 20 μm, less than about 10 μm, less than about 5 μm, or less than about 1 μm (or less or less) Small sponge “drops” having dimensions of any other value or range or values (eg, spheroid or ellipsoidal surface shape), eg, chocolate, spread, jam, peanut butter , Butter, cereal, flour, sweets, candy, cake, dough, pasta, sucrose or fructose, or sugar such as glucose fructose liquid sugar, as well as soft or alcoholic drinks, juice and / or commonly sold Or any other meal served at the restaurant It may be present or in the above.

  By making these capsules small in size, they can be prevented from being destroyed during chewing, and they may not be detected by miso. For example, the compositions may be tasteless and / or scaled so that they provide a smooth “feel”. After entering the stomach, the device or “drop” can be released from any encapsulating material and then expanded to absorb fluid, the device being designed as such (herein In an embodiment (as described in), the absorbed or encapsulated fluid can be gelled.

  If the food containing the device requires further cooking and / or preparation (eg flour, pasta, etc.), the encapsulating material is selected to withstand exposure to heat and / or exposure to cooking fluids. May be. Such encapsulation may be provided by a material that can withstand such heat and / or fluid exposure, but otherwise decompose or dissolve in the GI tract. For example, an encapsulating material may be selected that is heat and / or heat stable and fluid resistant at normal pH, but dissolves in an acid environment (such as in the stomach). Exemplary materials include polylactic acid (PLA) that can be resistant to temperatures as high as 190 degrees Celsius.

  The devices and compositions may be used to absorb and prevent the digestive or biological effects of toxins or alcohol taken actively or unintentionally; in these embodiments, the devices or compositions Things do not have to be used on a daily basis, but may be taken with food at risk of containing toxins, or when the intake of toxins is found, or avoiding the effects of excessive consumption of alcohol or It may be used to suppress.

  It will be understood that the terms “isolate”, “shield”, “contain”, “avoid assimilation”, and similar terms used herein are not meant in an absolute sense. In other words, the effect of the present invention resides in the ability of the device to partially isolate and reduce / inhibit absorption.

  The following non-limiting examples illustrate various aspects of the present invention. It should be understood that the examples are merely illustrative of specific embodiments of the invention and are not intended to limit the scope of the invention as defined by the claims appended at the end of the specification. I want to be.

  In one example, a commercially pure cellulose sponge was obtained. The sponge was cut into small tube shapes having a diameter of approximately 3-4 mm and a length of approximately 1 inch. The strip was then coated with carboxymethylcellulose (CMC) powder (hydrogel). The cut hydrogel-coated strip was then inserted into a polyethylene terephthalate (PET) tube having a wall approximately 6 μm thick (eg, hair thickness) and an inner diameter of about 4-5 mm. A bundle of approximately 100 of these PET tubes filled with sponges was prepared.

  Twenty bundles of these sponge-filled PET tubes are then longitudinally aligned, compressed and inserted into a gelatin capsule approximately 25 mm long and approximately 9 mm in diameter to form a “pill”. did. Each pill weighed approximately 500 mg.

  A commercially available canned chicken soup was obtained and poured into a plastic container. Sugar, salt, and lemon juice were added to chicken soup to simulate gastric conditions (eg, acidic) and contents after food was ingested. The mixture was then warmed to a temperature around 35-40 ° C.

  One pill prepared as described above was then placed in the mixture and the mixture was stirred for several minutes. After approximately 2.5 minutes, the gelatin capsule dissolved and began to release the sponge. The sponge released from the dissolving gelatin capsule began to swell. Stirring was continued for approximately 10 minutes.

  The sponge saturated with soup was then removed from the mixture with a strainer and weighed. This experiment was repeated four more times for a total of five experiments. The total weight of the sponge ranged from about 13 grams to about 19 grams.

  The sponge tube became stiffer after absorbing the soup mixture. The fluid mixture was in a sponge bubble, where these fluids were gelled by CMC. Thus, in an exemplary experiment, from an initial weight of 0.5 grams to a final weight of 19 grams, the sponge absorbed approximately 18.5 grams of soup mixture.

  Based on the estimated caloric content of a soup mixture of about 4 kcal / g and considering dilution of the soup with water, an exemplary pill can absorb approximately 72 kcal of nutrients isolated from absorption and metabolism in the GI tract. Calculated. Thus, for example, with five pills as described, nutrients equivalent to small hamburgers can be isolated from the user's daily eating habits. Thus, a person who consumes approximately 5 exemplary pills with food can lose approximately 15 pounds of weight annually.

Further development and improvement of the sponge material described herein, its surface shape, the hydrogel used, and sponge packaging greatly enhance the caloric absorption capacity of the sponge and pills containing it in the present invention. It will be. For example, a sponge pill containing a sponge prepared from a sponge material that has an approximate volume of 2.5 cm ³ and expands and absorbs approximately 100 times its original volume can trap fluid up to approximately 250 cm ^3. it can. This volume (ie 250 cm ³ ) corresponds to at least 250 grams of nutrients and thus can achieve a caloric sequestration of approximately 1,000 kcal per pill.

  The embodiments described herein and illustrated by the foregoing examples are to be understood as illustrative of the invention and are not to be construed as limiting. On the contrary, the present disclosure encompasses alternatives and equivalents thereof as embodied by the appended claims.

Claims (21)

  Compression having a size, shape, and / or surface shape configured to be efficiently packed in a small space and / or configured to absorb and substantially retain digestive material in the stomach A device comprising one or more members of possible absorbent matrix material.   The apparatus of claim 1, wherein the absorbent matrix material has a defined shape.   The apparatus of claim 1, wherein the absorbent matrix material is a tube.   The apparatus of claim 3, wherein the tube includes one or more internal voids in communication with the exterior.   The apparatus of claim 4, wherein the internal void has a defined shape.   The device of claim 1, wherein the matrix material comprises an elastomer, latex, guayule rubber, polyurethane rubber, silicone rubber, cellulose, nanocellulose, nitrile rubber, elastin, collagen, or combinations thereof.   The apparatus of claim 1, wherein the apparatus recovers to its original shape after being compressed.   The device of claim 1 further comprising one or more additional compounds selected from hydrogels, soluble or insoluble fibers, waxes and gums, or mixtures thereof.   The hydrogel is polyvinyl alcohol, poly (ethyloxazoline), polyvinyl acetate-polyvinyl alcohol copolymer, poly (2-hydroxyethyl acrylate), poly (2-hydroxyethyl methacrylate), carboxymethylcellulose, polyacrylic acid, apolyacryl. Acid copolymer, disaccharide, polysaccharide, chitosan, alginate, water soluble protein, polynucleic acid, natural clay, montmorillonite, sodium bentonite, absorbent fiber, superabsorbent fiber, microfiber, nanofiber, micropowder, nanopowder, and The apparatus of claim 8, comprising a combination thereof.   9. The device of claim 8, comprising exopolysaccharide mucus, cellulose, cellulose derivatives, hemicellulose, keratin, elastin, collagen, and mixtures thereof.   Agar, alginic acid, sodium alginate, carrageenan, gum arabic, gati gum, tragacanth gum (E413), karaya gum, guar gum, locust bean gum, beta glucan, chicle gum, damar gum, glucomannan, mastic gum, psyllium seed peel, spruce gum, tara gum, gellan gum, 9. The device of claim 8, comprising xanthan gum, and mixtures thereof.   The device of claim 1, wherein the device is suitable for daily use and is safe.   27. The apparatus of claim 1 having a surface shape substantially as shown in one of FIGS. 1-16 and 21-26.   The apparatus of claim 1 in the form of a capsule.   The device of claim 1, wherein the device passes through the subject's gastrointestinal tract and remains substantially intact.   The device of claim 1, wherein the device dissolves in the gastrointestinal tract of the subject.   17. A method for sequestering nutrients or compounds from absorption in the gastrointestinal tract, comprising ingesting a device according to any one of claims 1-16.   17. A method for treating obesity, comprising providing a device according to any one of claims 1 to 16 to an obese subject.   19. A method according to claim 17 or claim 18, wherein the device is used routinely.   A food or drinking water comprising the device according to any one of claims 1 to 16.   A kit comprising food or drinking water and the device according to any one of claims 1 to 16.

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