WO2011032087A2 - Dispositif polymère gonflable utilisé pour la régulation alimentaire - Google Patents

Dispositif polymère gonflable utilisé pour la régulation alimentaire Download PDF

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Publication number
WO2011032087A2
WO2011032087A2 PCT/US2010/048626 US2010048626W WO2011032087A2 WO 2011032087 A2 WO2011032087 A2 WO 2011032087A2 US 2010048626 W US2010048626 W US 2010048626W WO 2011032087 A2 WO2011032087 A2 WO 2011032087A2
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WO
WIPO (PCT)
Prior art keywords
implant
stomach
volume
state
reinforcement member
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PCT/US2010/048626
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English (en)
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WO2011032087A3 (fr
Inventor
Ann Prewett
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Replication Medical Inc.
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Application filed by Replication Medical Inc. filed Critical Replication Medical Inc.
Publication of WO2011032087A2 publication Critical patent/WO2011032087A2/fr
Publication of WO2011032087A3 publication Critical patent/WO2011032087A3/fr

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L31/00—Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
    • A61L31/14—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
    • A61L31/145—Hydrogels or hydrocolloids
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F5/00—Orthopaedic methods or devices for non-surgical treatment of bones or joints; Nursing devices; Anti-rape devices
    • A61F5/0003—Apparatus for the treatment of obesity; Anti-eating devices
    • A61F5/0013—Implantable devices or invasive measures
    • A61F5/0036—Intragastrical devices
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L31/00—Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
    • A61L31/04—Macromolecular materials
    • A61L31/048—Macromolecular materials obtained by reactions only involving carbon-to-carbon unsaturated bonds
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L31/00—Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
    • A61L31/14—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F2/00—Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
    • A61F2/02—Prostheses implantable into the body
    • A61F2/04—Hollow or tubular parts of organs, e.g. bladders, tracheae, bronchi or bile ducts
    • A61F2002/045—Stomach, intestines
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F2210/00—Particular material properties of prostheses classified in groups A61F2/00 - A61F2/26 or A61F2/82 or A61F9/00 or A61F11/00 or subgroups thereof
    • A61F2210/0061—Particular material properties of prostheses classified in groups A61F2/00 - A61F2/26 or A61F2/82 or A61F9/00 or A61F11/00 or subgroups thereof swellable

Definitions

  • [001] Technical Field - the invention relates to treatment of obesity by reducing the volume of the stomach.
  • Obesity is a growing problem in developed countries. High caloric diets and fatty foods have led to weight and health problems now commonly treated with surgery. In particular, bariatric surgery is a treatment for morbid obesity that involves alteration of a patient's digestive tract to encourage weight loss and to help maintain normal weight. Examples include gastric bypass, stomach stapling and banding which are highly invasive and have been associated with complications. For example, gastric bypass and/or intestinal bypass have been associated with malnutrition, uncontrollable diarrhea, dehydration and electrolyte imbalance. Stomach stapling involves stapling two walls of the stomach together while leaving a small gap. Food is held up in the segment of stomach above the staple line causing the sensation of fullness.
  • Another technique involves disposing an inflated bag within a patient's stomach to decrease the effective volume of the stomach. See, e.g., US Pat. No. 4,416,267.
  • Endoscopic procedures that have been used to assist weight loss have been primarily focused on the placement of a balloon or other space occupying device in the patient's stomach to fill portions of the stomach and provide the patient with the feeling of fullness, thereby reducing food intake.
  • an endoscope is utilized to guide the balloon through the patient's mouth and down the esophagus to the stomach.
  • free floating balloons may block the pyloric sphincter or the cardiac orifice.
  • the present invention describes a swellable pH- sensitive indwelling stomach implant adapted for reducing the stomach volume for the purposes of dietary regulation.
  • the implant is configured to transition from an expanded state to a reduced volume state when exposed to a stomach acid.
  • the purpose for reducing volume when exposed to acid is to prevent blocking of the stomach or a pyloric orifice when food is present in the stomach.
  • Figure 1 shows an implant of the invention in which multiple elements are connected together with flexible ties to form a chain
  • FIG 2 shows schematically an implant of the invention including internal air pockets configured to alter the density of the implant to make it buoyant;
  • Fi ure 3 shows an implant of the invention with multiple voids and openings configured to allow stomach content to pass through.
  • An indwelling fluid-absorbing swellable pH-sensitive polymeric stomach implant is used to add permanent or semi-permanent physical bulk to the stomach in order to reduce stomach volume.
  • the product can be placed into the stomach without surgery using minimally invasive techniques.
  • laparoscopic or endoscopic techniques are utilized.
  • an endoscope or a cannula may be passed through the throat into the esophagus and advanced into the stomach cavity.
  • the endoscope may be covered with a thin polyurethane or other suitable polymeric deployment sheath which will enable removal of the endoscope leaving the sheath resident in the stomach.
  • the implant may be advanced through the sheath by any suitable mans.
  • the implant may incorporate a contrast material to aid in such visualization.
  • the implant may contain a mesh or other reinforcing or anchoring elements configured for attachment of the implant to the stomach wall in order to prevent dislodgement or migration of the device.
  • the mesh allows for fixation of the implant through the endoscope to the wall of the stomach such as using suturing or stapling technique.
  • Alternative anchoring elements may include a fabric strip made for example from biocompatible polyethylene or Dacron material. Anchoring the implant to the wall of the stomach may be helpful in preventing the implant from being thrown out of the stomach if the patient experiences nausea and vomiting.
  • the implant in order to prevent the implant from blocking the stomach openings, it can be made buoyant i.e. having a similar or lower density to that of the stomach content. This may allow the implant to retain buoyancy in the presence of food and digestive stomach fluids. Buoyancy may be imparted by, e.g., infiltrating the implant with suitable voids such as for example closed cells containing air as shown in Fig. 2.
  • the implant may be characterized by being in one of three characteristic states: a collapsed state, an expanded state, and a reduced volume state.
  • a collapsed state In its collapsed state, the implant has a smallest volume of all three states and is suitable for insertion.
  • the implant may be placed in its collapsed state by dehydration.
  • the expanded state is characterized by the implant absorbing fluid and expanding. The volume of the implant is the largest in the expanded state.
  • the pH- sensitive nature of the polymer causes the implant to constrict in size with exposure to decreasing pH and enter its reduced volume state.
  • digestive processes result in production of stomach acid, lowering the pH of the stomach contents, whereby causing the polymer to shrink along with the implant as a whole so as to prevent blockage of the duodenum opening and allowing passage of digested food through the pyloric orifice.
  • the fluid-absorbing polymer is contained in a mesh bag that allows fluid to pass across the bag. The polymer must be highly resistant to pH extremes and be hydrolytically stable under these conditions. In the event smaller morsels or beads are employed, a mesh bag is necessary for retention.
  • the fluid-absorbing sponge polymer is dehydrated, e.g., to a xerogel, which markedly reduces the volume of the implant and places it in the collapsed state.
  • the dehydrated implant is then administered to the stomach via a tube or other suitable means where it imbibes fluid and expands.
  • the volume of dehydrated implants may range, e.g., from about 0.5 cubic centimeters to 3 cubic centimeters.
  • Expansion or swelling may range from about three fold to about twenty fold. Expansion of the implant causes a reduction in the empty volume of the stomach.
  • the reduced volume of the stomach constrains the amount of food that a patient consumes by providing a feeling of satiety after only a small amount of food has been consumed. Furthermore, the reduced cross- sectional area of the stomach reduces the rate in which food passes through the GI lumen. This increases the residence time of the food within the upper portion of the GI lumen, thereby enhancing the feeling of satiety.
  • pH-responsive hydrogels can shrink in response to lowering pH, e.g., from about two to five times a reduction in volume.
  • the implant may also be administered orally, in admixture with the food or drinking water, or by separate oral administration, or by gavage. They can also be administered by intragastric intubation, or directly into the stomach or small intestine when appropriate.
  • the polymers used in the invention are indigestible and pharmacologically- acceptable.
  • the term "indigestible” is used herein to indicate that the polymers are not absorbed from the gastrointestinal tract, nor are they degraded or metabolized to an appreciable extent in the gastrointestinal tract to produce components which are absorbed.
  • the polymers are also insoluble in the gastrointestinal liquids. They are insoluble in both the gastric fluid and bile produced by the animal. They are also insoluble in the ingesta, which can include both water and water-miscible liquids such as glycerol as well as water immiscible liquids such as liquid dietary fats, fatty acids and edible oils, under the gastrointestinal tract conditions.
  • the polymers are capable of remaining essentially undissolved throughout their residence in the gastrointestinal tract, and are not absorbed through the stomach or intestinal wall either as a solid or as a solution in the aqueous or fatty liquids which are absorbed in the digestive process. It is understood that the polymers are thus not degraded by acidic gastric fluid, or by digestive enzymes. They are not soluble in either gastric fluid or in the bile, nor are they solubilized by the surfactant action of the bile salts.
  • Preferred fluid-absorbing polymers are hydrogels that contain carboxyl groups which cause the pH-sensitive response of volume reduction.
  • Water-soluble polymers with charged side groups may be crosslinked by reacting the polymer with an aqueous solution containing ions of the opposite charge, either cations if the polymer has acidic side groups or anions if the polymer has basic side groups.
  • Examples of cations for cross-linking of the polymers with acidic side groups to form a hydrogel are monovalent cations such as sodium, divalent cations such as calcium, and multivalent cations such as copper, calcium, aluminum, magnesium, strontium, barium, and tin, and di-, tri- or tetra-functional organic cations such as alkylammonium salts.
  • Aqueous solutions of the salts of these cations are added to the polymers to form soft, highly swollen hydrogels and membranes. The higher the concentration of cation, or the higher the valence, the greater the degree of cross-linking of the polymer.
  • the polymers may be crosslinked enzymatically, e.g., fibrin with thrombin.
  • the polymers can be covalently crosslinked as well through the addition of ethylene diamine, NBS or a host of crosslinking agents routinely to react with amino, nitrile, urethane and carboxylic functional groups found on the polymer chain.
  • Suitable ionically crosslinkable groups include phenols, amines, imines, amides, carboxylic acids, sulfonic acids and phosphate groups.
  • Negatively charged groups such as carboxylate, sulfonate and phosphate ions, can be crosslinked with cations such as calcium ions. The crosslinking of alginate with calcium ions is an example of this type of ionic crosslinking.
  • Positively charged groups, such as ammonium ions can be crosslinked with negatively charged ions such as carboxylate, sulfonate and phosphate ions.
  • the negatively charged ions contain more than one carboxylate, sulfonate or phosphate group.
  • Anions for cross-linking of the polymers to form a hydrogel are monovalent, divalent or trivalent anions such as low molecular weight dicarboxylic acids, for example, terepthalic acid, sulfate ions and carbonate ions.
  • Aqueous solutions of the salts of these anions are added to the polymers to form soft, highly swollen hydrogels, as described with respect to cations.
  • a variety of polycations can be used to complex and thereby stabilize the polymer hydrogel into a semi-permeable surface.
  • materials that can be used include polymers having basic reactive groups such as amine or imine groups, having a preferred molecular weight between 3,000 and 100,000, such as polyethylenimine and polylysine. These are commercially available.
  • One polycation is poly(L-lysine); examples of synthetic polyamines are: polyethyleneimine, poly(vinylamine), and poly(allyl amine).
  • There are also natural polycations such as the polysaccharide, chitosan.
  • the implant is made of a hydrogel.
  • the liquid form of a suitable hydrogel Prior to coagulation, the liquid form of a suitable hydrogel is used to form the expanded configuration as it would be in the hydrated state.
  • the hydrogel is then coagulated to form the implant in an expanded configuration.
  • the implant is then dehydrated to a xerogel state which reduces the volume of the implant to the reduced configuration.
  • Many hydrogel polymers behave in a similar manner, which is to say they can be deformed, frozen into a deformed shape and they can maintain that shape indefinitely or until, e.g., a temperature change causes the polymer to "relax" into the shape originally held prior to freezing. This property can be referred to as shape memory or frozen deformation by those skilled in the art.
  • the temperature at which frozen deformation occurs is referred to as the glass transition temperature or T g .
  • T g glass transition temperature
  • polymer properties such as density, entropy and elasticity may sharply change.
  • Many polymers can be mixed with agents that can have a drastic effect on a polymer T g .
  • Polymers which absorb fluid are of particular interest and water is the preferred T g altering agent.
  • Hydrogels which contain less than about five percent water may be considered dehydrated or xerogels.
  • the T g of a xerogel will change as it absorbs fluids containing water. Once the T g becomes lower than ambient the now partially hydrated hydrogel becomes pliant and may be elastically deformed.
  • the polymer If the polymer is held in a state of elastic deformation while the T g is raised above ambient the polymer will maintain the deformed state indefinitely. This can be accomplished by either lowering the ambient temperature (freezing) or by returning the polymer to its xerogel state thus raising the T g .
  • a preferred polymer configuration includes two polymer phases of different hydrophilicity, the less hydrophilic phase having higher content of hydrophobic groups and more hydrophilic phase having higher content of hydrophilic groups.
  • the less hydrophilic phase is preferably crystalline and more hydrophilic phase is preferably amorphous, as can be established from X-ray diffraction.
  • Advantageous hydrophobic groups are pendant nitrile substituents in 1,3 positions on a polymethylene backbone, such as poly(acrylonitrile) or poly(methacrylonitrile).
  • the hydrophilic phase may preferably contain a high concentration of ionic groups.
  • Preferred hydrophilic groups are derivatives of acrylic acid and/or methacrylic acid including salts, acrylamidine, N-substituted acrylamidine, acrylamide and N-substituted acryl amide, as well as various combinations thereof.
  • a particularly preferred combination contains approximately two thirds acrylic acid and its salts (on molar basis), the rest being a combination of plain and N-substituted acrylamides and acrylamidines.
  • At least one polymeric component is preferably a multiblock copolymer with alternating sequences of hydrophilic and hydrophobic groups. Such sequences are usually capable of separating into two polymer phases and form strong physically crosslinked hydrogels.
  • Such multiblock copolymers can be, for example, products of hydrolysis or aminolysis of polyacrylonitrile or polymethacrylonitrile and copolymers thereof.
  • PAN polymers and copolymers having at least about 80 molar % of acrylonitrile and/or methacrylonitrile units in their composition may be referred to as "PAN”. Hydrolysis and aminolysis of PAN and products thereof are described, for example, in U.S. Pat. Nos.
  • a preferred fluid absorbing polymer for the implant is a synthetic composite of a cellular (or domain) type with continuous phase formed by a hydrophobic polymer or a hydrophilic polymer with low to medium water content forming a "closed cell" spongy structure that provides a composite with good strength and shape stability.
  • suitable polymers are polyurethanes, polyureas, PAN, and highly crystalline multiblock acrylic and methacrylic copolymers.
  • the polymer should be sufficiently permeable to water. More preferably, the continuous phase is formed by a strong hydrophilic polymer with sufficient permeability for water but impermeable to high-molecular solutes.
  • polymers examples include highly crystalline hydrogels based on segmented polyurethanes, polyvinylalcohol or multiblock acrylonitrile copolymers with derivatives of acrylic acid.
  • suitable polymers for the continuous phase in cellular composites have a water content in fully hydrated state between about 60% by weight and about 90% by weight, preferably between about 70% and about 85% by weight.
  • the second component of the fluid-absorbing polymer may be a highly hydrophilic polymer of high enough molecular weight to prevent permeation of the hydrophilic polymer through the continuous phase. This component is contained inside the matrix of the continuous phase.
  • the entrapped hydrophilic polymers (the so-called "soft block”) may be high-molecular weight water-soluble polymers, associative water-soluble polymers or highly swellable hydrogels containing, in a fully hydrated state, an amount of hydration which is preferably at least about 5% greater than the hydrophobic component.
  • the second component hydrated to at least about 65% when the first component is hydrated to about 60%.
  • from the second component could be fully hydrated at from about 95% of water and up to about 99.8% of water.
  • Such hydrogels are very weak mechanically. However, it may not matter in composites where such polymers' role is generation of osmotic pressure rather than load-bearing, with e.g., compression strength in full hydration in the range of about 0.01 MN/m or lower.
  • a system with closed cells (or domains) containing highly swellable or water-soluble polymers can form composites with very high swelling pressure as needed for the implant anchoring function.
  • suitable hydrophilic polymers are high-molecular weight polyacrylamide, polyacrylic acid, polyvinylpyrrolidone, polyethyleneoxide, copolymers of ethyleneoxide and propyleneoxide or hyaluronic acid; covalently crosslinked hydrogels such as hydrophilic esters or amides of polyacrylic or polymethacrylic acids; and physically crosslinked hydrogels, such as hydrolyzates or aminolysates of PAN.
  • associative water-soluble polymers capable of forming very highly viscous solutions or even soft physical gels.
  • Preferred are associative polymers containing negatively charged groups, such as carboxylates, sulpho-groups, phosphate groups or sulfate groups.
  • Particularly preferred are associative polymers formed by hydrolysis and/or aminolysis of PAN to high but finite conversions that leave a certain number of nitrile groups (typically, between about 5 and 25 molar %) unreacted.
  • Preferred fluid-absorbing polymer composites have both a continuous phase and a dispersed phase formed by different products of hydrolysis or aminolysis of PAN.
  • both components are compatible and their hydrophobic blocks can participate in the same crystalline domains. This improves anchorage of the more hydrophilic component and prevents its extraction or disassociation.
  • the size of more hydrophilic domains may vary widely, from nanometers to millimeters, preferably from tens of nanometers to microns.
  • the ratio between the continuous and discrete phases may vary from about 1:2 to about 1:100 on a dry weight basis, and a preferred ratio ranges from about 1:5 to about 1:20.
  • compositions and implants are described in US Pat. Nos. 6,264,695 and 6,726,721, both of which are incorporated herein by reference in their entireties.
  • a preferred method of making the fluid absorbing polymer composite is described in US Pat. No. 6,232,406, herein incorporated by reference in its entirety.
  • hydrogel forming copolymers are prepared by a partial alkaline hydrolysis of polyacrylonitrile ("HPAN”) in the presence of sodium thiocyanate (NaSCN).
  • HPAN polyacrylonitrile
  • NaSCN sodium thiocyanate
  • the resulting hydrolysis product is a multi-block acrylic copolymer, containing alternating hydrophilic and hydrophobic blocks. Hydrophilic blocks contain acrylic acid, acrylamidine, and acrylamide.
  • a PAN hydrolysate polymer (referred to herein HPAN I) (46+1% conversion of hydrolysis) having the following composition: acrylonitrile units -53-55%, acrylic acid units -22-24%, acrylamide units -17-19%, acrylamidine units -4-6%, as determined by 13 C NMR, is dissolved in a suitable solvent such as a -55% solution of sodium thiocyanate in water to form a viscous solution.
  • the viscous solution is poured into an extruder or porous mold having, e.g., a cavity defining the dimensions of the rod.
  • the solution can then be solvent cast, e.g., by solvent exchange (e.g., water for NaSCN).
  • the hydrogel used to make the implant is obtained by reacting an aquagel of PAN, formed by dissolving the polymer in an aqueous solvating solution such as high concentration of sodium thiocyanate.
  • the resulted solution of PAN is thereupon coagulated through addition of a suitable aqueous solvent or water miscible solvent.
  • the coagulum is further reacted in a hydrolyzing basic or acidic medium.
  • the PAN aquagel can then be processed as a thermoplastic and molded to obtain the desired shape.
  • a more rigid fluid absorbing polymer may be another PAN hydrosylate polymer, referred to herein as HP AN II (28+1% conversion of hydrolysis), having the following composition: acrylonitrile units -71-73%, acrylic acid units -13-15%, acrylamide units -10- 12%, acrylamidine units -2-4%, as determined by 13 C NMR, disolved in -55% NaSCN which can be solvent cast, washed, dried and cut to a suitable shape.
  • HP AN hydrogel is preferred for this application. It is inert, biocompatible and very stable to other acidic hydrolytic conditions. However, other suitable hydrogel polymers may be utilized as well for this application.
  • the shape of the implant when in its expanded state may be generally round or oval. More than one element may be connected into a chain using flexible ties such as sutures. This configuration is shown in Fig. 1 and has an advantage of allowing to use flexible ties for attaching the implant to the stomach wall as well as making it easy to adjust the total volume of the implant by cutting one or more of the implant elements off prior to implantation into a patient.
  • the shape of the implant may include one or more protrusions.
  • protrusions are envisioned to extend from the main body of the implant and are configured to prevent the body of the implant from blocking various openings of the stomach and surrounding organs of the digestive system.
  • between two and 10 protrusions may be formed on the main body of the implant.
  • Each protrusion may be about 1 ⁇ 4 to 3 ⁇ 4 of an inch high and contain a free end which in itself is formed to be rounded so as to prevent trauma or irritation to the stomach wall tissues.
  • the shape of the implant may be generally round or oval and include internal openings or passages therethrough. At least one such internal passage is envisioned. In embodiments, up to one hundred such internal passages may be formed inside the implant.
  • the openings of such internal passages are located throughout the outer surface of the implant (as shown in Fig. 3) so as to provide for unrestricted flow of digested food and other stomach content therethrough even in case the implant is located up against the entrance or exit from the stomach.
  • the size or diameter of such internal passage has to satisfy the requirement of being able to pass through the digested food with minimum flow restriction.
  • the shape of the implant may allow for customization at the time of implantation.
  • the implant may for example contain a number of breakaway sections which can be snapped off by the practitioner before implantation so as to adjust the overall volume of the implant based on specific needs of each individual patient. Between one and 5 of such breakaway sections may be provided. They may be made in the form of protrusions as described above. Reducing the number of protrusions will allows adjusting the volume of the implant while remaining protrusions will still prevent blocking of the stomach openings by the implant of the invention.
  • the breakaway sections of the implant may be shaped to be grasped by an endoscope so as to provide for the opportunity to reduce the volume of the implant at some point of time after the initial implantation. This may be desirable for gradual weaning of the patient from relying on the implant of the invention to reduce obesity.
  • a portion of the implant is envisioned to be removed by an endoscope once or over a number of occasions after initial implantation of the device therefore providing for gradual decrease in the implant volume over time.
  • the size of the implant may be selected to prevent its ejection in case of forceful vomiting by the patient.
  • the normal diameter of the esophagus generally varies between 2 and 3 cm
  • the smallest size of the implant when expanded is selected preferably to exceed the esophageal diameter.
  • the implant of the invention may be made using a radiopaque hydrogel material or contain radiopaque inclusions so as to facilitate it imaging using X-Ray or fluoroscopy techniques.
  • the implant may optionally include an interiorly-embedded reinforcement member.
  • the reinforcement member occupies at least a portion of the interior of the implant.
  • the reinforcement member can have a planar configuration or it can be one or more rods or beams of relatively rigid material which can extend for a portion of or the entire length of the implant or it can consist of two or more members.
  • the reinforcement member extends from the interior of the implant to the exterior, thereby extending beyond the main body of implant.
  • the reinforcement member may be made of a series of individual fibers or ribbons which are arranged in parallel or non-parallel fashion and extend throughout the implant.
  • the reinforcement member can be a fabric or mesh. Woven, non-woven, knitted or braided configurations are suitable.
  • a reinforcement member may be made of a polymeric material which is natural, e.g., cotton, or synthetic, e.g., polyester, polyamide, or other materials such as metal fiber, fiber glass, and carbon fiber. Methods of making shaped objects from these materials and others are well-known to those skilled in the art. Foils or ribbons herein may also be made of metal or polymeric material and are well-known.
  • the reinforcement member may be constructed from relatively durable materials including, but not limited to, metal foil, plastic foil, metal fibers, polymeric fibers of materials such as polycarbonate, polyethylene, polypropylene, polystyrene, polyethylene terephthalate, polyamide, polyurethane, polyurea, polysulfone, polyvinyl chloride, acrylic and methacrylic polymers, expanded polytetrafluoroethylene (Goretex®), ethylene tetrafluoroethylene, graphite, etc. These materials can be used either alone, or in a composite form in combination with elastomers or hydro gels.
  • the reinforcement member may be exteriorly disposed, e.g., a jacket which surrounds all or part of the implant.
  • the reinforcement member is designed to provide support for the implant and to buttress any fastener which may be used to help maintain the implant in place in the stomach.
  • Suitable fasteners include, but are not limited to sutures, screws, staples, barbs and the like.
  • the reinforcement member may be pre-loaded with one or more fasteners or not, e.g., in the situation where a fastener is applied by the surgeon during implantation.
  • a reinforced implant herein may be manufactured by providing a reinforcement member of desired configuration and placing it in a mold.
  • a pH-sensitive fluid-absorbing liquid polymer is added to the mold and surrounds the reinforcement member.
  • a gap e.g., about l-3mm or more, is left between one or more sides of the reinforcement member and the walls of the mold.
  • Fluid-absorbing liquid polymer is allowed to fill the gap between the mold and the reinforcement member.
  • the fluid absorbing polymer is cured or fixed, e.g., by solvent casting, ionic gelation, photo-polymerization and the like, it solidifies and encapsulates the reinforcement member.
  • the mold may be made of material which is impermeable to the fluid absorbing polymer but permeable to water.
  • the mold is placed in a water bath to extract the solvent (e.g., sodium thiocyanate) which causes the polymer to coagulate.
  • the mold may then be opened and any remaining solvent in the implant is extracted. If it is desired to leave one or more sides of the implant open to the reinforcement member, then the desired side(s) of the reinforcement member is placed up against the wall of the mold to prevent formation of a gap for the liquid fluid-absorbing polymer to fill.
  • the fluid-absorbing polymer is made to achieve a strong physical bond to the reinforcement member by incorporating an initial treatment of the reinforcement member with a relatively hydrophobic fluid- absorbing polymer to create an encapsulating layer of the relatively hydrophobic fluid-absorbing polymer.
  • a hydrogel such as HP AN II is applied to the reinforcement member as a 10% solution by weight in a solvent (sodium thiocyanate 55% by weight in water) and then coagulated onto the reinforcement member by solvent exchange with an aqueous solution such as water. As the polymer coagulates, it shrinks volumetrically around the reinforcement member, causing a tight physical bond to the reinforcement member.
  • the treated reinforcement member is placed in a mold and a relatively more hydrophilic fluid-absorbing polymer in the liquid state is added to create a cohesive continuous polymer matrix which surrounds the reinforcement member.
  • a relatively more hydrophilic fluid-absorbing polymer in the liquid state is added to the mold.
  • the solvent from the HP AN I solution causes the outermost surface of the coagulated HP AN II layer surrounding the braided fibers to dissolve and allow commingling of the HP AN I and HP AN II hydrogel polymers at the surface interface which forms a strong adhesive bond when the HP AN I and commingled hydrogels are coagulated by solvent exchange.
  • the reinforcement member is optional and that a mold may be filled without such a reinforcement member.
  • the implant may be hydrated to its fullest extent (-90% equilibrium water content (EWC)). In this fully hydrated state the implant is readily deformed under modest loads and the hydrogel, e.g., HP AN I or HP AN II, glass transition temperature (T g ) is well below room temperature. This is the "relaxed" state of the implant, the state to which it will return after loading below the critical level. The critical level is the point at which permanent deformation occurs and is further discussed below. In order to provide a reduced configuration (also referred to herein as the first configuration), the implant may be allowed to dehydrate and enter the xerogel state.
  • EWC equilibrium water content
  • the fully hydrated implant may be deformed into any desirable insertion shape and the temperature of the implant is lowered below its T g (near freezing point of water).
  • T g near freezing point of water
  • the T g of the hydrogel increases with decreasing water content. This characteristic is exploited by simultaneously raising the T g while deforming the implant into a desired shape. In other words, as the implant dehydrates it is freezing the position of the polymer chains. To regain the original shape of the implant, the T g may be lowered by hydration.

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  • Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Animal Behavior & Ethology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Vascular Medicine (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Veterinary Medicine (AREA)
  • General Health & Medical Sciences (AREA)
  • Surgery (AREA)
  • Epidemiology (AREA)
  • Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Child & Adolescent Psychology (AREA)
  • Obesity (AREA)
  • Nursing (AREA)
  • Orthopedic Medicine & Surgery (AREA)
  • Engineering & Computer Science (AREA)
  • Biomedical Technology (AREA)
  • Dispersion Chemistry (AREA)
  • Prostheses (AREA)
  • Coloring Foods And Improving Nutritive Qualities (AREA)

Abstract

L'invention concerne un implant gastrique destiné à réduire le volume de l'estomac, dans le traitement de l'obésité et pour la régulation alimentaire. Cet implant est fabriqué à partir d'un hydrogel apte à réduire son propre volume lorsqu'il est exposé aux acides gastriques. Cette réduction de volume permet le libre passage des aliments digérés, par l'estomac et dans le duodénum, sans que l'implant n'obstrue une des ouvertures de l'estomac. Dans des modes de réalisation, l'implant selon l'invention est fabriqué à partir d'un hydrogel et peut être déshydraté pour que son volume soit réduit au minimum avant l'insertion.
PCT/US2010/048626 2009-09-11 2010-09-13 Dispositif polymère gonflable utilisé pour la régulation alimentaire WO2011032087A2 (fr)

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US61/241,727 2009-09-11

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* Cited by examiner, † Cited by third party
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WO2017205844A3 (fr) * 2016-05-27 2018-01-04 Lyndra, Inc. Architecture de matériaux destinée à des systèmes pour séjour gastrique
US10182985B2 (en) 2014-06-11 2019-01-22 Massachusetts Institute Of Technology Residence structures and related methods
US10596110B2 (en) 2014-06-11 2020-03-24 Massachusetts Institute Of Technology Residence structures and related methods
US11576859B2 (en) 2015-10-23 2023-02-14 Lyndra Therapeutics, Inc. Gastric residence systems for sustained release of therapeutic agents and methods of use thereof
US11576866B2 (en) 2016-09-30 2023-02-14 Lyndra Therapeutics, Inc. Gastric residence systems for sustained delivery of adamantane-class drugs
US11992552B2 (en) 2015-12-08 2024-05-28 Lyndra Therapeutics, Inc. Geometric configurations for gastric residence systems

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US20040098113A1 (en) * 2002-08-02 2004-05-20 Peter Forsell Implantable ceramic valve pump assembly
US20080172079A1 (en) * 2006-09-29 2008-07-17 Allergan, Inc. Apparatus and method for intragastric balloon with in situ adjustment means
US20090182303A1 (en) * 2008-01-14 2009-07-16 Steven Walak Targeted Therapeutic Agent Release for Weight Loss Therapy

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* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20040098113A1 (en) * 2002-08-02 2004-05-20 Peter Forsell Implantable ceramic valve pump assembly
US20080172079A1 (en) * 2006-09-29 2008-07-17 Allergan, Inc. Apparatus and method for intragastric balloon with in situ adjustment means
US20090182303A1 (en) * 2008-01-14 2009-07-16 Steven Walak Targeted Therapeutic Agent Release for Weight Loss Therapy

Cited By (15)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US10610482B2 (en) 2014-06-11 2020-04-07 Massachusetts Institute Of Technology Residence structures and related methods
US10716752B2 (en) 2014-06-11 2020-07-21 Massachusetts Institute Of Technology Residence structures and related methods
US10517819B2 (en) 2014-06-11 2019-12-31 Massachusetts Institute Of Technology Residence structures and related methods
US10517820B2 (en) 2014-06-11 2019-12-31 Massachusetts Institute Of Technology Residence structures and related methods
US10532027B2 (en) 2014-06-11 2020-01-14 Massachusetts Institute Of Technology Residence structures and related methods
US10596110B2 (en) 2014-06-11 2020-03-24 Massachusetts Institute Of Technology Residence structures and related methods
US10182985B2 (en) 2014-06-11 2019-01-22 Massachusetts Institute Of Technology Residence structures and related methods
US10716751B2 (en) 2014-06-11 2020-07-21 Massachusetts Institute Of Technology Residence structures and related methods
US11389399B2 (en) 2014-06-11 2022-07-19 Massachusetts Institute Of Technology Residence structures and related methods
US11246829B2 (en) 2014-06-11 2022-02-15 Massachusetts Institute Of Technology Residence structures and related methods
US11357723B2 (en) 2014-06-11 2022-06-14 Massachusetts Institute Of Technology Residence structures and related methods
US11576859B2 (en) 2015-10-23 2023-02-14 Lyndra Therapeutics, Inc. Gastric residence systems for sustained release of therapeutic agents and methods of use thereof
US11992552B2 (en) 2015-12-08 2024-05-28 Lyndra Therapeutics, Inc. Geometric configurations for gastric residence systems
WO2017205844A3 (fr) * 2016-05-27 2018-01-04 Lyndra, Inc. Architecture de matériaux destinée à des systèmes pour séjour gastrique
US11576866B2 (en) 2016-09-30 2023-02-14 Lyndra Therapeutics, Inc. Gastric residence systems for sustained delivery of adamantane-class drugs

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