Expanded device

Abstract

A folded expandable gastro-retentive device and its uses in human medical care include, inter alia, appetite suppression in a subject in need thereof. The expanded device can be included in kits.

Claims

1. A folded expandable gastro-retentive device having an initial folded form, said form being transformable, in sequence, upon delivery to a subject gastrointestinal system, into (a) an expanded 3-dimensional form, (b) a declined form, and (c) a disintegrated form, said device comprising at least one compartment having an external enteric-biodegradable film that allows stomach liquid permeation therethrough, said at least one compartment enclosing a film that comprises at least one gel-forming compound; wherein said at least one gel-forming compound is configured to undergo swelling into a gel upon contact with liquid in the stomach to transform said device into the expanded, 3-dimensional form (a); wherein said at least one gel-forming compound is configured to, upon continued stomach residence, undergo at least partial degradation thereby causing the device in the expanded form (a) to adopt the declined form (b) and evacuate through the pylorus into the intestine; and wherein the external enteric biodegradable film is configured to enterically degrade in the intestine to transform the device to the disintegrated form (c).

2. The device according to claim 1, wherein said liquid is stomach fluids.

3. The device according to claim 1, wherein said continued stomach residence lasts between about 0.5 hrs to about 12 hrs.

4. The device according to claim 1, wherein said film comprising the at least one gel-forming compound is a multilayered film.

5. The device according to claim 1, wherein enteric degradation of said external enteric-biodegradable film causes reduction in at least one of tensile strength and elasticity of said external enteric-biodegradable film.

6. The device according to claim 1, wherein said external enteric-biodegradable film has a thickness between about 3 and about 60 microns.

7. The device according to claim 1, wherein said external enteric-biodegradable film comprises at least one mechanical or chemically formed aperture permitting liquid penetration therethrough.

8. The device according to claim 1, wherein said at least one gel-forming compound is selected from gelatin, alginate, chitosan, dextran, collagen, hyaluronic acid, polyglutamic acid, elastin, calcium polycarbophil, acrylamides, styrene maleic anhydride, polyethylene oxide, polyacrylic acid, polyethylene glycol, carboxymethylcellulose, polyvinyl pyrrolidone, sodium polyacrylate, hydroxypropylmethylcellulose, poly glutamic acid (PGA), polyacrylamide, alginic acid, pullulan, starch, and any combination thereof.

9. The device according to claim 1, wherein said at least one gel-forming compound is a charged gel-forming compound.

10. The device according to claim 9, wherein said at least one charged gel-forming compound is at least one super absorbent polymer.

11. The device according to claim 1, being encased within a gastric degradable swallowable capsule.

12. The device according to claim 11, wherein the capsule is configured to expose in the initial folded form to stomach fluids.

13. The device according to claim 1, wherein said film that comprises the at least one gel-forming compound has a thickness of about 400 microns, about 500 microns, about 600 microns, about 700 microns, or about 800 microns.

14. The device according to claim 1, wherein said film that comprises the at least one gel-forming compound has a thickness of between about 5 microns and about 500 microns.

15. The device according to claim 1, wherein said film that comprises the at least one gel-forming compound has a thickness of less than 1500 microns.

16. The device according to claim 1, wherein said at least one gel-forming compound has a swelling ratio of about 10 to about 100.

17. The device according to claim 1, wherein said at least one compartment comprises at least two compartments connected to each other.

18. The device according to claim 17, wherein said at least two compartments form a closed ring 3-dimensional shape when the at least two compartments are connected to one to the other.

19. The device according to claim 18, wherein, in the expanded form (a), said closed ring 3-dimensional shape is a polygon.

20. The device according to claim 19, wherein said polygon is a triangle, a square, a pentagon, or a hexagon.

Description

BRIEF DESCRIPTION OF THE DRAWINGS

(1) In order to understand the disclosure and to see how it may be carried out in practice, embodiments will now be described, by way of non-limiting example only, with reference to the accompanying drawings, in which:

(2) FIG. 1 is a schematic illustration depicting the route of said device of the invention within the stomach until evacuation to the intestine.

(3) FIG. 2 is a schematic view of one compartment of an orally administrable device according to the invention, having a 3-dimensional “ellipse” shape at the expanded form, where the expanded-film is swelled after contact with gastric fluids.

(4) FIG. 3 is a schematic top-view of one compartment of an orally administrable device according to the invention, having a 3-dimensional “rectangle” shape at the expanded form where the expandable-film is swelled after contact with gastric fluids.

(5) FIG. 4 is a schematic view of four connected compartments of an orally administrable device according to the invention, which form an “open chain” shape at the expanded form, where the expandable-film is swelled after contact with gastric fluids.

(6) FIG. 5 is a schematic view of four connected compartments of an orally administrable device according to the invention, which form a “closed chain” shape at the expanded form, where the expandable-film is swelled after contact with gastric fluids.

(7) FIG. 6 is a schematic lop-view of five connected compartments of an orally administrable device according to the invention, which form a “pentagon” shape” at the non-expanded form (where the expandable-film is not swelled) before folding into swallowable capsule.

(8) FIG. 7 is a schematic top-view of three connected compartments of an orally administrable device according to the invention, which form a “triangle shape” at the non-expanded form (where the expandable-film is not swelled) before folding into swallowable capsule.

(9) FIG. 8 and FIG. 10 are schematic views of one or several connected compartments of an orally administrable device according to the invention, at the non-expanded form (where the expandable-film is not swelled), rolled (in FIG. 8) or folded (in FIG. 10) and encased within a swallowable capsule before use.

(10) FIG. 9 is a schematic top-view of one compartment or several connected compartments of an orally administrable device according to the invention, which forms a “ring shape” at the expanded form, where the expandable-film is swelled after contact with gastric fluids.

(11) FIG. 11 is a schematic lop-view of one compartment or several connected compartments of an orally administrable device according to the invention, forming an “octet” structure at the expanded form, where the expandable-film is swelled after contact with gastric fluids.

(12) FIG. 12 is a schematic top-view of three connected compartments of an orally administrable device according to the invention, which form a “triangle shape” at the expanded form, where the expandable-film is swelled after contact with gastric fluids.

(13) FIG. 13 is a schematic view of three connected compartments of an orally administrable device according to the invention, which form a “square shape” at the non-expanded form (where the expand able-film is not swelled) before folding into swallowable capsule.

(14) FIG. 14 is a schematic top-view of one compartment of an orally administrable device according to the invention, which forms a “square shape” at the non-expanded form (where the expandable-film is not swelled) before folding into swallowable capsule, and “ball” structure at the expanded form where the expandable-film is swelled alter contact with gastric fluids.

(15) FIG. 15 is a schematic top-view of four connected compartments of an orally administrable device according to the invention, which form a “square shape” at the non-expanded form (where the expandable-film is not swelled) before folding into swallowable capsule.

(16) FIG. 16 is a schematic view of three connected compartments of an orally administrable device according to the invention, which form a “multi-rings shape” at the expanded form, where the expandable-film is swelled after contact with gastric fluids.

(17) FIG. 17 is a schematic view of one compartment or several connected compartments of an orally administrable device according to the invention, forming a “submarine shape” at the expanded form, where the expandable-film is swelled after contact with gastric fluids.

(18) FIG. 18 is a schematic top-view of three connected compartments of an orally administrable device according to the invention, which form a “square shape” at the non-expanded form (where the expandable-film is not swelled top view) before folding into swallowable capsule, and a “sea mattress” at the expanded form where the expandable-film is swelled after contact with gastric fluids.

(19) FIG. 19 is a schematic view of one compartment or several connected compartments of an orally administrable device according to the invention, forming a “square shape” with an elliptic hollow inside at the expanded form, where the expandable-film is swelled after contact with gastric fluids.

(20) FIG. 20 is a schematic view of one compartment or several connected compartments of an orally administrable device according to the invention, showing the connector element made of said external biodegradable film or any absorbable medical suture.

(21) FIG. 21 is a schematic cross-section view of one compartment at the non-expanded form having an external biodegradable film enclosing a composition (marked in bold) composed of at least one gel-film and/or at least one combination of gel-gas film.

(22) FIG. 22 is a schematic cross-section view of one compartment at the non-expanded form having at least one expandable multilayered biodegradable film comprising: at least one layer of external biodegradable film, and at least one expandable layer formed of gel-film and/or combination of gel-gas film.

DETAILED DESCRIPTION OF EMBODIMENTS

(23) 1. General Structure of a Device of the Invention

(24) While looking for in-situ expanding & degradable intra-gastric device it has been founded that a device containing high swelling-ratio agent wrapped with an ultrathin film is capable of bursting out of a 000 or 00-(gelatin or vegetarian) capsule and swells into a stiff tri-dimension shape with an effective volume inside the gastric. Said internal solid-like gel/gas construction (herein the swelling-ratio agent) enables the whole device of the invention to be maintained in the stomach and not be evacuated too easily into the intestine. In order to facilitate insertion of such swelling agent compound into the volume of a standard 000/00-capsule (designed for oral administration), some embodiments of the invention provide a thin film as the envelope-layer forming a compartment that holds tire swelling agent in a form of a film. The integration of both swelling agent film and envelope-film enables the compact encapsulation within the swallowable capsule.

(25) In some embodiments, a device is composed of 3 major elements: (i) an outer gelatin or vegetarian capsule at 000/00-size (commercially purchased) which used as the device's shell; (ii) a thin synthetic polymers-based microfilm which used as the envelope-layer of the swelling filler; and (iii) a polymers-based hydrogel-film and/or gel-gas forming film which used as the swelling filler.

(26) 2. Composition of an External Biodegradable Envelope-Film of a Device of the Invention

(27) In some embodiments of the invention, an envelope-film is composed of at least two layers pre-casted upon a support sheet. The support sheet, in a form of film or substrate [Teflon® film, Teflon® coated substrate, silicon film, silicon made or coated substrate, PET (polyethylene terephthalate) film, BoPET film, Melinex®, MYLAR-A®, Hostaphan®, Kapton® (polyimide) film], enables the casting of a first-layer without an adhesive material. The first casted-layer (composed of one or combination of, but not limited to, PVOH or hydroxypropylcellulose or Kollicoat-IR® or methylcellulose or hypromellose or Povidone or polyvinylpyrrolidone) provides elasticity and protection for the other casted layers during manufacturing and storage of the final device since the support sheet is actually detached and removed in the course of the final device preparation. The other casted layers (composed of, but not limited to, HP-55:DEP:Ethocel-45:Klucel or EudragitL100-55:EudragitRS:TEC:GMS or CAP:DEP:CA: or AS-LF:CA:DEP:ATBC or Cellulose Acetate:PEG 400:TEC) provide the major structure of the envelope-film and are the only layers dial actually endures under the acidic solution of the stomach.

(28) Non-limiting examples of envelope-film compounds include: Polyethylene-Phthalate polymer film; purchased as film (MYLAR-A®; DuPont, USA). Polyvinyl Alcohol 4-88; purchased as powder (Merck, Germany)— Methocel LV-50; purchased as powder (DOW, USA) Poly-Vinyl-Alcohol[PVA]:Poly-Ethylene-Glycol[PEG] graft-copolymer; purchased as powder (Kollicoat-IR®; BASF, Germany) Hydroxy-Propyl-Cellulose polymer; purchased as powder (Klucel-LF®; Ashland, USA) Povidone (Kollidone 25; BASF, Germany). Hypromellose Phthalate [HP-55] and Hypromellose Acetate Succinate [AQOAT AS-LF]; purchased as powders (Shin-Etsu, Korea) CAP [Cellulose-Acetate-Phthalate] and CA [Cellulose-Acetate]; purchased as powders (Eastman, USA). Triethyl citrate [TEC] and Acetyl tributyl citrate [ATBC]; purchased as liquids (Merck, Germany). DEP [Diethyl-Phthalate]; purchased as liquid (Spectrum, USA)—. Glycerol Monostearate [GMS]; purchased as liquid (Cognis, Germany)—.

(29) Ethanol, Methanol, Isopropyl Alcohol [IPA], Ethyl Acetate, Acetic-acid, and Acetone (BioLab, Israel) are organic solvents used for the polymers dissolving.

(30) 3. Process for the Manufacture of the External Envelope Biodegradable Film of a Device of the Invention

Example 1

(31) The manufacture of an envelope-film is based on solutions preparation followed by two casting processes performed:

(32) 1) Polyvinyl alcohol Solution (PVOH)—PVOH powder is dissolved in Water.

(33) 2) PVOH Casting—The PVOH solution is casted as the first-layer upon the support sheet and kept to dry.

(34) 3) HP-55:DEP:Ethocel-45:Klucel (60:20:15:5; % ratio) Solution—Hypromellose phthalate (HP-55) powder and Ethocel-45 powder (in this order) are first dissolved in Acetone, followed by the addition of DEP solution. Then, pre-prepared Klucel solution is added.

(35) 4) HP-55:DEP:Ethocel-45:Klucel Casting—The HP-55:DEP:Ethocel-45:Klucel solution is casted as the second-layer upon the dry PVOH (first-layer) film and kept to dry.

Example 2

(36) The manufacture of an envelope-film is based on solutions preparation followed by two casting processes performed:

(37) 1) Hydroxypropyl cellulose Solution—Klucel LF powder is dissolved in Ethanol

(38) 2) Klucel LP Casting—The Klucel LF solution is casted as the first-layer upon the support sheet and kept to dry

(39) 3) Eudragit L100-55:Eudragit RS:TEC:GMS (60:15:20:5; % ratio) Solution—Eudragit L100-55 powder and Eudragit RS powder (in this order) are first dissolved in a mixture of Acetone:IPA (65:35), followed by the addition of TEC (purchased as a solution). Then, Glycerol Monostearate (GMS) solution is added.

(40) 4) Eudragit L100-55:Eudragit RS:TEC:GMS Casting—The Eudragit L100-55:Eudragit RS:TEC:GMS solution is casted as the second-layer upon the dry Klucel LF (first-layer) film and kept to dry

Example 3

(41) The manufacture of an envelope-film is based on solutions preparation followed by two casting processes performed:

(42) 1) Kollicoat Solution—Kollicoat-IR powder is dissolved in Ethanol:Water (1:1) solution.

(43) 2) Kollicoat Casting—The Kollicoat solution is casted as the first-layer upon the support sheet and kept to dry

(44) 3) CAP:DEP:CA (70:20:10% ratio) Solution—CAP powder and CA powder (in this order) are first dissolved in Acetone, followed by the addition of DEP solution. Then, pre-prepared Klucel solution is added.

(45) 4) CAP:DEP:CA: Casting—The CAP:DEP:CA: solution is casted as the second-layer upon the dry Kollicoat (first-layer) film and kept to dry

Example 4

(46) The manufacture of an envelope-film is based on solutions preparation followed by two casting processes performed:

(47) 1) Methyl cellulose Solution—Methocel EV-50 powder is dissolved in Water.

(48) 2) Methocel Casting—The Methocel EV-50 solution is casted as the first-layer upon the support sheet and kept to dry.

(49) 3) AS-LF:CA:DEP:ATBC (65:15:10:10; % ratio) Solution—Hypromellose Acetate Succinate (AS-LP) powder and Cellulose Acetate (CA) powder (in this order) are first dissolved in Acetone, followed by the addition of DEP solution and ATBC (purchased as solutions).

(50) 4) AS-LF:CA:DEP:ATBC Casting—The AS-LF:CA:DEP:ATBC solution is casted as the second-layer upon the dry Methocel (first-layer) film and kept to dry

Example 5

(51) The manufacture of an envelope-film is based on solutions preparation followed by two casting processes performed:

(52) 1) Plasdone Solution—Kollidon 25 powder is dissolved in Ethanol

(53) 2) Kollidon 25 Casting—The Kollidon 25 solution is casted as the first-layer upon the support sheet and kept to dry

(54) 3) Cellulose Acetate:PEG 400:TEC (75:10:15% ratio) Solution—Cellulose Acetate powder is first dissolved in Acetone, followed by the addition of PEG 400 solution.

(55) 4) Cellulose Acetate:PEG 400 Casting—The Cellulose Acetate:PEG 400 solution is casted as the second-layer upon the dry Kollidon 25 (first-layer) film and kept to dry.

(56) 4. Composition of a Hydrogel-Film of a Device of the Invention

(57) In some embodiments of the invention the hydrogel-film is composed of at least two layers pre-casted upon a support sheet (described above). The support sheet enables the casting of the first-layer (PVOH or Klucel or Kollicoat-IR® or Methocel or Povidone) without an adhesive material, while it provides elasticity and protection for the other casted layers during manufacturing and storage of the final device since the support sheet is actually detached and removed in the course of the device preparation. However, the casted layers [Luquasorb(FP800):Lactose:PEG:Kollidon or Carbopol:Chitosan:PEG:Klucel or Poly-Acrylic-Acid:Chitosan:PEG:Klucel or SephadexG-100:Lactose:TEC:Klucel] contain: particles suspension (rather than a polymer solution) of polymers that compose a swellable gel-matrix, plasticizer and binder to assemble the particles into a suspension.

(58) Non-limiting list of hydrogel compounds include: Polyethylene-Phthalate polymer; purchased as film (MYLAR-A®; DuPont, USA). Polyvinyl alcohol polyethylene glycol graft copolymer; purchased as powder (Kollicoat-IR®; BASF, Germany). Povidone (Kollidone 25; BASF, Germany). Polyvinyl Alcohol 4-88; purchased as powder (Merck, Germany)—. Methocel LV-50; purchased as powder (DOW, USA). Poly-Vinyl-Alcohol[PVA]:Poly-Ethylene-Glycol[PEG] graft-copolymer; purchased as powder (Kollicoat-IR®; BASF, Germany). Hydroxy-Propyl-Cellulose polymer; purchased as powder (Klucel-LF®; Ashland, USA). Cross-linked Sodium Polyacrylic-Acid; purchased as powder (Luquasorb®; BASF, USA)—. Cross-linked Poly Glutamic-Acid; purchased as powder (PGA; hayashibira, Japan). Cross-linked Poly-Acrylic-Acid; purchased as powder (Carbopol 974; Lubrizol, USA). Cross-linked Sodium Polyacrylic-Acid; purchased as powder (FavorPac®; Evonik, Germany). Cross-linked Dextrane gel; purchased as powder (Sephadex G-100; GE Medical). Chitosan; purchased as powder (Chitoclear®; Pre mix, Iceland or 90/200/A1; Kraeber, Germany or Protasan UP CL 114, 113, 213, 214; Novamatrix, Norway). Poly-Ethylene-Glycol; purchased as liquid (PBG-400; Sigma, USA)—. Chitosan; purchased as powder (KiOnutrime-CsG; kitozyme, Belgium)—. Lactose monohydrate; purchased as powder (Pharmatose 200, Fonterra, New Zealand).

(59) 5. Process for the Manufacture of a Hydrogel-Film of a Device of the Invention

Example 1

(60) The manufacture of the hydrogel-film is generally similar to the manufacture of the envelope-film; slurries (in this case one solution and one suspension) preparation followed by two casting processes performed at RT:

(61) 1) Polyvinyl alcohol Solution—PVOH powder is dissolved in Water

(62) 2) PVOH Casting—The PVOH solution is casted as the first-layer upon the support sheet and kept to dry.

(63) 3) Sephadex G-100:Lactose:TEC:Klucel (70:10:5:15; % ratio) Suspension—Sephadex and Lactose monohydrate granules are first ground. The Sephadex particles are then added to a Klucel solution, and after mixing the Lactose particles are added and mixed, forming a particles suspension. Finely TEC is added into the suspension under mixing.

(64) 4) Sephadex:Lactose:TEC:Klucel Casting—The suspension is casted as the second-layer upon the dry PVOH (first-layer) film and kept to dry

Example 2

(65) The manufacture of the hydrogel-film is generally similar to the manufacture of the envelope-film; slurries (in this case one solution and one suspension) preparation followed by two casting processes performed at RT:

(66) 1) Polyvinyl alcohol Solution—PVOH powder is dissolved in Water

(67) 2) PVOH Casting—The PVOH solution is casted as the first-layer upon support sheet and kept to dry.

(68) 3) Luquasorb(FP800):Lactose:PEG:Kollidon (75:10:5:10; % ratio) Suspension—Luquasorb and Lactose monohydrate granules are first ground. The Luquasorb particles are then added to a Kollidon solution, and after mixing, the lactose particles are added and mixed, forming a particles suspension. Finely, PEG is added into the suspension under mixing.

(69) 4) Luquasorb(FP800):Lactose:PEG:Kollidon Casting—The suspension is casted as the second-layer upon the dry Kollicoat (first-layer) film and kept to dry

Example 3

(70) The manufacture of the hydrogel-film is generally similar to the manufacture of the envelope-film; slurries (in this case one solution and one suspension) preparation followed by two casting processes performed at RT:

(71) 1) Kollicoat Solution—Kollicoat-IR powder is dissolved in Ethanol:Water (1:1) solution

(72) 2) Kollicoat Casting—The Kollicoat solution is casted as the first-layer upon the support sheet and kept to dry.

(73) 3) FavorPac(FP):Chitosan(CS):PEG:Klucel (65:15:10:10; % ratio) Suspension—FP and CS granules are first ground. The FP particles are then added to a Klucel solution, and after mixing, the CS particles are added and mixed, forming a particles suspension. Finely, PEG solution is added into the suspension under mixing.

(74) 4) FavorPac:Chitosan:PEG:Klucel Casting—The suspension is casted as the second-layer upon the dry Kollicoat (first-layer) film and kept to dry

Example 4

(75) The manufacture of the hydrogel-film is generally similar to the manufacture of the envelope-film; slurries (in this case one solution and one suspension) preparation followed by two casting processes performed at RT:

(76) 1) Kollicoat Solution—Kollicoat-IR powder is dissolved in Ethanol:Water (1:1) solution

(77) 2) Kollicoat Casting—The Kollicoat solution is casted as the first-layer upon the support sheet and kept to dry

(78) 3) Carbopol 974 solution (1.5%) is dissolved in water and 1.75M NaOH solution is added under steering to raise pH 5-5.5 where stable gel is accepted. Then gel is dried in oven.

(79) 4) Carbopol:Chitosan(CS):PEG:Klucel (65:15:5:15; % ratio) Suspension—Carbopol and CS granules are first ground. The Carbopol particles are then added to a Klucel solution, and after mixing, the CS particles are added and mixed, forming a particles suspension. Finely, PEG solution is added into the suspension under mixing.

(80) 5) Carbopol:Chitosan:PEG:Klucel Casting—The suspension is casted as the second-layer upon the dry Kollicoat (first-layer) film and kept to dry.

(81) 6. Composition of a Gel-Gas Forming Film of a Device of the Invention

(82) In some embodiments of the invention the gel-gas forming film is composed of at least two layers pre-casted upon a support sheet (described above). The support sheet enables the casting of the first-layer without an adhesive material, while it provides elasticity and protection for the other casted layers during manufacturing and storage of the final device since the support sheet is actually detached and removed in the course of the device preparation. However, the other casted layers contain particles suspension (rather than a polymer solution) of polymers that composes a gel producing-matrix, gas producing-matrix, plasticizer and binder to assemble the particles into a suspension.

(83) Non-limiting list of gas-producing compounds include: Polyethylene-Phthalate polymer film (MYLAR-A®; DuPont, USA) Polyvinyl alcohol polyethylene glycol graft copolymer (Kollicoat-IR®; BASF, Germany) Polyvinyl Alcohol 4-88; purchased as powder from Merck—the first casted layer—is used as the surface coater for the second layer. Sodium Bicarbonate (Brunner Mond, UK) Citric Acid (Merck, Germany) Malic Acid (Sigma, USA) Tartaric Acid (Sigma, USA) Calcium Carbonate (Sigma, USA). Poly-Ethylene-Glycol (PEG-400; Sigma, USA) Hydroxy-Propyl-Cellulose polymer (Klucel-LF®; Ashland, USA) and Polyvinylpyrrolidone (Kollidon 25, BASF, USA)

(84) 7. Process for the Manufacture of a Gel-Gas Forming Film of a Device of the Invention Example 1

(85) The manufacture of gel-gas forming film is generally similar to the manufacture of the envelope-film or the Gel-film; slurries (in this case one solution and one suspension) preparation followed by two casting processes performed at RT:

(86) 1) Kollicoat Solution—Kollicoat-IR powder is dissolved in Ethanol:Water (1:1) solution

(87) 2) Kollicoat Casting—The Kollicoat solution is casted as a first-layer upon the support sheet and kept to dry

(88) 3) Sodium Bicarbonate (NaHCO3):Citric Acid (C6H8O7):PEG:Klucel (50:30:8:12; % ratio) Suspension. The C6H8O7 particles are then added to a Klucel solution (10% powder pre-dissolved in Ethanol), and after mixing, the NaHCO3 particles are added and mixed, forming a particles suspension. Finely PEG is added into the suspension under mixing.

(89) 4) Sodium Bicarbonate (NaHCO3):Citric Acid (C6H8O7):PEG:Klucel Casting—The suspension is casted as a second-layer upon the dry Kollicoat (first-layer) film and kept to dry

Example 2

(90) The manufacture of the gas forming film is generally similar to the manufacture of the envelope-film or the Gel-film; slurries (in this case one solution and one suspension) preparation followed by two casting processes performed at RT:

(91) 1) Kollicoat Solution—Kollicoat-IR powder is dissolved in Ethanol:Water (1:1) solution

(92) 2) Kollicoat Casting—The Kollicoat solution is casted as a first-layer upon the support sheet and kept to dry

(93) 3) Calcium Carbonate (CaCO3):Tartaric Acid (C4H6O6):PEG:Klucel (33.2:49.8:5:12; % ratio) Suspension.

(94) The C4H6O6 particles are then added to a Klucel solution (10% powder pre-dissolved in Ethanol), and after mixing, the CaCO3 particles are added and mixed, forming a particles suspension. Finely PEG is added into the suspension under mixing.

(95) 4) Calcium Carbonate (CaCO3):Tartaric Acid (C4H6O6):PEG:Klucel Casting—The suspension is casted as a second-layer upon the dry Kollicoat (first-layer) film and kept to dry

Example 3

(96) The manufacture of the gas forming film is generally similar to the manufacture of the envelope-film or the Gel-film; slurries (in this case one solution and one suspension) preparation followed by two casting processes performed at RT:

(97) 1) PVOH Solution—PVOH powder is dissolved in Ethanol:Water (1:1) solution

(98) 2) PVOH Casting—The PVOH solution is casted as a first-layer upon the support sheet and kept to dry

(99) 3) Potassium Bicarbonate (KHCO.sub.3):Tartaric Acid (C.sub.4H.sub.6O.sub.6):PEG:Klucel (47.4:35.6:5:12; % ratio) Suspension.

(100) The C4H6O6 particles are then added to a Klucel solution (10% powder pre-dissolved in Ethanol), and after mixing, the KHCO3 particles are added and mixed, forming a particles suspension. Finely PEG is added into the suspension under mixing.

(101) 4) Potassium Bicarbonate (KHCO3):Tartaric Acid (C4H6O6):PEG:Klucel Casting—The suspension is casted as a second-layer upon the dry PVOH (first-layer) film and kept to dry

(102) 8. Process for the Manufacture of a Device of the Invention

(103) 1) Forming an envelope film (for example as described above in Section 3, Examples 1-5);

(104) 2) Forming a gel film (for example as described above in Section 5, Examples 1-4) and/or gas-gel film (for example as described above in Section 7. Examples 1-3);

(105) 3) Creating a multi-layered formation of envelope and gel films (as an alternative, forming a multilayered biodegradable film comprising both features of said envelope layer and said expandable layer);

(106) 4) Cutting and connecting the multi layered formation to form a compartment and compartments structure;

(107) 5) Folding the compartment/s into a swallowable capsule.

(108) 9. Process for the Manufacture of a Device of the Invention

(109) 1) Forming an envelope film (for example as described above in Section 3, Examples 1-5);

(110) 2) Casting a gel film (for example as described above in Section 5, Examples 1-4) and/or gas-gel film (for example as described above in Section 7, Examples 1-3) on selected area;

(111) 3) Casting or attaching another envelope film (for example as described above in Section 3, Examples 1-5);

(112) 4) The above process creates a multi-layered formation of envelope and gel films (as an alternative, forming a multilayered biodegradable film comprising both features of said envelope layer and said expandable layer);

(113) 5) Cutting and connecting the multi layered formation to form a compartment and compartments structure;

(114) 6) Folding the compartment/s into a swallowable capsule.

(115) 10. Shape and Form of a Device of the Invention

(116) The present invention provides a device comprising at least one compartment having an external biodegradable film enclosing at least one gel forming compound or one gel/gas forming compound, wherein said at least one compartment is encased within a gastric degradable swallowable capsule.

(117) FIG. 2 and FIG. 3 present schematic illustrations of the expanded form of an orally administrable device of the invention (100 and 101 respectively) having one compartment (102 and 103 respectively) having an external biodegradable film (104 and 105 respectively), wherein said expansion of device occurs due to the contact of the expandable-film with gastric fluids forming a gel matrix within said compartment (106 and 107 respectively).

(118) In some embodiments a device of the invention comprises at least two, three, four, five, six, seven, eight, nine, ten, eleven, twelve, thirteen, fourteen, fifteen, sixteen, seventeen, eighteen, nineteen, twenty individual compartments (that may be the same or different, in either contents or external biodegradable film), having each an external biodegradable film enclosing at least one gel forming compound or one gel/gas forming compound in each compartment, wherein said compartments are encased within a gastric degradable swallowable capsule.

(119) In some embodiments, said device comprises four compartments: FIG. 4 presents a schematic view of orally administrable device according to the invention (200), which comprises four compartments forming an “open chain shape” at the expanded form; FIG. 5 presents a schematic view of orally administrable device according to the invention (201), which comprises four compartments forming a “closed chain shape” at the expanded form.

(120) In some embodiments, said device comprises five compartments; FIG. 6 presents a schematic view of an orally administrable device according to the invention (300), having five compartments (301) forming a “closed chain shape” (in the form of a pentagon) at its non-expanded form before folding into swallowable capsule, each having an external biodegradable film (302) and a composition capable of expanding said compartment upon absorption of liquids (303).

(121) In some embodiments, said device comprises three compartments: FIG. 7 presents a schematic view of an orally administrable device according to the invention (400), having three compartments (401) forming a “closed chain shape” (in the form of a triangle) at its non-expanded form before folding into swallowable capsule, each having an external biodegradable film (402) and a composition capable of expanding said compartment upon absorption of liquids (403).

(122) In some embodiments, said device comprises up to twenty connected compartments lightly encasing within a small volume.

(123) FIG. 8 presents a schematic view of a device of the invention (500) having several connected compartments at the non-expanded form rolled (501) having an external biodegradable film (502), said three compartments comprise a composition capable of expanding the compartment upon exposure to liquid (503). Said compartment is encased within a swallow-able capsule (504).

(124) FIG. 10 presents a schematic view of an orally administrable device according to the invention (600), having three connected compartments at the non-expanded form folded (601), having an external biodegradable film (602), said three compartments comprise a composition capable of expanding the compartment upon exposure to liquid (603) and encased within a swallowable capsule (604).

(125) In some embodiments, said at least one compartment will have any shape including but not limited to rectangular, ring (round), polygon, and so forth: FIG. 9 presents a schematic view of at least one compartment (700) of an orally administrable device according to the invention, which forms a “ring shape” at the expanded form, where the expandable-film is swelled after contact with gastric fluids. Said compartment having an external biodegradable film (702), and a composition expanding the compartment upon exposure to liquid (703).

(126) FIG. 11 presents a schematic view of at least one compartment (800) or an orally administrable device according to the invention, formed of two interconnected rings (801) having a mutual overlapping volume or being connected only at the outer external envelope, at the expanded form, where the compartment is expanded after contact with gastric fluids. Said compartment having an external biodegradable film (802), and a composition expanding the compartment upon exposure to liquid (803).

(127) FIG. 12 presents a schematic view of three compartments (900) of an orally administrable device according to the invention, which form a “triangle shape” at the expanded form where the compartment is swelled after contact with gastric fluids. Said compartment having an external biodegradable film (902), and a composition expanding the compartment upon exposure to liquid (903).

(128) FIG. 13 is a schematic view of four compartments (1000) of an orally administrable device according to the invention, which form a “square shape” at the non-expanded form (where the expandable-film is not swelled) before folding into swallowable capsule. Said compartments having an external biodegradable film (1002), and a composition expanding the compartment upon exposure to liquid (1003).

(129) FIG. 14 is a schematic view of one compartment (2000) of an orally administrable device according to the invention, which forms a “square shape” at the expanded form where the expandable-film is swelled after contact with gastric fluids. Said compartments having an external biodegradable film (2002), and a composition expanding the compartment upon exposure to liquid (2003).

(130) FIG. 15 is a schematic view of four compartments (3000) of an orally administrable device according to the invention, which form a “square shape” at the non-expanded form (where the expandable-film is not swelled) before folding into swallowable capsule. Said compartments having an external biodegradable film (3002), and a composition expanding the compartment upon exposure to liquid (3003).

(131) In some embodiments, said device composed of a multi-structure shape; FIG. 16 is a schematic view of three rings (4000) of an orally administrable device according to the invention, connected together to form a tri-dimensional shape at the expanded form where the expandable-film is swelled after contact with gastric fluids. Said compartments having an external biodegradable film (4001), and a composition expanding the compartment upon exposure to liquid (4003).

(132) FIG. 17 is a schematic view of one compartment or several connected compartments of an orally administrable device according to the invention (5000), forming a “submarine shape” at the expanded form where the expandable-film is swelled after contact with gastric fluids. Said compartments having an external biodegradable film (5001), and a composition expanding the compartment upon exposure to liquid (5002).

(133) FIG. 18 presents a schematic view of three compartments (6000) of an orally administrable device according to the invention, which form a “square shape” at the non-expanded form (where the compartment is not swelled) before folding into swallowable capsule, and a “sea mattress” structure at the expanded form where the hydrogel-film is swelled after contact with gastric fluids. Said compartments having an external biodegradable film (6001), and a composition expanding the compartment upon exposure to liquid (6002).

(134) FIG. 19 is a schematic view of three compartment is (7000) of an orally administrable device according to the invention, which form a “square shape” with an elliptic hollow inside at the expanded form where the expandable-film is swelled after contact with gastric fluids. Said compartments having an external biodegradable film (7001), and a composition expanding the compartment upon exposure to liquid (7002).

(135) FIG. 20 is a schematic view of one compartment (8000) of an orally administrable device according to the invention, which forms a connector element (8001) made of said external biodegradable film (8002) (in some embodiments said connector may be a absorbable medical suture) at the expanded form where the expandable-film is swelled after contact with gastric fluids. The gel matrix is formed within the compartment (8003), expanding said compartment.

(136) The construction of the compartment at the non-expanded form is illustrated in FIG. 21 where a cross-section view describes one compartment (9000) at the non-expanded form having an external biodegradable film (9001) enclosing a composition (9002) composed of at least one gel-film and/or at least one combination of gel-gas film. FIG. 22 where a cross-section view describes one compartment (10000) at the non-expanded form having an expandable multilayered biodegradable film (10001) comprising: at least one layer of external biodegradable film (10002), and an expandable layer formed of gel-film and/or combination of gel-gas film (10003).