IMPLANTABLE INTESTINAL REACTOR

Abstract

The device, that can be implanted in the intestinal cavity, comprises a reactor comprising a semi-permeable or porous membrane or coating linked to a element for attachment to an intestinal or gastric wall. The reactor can be in the form of a ribbon, a structure having more than two faces or an open structure delimiting a lumen, comprising, or formed from, a semi-permeable or porous membrane. The reactor can also delimit, at least partially with the semi-permeable or porous membrane of same, a closed inner space. The reactor can comprise or carry enzymes or micro-organisms, in particular bacteria or yeast. The reactor is used for generating a chemical reaction with one or more molecules present in the intestine, or for producing one or more biologically active molecules. It can, in particular, be used for consuming sugars, disaccharides and simple sugars or producing essential amino acids or other molecules having a positive effect on the health.

Claims

1. A device implantable in the intestinal cavity, comprising a reactor and an element for fastening the reactor to an intestinal or gastric wall.

2. The device according to claim 1, wherein the reactor comprises a semi-permeable membrane or a semi-permeable coating or a semi-permeable material, in particular in the form of a ribbon, a tube or a structure comprising more than two faces.

3. The device according to claim 1, wherein the reactor is fastened to a cord that secures it to the fastening element.

4. The device according to claim 3, wherein the cord is surrounded by gyroplane cylindrical segments.

5. The device according to claim 3, wherein the cord is mounted on a swivel.

6. The device according to claim 1, wherein the fastening device is chosen from among a gastric clip, a pyloric stent and an intestinal stent.

7. The device according to claim 1, wherein the reactor includes a semi-permeable or porous membrane, and defines a closed inner space.

8. The device according to claim 1, wherein the reactor defines an inner space containing at least one active element or product, preferably enzyme, molecule, microorganism or eukaryotic cells.

9. The device according to claim 1, wherein the reactor comprises a particulate or granular biocompatible material or a mass of biocompatible material.

10. The device according to claim 1, wherein the reactor contains a disaccharidase, preferably maltase, lactase, beta-fructosidase, alpha-glucosidase, beta-glucosidase, beta-galactosidase, alone or combined with an enzyme capable of breaking down at least one monosaccharide, such as glucose, in particular chosen from among glucose oxidase and a combination of glucose dehydrogenase, aldose reductase and NADP or NAD; or contains bacteria capable of breaking down the glucose, in particular bacteria of the Lactobacillus type, in particular bacteria of the Lactobacillus acidophilus type; or contains enzymes capable of breaking down gluten, in particular glutenases, in particular enzymes ALV001, ALV002 and ALV003, a digestive enzyme inhibitor and/or an anorectic hormone, microorganisms producing one or more essential amino acids, microorganisms breaking down cellulose, microorganisms producing dimethyl-butanol, bacteria producing insulin, acetohexamide or acarbose.

11. The device according to claim 1, comprising genetically modified microorganisms, for example Pseudomonas aeruginosa or E. coli, or eukaryotic cells, capable of producing at least one molecule of therapeutic interest, in particular a polypeptide, for example L-dopa, GLP1, insulin or elefin.

12. The device according to claim 1, comprising a microorganism genetically modified to produce a molecule, the production of this molecule being inducible by a signaling molecule ingested by the host.

13. The device according to claim 1, for use to generate at least one chemical reaction with one or more molecules present in the intestine or to produce at least one biologically active molecule, in particular for the production of molecules of therapeutic interest or for the consumption of glucose present in the intestine, in particular in the duodenum and/or the jejunum, before it is absorbed, the reactor comprising: one or more enzymes of the disaccharidase type (preferably maltase, lactase, beta-fructosidase, alpha-glucosidase, beta-glucosidase, beta-galactosidase) and glucose oxidase and/or a combination of glucose dehydrogenase, aldose reductase and NAD or NADP; or microorganisms, in particular genetically modified microorganisms, or eukaryotic cells, capable of producing at least one molecule of therapeutic interest, in particular a polypeptide, for example L-dopa, GLP1, insulin or elefin.

14. The device according to claim 1, wherein the reactor includes at least two faces on the surface of at least one of which a biofilm of microorganisms is formed.

15. The device according to claim 1, wherein the reactor includes one or several parts centered on the cord, part having an essentially cylindrical shape or cross-section, but irregular in order to prevent a laminar flow in contact with the part.

16. The device according to claim 15, characterized in that the outer surface of the part has a helical shape or a twist segment shape.

17. The device according to claim 1, wherein the length of the device is comprised between about 5 cm and about 150 cm.

18. A method of treating a mammal, human or animal, in which a device according to claim 1 is implanted, comprising a reactor bearing an active element, and an element fastening the reactor to an intestinal or gastric wall, the method comprising fastening the fastening element to the intestinal or gastric wall, and positioning the reactor in the intestinal lumen, owing to which the active element produces its biological or chemical effect.

Description

[0084] The invention will now be described in more detail using embodiments taken as non-limiting examples and in reference to the drawing, in which:

[0085] FIG. 1 is a diagrammatic illustration of a segmented device.

[0086] FIG. 2 shows the device of FIG. 1 in cross-section at a segment.

[0087] FIG. 3 is a schematic illustration of one embodiment of a segmented device according to another embodiment.

[0088] FIG. 4 is a schematic illustration of a segment of the device of FIG. 3.

EXAMPLE 1

[0089] 200 mg of chitosan is dissolved in 20 mL of acetic acid diluted at 0.5 vol % in water. A cross-linking agent, genipin at 0.0045 wt % by volume (g/100 mL) and cafeic acid are added to the initial mixture in a proportion of 0.0032 wt % by volume (g/100 mL) and the viscous chitosan solution after two hours of agitation. The genipin is solubilized beforehand in a solution of 12% dimethyl sulfoxide (DMSO) and 88% water (H.sub.2O). The cafeic acid is solubilized beforehand at 4% in ethanol.

[0090] After 30 minutes of agitation, 3 g of this mixture is removed, which is spread on a smooth, non-adhesive substrate (diameter 28 cm), for example an antistatic polystyrene cup, and dried for 2 to 4 days at ambient temperature (a temperature comprised between 20 and 30 C. is appropriate). In another test, it is dried for three days at 25 C.

[0091] Flexible nanoporous membranes are thus obtained. Experiments done by the applicant have shown that this flexibility was related to the fact that the drying is done for a longer duration at ambient temperature. This feature is not obtained, for example, if drying temperatures above 40 C. are used. For a film thickness of about 7 to 15 m, for example 10 m, a porous membrane was obtained with mean pore diameters of about 1 to 10 nanometers. Preference will be given to conditions where this mean diameter is about 5 to 8 nm to allow the glucose to pass and to filter the largest compounds.

EXAMPLE 2

[0092] In a cylindrical tube (about 1 cm diameter and about 20 cm long) of cellulose acetate with a cutoff threshold at 5000 g.Math.mole.sup.1 closed at one end, bacteria genetically modified to produce insulin is introduced up to a height of 4 cm in the tube. The other end of the tube is closed.

[0093] Then, the tube comprising the bacteria is flattened, and this flattened tube (thickness of about 1 to 2 mm) is placed on a first Dacron ribbon (about 20 cm long and about 1.5 cm wide), then a second Dacron ribbon is placed (about 20 cm long and about 1.5 cm wide) to form a device according to the invention in the form of a sandwich, having sewn the edges of the two ribbons together.

[0094] The assembly is fastened to a gastric clip using a Dacron ribbon (about 15 cm long and about 1 cm wide). The clip is positioned endoscopically in the wall of the gastric antrum. Through the operating channel of the endoscope and with the clip, the ribbon is unwound and passed through the pylorus. The reactor containing the microorganisms is then positioned in the duodenum, after the ampulla of Vater, where the pancreatic and biliary ducts arrive.

EXAMPLE 3

[0095] A woven Dacron ribbon is used to form a 50 cm1 cm ribbon. At one of its ends, this ribbon is sutured to a gastric clip. The device is incubated for 48 hours in a culture medium of bacteria of the Lactobacillus acidophilus type. The clip is positioned endoscopically in the wall of the gastric antrum. Through the operating channel of the endoscope and with the clip, the ribbon is unwound and passed through the pylorus.

EXAMPLE 4

[0096] A Dacron ribbon measuring 50 cm1 cm is bent on a gastric clip. Added to the 200 mg of chitosan of example 1 is a mixture of 60 mg of glucose oxidase (100 International Units/mg), 60 mg of catalase (1000 International Units/mg) and 60 mg of beta-galactosidase (100 International Units/mg). After 30 min. of agitation, 3 g of the mixture is spread on one of the faces of the ribbon, over a length of 35 cm from the free end of the 50 cm1 cm woven Dacron ribbon. It is dried for 3 days at 25 C. The clip is positioned endoscopically in the wall of the gastric antrum. Through the operating channel of the endoscope and with the clip, the ribbon is unwound and passed through the pylorus. The reactor containing the microorganisms is then positioned in the duodenum, after the ampulla of Vater, where the pancreatic and biliary ducts arrive.

EXAMPLE 5

[0097] The device of FIG. 1 is made up of a stomach staple 1 fastened to one end of an anchoring rope or cord 2, which is fastened at its other end to one end of a swivel 3. The anchoring rope is a single-strand Teflon thread with a length of about 200 mm and a diameter of 1.0 mm. A second cord or rope 4 of single-strand Teflon has a length of about 300 mm and a diameter of 1.0 mm. It is fastened to the other end of the swivel 3, such that the ropes 2 and 4 and the swivel can rotate relative to one another. Mounted on the rope 4, over its entire length, are ten segments 5, called gyroplane segments because they can rotate around the rope 4. The structure will be better understood in reference to FIG. 2, which shows, in cross-section, a segment 5 and the rope 4 that it surrounds. Each segment is made up of a Teflon tube 6 with an outer diameter of 3 mm, an inner diameter of 1.6 mm and a length of 30 mm. Fastened on each tube 6 is a thick layer of expanded PVA 7, the outer diameter of the segment thus obtained being 6 mm. The expanded PVA can be the substrate for an active element, for example for development of a biofilm. The set of segments can thus be treated by the active element, or only some of them, depending on the area of the intestine in which one wishes to act. The mounting by freely rotating segments makes it possible to prevent the rope 4 from twisting under the influence of the forces that will be exerted on the device inside the intestine. The length of the rope 4 will depend on the furthest area that must be reached in the intestine. A length of 150 mm can be used for the duodenal area. An additional length of 150 to 350 mm can be used for the jejunal area. The stomach staple 1 in turn is able to be fastened to the inner wall of the stomach, and its anchoring point as well as the length of the anchoring rope 2 allow the latter to extend into the vicinity of the pylorus.

[0098] In another embodiment, the device differs from that described above by the absence of the swivel 3, by a single tubular anchoring film (2+4) with an outer diameter of 2 mm, an inner diameter of 1 mm and a length of 500 mm, ten segments 5 with a length of 30 mm, and an inner diameter of 2.2 mm. In this embodiment, the tubular anchoring film allows the use of a coaxial rigid guidewire to place the device in the digestive tube. To that end, the rigid guidewire is placed beforehand from the oral opening, then the device is wound on this guidewire and pushed to the furthest distance that must be reached in the intestine.

EXAMPLE 6

[0099] This embodiment, shown in FIGS. 3 and 4, is fairly close to that of FIG. 1 regarding its general structure, with, in order, a stomach staple 10, a single-strand anchoring rope 11, a swivel 12, segments 13 mounted rotating on a single-strand nylon rope 15. Numerical reference 14 designates a spiral structure that is fastened on one of the segments 13. Like in example 5, the spiral structure, for example made from expanded PVA, can be the substrate for an active element, for example for development of a biofilm. One or several segments can be equipped with such a substrate, and the length of the rope 15 and the length and number of segments can easily be adjusted, to place the substrate(s) in the desired location in the intestine.