METHOD FOR PRODUCING A CONTINUOUS MULTILAYER CYLINDRICAL SHEET OF A POLYANIONIC COMPOUND

Abstract

The invention relates to a continuous multilayer cylindrical sheath of a polyanionic compound comprising at least two coaxial layers, each based on a polyanionic compound chelated by at least one divalent cation, each layer being able to slide freely relative to the adjacent layer, the continuous central space of the sheath extending around the axis being free of polyanionic compound, as well as a method for manufacturing such a sheath.

Description

Title of the invention: METHOD FOR PRODUCING A CONTINUOUS MULTILAYER CYLINDRICAL SHELL OF A POLYANIONIC COMPOUND Technical field of the invention

[0001] The present invention relates to the field of polymers based on polyanionic compounds and processes for manufacturing such polymers. Prior art

[0002] Alginate-based containers, whether these containers are in the shape of, for example, spherical or cylindrical, have long been known and used in particular for the progressive diffusion of compounds encapsulated within these containers.

[0003] Numerous methods have been described in the literature. US patent 4,614,794 describes the preparation of a collagen / alginate solution which is precipitated in a solution containing a calcium ion, or in a collagen solution containing calcium to which alginate is added. The alginate-based compound formed is obtained in the form of spherical beads, or possibly in the form of short, dispersed fibers.

[0004] Document WO 94 / 00164 describes the preparation of a solution comprising an alginate and the active ingredient, this solution being extruded into a calcium chloride bath to obtain a fiber consisting of alginate and the active ingredient. The alginate and the active ingredient are intimately mixed.

[0005] US patent 2006 / 0093652 describes a process for forming an alginate sheath-encapsulated collagen fiber in which a collagen solution comprising a salt of an alkaline earth metal is injected into an alginate bath so as to form a fiber having a collagen core / alginate sheath structure.

[0006] The alginate sheaths formed may prove to be fragile or have defects that simply increasing the sheath thickness, for example by varying the residence time in the bath, does not resolve.

[0007] Continuing its research, the applicant discovered a process for producing a continuous cylindrical sheath of a multilayer polyanionic compound. Detailed description of the invention

[0008] The invention relates to a continuous multilayer cylindrical sheath of a polyanionic compound comprising at least two coaxial layers, each based on a polyanionic compound chelated by at least one divalent cation, each layer being able to slide freely relative to the adjacent layer, the continuous central space of the sheath extending around the axis being free of polyanionic compound.

[0009] The invention also relates to a cylindrical sheath in which the polyanionic compound is chosen from poly(acrylic acid) and polysaccharides, preferably is chosen from polysaccharides, preferably is chosen from pectins and alginates, and most preferably is an alginate.

[0010] The invention also relates to a cylindrical sheath in which the polyanionic compound at the base of each layer has a number molar mass of at least 100,000 g / mol and a weight molar mass of at least 300,000 g / mol, the molar masses being determined by size exclusion chromatography in the manner described in the Measurement Methods section of the description.

[0011] The invention also relates to a cylindrical sheath in which the at least divalent cation is chosen from the cations of calcium, copper, magnesium, iron, zinc, lead, cobalt, nickel, barium, strontium, aluminum and manganese, preferably chosen from the cations of calcium, copper, magnesium, iron, zinc, and aluminum, preferably chosen from the cations of calcium, copper and aluminum and most preferably is a calcium cation.

[0012] The invention also relates to a cylindrical sheath in which the continuous central space of the multilayer sheath also comprises a compound selected from a dye, a biologically active compound such as a drug or any biologically active compound whose controlled diffusion is desired, a polymer, a biopolymer, proteins or nutrients.

[0013] The invention also relates to a cylindrical sheath in which at least one layer of the multilayer sheath also comprises a compound selected from a dye, a biologically active compound such as a drug or any biologically active compound whose controlled diffusion is desired, a polymer, a biopolymer, proteins or nutrients.

[0014] The invention also relates to a method for manufacturing a continuous multilayer cylindrical sheath in which:

[0015] a. A matrix is ​​continuously injected, by means of a die, into a chelation bath comprising a polyanionic compound in solution, the matrix comprising a solution of a salt of at least one divalent cation and being free of the polyanionic compound, so as to form a filament element;

[0016] b. The following sequence of steps is performed at least once:

[0017] i. The wire element is passed through a bath comprising a solution of a salt of a cation at least divalent and being free of polyanionic compound;

[0018] ii. The wire element from step i) is passed through a chelation bath comprising a polyanionic compound in solution, identical or different from the compound polyanionic of the chelation bath of step a), so as to form an additional layer around the wire element;

[0019] c. The continuous multilayer cylindrical sheath is recovered at the end of step b).

[0020] The invention also relates to a process in which the matrix comprises a solution comprising a biocompatible solvent, preferably chosen from water, ethanol, isopropanol, dimethyl sulfoxide and mixtures thereof.

[0021] The invention also relates to a method in which the matrix also comprises a compound selected from a dye, a biologically active compound, a polymer, a biopolymer, proteins or nutrients.

[0022] The invention also relates to a process in which the matrix is ​​a solution consisting of a biocompatible solvent, preferably chosen from water, ethanol, isopropanol, dimethyl sulfoxide and mixtures thereof, and a salt of at least one divalent cation.

[0023] The invention also relates to a process in which the mass content of salt of at least one divalent cation in the matrix ranges from 2% to 80% relative to the mass of the matrix, preferably from 5% to 40%, and preferably from 5% to 30%.

[0024] The invention also relates to a process in which the salt of at least one divalent cation is selected from the salts of calcium, copper, magnesium, iron, zinc, lead, cobalt, nickel, barium, strontium, aluminum, manganese, preferably selected from the salts of calcium, copper, magnesium, iron, zinc, and aluminum, preferably selected from the salts of calcium, copper and aluminum and most preferably is a calcium salt.

[0025] The invention also relates to a process in which the die comprises one or more injection devices, the injection device or each injection device being a co-injection device allowing simultaneous injection at the periphery of the matrix and at the center of a fluid, said fluid being free of salt of at least one divalent cation.

[0026] The invention also relates to a process in which the polyanionic compound is chosen from poly(acrylic acid) and polysaccharides, preferably is chosen from polysaccharides, preferably is chosen from pectins and alginates, and most preferably is an alginate.

[0027] The invention also relates to a method in which the chelation bath of step a) also comprises a compound selected from a dye, a biologically active compound, a polymer, a biopolymer, proteins or nutrients.

[0028] The invention also relates to a method in which the, or at least one chelation bath of step ii) also comprises a compound selected from a dye, a biologically active compound, a polymer, a biopolymer, proteins or nutrients.

[0029] The invention also relates to a method in which the mass content of polyanionic compound in the chelation bath ranges from 0.5% to 8% relative to the mass of the chelation bath, preferably from 1% to 6% by weight and preferably from 1.1% to 3% by weight.

[0030] The invention also relates to a process in which the mass content of salt of at least one divalent cation in the bath of the at least one step i) goes from 2% to 80% relative to the mass of the bath, preferably goes from 5% to 40%, and preferably goes from 5% to 30% and the mass content of polyanionic compound in the chelation bath of the at least one step ii) goes from 0.5 to 8% relative to the mass of the chelation bath, preferably from 1% to 6% by weight and preferably from 1.1% to 3% by weight.

[0031] The invention also relates to a method in which, at the end of step c), a stabilization step is carried out by passing the continuous multilayer cylindrical sheath through a stabilization bath comprising an aqueous solution of a salt of at least one divalent cation, the mass content of which is at least one divalent cation, from 2% to 80% relative to the mass of aqueous solution, preferably from 5% to 40%, and preferably from 5% to 30%.

[0032] The invention also relates to a method in which the continuous multilayer cylindrical sheath undergoes a heat treatment step.

[0033] The invention also relates to a method in which each chelation bath is, independently of each other, at a temperature ranging from 10°C to 40°C, preferably ranging from 15°C to 30°C.

[0034] The invention also relates to a method in which each bath of at least one step i) is at a temperature ranging from 10°C to 40°C, preferably ranging from 15°C to 30°C.

[0035] The invention also relates to a continuous single-layer cylindrical sheath based on a polyanionic compound chelated by at least one divalent cation, obtained by a process comprising at least the following steps:

[0036] a. A matrix is ​​continuously injected, by means of a die, into a chelation bath comprising a polyanionic compound in solution, the matrix comprising a solution of a salt of at least one divalent cation and being free of the polyanionic compound, so as to form a filament element;

[0037] b. The following sequence of steps is performed at least once:

[0038] i. The wire element is passed through a bath comprising a solution of a salt of a cation at least divalent and being free of polyanionic compound;

[0039] ii. The wire element from step i) is passed through a chelation bath comprising a polyanionic compound in solution, identical or different from the compound polyanionic of the chelation bath of step a), so as to form an additional layer around the wire element;

[0040] c. A continuous multilayer cylindrical sheath is recovered at the end of step b);

[0041] d. All the radially innermost layers of the cylindrical sheath are removed multilayered to retain only the radially outermost layer. Definitions

[0042] By continuous cylindrical sheath, we mean a wire element of overall cylindrical shape, extending along a main direction coinciding with the axis of the cylinder, the central space of which is free, that is to say, able to contain a material different from the material of the sheath such as a gas or a liquid.

[0043] By multilayer, it is understood that the sheath according to the invention is made up of at least two superimposed coaxial layers, each based on a material identical to or different from the adjacent layer and independent of the adjacent layer, that is to say, not being bonded to the adjacent layer. The adjacent layers of the sheath according to the invention can therefore slide freely relative to each other. Each layer is cylindrical in shape and extends along the principal direction of the sheath, the continuous central space of said layer being free so as to accommodate either an adjacent inner layer or the continuous central space of the multilayer cylindrical sheath.

[0044] The continuous multilayer cylindrical sheath according to the invention is continuous, that is to say, it extends along its main dimension as much as desired, until an external intervention interrupts it, for example by cutting. Layers of the sheath according to the invention

[0045] The continuous multilayer cylindrical sheath according to the invention comprises at least two coaxial layers, each based on a polyanionic compound chelated by at least one divalent cation, each layer being able to slide freely relative to the adjacent layer.

[0046] The expression "layer based on a polyanionic compound" should of course be understood to mean a layer comprising the polyanionic compound and / or the product of the reaction of the polyanionic compound and at least one divalent cation by ionotropic gelation. Thus, the basic constituents are the reactants intended to react together during the formation of the layer by gelation.

[0047] The polyanionic compound at the base of each layer of the continuous multilayer cylindrical sheath according to the invention is capable of forming a chelate with at least one divalent cation by ionotropic gelation. Ionotropic gelation is a phenomenon well known to those skilled in the art. Said polyanionic compound is an anionic polymer, that is to say, a polyelectrolyte bearing negative charges. The polyanionic compound is selected from poly(acrylic acid) and The polysaccharides are preferably chosen from among other polysaccharides, preferably from among pectins and alginates, and most preferably from an alginate. Preferably, the polyanionic compound at the base of each layer has a number molar mass of at least 100,000 g / mol and a weight molar mass of at least 300,000 g / mol. Such compounds exhibit very good chelation kinetics and allow for the production of layers with good mechanical properties.

[0048] The at least divalent cation enabling the ionotropic gelation of the polyanionic compound is chosen from the cations of calcium, copper, magnesium, iron, zinc, lead, cobalt, nickel, barium, strontium, aluminum and manganese, preferably chosen from the cations of calcium, copper, magnesium, iron, zinc, and aluminum, preferably chosen from the cations of calcium, copper and aluminum and most preferably is a calcium cation.

[0049] Each layer can be based on a polyanionic compound chelated by at least one divalent cation, identical or different from those of the adjacent layer. By choosing the polyanionic compound and / or the cation, it is thus possible to adjust the properties of the continuous multilayer cylindrical sheath according to the invention, such as its degradation rate, permeability, or rigidity.

[0050] Each layer may also include, independently from one layer to another, a compound selected from among a dye, a biologically active compound such as a drug or any biologically active compound whose controlled release is desired, a polymer such as polyethylene glycol, poly(glycerol sebacate), cyclodextrin, a biopolymer such as lignin, collagen, a polysaccharide such as cellulose or starch, proteins, or nutrients. Thus, in a preferred arrangement, at least one layer of the continuous cylindrical sheath comprises such a compound.

[0051] Each layer of the continuous multilayer cylindrical sheath can slide freely relative to the adjacent layer. A defect in an internal layer, such as a hole for example, therefore does not affect the next layer, which can thus ensure the overall sealing of the sheath when it is filled in its central space with a product, while continuing to allow the product to permeate through the sheath if such a phenomenon is desired.

[0052] Since each layer can slide freely relative to the adjacent layer, the interlayer area can be filled with a solution comprising an active ingredient intended to diffuse through the outermost layer(s) or to be released once the outermost layer(s) have been degraded. In this way, several active ingredients with different diffusion kinetics can be implemented in a single sheath. and controlled by their position in the sheath, central or between two layers, and by the nature of the polyanionic compound and / or the cation at the base of each layer. Continuous central space of the multilayer sheath

[0053] The continuous central space of the multilayer cylindrical sheath is free of polyanionic compound. The sheath according to the invention thus has a continuous central space, extending along the main direction of the sheath, and of an overall cylindrical shape.

[0054] This continuous central space offers the advantage of not having "pockets", i.e. closed spaces, which could be generated by the presence of polyanionic compound in this space, this or these compounds being able to chelate and form a wall with the innermost sheath of the multilayer sheath.

[0055] The continuous central space of the multilayer sheath according to the invention can therefore be filled either during the manufacture of the sheath by acting on the composition of the matrix injected into the chelation bath, or subsequently, by any product sufficiently fluid to flow into the central space, for example by a gas or a liquid, possibly including an active ingredient such as a drug, a dye, or any other product for which controlled diffusion is desired.

[0056] The continuous central space of the multilayer sheath can therefore also include a compound selected from a dye, a biologically active compound such as a drug or any biologically active compound whose controlled diffusion is desired, a polymer such as polyethylene glycol, poly(glycerol sebacate), cyclodextrin, a biopolymer such as lignin, collagen, a polysaccharide such as cellulose or starch, proteins or nutrients.

[0057] The continuous cylindrical sheath according to the invention can be cut leaving the central space accessible, for example by means of a blade, or can be cut by sealing the cut end, for example by pinching the sheath, the central space closing at the pinched part by self-sealing via the ionotropic gelation of the polyanionic compounds. Manufacturing process

[0058] The invention also relates to a method for manufacturing a continuous multilayer cylindrical sheath as described above, wherein:

[0059] a. A matrix is ​​continuously injected, by means of a die, into a chelation bath comprising a polyanionic compound in solution, the matrix comprising a solution of a salt of at least one divalent cation and being free of the polyanionic compound, so as to form a filament element;

[0060] b. The following sequence of steps is performed at least once:

[0061] i. The wire element is passed through a bath comprising a solution of a salt of at least one divalent cation and being free of polyanionic compounds;

[0062] ii. The wire element from step i) is passed through a chelation bath comprising a polyanionic compound in solution, identical or different from the polyanionic compound of the chelation bath of step a), so as to form an additional layer around the wire element;

[0063] c. The continuous multilayer cylindrical sheath is recovered at the end of step b). Injection step a)

[0064] The process according to the invention includes a step a) in which a matrix is ​​continuously injected, by means of a die, into a chelation bath comprising a polyanionic compound in solution, the matrix comprising a solution of a salt of at least one divalent cation and being free of the polyanionic compound, so as to form a wire element.

[0065] Matrix

[0066] The matrix injected into a chelation bath is a fluid medium whose characteristics, in particular the viscosity and the size of the particles possibly present in said matrix, allow its injection into the bath by means of a die.

[0067] The matrix comprises a solution of a salt of at least one divalent cation and is free of polyanionic compounds. The absence of polyanionic compounds within the matrix ensures that no ionotropic gelation occurs prior to the injection of the matrix into the chelation bath.

[0068] The salt of at least one divalent cation is preferably chosen from the salts of calcium, copper, magnesium, iron, zinc, lead, cobalt, nickel, barium, strontium, aluminum, manganese, preferably chosen from the salts of calcium, copper, magnesium, iron, zinc, and aluminum, most preferably chosen from the salts of calcium, copper and aluminum and most preferably is a calcium salt.

[0069] The salt of at least one divalent cation will be selected according to the intended application, with regard in particular to its bio-activity or its impact on the properties of the sheath formed by chelation.

[0070] The mass content of a salt of at least one divalent cation in the matrix preferably ranges from 2% to 80% relative to the mass of the matrix, preferably from 5% to 40%, and preferably from 5% to 30%. These contents, and in particular when the preferred contents are used, allow the rapid formation of a homogeneous sheath within the chelation bath at the point of matrix injection and around the matrix when it is injected into the chelation bath.

[0071] The salt of at least one divalent cation is in solution in a solvent, preferably biocompatible, and preferably chosen from water, ethanol, isopropanol, dimethyl sulfoxide and mixtures thereof.

[0072] In a preferred arrangement, the matrix is ​​a solution consisting of a solvent, preferably biocompatible, and preferably chosen from water, ethanol, isopropanol, dimethyl sulfoxide, and mixtures thereof, and a salt of at least one divalent cation.

[0073] In another preferred arrangement, the matrix also comprises a compound other than a solution of a salt of at least one divalent cation. This compound may be any compound that can pass through the die without clogging it and that allows diffusion of the at least one divalent cation sufficiently rapid for the chelation reaction to occur. Preferably, this compound is selected from a dye, a biologically active compound such as a drug or any biologically active compound for which controlled diffusion is desired, a polymer such as polyethylene glycol, poly(glycerol sebacate), cyclodextrin, a biopolymer such as lignin, collagen, a polysaccharide such as cellulose or starch, proteins, or nutrients.

[0074] The die may include one or more injection devices, the individual diameter of which determines the internal diameter of the resulting sheath. Preferably, the diameter of the injection device ranges from 50 µm to 5000 µm, and more preferably from 100 µm to 1100 µm.

[0075] The injection device can be any device known to a person skilled in the art used for wet spinning, for example a hole or a needle.

[0076] The matrix is ​​injected into a chelation bath. By "into," it is meant that the injection point is completely immersed in the chelation bath, at a distance from any free surface greater than the thickness of the sheath formed. This position of the injection point allows the formation of a uniform sheath with a circular cross-section.

[0077] In a preferred arrangement, the injection device, or each injection device, is a co-injection device allowing the simultaneous injection of a salt-free fluid of at least one divalent cation at the periphery of the matrix and at its center. Such a co-injection device is known to those skilled in the art and may, for example, be a coaxial needle. Under the conditions of the process according to the invention, the sheath forms very rapidly around the matrix, and the matrix and the co-injected fluid do not mix. Thus, the continuous central space of the wire element formed by the co-injected fluid is completely free of salt of at least one divalent cation. This arrangement therefore minimizes the amount of salt of at least one divalent cation used and accelerates the chelation process with increased availability of at least one divalent cation.

[0078] Chelation bath

[0079] The chelating bath comprises a polyanionic compound in solution. The polyanionic compound is capable of forming a chelate with at least one divalent cation by ionotropic gelation. Said polyanionic compound is an anionic polymer, that is to say, a polyelectrolyte bearing negative charges. The polyanionic compound is selected from poly(acrylic acid) and polysaccharides, preferably from polysaccharides, preferably from pectins and alginates, and most preferably from alginates.

[0080] Preferably, the mass content of the polyanionic compound in the chelating bath ranges from 0.5% to 8% relative to the mass of the chelating bath, preferably from 1% to 6% by weight, and preferably from 1.1% to 3% by weight. The higher the concentration of the polyanionic compound, the greater the viscosity of the bath. When the viscosity becomes too high, defects may appear in the forming layer. Therefore, the viscosity of the chelating bath is preferably limited to a maximum of 1500 cP, and preferably to a maximum of 600 cP. Thus, the higher the molar mass of the polyanionic compound, the lower its concentration in the chelating bath can be.Mass contents of polyanionic compound ranging from 0.5% to 8% relative to the mass of chelation bath, preferably from 1% to 6% by weight and preferably from 1.1% to 3% by weight, allow the formation of a uniform layer and limit the risk of defect formation as well as at least partial breakage of the forming wire element.

[0081] The polyanionic compound is, in the chelation bath of step a), in solution in a solvent preferably chosen from water, ethanol, isopropanol, dimethyl sulfoxide and their mixture.

[0082] In another preferred arrangement, the chelation bath of step a) also includes a compound selected from a dye, a biologically active compound such as a drug or any biologically active compound whose controlled diffusion is desired, a polymer such as polyethylene glycol, poly(glycerol sebacate), cyclodextrin, a biopolymer such as lignin, collagen, a polysaccharide such as cellulose or starch, proteins or nutrients.

[0083] In a preferred arrangement, the chelation bath of step a) is a solution consisting of a solvent selected from water, ethanol, isopropanol, dimethyl sulfoxide and mixtures thereof and a polyanionic compound.

[0084] A filament element is continuously formed at the injection point, said filament element consisting of a central space comprising the matrix and a skin comprising the polyanionic compound chelated by the at least divalent cation. This filament element passes through the chelation bath and then feeds into step b) of the process according to the invention. The residence time of the filament element in the chelation bath is adapted depending on the chelation kinetics. It typically ranges from a few seconds to a few minutes, for example, from 10 seconds to 2 minutes. Preferably, the wire element is passed through the chelation bath without tension, for example, using pulleys. By "without tension," we mean that the wire element is not stretched, or is stretched as little as possible. This ensures that the integrity of the formed sheath is maintained. Step b) of layer formation

[0085] The process according to the invention comprises a step b) of layer formation in which the following sequence of steps is carried out at least once: i. The wire element is passed through a bath comprising a solution of a salt of at least one divalent cation and being free of polyanionic compounds; ii. The wire element from step i) is passed through a chelation bath comprising a polyanionic compound in solution, identical or different from the polyanionic compound of the chelation bath of step a), so as to form an additional layer around the wire element.

[0086] Each sequence of steps i) and ii) allows for the formation of an additional layer on the wire element. Thus, step b), consisting of carrying out the sequence of steps i) and ii), is performed as many times as the number of layers desired for the multilayer sheath.

[0087] Step i)

[0088] In step i), the wire element obtained either at the end of step a), or obtained at the end of a previous succession of steps i) and ii), is passed through a bath comprising a solution of a salt of at least one divalent cation and being free of polyanionic compound.

[0089] By free from polyanionic compounds, it is understood that the bath used in step i) does not contain any polyanionic compounds when it is formed. It may, during its use, contain traces of polyanionic compounds that may have been introduced by the filament element (so-called "polluting" polyanionic compounds).

[0090] The absence of polyanionic compounds in the bath prevents the sheath of the wire element from continuing to grow, while the external surface of said element is in contact with a fluid medium rich in at least a divalent cation. "Free of polyanionic compounds" means that no polyanionic compounds are introduced into the bath during its preparation. Polyanionic compounds may be present in this bath because they are introduced by the wire element as it passes through the bath. However, this contamination remains sufficiently low so as not to lead to the formation of priming agents that would prevent adjacent sheaths from sliding freely relative to each other.

[0091] The salt of at least one divalent cation is preferably chosen from the salts of calcium, copper, magnesium, iron, zinc, lead, cobalt, nickel, barium, strontium, aluminum, manganese, preferably chosen from the salts of calcium, copper, magnesium, iron, zinc, and aluminum, most preferably chosen from the salts of calcium, copper and aluminum and most preferably is a calcium salt.

[0092] The salt of at least one divalent cation used in the bath of step i) may be the same as or different from the salt of at least one divalent cation used in step a), and may be the same as or different from the salt of at least one divalent cation used in the bath of a previously carried out step i) if several successions of steps i) and ii) are carried out.

[0093] The salt of at least one divalent cation is, in the bath, in solution in a solvent, preferably a biocompatible solvent, and preferably chosen from water, ethanol, isopropanol, dimethyl sulfoxide and mixtures thereof.

[0094] In a preferred arrangement, the bath is a solution consisting of a solvent selected from water, ethanol, isopropanol, dimethyl sulfoxide and mixtures thereof and a salt of at least one divalent cation.

[0095] In another preferred arrangement, the bath also includes a compound selected from a dye, a biologically active compound such as a drug or any biologically active compound whose controlled release is desired, a polymer such as polyethylene glycol, poly(glycerol sebacate), cyclodextrin, a biopolymer such as lignin, collagen, a polysaccharide such as cellulose or starch, proteins, or nutrients. The presence of such a compound makes it possible to encapsulate an active compound between two layers of the multilayer sheath, ensuring its controlled release. Thus, by layering several layers and placing different compounds between these layers, controlled and delayed release of several compounds can be achieved.

[0096] This compound may be identical or different from the compound possibly used in step a), and may be identical or different from the compound possibly used in the bath of a previously performed step i) if several sequences of steps i) and ii) are implemented. It is thus possible to introduce between the layers of the multilayer cladding compounds of different natures, or of the same nature but with different characteristics (for example, molar mass, functionalization), which allows, particularly when the multilayer cladding is used to implement controlled diffusion of active compounds, for fine-tuning of the release rates of the compounds and / or their release sequence.

[0097] Step ii)

[0098] In step ii), the wire element obtained at the end of step i) is passed through a chelation bath comprising a polyanionic compound in solution, identical or different from the polyanionic compound of the chelation bath of step a), so as to form an additional layer around the wire element.

[0099] Upon contact with the cations deposited on the external surface of the wire element during step i), the polyanionic compound will gel and form a new layer. Surprisingly, this newly formed layer in the process according to the invention can slide freely relative to the adjacent pre-existing layer.

[0100] The chelation bath of step ii) comprises a polyanionic compound in solution. The polyanionic compound is capable of forming a chelate with at least one divalent cation by ionotropic gelation. Said polyanionic compound is an anionic polymer, i.e., a polyelectrolyte bearing negative charges. The polyanionic compound is selected from poly(acrylic acid) and polysaccharides, preferably from polysaccharides, preferably from pectins and alginates, and most preferably from alginates.

[0101] The polyanionic compound used in the bath of step ii) may be the same as or different from the polyanionic compound used in step a), and may be the same as or different from the polyanionic compound used in the bath of a previously carried-out step ii) if several successions of steps i) and ii) are carried out.

[0102] The polyanionic compound is, in the bath of step ii), in solution in a solvent preferably chosen from water, ethanol, isopropanol, dimethyl sulfoxide and their mixture.

[0103] In another preferred arrangement, the bath of step ii) also comprises a compound selected from a dye, a biologically active compound such as a drug or any biologically active compound whose controlled diffusion is desired, a polymer such as polyethylene glycol, poly(glycerol sebacate), cyclodextrin, a biopolymer such as lignin, collagen, a polysaccharide such as cellulose or starch, proteins or nutrients.

[0104] In a preferred arrangement, the bath of step ii) is a solution consisting of a solvent selected from water, ethanol, isopropanol, dimethyl sulfoxide and mixtures thereof and a polyanionic compound.

[0105] Preferably, the mass content of salt of at least one divalent cation in the bath of the at least one step i) is preferably from 2% to 80% relative to the mass of bath, preferably from 5% to 40%, and preferably from 5% to 30% and the mass content of polyanionic compound in the chelation bath of the at least one step ii) is from 0.5% to 8% relative to the mass of chelation bath, preferably from 1% to 6% by weight and preferably from 1.1% to 3% by weight.

[0106] Preferably, the wire element is subjected to at least one succession of steps i) and ii) without tension, for example by means of pulleys. By "without tension" it is understood that the wire element does not undergo any stretching, or undergoes as little stretching as possible.

[0107] In the case where the sequence of steps i) and ii) is carried out several times, each step i) and ii) can be carried out in an independent bath. In other words, as many successive baths are used as there are steps i) and ii) carried out successively.

[0108] In the case where the sequence of steps i) and ii) is performed several times, each step i) and ii) can be performed in the same bath. In other words, one bath is used for performing all of steps i), and another bath for performing all of steps ii). In this embodiment, the wire element is guided, at the end of step ii) and as long as there remains a sequence of steps i) and ii) to be performed, so as to pass again through the baths of steps i) and ii) previously performed.

[0109] The bath in step ii) can also be the same bath as that used for step a).

[0110] Step c) of collecting the continuous multilayer cylindrical sheath

[0111] At the end of the last step ii) of at least one succession of steps i) and ii), the continuous multilayer cylindrical sheath is recovered. This sheath can then be stored, for example by winding onto a reel or by coiling. When the sheath is stored, it is preferably stored in a humid atmosphere so as not to dry out the sheath and to maintain its flexibility.

[0112] Preferably, at the end of step c) a stabilization step is carried out by passing the continuous multilayer cylindrical sheath through a stabilization bath comprising an aqueous solution of a salt of at least one divalent cation, the mass content of which is at least one divalent cation, from 2% to 80% relative to the mass of aqueous solution, preferably from 5% to 40%, and preferably from 5% to 30%.

[0113] This finishing operation chelates the polyanionic compounds present on the external surface of the multilayer sheath that had not yet reacted. This limits the stickiness of the sheath while strengthening it.

[0114] Preferably, after the stabilization step, a washing step is carried out by passing the continuous multilayer cylindrical sheath through a washing bath comprising water in order to clean the salt of at least one divalent cation possibly present on the surface of the multilayer cylindrical sheath.

[0115] Preferably, each chelation bath is, independently of each other, at a temperature ranging from 10°C to 40°C, preferably ranging from 15°C to 30°C.

[0116] Preferably, each bath in at least one step i) is at a temperature ranging from 10°C to 40°C, preferably ranging from 15°C to 30°C.

[0117] The expression "at least one step i)" means "step i)" when the sequence of steps i) and ii) is carried out only once, or "each step i)" when the sequence of steps i) and ii) is carried out several times. The expression "at least one step ii)" has a similar meaning.

[0118] Preferably, all baths are operated at room temperature, thus allowing great simplicity of operation of the process. Large inner diameter sheath

[0119] The continuous, multilayer cylindrical sheath obtained by the process according to the invention comprises at least two layers, each layer being able to slide freely relative to the adjacent layer. It is therefore possible to remove the innermost radially positioned layers so as to obtain a sheath consisting of a single layer and having a larger internal diameter than the sheaths described so far in the prior art. Indeed, the formation of the inner layers creates a skeleton around which the outermost layer forms. By adjusting the number of inner layers, the internal diameter of the outer layer can thus be freely adjusted to a value much greater than that which would be possible by injecting a matrix into a chelating bath alone.

[0120] Thus, the invention also relates to a continuous single-layer cylindrical sheath based on a polyanionic compound chelated by at least one divalent cation, obtained by a process comprising at least the following steps:

[0121] a. A matrix is ​​continuously injected, by means of a die, into a chelation bath comprising a polyanionic compound in solution, the matrix comprising a solution of a salt of at least one divalent cation and being free of the polyanionic compound, so as to form a filament element;

[0122] b. The following sequence of steps is performed at least once:

[0123] i. The wire element is passed through a bath comprising a solution of a salt of a cation at least divalent and being free of polyanionic compound;

[0124] ii. The wire element from step i) is passed through a chelation bath comprising a polyanionic compound in solution, identical or different from the polyanionic compound of the chelation bath of step a), so as to form an additional layer around the wire element;

[0125] c. A continuous multilayer cylindrical sheath is recovered at the end of step b);

[0126] d. All the radially innermost layers of the cylindrical sheath are removed multilayered to retain only the outermost radial layer.

[0127] Steps a), b) and c) correspond to the steps described previously. Description of the figures

[0128] [Fig. 1] [Fig. 1] illustrates schematically an arrangement of the process according to the invention. A matrix is ​​continuously injected from a reservoir (1) via a die (2) into a chelation bath (A) so as to form a wire element (3). The wire element is conveyed from one bath to the other by means of pulleys (4).

[0129] The wire element then passes through a bath comprising a solution of a salt of at least one divalent cation and being free of polyanionic compounds (B), the free surface of which is located at a height lower than that of the chelation bath (A), and then through a chelation bath comprising a polyanionic compound in solution (C) so as to form an additional layer around the wire element. A continuous, multilayer cylindrical sheath (5) is obtained at the outlet of this bath.

[0130] The continuous multilayer cylindrical sheath (4) is recovered at the outlet of this bath.

[0131] [Fig.2] Fig.2 illustrates in a very schematic way a cross-section of the sheath A continuous cylindrical multilayer sheath consists of two layers. A central space (10) is surrounded by a first continuous cylindrical layer (11) and a second continuous cylindrical layer (13), the layers (11) and (13) being coaxial and free to slide relative to each other. The interlayer space (12), the central space (10), and the layers (11) and (13) may optionally, independently of each other, comprise a compound selected from a dye, a biologically active compound such as a drug or any biologically active compound whose controlled release is desired, a polymer such as polyethylene glycol, poly(glycerol sebacate), cyclodextrin, a biopolymer such as lignin, collagen, a polysaccharide such as cellulose or starch, proteins, or nutrients.

[0132] The interlayer space (12) may possibly not exist, that is to say that the two coaxial layers (11) and (13) are in contact with each other, while being free to slide relative to each other. Measurement methods

[0133] Analysis of the macrostructure of alginates: SEC RI / MALS

[0134] The SEC (Size Exclusion Chromatography) technique allows the separation of macromolecules in solution according to their size through columns filled with a porous gel. The macromolecules are separated according to their hydrodynamic volume, with the largest being eluted first.

[0135] While not an absolute method, dual-detector SEC allows for the determination of the molar mass distribution of a polymer. Starting from a product chosen as a model, the various number-average (Mn) and weight-average (Mw) molar masses can be determined, and the polydispersity index (Ip = Mw / Mn), also called "dispersity," can be calculated.

[0136] Size-exclusion chromatography analyses of alginates can be performed with two detectors: a refractometer (Optilab rEX) and a MALS (Dawn Heleos), each equipped with three PL aquagel-OH Mixed M columns. For these analyses, 1 mL of a 1 mg mL sample solution in ultrapure water supplemented with Ig / L NaCl is filtered through a 0.45 µm PTFE membrane. 100 µL of this solution is eluted in ultrapure water supplemented with Ig / L NaCl at a flow rate of 1 mL min⁻¹ at 40 °C. The Astra software can be used for data acquisition and analysis. The number molar masses (Mn) are calculated using a dn / dC determined by the 100% recovered method on a sample of Vivapure brand sodium alginate grade FD155.

[0137] The samples are dissolved at a concentration of approximately Ig / L in ultrapure water with added NaCl at a concentration of 1 g / L, then stirred for two hours before being injected.

[0138] The following analytical conditions may be used: Eluent: Ultrapure water + Ig / L NaCl; Injection volume: 100 pL; Temperature: 40°C; Detector: Wyatt Refractometer / MALS (“Optilab r EX”; “DAWN HELEOS”); Mobile phase flow rate: 1 mL / min; Columns: 3 PL aquagel-OH MIXED M

[0139] The light diffusion model used is that of Zimm. Examples Example 1

[0140] In this example, a continuous multilayer cylindrical sheath is manufactured consisting of a double hollow alginate sheath containing in its center an active principle in aqueous medium.

[0141] A matrix consisting, by weight, of 89% water, 1% amoxicillin and 10% CaC12 is injected into a first bath, called a chelation bath, consisting of an aqueous solution of alginate with an alginate concentration of 12 g / l, the bath being at a temperature of 24°C.

[0142] The injection is carried out continuously using a channel consisting of a needle with an internal diameter of 1.1 mm, at a flow rate of 0.6 ml / min and is performed below the surface of the chelation bath.

[0143] The formed wire element passes through the chelation bath. The residence time of the wire element in this bath is approximately ten seconds. The wire element is transported by means of pulleys, allowing its movement while minimizing the tension on the element. The wire element exits the chelation bath as close as possible to its free surface and then passes through a second bath containing a saturated aqueous solution of CaCl₂, the free surface of which is located at a height lower than the free surface of the chelation bath.

[0144] The formed wire element passes through the chelation bath again. The residence time in this bath is approximately 5 seconds. The wire element is transported by means of pulleys, allowing its movement while minimizing tension on the element. At the end of this step, a continuous cylindrical sheath consisting of two layers is obtained.

[0145] The continuous cylindrical sheath made up of two layers then passes through a stabilization bath, the free surface of which is located at a height lower than the free surface of the chelation bath, made up of an aqueous solution saturated with CaC12.

[0146] The continuous cylindrical sheath made up of two layers is wound around a reel and stored in humid conditions (90% humidity) to prevent it from drying out completely.

[0147] This example results in a continuous cylindrical sheath of uniform appearance consisting of two layers of alginate sliding freely relative to each other, the central space of which is filled with an aqueous solution of amoxicillin. Example 2

[0148] In this example, a continuous multilayer cylindrical sheath is manufactured consisting of a double hollow alginate sheath containing poly(ethylene glycol) denoted PEG in its center.

[0149] A matrix consisting, by weight, of 4% PEG having a molar mass by weight Mw=600000g / mol, 81% water and 15% CaC12 is injected into a chelation bath consisting of an aqueous alginate solution with an alginate concentration of 12 g / l, the bath being at a temperature of 24°C.

[0150] The injection is carried out continuously using a channel consisting of a needle with an internal diameter of 1.1 mm, at a flow rate of 0.6 ml / min and is performed below the surface of the chelation bath.

[0151] The formed wire element passes through the chelation bath. The residence time of the wire element in this bath is approximately ten seconds. The wire element is transported by means of pulleys, allowing its movement while minimizing tension on the element. The wire element exits the chelation bath as close as possible to its free surface and then passes through a second bath containing a saturated aqueous solution. CaC12, whose free surface is located at a height lower than the free surface of the chelation bath.

[0152] The formed wire element passes through the chelation bath again. The residence time in this bath is approximately 5 seconds. The wire element is transported by means of pulleys, allowing its movement while minimizing tension on the element. At the end of this step, a continuous cylindrical sheath consisting of two layers is obtained.

[0153] The continuous cylindrical sheath made up of two layers then passes through a stabilization bath, the free surface of which is located at a height lower than the free surface of the chelation bath, made up of an aqueous solution saturated with CaC12.

[0154] The continuous cylindrical sheath made up of two layers is wound around a reel and stored in humid conditions (90% humidity) to prevent it from drying out completely.

[0155] This example yields a continuous cylindrical sheath of uniform appearance, consisting of two layers of alginate sliding freely relative to each other, the central space of which is filled with an aqueous solution of poly(ethylene glycol). Example 3

[0156] In this example, a continuous multilayer cylindrical sheath is manufactured consisting of a double hollow alginate sheath containing poly(ethylene glycol) denoted PEG in its center.

[0157] A matrix consisting, by weight, of 52% PEG having a molar mass by weight Mw=35000g / mol, 41% water and 7% CaC12 is injected into a chelation bath consisting of an aqueous alginate solution with an alginate concentration of 12 g / l, the bath being at a temperature of 24°C.

[0158] The injection is carried out continuously using a channel consisting of a needle with an internal diameter of 1.1 mm, at a flow rate of 1.4 ml / min and is performed below the surface of the chelation bath.

[0159] The formed wire element passes through the chelation bath. The residence time of the wire element in this bath is approximately ten seconds. The wire element is transported by means of pulleys, allowing its movement while minimizing the tension on the element. The wire element exits the chelation bath as close as possible to its free surface and then passes through a second bath containing a saturated aqueous solution of CaCl₂, the free surface of which is located at a height lower than the free surface of the chelation bath.

[0160] The formed wire element passes through the chelation bath again. The residence time in this bath is approximately 5 seconds. The wire element is transported by means of pulleys, allowing its movement while minimizing tension on the element. at the end of this step recovers a continuous cylindrical sheath made up of two layers.

[0161] The continuous cylindrical sheath made up of two layers then passes through a stabilization bath, the free surface of which is located at a height lower than the free surface of the chelation bath, made up of an aqueous solution saturated with CaC12.

[0162] The continuous cylindrical sheath made up of two layers is wound around a reel and then undergoes a drying step at 24°C for 48 hours.

[0163] This example results in a continuous cylindrical sheath of uniform appearance made up of two layers of dried alginate, the central space of which is filled with dry poly(ethylene glycol). Example 4

[0164] In this example, a continuous multilayer cylindrical sheath is manufactured consisting of a double hollow alginate sheath containing poly(ethylene glycol) denoted PEG in its center, one of the sheaths comprising an active principle.

[0165] A matrix consisting, by weight, of 4% PEG having a molar mass by weight Mw=600000g / mol, 81% water and 15% CaCl2 is injected into a first chelation bath consisting of an aqueous alginate solution with an alginate concentration of 12 g / l, the bath being at a temperature of 24°C.

[0166] The injection is carried out continuously using a channel consisting of a needle with an internal diameter of 1.1 mm, at a flow rate of 0.6 ml / min and is performed below the surface of the first chelation bath.

[0167] The formed wire element passes through the first chelation bath. The residence time of the wire element in this bath is approximately ten seconds. The wire element is transported by means of pulleys, allowing its movement while minimizing tension on the element. The wire element exits the first chelation bath as close as possible to its free surface and then passes through a second bath containing a saturated aqueous solution of CaCl₂, the free surface of which is located at a height lower than the free surface of the chelation bath.

[0168] The formed filament passes through a second chelation bath consisting of an aqueous alginate solution loaded with amoxicillin. The alginate concentration is 12 g / L and the amoxicillin concentration is 0.5 g / L. The residence time in this bath is approximately 5 seconds. The filament is transported by means of pulleys, allowing its movement while minimizing tension on the filament. At the end of this step, a continuous cylindrical sheath consisting of two layers is obtained.

[0169] The continuous cylindrical sheath made up of two layers is wound around a reel and then undergoes a drying step at 50°C for 24 hours.

[0170] This example results in a continuous cylindrical sheath of uniform appearance consisting of two layers of dried alginate, the central space of which is filled with dry poly(ethylene glycol), the outer sheath containing amoxicillin. Example 5

[0171] In this example, a continuous multilayer cylindrical sheath is manufactured consisting of a double hollow alginate sheath containing water in its center, and between the two sheaths a layer of PEG.

[0172] A matrix consisting, by weight, of 90% water and 10% CaCl2 is injected into a first chelation bath consisting of an aqueous alginate solution with an alginate concentration of 12 g / l, the bath being at a temperature of 24°C.

[0173] The injection is carried out continuously using a channel consisting of a needle with an internal diameter of 1.1 mm, at a flow rate of 2.0 ml / min and is performed below the surface of the first chelation bath.

[0174] The formed wire element passes through the first chelation bath. The residence time of the wire element in this bath is approximately ten seconds. The wire element is transported by means of pulleys, allowing its movement while minimizing the tension on the element. The wire element exits the first chelation bath as close as possible to its free surface and then passes through a second bath consisting, by weight, of a solution of 4% PEG having a molar mass by weight Mw = 600,000 g / mol, 81% water, and 15% CaCl2, the free surface of which is located at a height lower than the free surface of the chelation bath.

[0175] The formed wire element passes through a second chelation bath consisting of an aqueous alginate solution. The alginate concentration is 12 g / L. The residence time in this bath is approximately 5 seconds. The wire element is transported by means of pulleys, allowing its movement while minimizing tension on the element. At the end of this step, a continuous cylindrical sheath consisting of two layers is obtained.

[0176] The continuous cylindrical sheath made up of two layers then passes through a stabilization bath, the free surface of which is located at a height lower than the free surface of the chelation bath, made up of an aqueous solution saturated with CaC12.

[0177] The continuous cylindrical sheath made up of two layers is wound around a reel and stored in humid conditions (90% humidity) to prevent it from drying out completely.

[0178] This example results in a continuous cylindrical sheath of uniform appearance consisting of two layers of alginate, the central space of which is filled with water, comprising between the two sheaths a thin layer of PEG. Example 6

[0179] In this example, a continuous multilayer cylindrical sheath is manufactured consisting of a double alginate sheath containing in its center a PGS core covered with PEG using a die consisting of two coaxial needles.

[0180] The matrix consists, by weight, of 40% PEG with a molar mass by weight Mw = 35,000 g / mol, 40% water, and 20% CaCl₂. A fluid consisting of 100% PGS with a molar mass by weight Mw = 260,000 g / mol is also used. The matrix and the fluid are injected simultaneously into a first chelation bath consisting of an aqueous alginate solution with an alginate concentration of 12 g / L, the bath being at a temperature of 24°C. The matrix and the fluid are heated to 60°C.

[0181] The injection is performed continuously using a coaxial dynamometer consisting of two needles, an inner needle and an outer needle, the inner and outer needles being coaxial. The inner needle has an internal diameter of 600 µm. The outer needle has an internal diameter of 1.1 mm. The matrix passes through the outer needle, and the PGS fluid passes through the inner needle. The injections are made at a flow rate of 0.5 ml / min in the inner needle and 0.1 ml / min in the outer needle, and are performed below the surface of the first chelation bath.

[0182] The formed wire element passes through the first chelation bath. The residence time of the wire element in this bath is approximately ten seconds. The wire element is transported by means of pulleys, allowing its movement while minimizing the tension on the element. The wire element exits the first chelation bath as close as possible to its free surface and then passes through a second bath containing a saturated aqueous solution of CaCl2, the free surface of which is located at a height lower than the free surface of the chelation bath.

[0183] The formed wire element passes through a second chelation bath consisting of an aqueous alginate solution. The alginate concentration is 12 g / L. The residence time in this bath is approximately 5 seconds. The wire element is transported by means of pulleys, allowing its movement while minimizing tension on the element. The wire element then passes through a stabilization bath, the free surface of which is located at a lower height than the free surface of the chelation bath, consisting of a saturated aqueous solution of CaCl₂.

[0184] The continuous cylindrical sheath consisting of two layers of alginate, a layer of PEG and a core of PGS is wound around a reel and stored in humid conditions (90% humidity) to prevent it from drying out completely.

[0185] This example results in a continuous cylindrical sheath of uniform appearance consisting of two layers of alginate, the central space of which is filled with a PGS core covered with a layer of PEG,

Claims

Demands

1. Continuous multilayer cylindrical sheath of a polyanionic compound comprising at least two coaxial layers, each based on a polyanionic compound chelated by at least one divalent cation, each layer able to slide freely relative to the adjacent layer, the continuous central space of the sheath extending around the axis being free of polyanionic compound.

2. Cylindrical sheath according to the preceding claim in which the polyanionic compound is selected from poly(acrylic acid) and polysaccharides, preferably is selected from polysaccharides, preferably is selected from pectins and alginates, and most preferably is an alginate.

3. Cylindrical sheath according to any one of the preceding claims wherein the continuous central space of the multilayer sheath also comprises a compound selected from a dye, a biologically active compound such as a drug or any biologically active compound whose controlled diffusion is desired, a polymer, a biopolymer, proteins or nutrients.

4. Cylindrical sheath according to any one of the preceding claims wherein at least one layer of the multilayer sheath also comprises a compound selected from a dye, a biologically active compound such as a drug or any biologically active compound whose controlled release is desired, a polymer, a biopolymer, proteins or nutrients.

5. A method for manufacturing a continuous multilayer cylindrical sheath in which: a. A matrix is ​​continuously injected, by means of a die, into a chelation bath comprising a polyanionic compound in solution, the matrix comprising a solution of a salt of at least one divalent cation and being free of the polyanionic compound, so as to form a wire element; b. The following sequence of steps is carried out at least once: i. The wire element is passed through a bath comprising a solution of a salt of at least one divalent cation and being free of polyanionic compound; ii. The wire element from step i) is passed through a chelation bath comprising a polyanionic compound in solution, identical or different from the polyanionic compound of the chelation bath of step a), so as to form an additional layer around the wire element; c. The continuous multilayer cylindrical sheath is recovered at the end of step b).

6. A method according to the preceding claim wherein the matrix also comprises a compound selected from a dye, a biologically active compound, a polymer, a biopolymer, proteins or nutrients.

7. A method according to any one of claims 5 to 6 wherein the matrix is ​​a solution consisting of a biocompatible solvent, preferably selected from water, ethanol, isopropanol, dimethyl sulfoxide and mixtures thereof, and a salt of at least one divalent cation.

8. A method according to any one of claims 5 to 7 wherein the salt of at least a divalent cation is selected from the salts of calcium, copper, magnesium, iron, zinc, lead, cobalt, nickel, barium, strontium, aluminum, manganese, preferably selected from the salts of calcium, copper, magnesium, iron, zinc, and aluminum, most preferably selected from the salts of calcium, copper and aluminum and most preferably is a calcium salt.

9. A method according to any one of claims 5 to 8 wherein the die comprises one or more injection devices, the injection device or each injection device being a co-injection device allowing simultaneous injection at the periphery of the matrix and at the center of a fluid, said fluid being free of salt of at least one divalent cation.

10. A method according to any one of claims 5 to 9 wherein the polyanionic compound is selected from the poly(acid acrylic) and polysaccharides, preferably is chosen from polysaccharides, preferably is chosen from pectins and alginates, and most preferably is an alginate.

11. A method according to any one of claims 5 to 10 wherein the mass content of polyanionic compound in the chelation bath is from 0.5% to 8% relative to the mass of the chelation bath, preferably from 1% to 6% by weight and preferably from 1.1% to 3% by weight.

12. A method according to any one of claims 5 to 11 wherein the mass content of salt of at least one divalent cation in the bath of the at least one step i) is from 2% to 80% relative to the mass of the bath, preferably from 5% to 40%, and preferably from 5% to 30% and the mass content of polyanionic compound in the chelation bath of the at least one step ii) is from 0.5% to 8% relative to the mass of the chelation bath, preferably from 1% to 6% by weight and preferably from 1.1% to 3% by weight.

13. A method according to any one of claims 5 to 12 wherein, at the end of step c), a stabilization step is carried out by passing the continuous multilayer cylindrical sheath through a stabilization bath comprising an aqueous solution of a salt of at least one divalent cation, the mass content of which is at least divalent and ranges from 2% to 80% relative to the mass of aqueous solution, preferably from 5% to 40%, and preferably from 5% to 30%.

14. A method according to any one of claims 5 to 13 wherein the continuous multilayer cylindrical sheath undergoes a heat treatment step.

15. Continuous single-layer cylindrical sheath based on a polyanionic compound chelated by at least one divalent cation, obtained by a process comprising at least the following steps: a. A matrix is ​​continuously injected, by means of a die, into a chelation bath comprising a polyanionic compound in solution, the matrix comprising a solution of a salt of at least one divalent cation and being free of the polyanionic compound, so as to form a wire element; b. The following sequence of steps is performed at least once: i. The wire element is passed through a bath comprising a solution of a salt of at least one divalent cation and being free of polyanionic compounds; ii. The wire element from step i) is passed through a chelation bath comprising a polyanionic compound in solution, identical or different from the polyanionic compound of the chelation bath of step a), so as to form an additional layer around the wire element; c. At the end of step b) we recover a continuous multilayer cylindrical sheath; d. All the innermost radial layers of the multilayer cylindrical sheath are removed, leaving only the outermost radial layer.

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