Single-use biodegradable tubular cross-linking reactor

Abstract

The invention relates to a biodegradable continuous tubular reactor, the wall of which comprises at least one cylindrical layer based on a polyanionic compound chelated by an at least divalent cation, and the central space of which comprises a cross-linkable fluid free of polyanionic compound.

Description

[0001] I

[0002] Single-use biodegradable tubular crosslinking reactor

[0003] Technical field of the invention

[0004] The present invention relates to the field of crosslinking reactors and processes implementing such reactors.

[0005] Previous art

[0006] Wire elements are used in a wide variety of applications, from clothing and medical devices to the creation of composite objects. Depending on the requirements, numerous materials can be used, such as glass fibers, cellulose fibers, or synthetic polymers like polyesters.

[0007] Numerous yarn manufacturing processes exist, depending on the physicochemical properties of the material to be spun. For example, spinning can be used to form yarns from natural fibers such as wool or cotton, while melting and extrusion through dies can be used to manufacture yarns from synthetic polymers such as polyethylene terephthalate or aramids.

[0008] However, some materials remain difficult to assemble into wire, because the kinetics of crosslinking, or assembly, are slow and / or because their physico-chemical properties make shaping them into wire difficult.

[0009] One object of the present invention is therefore to provide a tubular reactor for shaping and maintaining a reaction medium comprising a crosslinkable fluid in a filamentous form. This tubular reactor can be kept in place until the crosslinking of the crosslinkable fluid has occurred, and can then be removed without affecting the filament formed. Furthermore, this tubular reactor is made from biodegradable compounds.

[0010] Detailed description of the invention

[0011] The invention relates to a continuous biodegradable tubular reactor whose wall comprises at least one cylindrical layer based on a polyanionic compound chelated by at least one divalent cation and whose central space comprises a crosslinkable fluid free of polyanionic compound.

[0012] Definitions

[0013] By continuous tubular reactor, we mean a wire element whose wall is generally cylindrical in shape, extending along a main direction coinciding with the axis of the cylinder, whose central space is free, that is to say, able to contain a material different from the material of the reactor wall such as a gas or a liquid.

[0014] The continuous tubular reactor 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.

[0015] Reactor layer according to the invention

[0016] The continuous tubular reactor according to the invention comprises at least one cylindrical layer based on a polyanionic compound chelated by at least one divalent cation.

[0017] The term "polyanionic compound-based layer" refers to a layer containing the polyanionic compound and / or the product of the reaction between the polyanionic compound and at least one divalent cation via ionotropic gelation. Thus, the basic constituents are the reactants intended to react together during the formation of the layer by gelation.

[0018] 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. This polyanionic compound is an anionic polymer, that is, 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 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.

[0019] The at least divalent cation enabling ionotropic gelation of the polyanionic compound is chosen from among the cations of calcium, copper, magnesium, iron, zinc, lead, cobalt, nickel, barium, strontium, aluminum, and manganese, preferably from among the cations of calcium, copper, magnesium, iron, zinc, and aluminum, most preferably from among the cations of calcium, copper, and aluminum, and most preferably is a calcium cation. In a preferred arrangement, the wall of the biodegradable continuous tubular reactor comprises at least two coaxial layers, each based on a polyanionic compound chelated by at least a divalent cation, each layer being able to slide freely relative to the adjacent layer.

[0020] 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 wall of the continuous tubular reactor according to the invention, such as its degradation rate, permeability, or rigidity.

[0021] In this arrangement, each layer of the wall of the biodegradable continuous tubular reactor can slide freely relative to the adjacent layer. A defect in an internal layer, such as a hole, therefore does not affect the next layer, which can thus ensure the overall seal of the continuous tubular reactor wall, maintaining the integrity of the central space until the fluid crosslinks.

[0022] Since each layer can slide freely relative to the adjacent layer, the interlayer area can be filled with a crosslinkable fluid. This allows the production of a multilayer composite fiber.

[0023] Central space of the multilayer sheath

[0024] The central space of the continuous tubular reactor comprises a crosslinkable fluid free of polyanionic compounds. The tubular reactor according to the invention thus has a continuous central space, extending along the main direction of the reactor, and of an overall cylindrical shape, allowing the crosslinkable fluid to be maintained in shape until it crosslinks.

[0025] This continuous central space offers the advantage of not presenting "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 wall of the continuous tubular reactor, which would generate discontinuities in the wire formed once the crosslinkable fluid has been crosslinked.

[0026] The crosslinkable fluid may also include a compound selected from a dye, a biologically active compound such as a drug or any biologically active compound for which controlled release is desired, a polymer such as polyethylene glycol, cyclodextrin, a biopolymer such as lignin, collagen, a polysaccharide such as cellulose or starch, proteins or nutrients.

[0027] The continuous tubular reactor according to the invention can be cut while 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.

[0028] The fluid is crosslinkable, that is to say, it is capable of forming, when subjected to appropriate conditions such as sufficient residence time, suitable thermal conditions, exposure to radiation or suitable physico-chemical conditions, one or more three-dimensional networks by chemical or physical means.

[0029] Manufacturing process

[0030] The invention also relates to a method for manufacturing a crosslinked wire in which ■ a) A crosslinkable fluid and a salt of at least one divalent cation are continuously injected by means of a die into a chelation bath comprising a polyanionic compound in solution, the crosslinkable fluid being free of the polyanionic compound, so as to form a continuous tubular reactor; b) The continuous tubular reactor is then subjected to a crosslinking step so as to crosslink the crosslinkable fluid; c) The wire element is then subjected to a treatment so as to remove the wall of the continuous tubular reactor.

[0031] Preferably, between steps a) and b), the following sequence of steps is carried out at least once: i. The continuous tubular reactor 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 continuous tubular reactor 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 continuous tubular reactor.

[0032] Step a) of injection

[0033] The process according to the invention includes a step a) in which a crosslinkable fluid and a salt of at least one divalent cation are continuously injected by means of a die into a chelation bath comprising a polyanionic compound in solution, the crosslinkable fluid being free of the polyanionic compound, so as to form a filament element.

[0034] Crosslinkable fluid

[0035] The crosslinkable fluid 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 fluid, allow its injection into the bath by means of a die.

[0036] The crosslinkable fluid can be injected at room temperature, or at a different temperature, for example, warmer or cooler, as long as this temperature is compatible with the ionotropic gelation reaction taking place in the chelation bath. For example, the crosslinkable fluid can be injected at a temperature higher than room temperature to lower its viscosity.

[0037] A "crosslinkable fluid" is defined as a fluid capable of crosslinking, that is, forming one or more three-dimensional networks through chemical or physical means. A crosslinkable fluid therefore comprises one or more families of molecules capable of crosslinking, as well as, where applicable, the necessary crosslinking agent(s).

[0038] Crosslinking can be any type of crosslinking known to a person skilled in the art, and in particular chemical crosslinking involving a radical, ionic, condensation, click chemistry, or addition reaction, or physical crosslinking involving assembly by ionic association, hydrogen bonding, or Van der Waals.

[0039] Preferably, the crosslinkable fluid can be crosslinked by a crosslinking chosen from among radical reactions, condensation reactions, ionic reactions, and hydrogen bond association reactions.

[0040] The crosslinkable fluid is free of polyanionic compounds. The absence of polyanionic compounds in the crosslinkable fluid ensures that no ionotropic gelation occurs prior to the injection of the crosslinkable fluid into the chelation bath.

[0041] Preferably, the crosslinkable fluid 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 such as polyethylene glycol, cyclodextrin, a biopolymer such as lignin, collagen, a polysaccharide such as cellulose or starch, proteins, or nutrients.

[0042] Salt of at least one divalent cation

[0043] The salt of at least one divalent cation is preferentially 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, preferably chosen from the salts of calcium, copper and aluminum, and most preferably is a calcium salt.

[0044] 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 wall of the tubular reactor formed by chelation.

[0045] Sector

[0046] 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.

[0047] 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.

[0048] The crosslinkable fluid and the salt of at least one divalent cation are injected into a chelating bath. "Into the bath" means that the injection point is completely immersed in the chelating 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.

[0049] In a preferred arrangement, the salt of at least one divalent cation is mixed with the crosslinkable fluid prior to their injection into the chelation bath.

[0050] In this arrangement, the mass content of at least one divalent cation in the crosslinkable fluid is preferably from 2% to 80% relative to the mass of the crosslinkable fluid, preferably from 5% to 40%, and preferably from 5% to 30%. These contents, and particularly when the preferred contents are used, allow for the rapid formation of a homogeneous sheath within the chelating bath at the point of injection of the crosslinkable fluid and around the fluid as it is injected into the chelating bath.

[0051] In another preferred arrangement, the injection device, or each injection device, is a co-injection device allowing the simultaneous injection, at the periphery of a matrix comprising the salt of at least one divalent cation, and at the center of the crosslinkable fluid, said crosslinkable fluid being free of the salt of at least one divalent cation. Such a co-injection device is known to those skilled in the art and may, for example, be a coaxial needle.

[0052] In this arrangement, the salt of at least one divalent cation is preferably in solution in a solvent, preferably biocompatible, and preferably chosen from water, ethanol, isopropanol, dimethyl sulfoxide and mixtures thereof.

[0053] In a preferred variant of this 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.

[0054] Under the conditions of the process according to the invention, the sheath forms very rapidly around the crosslinkable fluid, and the matrix and the co-injected crosslinkable fluid do not mix. Consequently, the central space formed by the co-injected crosslinkable 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, while simplifying the processing steps to eliminate the tubular reactor around the wire formed after crosslinking of this wire.

[0055] Chelation bath

[0056] 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. This polyanionic compound is an anionic polymer, that is, 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.

[0057] Preferably, the mass concentration of the polyanionic compound in the chelating bath ranges from 0.5% to 8% by 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 can 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 formation of defects as well as at least partial rupture of the wire element in formation.

[0058] 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.

[0059] 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.

[0060] The continuous tubular reactor is formed continuously at the injection point, said reactor consisting of a central space comprising the crosslinkable fluid and a skin comprising the polyanionic compound chelated by the at least divalent cation. This continuous tubular reactor passes through the chelation bath and then feeds into step b) of the process according to the invention. The residence time of the continuous tubular reactor in the chelation bath is adjusted according to the chelation kinetics. It typically ranges from a few seconds to a few minutes, for example, from 10 s to 2 min. Preferably, the continuous tubular reactor is made to pass through the chelation bath without tension, for example, by means of pulleys. By "without tension," it is meant that the continuous tubular reactor is not stretched, or is stretched as little as possible. This ensures that the integrity of the wall of the formed continuous tubular reactor is maintained.

[0061] Preferably, between step a) and step b), the following sequence of steps is carried out at least once: ■ i. The continuous tubular reactor 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 continuous tubular reactor 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 continuous tubular reactor.

[0062] Each successive step (i) and (ii) forms an additional layer on the continuous tubular reactor. This sequence of steps ensures the integrity of the reactor wall, as an additional layer can compensate for an accidental defect in an internal layer of the wall. This sequence of steps can also be used to produce a multilayer filament by inserting a layer of crosslinkable fluid between two wall layers.

[0063] Step i)

[0064] In step i), the continuous tubular reactor 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.

[0065] By "free of polyanionic compounds," we mean that the bath used in step i) does not contain any polyanionic compounds when it is prepared. During its use, it may contain traces of polyanionic compounds that may have been introduced by the filament (so-called "polluting" polyanionic compounds).

[0066] The absence of polyanionic compounds in the bath prevents further growth of the continuous tubular reactor wall while exposing the reactor's external surface to a fluid medium rich in at least divalent cations. "Free of polyanionic compounds" means that no polyanionic compounds are introduced into the bath during its preparation. Polyanionic compounds may be present in the bath, introduced by the continuous tubular reactor as it passes through the bath. However, this contamination remains sufficiently low to prevent the formation of priming agents that would prevent adjacent layers from sliding freely against each other.

[0067] The salt of at least one divalent cation is preferentially 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, preferably chosen from the salts of calcium, copper and aluminum, and most preferably is a calcium salt.

[0068] 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.

[0069] 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.

[0070] In a preferred arrangement, the bath is a solution consisting of a solvent chosen from water, ethanol, isopropanol, dimethyl sulfoxide and mixtures thereof and a salt of at least one divalent cation.

[0071] In another preferred arrangement, the bath also includes a crosslinkable reaction system, i.e., one or more compounds that can crosslink together under only additional exposure to a suitable temperature or radiation.

[0072] In a variation of this preferred arrangement, the bath may also include at least one component chosen 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 or cyclodextrin, a biopolymer such as lignin, collagen, a polysaccharide such as cellulose or starch, proteins, or nutrients. The presence of a crosslinkable reaction system allows for the formation of an additional filament layer around the filament formed from the crosslinkable fluid in the central space. An active compound whose controlled release is desired can also be encapsulated within each of the filament layers. Thus, by layering several components and placing different compounds between them, controlled and delayed release of multiple compounds can be achieved.

[0073] 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 step i) carried out previously if several successions of steps i) and ii) are carried out.

[0074] Step ii)

[0075] In step ii), the continuous tubular reactor 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 in the chelation bath of step a), so as to form an additional layer around the continuous tubular reactor.

[0076] Upon contact with the cations deposited on the external surface of the continuous tubular reactor 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.

[0077] 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, that is, 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.

[0078] 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.

[0079] 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.

[0080] In a preferred arrangement, the bath in step ii) is a solution consisting of a solvent selected from water, ethanol, isopropanol, dimethyl sulfoxide and mixtures thereof and a polyanionic compound.

[0081] Preferably, the mass content of salt of at least one divalent cation in the bath of 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 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.

[0082] Preferably, the continuous tubular reactor is subjected to at least one succession of steps i) and ii) without tension, for example, by means of pulleys. "Without tension" means that the wire element is not stretched, or is stretched as little as possible. If steps i) and ii) are repeated multiple times, each step i) and ii) can be carried out in a separate bath. In other words, as many successive baths are used as there are steps i) and ii) performed successively.

[0083] In the case where steps i) and ii) are repeated multiple times, each step i) and ii) can be performed in the same bath. In other words, one bath is used for all steps i), and another bath for all steps ii). In this embodiment, the wire element is guided, at the end of step ii) and as long as steps i) and ii) remain to be performed, through the baths of previously performed steps i) and ii) again.

[0084] The bath in step ii) can also be the same bath as that used for step a).

[0085] The continuous tubular reactor is recovered at the end of step a), or at the end of the last step ii) of at least one sequence of steps i) and ii) when this sequence of steps is implemented. This reactor can then be stored, for example by winding onto a reel or by coiling. When the reactor is stored, it is preferably stored in a humid atmosphere so as not to dry out the reactor and to maintain its flexibility.

[0086] Preferably, at the end of step a), or at the end of the last step ii) of the at least one succession of steps i) and ii) when this succession of steps is implemented, a stabilization step is carried out by passing the continuous tubular reactor 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%.

[0087] This finishing operation chelates the polyanionic compounds present on the external surface of the continuous tubular reactor that had not yet reacted. This reduces the stickiness of the reactor wall surface while simultaneously strengthening it.

[0088] Preferably, after the stabilization step, a washing step is performed by passing the continuous tubular reactor through a washing bath containing water to clean the salt of at least one divalent cation that may be present on the surface of the continuous tubular reactor wall. J 3

[0089] Step b) of crosslinking

[0090] At the end of step a), and possibly one or more successions of steps i) and ii), the continuous tubular reactor undergoes a treatment step so as to crosslink the crosslinkable fluid.

[0091] This step involves exposing the continuous tubular reactor to conditions that allow the crosslinking of the crosslinkable fluid. This treatment, adjusted to the nature of the crosslinking to be implemented, can be, for example, a thermal treatment, a radiation treatment, an ultrasonic treatment, or a waiting treatment, consisting of allowing the fluid time to crosslink, possibly under a humid atmosphere.

[0092] During the crosslinking step, porosity can appear in the reactor wall, posing a risk of matrix leakage before the matrix compounds have sufficiently crosslinked. When steps a), i), and ii) are performed sequentially, the integrity of the reactor wall can be much better maintained thanks to the presence of several independent layers.

[0093] When this crosslinking step is a heat treatment step, this heat treatment step can be carried out, for example, at a temperature between ambient temperature and 160°C, for a duration of between 1 and 72 hours. Of course, the conditions will be adapted to the system to be crosslinked.

[0094] These conditions allow the crosslinkable fluid to be crosslinked while maintaining the integrity of the continuous tubular reactor wall. Thus, the wire is kept in shape throughout the crosslinking step, resulting in a wire with a homogeneous shape.

[0095] Preferably the, or where appropriate 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.

[0096] Preferably, each bath in at least one step i), when implemented, is at a temperature ranging from 10°C to 40°C, preferably ranging from 15°C to 30°C.

[0097] 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)" is understood similarly. Preferably, all baths are operated at ambient temperature, thus allowing for great simplicity in the operation of the process.

[0098] Step c) of sheath removal treatment

[0099] Following the preceding steps, the continuous tubular reactor undergoes a treatment to remove the polyanionic compound-based wall. This treatment can be mechanical, such as passing the continuous tubular reactor over a capstan or a series of pulleys, or ultrasonic treatment to mechanically break down the wall. Alternatively, it can be physicochemical, such as washing with water, preferably at a temperature between 40°C and 90°C, followed by washing with an aqueous solution of ethylenediaminetetraacetic acid (EDTA).

[0100] Preferably, step c) of treatment includes a physico-chemical water washing treatment at a temperature between 40°C and 90°C followed by washing with an aqueous EDTA solution and then mechanical ultrasonic treatment to remove the polyanionic compound-based wall.

[0101] Description of the figures

[0102] [Fig 1] Figure 1 illustrates schematically an arrangement of the process according to the invention. A crosslinkable fluid and a salt of at least one divalent cation, the latter being mixed with the crosslinkable fluid, are continuously injected from a reservoir (1) via a die (2) into a chelation bath (A) so as to form a continuous tubular reactor (3). The continuous tubular reactor is moved from one bath to the other by means of pulleys (4).

[0103] The continuous tubular reactor is conducted in a stabilization bath (B) consisting of an aqueous solution saturated with a salt of at least one divalent cation. The free surface of this bath (B) is located at a height lower than the free surface of the chelation bath (A).

[0104] The continuous tubular reactor then undergoes a heat treatment step (C) to crosslink the crosslinkable fluid and then a mechanical treatment (D) to remove the polyanionic compound-based cladding.

[0105] This treatment yields a cross-linked wire (5) free of polyanionic compounds. Measurement methods

[0106] Analysis of the macrostructure of alginates : SEC RI / MALS

[0107] The SEC (Size Exclusion Chromatography) technique separates macromolecules in solution according to their size using columns filled with a porous gel. Macromolecules are separated according to their hydrodynamic volume, with the largest being eluted first.

[0108] While not an absolute method, dual-detector SEC allows for the assessment 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.

[0109] Size-exclusion chromatography analyses of alginates can be performed with two detectors: a refractometer (Optilab rEX) and a MALS (Multi-Angle Light Scattering) system (Dawn Heleos), each equipped with three PL aquagebOH Mixed M columns. Alternatively, a refractometer (Optilab rEX) and a MALS (Multi-Angle Light Scattering) system (Dawn Heleos) can be used for these analyses. For these analyses, 1 mL of a 1 mg / mL sample solution is used. 1The solution in ultrapure water supplemented with Ig / L NaCl is filtered through a 0.45 µm PTFE membrane. 100 pL of this solution is eluted in ultrapure water supplemented with Ig / L NaCl using a flow rate of 1 mL / min 1 at a temperature of 40 °C. The Astra software can be used for data acquisition and analysis. Number molar masses (Mn) are calculated using a dn / dC determined by the 100% recovered method on a Vivapure brand sodium alginate sample, grade FD155.

[0110] 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.

[0111] The following analytical conditions can be used ■

[0112] The light diffusion model used is the Zimm model. Examples

[0113] Example 1

[0114] In this example, a continuous alkali lignin filament is manufactured using the biodegradable tubular reactor according to the invention.

[0115] A matrix consisting, by weight, of 20% alkali lignin, 55% water in which sodium hydroxide (NaOH) has been added to achieve a pH of 10, 10% terephthalaldehyde (TP A) and 15% CaCla 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.

[0116] 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.

[0117] The formed filament element passes through the chelation bath. The filament element remains in this bath for approximately ten seconds. It is transported by pulleys, minimizing the tension on the element. The filament 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 lower height than the free surface of the chelation bath.

[0118] The formed filament element passes through the chelation bath again. Its residence time in this bath is approximately 5 seconds. The filament element is then transported using pulleys, minimizing tension on the element. At the end of this step, a continuous cylindrical sheath consisting of two layers is obtained.

[0119] 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, which consists of an aqueous solution saturated with CaCh.

[0120] The wire element is wound around a spool and then undergoes a crosslinking step at 110°C for 48 hours.

[0121] The wire element is then treated first by rinsing with warm water, the temperature of which is in the range of 50°C to 60°C, then soaked in an aqueous solution saturated with EDTA for 24 hours. The wire element is then cleaned ultrasonically to separate the wire from the sheath.

[0122] The resulting dry crosslinked alkali lignin wire has a uniform appearance.

[0123] Example 2

[0124] In this example, a continuous BSA (Bovine Serum Albumin) protein filament is manufactured using the biodegradable tubular reactor according to the invention.

[0125] A matrix consisting, by weight, of 35% BSA, 55% deionized ultrapure water, 9.93% Cadmium and 0.07% EDC (l-ethyl-3-[3 _ dimethylaminopropyl]carbodiimide hydrochloride) is injected into a chelation bath consisting of an aqueous alginate solution with an alginate concentration of 6g / l, the bath being at a temperature of 22°C.

[0126] 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.

[0127] The formed filament element passes through the chelation bath. The filament element remains in this bath for approximately ten seconds. It is transported by pulleys, minimizing the tension on the element. The filament 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 lower height than the free surface of the chelation bath.

[0128] The formed filament element passes through a second chelation bath containing an aqueous alginate solution with an alginate concentration of 12 g / L, at a temperature of 22°C. The residence time in this bath is approximately 5 seconds. The filament element is then transported using pulleys, minimizing tension on the element. At the end of this step, a continuous cylindrical sheath consisting of two layers is obtained.

[0129] The continuous cylindrical sheath, consisting 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, which consists of a saturated aqueous solution of CaCh. The wire element is wound around a spool and then undergoes a crosslinking step at 130°C for 4 hours.

[0130] The resulting cross-linked BSA protein filament surrounded by an alginate sheath has a uniform appearance.

[0131] Example 3

[0132] In this example, a continuous filament is manufactured from an aqueous thermosetting composition made up of bio-based aldehyde and polyphenol using the biodegradable tubular reactor according to the invention.

[0133] A matrix consisting, by weight, of 95% aqueous composition and 5% CaCl₂ dihydrate is injected into a chelation bath consisting of an aqueous alginate solution with an alginate concentration of 6g / l, the bath being at a temperature of 22°C.

[0134] The aqueous composition consists by weight of 0.9% furfuraldehyde, 1.7% phloroglucinol, 0.2% sodium hydroxide, 6.4% natural rubber latex (“Trang Latex” from Bee Tex; diluted to 61% by weight), 3.2% styrene-butadiene polymer latex (“Encord-201” from Jubilant; diluted to 41% by weight), 6.4% vinylpyridine-styrene-butadiene latex (“VP 106S” from Eliokemi diluted to 41%), 0.5% ammonia and 80.7% deionized water.

[0135] 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.

[0136] The formed filament element passes through the chelation bath. The filament element remains in this bath for approximately ten seconds. It is transported by pulleys, minimizing the tension on the element. The filament 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 lower height than the free surface of the chelation bath.

[0137] The formed filament passes through a chelation bath containing an aqueous alginate solution with an alginate concentration of 12 g / L, at a temperature of 22°C. The residence time in this bath is approximately 5 seconds. The filament is then transported using pulleys, minimizing tension on the filament. At the end of this step, a continuous cylindrical sheath consisting of two layers is obtained.

[0138] 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, which consists of an aqueous solution saturated with CaCh.

[0139] The wire element is wound around a spool and then undergoes a crosslinking step at 130°C for 4 hours.

[0140] The wire element is then treated first by rinsing with warm water, the temperature of which is in the range of 50°C to 60°C, then soaked in an aqueous solution saturated with EDTA for 24 hours. The wire element is then cleaned ultrasonically to separate the wire from the sheath.

[0141] The resulting cross-linked resin filament has a uniform appearance.

Claims

DEMANDS

1. Biodegradable continuous tubular reactor whose wall comprises at least one cylindrical layer based on a polyanionic compound chelated by at least one divalent cation and whose central space comprises a crosslinkable fluid free of polyanionic compound.

2. A continuous biodegradable tubular reactor according to the preceding claim, wherein 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. A continuous biodegradable tubular reactor according to any one of the preceding claims wherein the at least divalent cation is selected from the cations of calcium, copper, magnesium, iron, zinc, lead, cobalt, nickel, barium, strontium, aluminum and manganese, preferably selected from the cations of calcium, copper, magnesium, iron, zinc, and aluminum, most preferably selected from the cations of calcium, copper and aluminum and most preferably is a calcium cation.

4. A continuous biodegradable tubular reactor according to any one of the preceding claims, wherein the crosslinkable fluid 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.

5. A continuous biodegradable tubular reactor according to any one of the preceding claims, the wall of which 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.

6. A method for manufacturing a crosslinked wire in which ■ a. A crosslinkable fluid and a salt of at least one divalent cation are continuously injected, by means of a die, into a chelating bath comprising a polyanionic compound in solution, the crosslinkable fluid being free of the polyanionic compound, so as to form a continuous tubular reactor; b. The continuous tubular reactor is then subjected to a crosslinking step so as to crosslink the crosslinkable fluid c. The wire element is then subjected to a treatment so as to remove the wall of the continuous tubular reactor.

7. A method according to the preceding claim wherein, between steps a) and b), the following sequence of steps is carried out at least once: ■ i. The continuous tubular reactor 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 continuous tubular reactor 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 continuous tubular reactor.

8. A method according to any one of claims 6 to 7 wherein the crosslinkable fluid also comprises a compound selected from a dye, a biologically active compound, a polymer, a biopolymer, proteins or nutrients.

9. A method according to any one of claims 6 to 8 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.

10. A method according to any one of claims 6 to 9 wherein the salt of at least one divalent cation is mixed with the crosslinkable fluid prior to their injection, the mass content of the salt of at least one divalent cation in the crosslinkable fluid ranging from 2% to 80% relative to the mass of the crosslinkable fluid, preferably ranging from 5% to 40%, and preferably ranging from 5% to 30%.

11. A method according to any one of claims 6 to 10 wherein the die comprises one or more injection devices, the injection device or each injection device being a co-injection device allowing the simultaneous injection at the periphery of a matrix comprising the salt of at least one divalent cation and at the center of the crosslinkable fluid, said crosslinkable fluid being free of the salt of at least one divalent cation.

12. A method according to any one of claims 6 to 11 wherein 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.

13. A method according to any one of claims 6 to 12 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.

14. A method according to any one of claims 7 to 13 wherein the mass content of salt of at least one divalent cation in the bath at at least one step i) is preferably 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 at 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.

15. A method according to any one of claims 6 to 14 wherein, at the end of step a), or at the end of the last step ii) of the at least one succession of steps i) and ii) when this succession of steps is carried out, a stabilization step is performed by passing the continuous tubular reactor 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 ranges from 2% to 80% relative to the mass of aqueous solution, preferably from 5% to 40%, and preferably from 5% to 30%.

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