PROCESS FOR PRODUCING A CONTINUOUS POLYESTER FIBER OR YARN FROM GLYCEROL

Abstract

The invention relates to a method for manufacturing a continuous glycerol polyester yarn into 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 a glycerol polyester, said solution being free of the polyanionic compound, so as to form a yarn element, then the yarn element is subjected to a heat treatment so as to crosslink the glycerol polyester, and the yarn element is subjected to a treatment so as to remove the polyanionic compound-based sheath.

Description

Title of the invention: METHOD FOR PRODUCING A CONTINUOUS POLYESTER FIBER OR YARN FROM GLYCEROL Technical field of the invention

[0001] The present invention relates to the field of manufacturing processes for fibers or yarns based on glycerol polyesters. Previous art

[0002] Biodegradable and / or bio-based polyesters, such as polylactic acid (PLA), polyglycolic acid (PGA) and copolymers, such as poly(glycerol sebacate) (PGS), are now ubiquitous in the preparation of biomaterials useful both as medical biomaterials and for surface coating for various fields of application.

[0003] Conventionally, these polyesters are prepared by melt polycondensation of glycerol and a diacid at high temperature, with fairly long reaction times. These reaction times are further extended to modify the mechanical properties of the polyester via crosslinking to obtain a thermoset polymer.

[0004] Thus, the cross-linking of polyglycerol sebacate (PGS), described in the literature, consists of cooking at high temperature (generally 130-150°C) for a significant period of time, generally 24 or 48 hours.

[0005] Prior to their crosslinking, these polymers are fluid and can be relatively sticky. It is therefore difficult to shape them, especially if one seeks to form a thread.

[0006] US patent 2022 / 0042207 describes a process for forming a PGS fiber in which a solution of PGS and alginate is injected into a calcium chloride bath. The resulting fiber can then undergo heat treatment to crosslink the PGS, and the residual alginate can be washed off to obtain a PGS fiber substantially free of alginate. In this process, during fiber formation, the PGS and alginate are intimately mixed. The alginate is removed as a sacrificial material by washing with water to obtain a PGS fiber, although there is no guarantee that the PGS fiber will be completely free of alginate.

[0007] Injecting PGS and alginate into a calcium salt bath to form an alginate sheath is very difficult to control, even with the use of coaxial needles. Since PGS and alginate are incompatible, ruptures in the Alginate sheaths frequently form, allowing PGS to leak. The formation of an intact sheath requires very precise management of surface tension phenomena.

[0008] The applicant has discovered a process for simply producing a continuous PGS yarn free of polyanionic compound. Detailed description of the invention

[0009] The invention relates to a method for manufacturing a continuous polyester yarn from glycerol in which:

[0010] 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 a polyester of glycerol, said solution being free of the polyanionic compound, so as to form a filament element;

[0011] b. The wire element is then subjected to a heat treatment in order to crosslink the polyester of the glycerol;

[0012] c. The wire element is then subjected to a treatment in order to remove the polyanionic compound-based sheath. Definitions

[0013] By continuous wire, we mean a wire element extending along a principal direction, its dimension along the principal direction being very large compared to its largest dimension in a plane perpendicular to the principal dimension, that is to say, the ratio of these two dimensions is greater than 10, preferably greater than 100. This wire is continuous, that is to say, its principal dimension is as large as desired, until an external intervention interrupts it, for example by cutting. Manufacturing process

[0014] The invention relates to a method for manufacturing a continuous polyester fiber or yarn from glycerol 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 a polyester of glycerol, said solution being free of the polyanionic compound, so as to form a filament element;

[0016] b. The wire element is then subjected to a heat treatment in order to crosslink the polyester with glycerol;

[0017] c. The wire element is then subjected to a treatment in order to remove the polyanionic compound-based sheath. Step a) of injection

[0018] 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 a polyester of glycerol, said solution being free of the polyanionic compound, so as to form a wire element.

[0019] 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.

[0020] 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.

[0021] 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.

[0022] 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.

[0023] 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, magnesium and aluminum and most preferably is a calcium salt.

[0024] 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.

[0025] The matrix also comprises a polyester of glycerol in solution. Glycerol is a triol, also known as trihydroxypropane.

[0026] Glycerol polyester is a polyester of glycerol and a monomer selected from dicarboxylic acid monomers and dicarboxylic acid diester monomers.

[0027] The dicarboxylic acid monomer can be aliphatic, aromatic, or aliphatic / aromatic. An aliphatic / aromatic dicarboxylic acid monomer comprises an aliphatic part and an aromatic part. The dicarboxylic acid monomer preferably comprises from 4 to 36 carbon atoms.

[0028] According to preferred embodiments of the invention, the dicarboxylic acid monomer is aliphatic, in particular saturated, especially linear or branched, and preferably it is a (C4-C2o)alkanediyldiacid carboxylic acid, more preferably a (C4-Ci5)alkanediyldiacid carboxylic acid. A (Cx-Cy)alkanediyl group is a divalent, saturated, linear or branched hydrocarbon group comprising x to y carbon atoms.

[0029] Advantageously, the dicarboxylic acid monomer comprises or consists of a diacid of general formula [HOOC-(CH2)P-COOH] in which p is a number from 1 to 30, preferably a number from 1 to 10, more preferably a number from 2 to 8.

[0030] In particular, the dicarboxylic acid monomer can be selected from malonic acid, succinic acid, glutaric acid, adipic acid, pimelic acid, suberic acid, azelaic acid, sebacic acid, dodecanedioic acid, hexadecanedioic acid, octadecanedioic acid and a mixture of two or more of these dicarboxylic acids.

[0031] Preferably, the dicarboxylic acid monomer can be chosen from malonic acid, succinic acid, glutaric acid, adipic acid, pimelic acid, suberic acid, azelaic acid, sebacic acid and a mixture of two or more of these dicarboxylic acids.

[0032] According to variants of the invention, the dicarboxylic acid monomer can be a mixture of at least two dicarboxylic acids. Preferably, the dicarboxylic acid monomer comprises sebacic acid.

[0033] Preferably, the dicarboxylic acid monomer comprises or consists of sebacic acid.

[0034] According to preferred embodiments of the invention, the dicarboxylic acid monomer and glycerol are the only monomers during polycondensation. Most preferably, the sebacic acid monomer and glycerol are the only monomers constituting the glycerol polyester and a dicarboxylic acid monomer.

[0035] The dicarboxylic acid diester monomer according to the invention may be aliphatic, aromatic, or aliphatic / aromatic. In the latter case, the dicarboxylic acid diester comprises an aliphatic portion and an aromatic portion. It preferably comprises from 3 to 36 carbon atoms. By aliphatic, we mean linear, cyclic, or branched aliphatic, whether saturated or unsaturated.

[0036] According to preferred embodiments of the invention, the dicarboxylic acid diester monomer is aliphatic and comprises 4 to 36 carbon atoms.

[0037] According to these variants, the dicarboxylic acid diester monomer can preferentially correspond to the following formula (I) ROOC-(CH2)n-COOR', in which n represents an integer from 1 to 30, preferably a number from 1 to 10, and R and R' represent, independently of each other, a linear or branched alkyl chain, in C1-C1, preferably in C1-C4, preferably also methyl or ethyl.

[0038] Preferably, according to these variants of the invention, the dicarboxylic acid diester monomer can be chosen from the diesters corresponding to malonic acid, succinic acid, glutaric acid, adipic acid, pimelic acid, suberic acid, azelaic acid, sebacic acid or a mixture of two or more of these dicarboxylic acid diesters, more preferably the dicarboxylic acid diester is chosen from the group consisting of dimethyl malonate, dimethyl succinate, dimethyl glutarate, dimethyl adipate, dimethyl pimelate, dimethyl suberate, dimethyl azelate, dimethyl sebacate, and mixtures thereof. According to variations of the invention, the dicarboxylic acid diester monomer can be a mixture of at least two different dicarboxylic acid diesters. Preferably, the dicarboxylic acid diester monomer comprises dimethyl sebacate.

[0039] According to preferred embodiments of the invention, the dicarboxylic acid diester monomer is dimethyl sebacate.

[0040] According to preferred embodiments of the invention, the dicarboxylic acid diester monomer and glycerol are the only monomers. Most preferably, the dimethyl sebacate monomer and glycerol are the only monomers.

[0041] Advantageously, the glycerol / monomer molar ratio varies from 1 / 2 to 10 / 1, in particular from 1 / 1 to 5 / 1, preferably from 1 / 1 to 2 / 1.

[0042] Glycerol polyester advantageously has one or more of the following characteristics: - an average number molar mass (Mn) of polyester greater than or equal to 800 g / mol, preferably greater than or equal to 900 g / mol, preferably even greater than or equal to 1500 g / mol, preferably even greater than or equal to 2000 g / mol; - an average number molar mass (Mn) of polyester less than or equal to 10,000 g / mol, preferably less than or equal to 7,000 g / mol, preferably less than or equal to 5,000 g / mol; - a polydispersity Ip (Mw / Mn) of the polyester less than 10, preferably less than or equal to 8; - a residual monomer content of less than or equal to 5% by weight of the polyester weight.

[0043] Glycerol polyester can be obtained in particular by implementing the processes described in documents EP3149067, EP1448656 and US2021 / 0380758.

[0044] The number-average molar mass (Mn), the mass-average molar mass (Mw), the dispersity (also called polydispersity and denoted D, which is the ratio Mw / Mn), can be measured in a known manner by size-exclusion chromatography (SEC) analysis with PS calibration, as can the residual monomer content by means of a glycerol calibration curve and a dicarboxylic acid calibration curve, in particular as described later.

[0045] Preferably, the matrix comprises a crosslinking activator, preferably selected from the association of a cyclic carboxylic polyanhydride with a metal triflate, preferably from the association of a cyclic carboxylic polyanhydride selected from Benzophenone-3,3',4,4'-tetracarboxylic acid bis-anhydride (BDTA), 4,4'-(4,4'-Isopropylidenediphenoxy)phthalic acid bis-anhydride (BPADA), 4,4'-diphthalic acid bis-anhydride (BPDA), 4,4'-Oxydiphthalic acid bis-anhydride (ODPA) and a metal triflate selected from Bismuth(III) trifluoromethylsulfonate, Scandium(III) trifluoromethylsulfonate and Iron(III) trifluoromethylsulfonate.Cyclic carboxylic polyanhydride is present at a content preferentially ranging from 0.1 to 200 parts by weight per 100 parts by mass of polyester, glycerol and a dicarboxylic acid monomer, and metal triflate is present at a content preferentially ranging from 0.0001% by mass to 1% by mass relative to the mass of polyester, glycerol and a dicarboxylic acid monomer.

[0046] Cyclic polycarboxylic anhydrides, in particular the cyclic bis-carboxylic anhydrides of the invention, are well known to those skilled in the art (see in particular US 7,425,650). They can be obtained by condensation of the corresponding tetracarboxylic acids, and some are commercially available.

[0047] The matrix may also include, depending on the intended use of the continuous yarn, 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, cyclodextrin, a biopolymer such as lignin, collagen, a polysaccharide such as cellulose or starch, proteins or nutrients or any other product whose controlled diffusion is desired.

[0048] 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.

[0049] 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.

[0050] 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.

[0051] In a preferred arrangement, the injection device, or each injection device, is a co-injection device allowing the simultaneous injection of a fluid comprising a glycerol polyester at the periphery of the matrix and at its center, said fluid being free of salts 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. 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 central space of the wire element formed by the co-injected fluid is completely free of salts 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 cations, while simplifying the processing steps to remove the polyanionic compound-based sheath from the wire to obtain a wire free of salt of at least one divalent cation.

[0052] 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 preferably chosen from poly(acrylic acid) and polysaccharides, most preferably from polysaccharides, most preferably from pectins and alginates, and most preferably from alginates.

[0053] 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, or even the risk of breakage of the forming wire element.

[0054] 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.

[0055] 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.

[0056] 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.

[0057] A wire element is continuously formed at the injection point, said wire element consisting of a central space comprising the matrix and a skin comprising the polyanionic compound chelated by the at least divalent cation. This wire element passes through the chelation bath and then feeds into step b) of the process according to the invention. The residence time of the wire element in the chelation bath is adjusted according to the chelation kinetics. It typically ranges from the order of seconds to a few minutes, for example, from 0.5 s to 2 min. Preferably, the wire element is made to pass through the chelation bath without tension, for example, by means of pulleys. By "without tension," it is meant 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.

[0058] Preferably, the means for transporting the wire element exiting the chelation bath in step a) is located as close as possible to the free surface of said bath. Preferably, and according to any one of the arrangements and preferred positions described herein, the wire element exits the chelation bath at the level of the free surface of said bath and is then transported at a height lower than that of the free surface of said bath. This limits the risk of herniation formation in the wire element being formed within the chelation bath due to matrix accumulation while the sheath is still insufficiently formed.

[0059] Preferably, when the process according to the invention uses several baths, the chelation bath of step a) of the process is located at a height at least equal to, and preferably greater than, the other baths used after step a). This maintains the homogeneity of shape of the wire element by limiting the risks of matrix accumulation within the wire element.

[0060] Preferably, when the process according to the invention uses a plurality of baths, each bath has a free surface whose height is greater than the height of the free surface of the next bath. These height differences help maintain the homogeneity of the wire element's shape by limiting the risk of matrix accumulation within the wire element.

[0061] Between step a) and step b) of the process according to the invention, the wire element can be stored, for example by winding onto a reel or by coiling.

[0062] Preferably, the following sequence of steps is performed at least once between steps a) and b):

[0063] 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;

[0064] 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.

[0065] Each sequence of steps i) and ii) allows for the formation of an additional layer on the wire element. Thus, the sequence of steps i) and ii) is executed as many times as additional layers are to be formed on the wire element.

[0066] The formation of at least one additional layer makes it possible to compensate for a possible at least partial rupture of an internal layer of the filament element, in particular prior to or during the crosslinking of the polyester of the glycerol, this at least partial rupture being able to lead to a leakage of the matrix, and therefore impair the homogeneity of the filament formed at the end of the process according to the invention.

[0067] 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.

[0068] By free from polyanionic compounds, it is meant that the bath used in step i) does not contain any polyanionic compounds when it is formed. During its use, it may contain traces of polyanionic compounds that may have been introduced by the filament element (so-called "contamination" polyanionic compounds).

[0069] The absence of polyanionic compounds in the bath prevents the sheath of the wire element from growing further while the external surface of said element is in contact with a fluid medium rich in at least a divalent cation. "Free from 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 primers that would cause adjacent sheaths not to slide freely relative to each other.

[0070] 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, preferably chosen from the salts of calcium, copper, magnesium and aluminum and most preferably is a calcium salt.

[0071] 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.

[0072] 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.

[0073] 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.

[0074] 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, so as to form an additional layer around the wire element.

[0075] 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.

[0076] 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 negatively charged polyelectrolyte. The polyanionic compound is selected from poly(acrylic acid) and polysaccharides, preferably from polysaccharides, preferably from pectins and alginates, and most preferably from alginates.

[0077] 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.

[0078] The polyanionic compound is, in the bath of step ii), in solution in a solvent preferably chosen from water, ethanol and their mixture.

[0079] In a preferred arrangement, the bath of step ii) is a solution consisting of a solvent selected from water, ethanol, and their mixture and a polyanionic compound.

[0080] 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 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 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.

[0081] 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.

[0082] In the case where the sequence of steps i) and ii) is performed 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) performed successively.

[0083] 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.

[0084] Preferably, prior to step b) a stabilization step is carried out by passing the wire element 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 the bath, preferably from 5% to 40%, and preferably from 5% to 30%.

[0085] 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. Step b) of heat treatment

[0086] Following step a), and possibly one or more successions of steps i) and ii), the wire element undergoes a heat treatment step so as to crosslink the polyester with glycerol.

[0087] This heat treatment step is preferably carried out at a temperature between 100°C and 160°C, for a duration of between 12 h and 72 h.

[0088] During the heat treatment step, porosity may appear in the sheath, with the risk of matrix leakage before the glycerol polyester has sufficiently crosslinked. When steps a), i), and ii) are carried out consecutively, the integrity of the sheath can be much better maintained thanks to the presence of several independent layers.

[0089] These conditions allow the polyester to be crosslinked while maintaining the integrity of the sheath. Thus, the yarn is kept in shape throughout the crosslinking step, resulting in a yarn of homogeneous shape.

[0090] Preferably, the heat treatment step is carried out under a controlled humid atmosphere so as to regulate the rate of water evaporation. This allows the rate of water evaporation to be adjusted to the crosslinking kinetics of the glycerol polyester.

[0091] 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.

[0092] 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.

[0093] 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 in a similar way.

[0094] Preferably, all baths are operated at room temperature, thus allowing great simplicity of operation of the process. Step c) of sheath removal treatment

[0095] Following the preceding steps, the wire element is subjected to a treatment to remove the polyanionic compound-based sheath. This treatment may be mechanical, such as passing the wire element over a capstan or a series of pulleys, or ultrasonic treatment to mechanically break the sheath. This treatment may also 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).

[0096] 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 coating. Description of the figures

[0097] [Fig. 1] Figure 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).

[0098] The wire element 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).

[0099] The wire element then undergoes a heat treatment step (C) to crosslink the polyester of the glycerol and then a mechanical treatment (D) to remove the polyanionic compound-based sheath.

[0100] Following this treatment, a PGS (5) wire free of polyanionic compound is obtained. Measurement methods

[0101] Analysis of the macrostructure of polyesters: SEC RI

[0102] 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.

[0103] While not an absolute method, SEC allows for the determination of the molar mass distribution of a polymer. From commercial standard products, 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.

[0104] Size exclusion chromatography analyses of polyesters can be performed using a Viscotek instrument (Malvern Instruments) equipped with four columns, a guard column, and three detectors (differential refractometer and viscometer, and light scattering). To perform these analyses, 1 mL of a 1 mg mL sample solution in THF is filtered through a 0.45 µm PTFE membrane. 100 µL of this solution are eluted in THF at a flow rate of 1 mL min⁻¹ at a temperature of 35 °C. OmniSEC software can be used for data acquisition and analysis. Number molar masses (Mn) are calculated using a calibration curve based on standard polystyrenes (Mp: 1,306 to 2,520,000 g mol⁻¹) from Polymer Standard Service (Mainz).

[0105] The samples are dissolved at a concentration of approximately Ig / L in THF without butylated hydroxytoluene (BHT), then stirred for two hours before being injected.

[0106] The following analytical conditions may be used: THF eluent without antioxidant. Injection volume 100 pL. Temperature 35°C. Detector RI Waters. Mobile phase flow rate 1 mL / min. Columns: 2 Mixed D + 2 Mixed E

[0107] The calibration used for the Moore calculation is a PS calibration, covering a range from 2,520,000 to 162 g.mol1.

[0108] The calibration used is a mixed low and medium weight PS calibration of PSS Standards. The mass range extends from 162 to 66,000 g.mol1. The calibration allows the determination of the Mn (g.mol1), Mw (g.mol1), and D (Mw / Mn) values ​​in PS equivalent.

[0109] The determination of the sebacic acid and glycerol levels is carried out by external calibration.

[0110] To do this, a standard range using samples of sebacic acid and glycerol at different concentrations is prepared.

[0111] Analysis of the macrostructure of alginates: SEC RI / MALS

[0112] 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.

[0113] 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.

[0114] Size-exclusion chromatography analyses of alginates can be performed with two detectors: a refractometer (“Optilab rEX”) and a MALS (“Dawn Heleos”) equipped with three PL aquagel-OH Mixed M columns, and two detectors: a refractometer (“Optilab rEX”) and a Multi-Angle Light Scattering (“Dawn Heleos”). To perform 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 using a flow rate of 1 mL / min at a temperature of 40 °C. The Astra software can be used for data acquisition and analysis. Molar numbers (Mn) are calculated using a dn / dC determined by the 100% recovered method on a Vivapure brand sodium alginate sample grade FD155.

[0115] 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.

[0116] The following analytical conditions may be used: Eluent: Ultrapure water + Ig / L NaCl; Injection volume: 100 pL; Temperature: 40°C; Detector: Refractometer / MALS (Optilab rE X; DAWN HELEOS); Wyatt; Mobile phase flow rate: 1 mL / min; Columns: 3 PL aquagel-OH MIXED M

[0117] The light diffusion model used is that of Zimm. Examples Example 1

[0118] In this example, a continuous filament of a poly(glycerol sebacate) polymer, denoted PGS, is manufactured.

[0119] A matrix consisting, by weight, of 40% PGS having a molar mass by weight Mw=260,000 g / mol, 30% ethanol and 30% CaCl2 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.

[0120] 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.

[0121] 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.

[0122] The wire element is wound around a reel and then undergoes a heat treatment step at a temperature of 140°C for a period of 48 h.

[0123] 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, and then soaked in an aqueous solution saturated with EDTA for 24 hours. The wire element is then cleaned ultrasonically to separate the PGS wire from the sheath. The resulting PGS wire is free of alginate and has a uniform appearance. Example 2

[0124] In this example, a continuous filament of a poly(glycerol sebacate) polymer, denoted PGS, is manufactured.

[0125] A matrix consisting, by weight, of 90% PGS having a molar mass by weight Mw = 1000 g / mol of 10% CaCl2 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. The matrix and salt mixture is heated to 50°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 0.6 ml / min and is performed below the surface of the chelation bath.

[0127] 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.

[0128] The wire element is wound around a reel and then undergoes a heat treatment step at a temperature of 140°C for a period of 72 h.

[0129] 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, and then soaked in an aqueous solution saturated with EDTA for 24 hours. The wire element is then cleaned ultrasonically to separate the PGS wire from the sheath. The resulting PGS wire is free of alginate and has a uniform appearance. Example 3

[0130] In this example, a continuous filament of a poly(glycerol sebacate) polymer, denoted PGS, is manufactured.

[0131] A matrix consisting, by weight, of 50% PGS having a molar mass by weight Mw=25,000 g / mol, 20% ethanol and 30% CaCl2 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.

[0132] 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.

[0133] 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 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.

[0134] 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.

[0135] The wire element is wound around a reel and then undergoes a heat treatment step at a temperature of 140°C for a period of 48 h.

[0136] 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, and then soaked in an aqueous solution saturated with EDTA for 24 hours. The wire element is then cleaned ultrasonically to separate the PGS wire from the sheath. The resulting PGS wire is free of alginate and has a uniform appearance. Example 4

[0137] In this example, a continuous filament of a poly(glycerol sebacate) polymer, denoted PGS, is manufactured.

[0138] A matrix consisting, by weight, of 70% PGS having a molar mass by weight Mw=37,000 g / mol, 10% ethanol and 20% CaCl2 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.

[0139] The injection is carried out continuously using a channel consisting of a needle with an internal diameter of 0.7 mm, at a flow rate of 0.6 ml / min and is performed below the surface of the chelation bath.

[0140] 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 chelation bath as close as possible to its free surface and then passes through a second bath comprising an aqueous solution saturated with CaC12, whose free surface is located at a height lower than the free surface of the chelation bath.

[0141] 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.

[0142] The wire element is wound around a reel and then undergoes a heat treatment step at a temperature of 140°C for a period of 48 h.

[0143] 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, and then soaked in an aqueous solution saturated with EDTA for 24 hours. The wire element is then cleaned ultrasonically to separate the PGS wire from the sheath. The resulting PGS wire is free of alginate and has a uniform appearance. Example 5

[0144] In this example, a continuous filament of a poly(glycerol sebacate) polymer, denoted PGS, is manufactured.

[0145] A matrix consisting, by weight, of 50% PGS having a molar mass by weight Mw=25,000 g / mol, 20% ethanol and 30% CaCO3 is injected into a chelation bath consisting of an aqueous alginate solution with an alginate concentration of 15 g / l, the bath being at a temperature of 24°C.

[0146] 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.

[0147] 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 chelation bath as close as possible to its free surface and then passes through a second bath containing a saturated aqueous solution of CaCO3, the free surface of which is located at a height lower than the free surface of the chelation bath.

[0148] The formed filament element passes through a second chelation bath consisting of an aqueous alginate solution. The alginate concentration is 12 g / L. The time of The immersion time in this bath is approximately 5 seconds. The wire element is transported using pulleys, minimizing the 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, which consists of a saturated aqueous solution of CaCl2.

[0149] The wire element is wound around a reel and then undergoes a heat treatment step at a temperature of 140°C for a period of 48 h.

[0150] 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, and then soaked in an aqueous solution saturated with EDTA for 24 hours. The wire element is then cleaned ultrasonically to separate the PGS wire from the sheath. The resulting PGS wire is free of alginate and has a uniform appearance. Example 6

[0151] In this example, a continuous filament of a poly(glycerol sebacate) polymer, denoted PGS, is manufactured.

[0152] A matrix consisting, by weight, of 60% PGS having a molar mass by weight Mw = 260,000 g / mol, 30% ethanol, and 10% CuCl2 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. The PGS, ethanol, and CuCl2 solution is heated to 40°C.

[0153] 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.

[0154] 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 chelation bath as close as possible to its free surface and then passes through a second bath containing a saturated aqueous solution of CuCl2, the free surface of which is located at a height lower than the free surface of the chelation bath.

[0155] 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.

[0156] The wire element is wound around a reel and then undergoes a heat treatment step at a temperature of 140°C for a period of 48 h.

[0157] 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, and then soaked in an aqueous solution saturated with EDTA for 24 hours. The wire element is then cleaned ultrasonically to separate the PGS wire from the sheath. The resulting PGS wire is free of alginate and has a uniform appearance. Example 7

[0158] In this example, a continuous filament of a poly(glycerol sebacate) polymer, denoted PGS, is manufactured.

[0159] A matrix consisting, by weight, of 33% PGS having a molar mass by weight Mw=260000g / mol, 33% ethanol, 1% amoxicillin and 33% CaCl2 is injected into a first chelation bath consisting of an aqueous alginate solution having an alginate concentration of 12 g / l, the bath being at a temperature of 24°C.

[0160] 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.

[0161] 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.

[0162] 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.

[0163] The wire element is wound around a reel and then undergoes a drying and crosslinking step at 140°C for 36 hours.

[0164] The wire element is then treated first by rinsing with lukewarm 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 by Ultrasound is used to separate the PGS wire from the sheath. The resulting PGS wire is alginate-free and amoxicillin-loaded. It has a uniform appearance. Example 8

[0165] In this example, a continuous filament of a poly(glycerol sebacate) polymer, denoted PGS, is manufactured using a die consisting of two coaxial needles.

[0166] The matrix consists, by weight, of 50% PGS with a molar mass Mw = 1000 g / mol, 20% ethanol, and 50% CaCl2. A fluid consisting of 100% PGS with a molar mass 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.

[0167] 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 at a flow rate of 0.1 ml / min, and the PGS fluid passes through the inner needle at a flow rate of 0.5 ml / min. The injections are performed below the surface of the first chelation bath.

[0168] 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.

[0169] 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.

[0170] The wire element is wound around a reel and then undergoes a drying and crosslinking step at 140°C for 36 hours.

[0171] The wire element is then treated first by rinsing with lukewarm water, the temperature of which is in the range of 50°C to 60°C, and then soaked in a solution The filament is soaked in an EDTA-saturated aqueous solution for 24 hours. It is then cleaned ultrasonically to separate the PGS filament from the sheath. The resulting PGS filament is alginate-free and has a uniform appearance.

Claims

Demands

1. A method for manufacturing a continuous glycerol polyester yarn into which: a. A matrix is ​​continuously injected, by means of a die, into a chelating bath comprising a polyanionic compound in solution, the matrix comprising a solution of a salt of at least one divalent cation and a glycerol polyester, said solution being free of the polyanionic compound, so as to form a yarn element; b. The yarn element is then subjected to a heat treatment so as to crosslink the glycerol polyester; c. The yarn element is then subjected to a treatment so as to remove the polyanionic compound-based coating.

2. 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 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.

3. A method according to any one of the preceding claims wherein the matrix comprises a solution comprising a solvent selected from water, ethanol, isopropanol, dimethyl sulfoxide and mixtures thereof.

4. A method according to any one of the preceding claims wherein 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%.

5. A method according to any one of the preceding claims 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, magnesium and aluminum, and most preferably is a calcium salt.

6. A method according to any one of the preceding claims wherein the matrix also comprises a dye, a biologically active compound, a polymer, a biopolymer, proteins, nutrients or any other product of which controlled diffusion is desired.

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

8. A method according to any one of the preceding claims 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.

9. A method according to any one of the preceding claims 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.

10. A method according to any one of claims 2 to 7 wherein the mass content of salt of at least one divalent cation in the bath at 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 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.

11. A method according to any one of the preceding claims wherein prior to step b) a stabilization step is carried out by passing the wire element through a stabilization bath comprising an aqueous solution of a salt of at least one divalent cation, the mass content of at least one divalent cation being from 2 to 80% relative to the mass of the bath, preferably from 5 to 40%, and preferably from 5 to 30%.

12. A method according to any one of the preceding claims in which the, or where applicable 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.

13. A method according to claim 2 or any one of claims 3 to 12 when they depend on claim 2 wherein each bath of at least one step i) is at a temperature from 10°C to 40°C, preferably from 15°C to 30°C.

14. A method according to any one of the preceding claims, wherein the matrix comprises a crosslinking activator, preferably selected from the combination of a cyclic carboxylic polyanhydride with a metal triflate, preferably from the combination of a cyclic carboxylic polyanhydride selected from benzophenone-3,3',4,4'-tetracarboxylic acid bis-anhydride (BDTA), 4,4'-(4,4'-Isopropylidenediphenoxy)phthalic acid bis-anhydride (BPADA), 4,4'-diphthalic acid bis-anhydride (BPDA), 4,4'-Oxydiphthalic acid bis-anhydride (ODPA) and a metal triflate selected from bismuth(III) trifluoromethylsulfonate, scandium(III) trifluoromethylsulfonate and iron(III) trifluoromethylsulfonate.

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