FR2908047A1 - Making an implantable tubular prosthesis from a porous material based tubular body, comprises applying a reception coating of a bioactive agent, heating, washing, drying and impregnating in a solution concentrated with a bioactive agent - Google Patents

Abstract

Making an implantable tubular prosthesis from a porous material based tubular body (12), comprises applying (50) a reception coating (14) of a bioactive agent comprising (a complex comprising) a cyclodextrin and/or a cydodextrin derivative, a poly(carboxylic) acid and optionally a catalyst on the tubular body, heating at 100-220[deg] C for 1-90 minutes, washing in water, drying and impregnating (46) in a solution concentrated with a bioactive agent, where the process comprises, after the drying step, a step of laying an additional coating (16) for sealing. Preparation of implantable tubular prosthesis from a tubular body (12) based on porous material, comprises application (50) of a reception coating (14) of a bioactive agent comprising a cyclodextrin, a cydodextrin derivative or a complex comprising cyclodextrin and/or cyclodextrin derivatives, a poly(carboxylic) acid and optionally a catalyst, on the tubular body, heating the tubular body at 100-220[deg] C for 1-90 minutes, washing in water, drying and impregnating (46) the tubular body in a solution concentrated with a bioactive agent, where the process comprises, after the drying step, a step of laying an additional coating (16) for sealing on the tubular body. The tubular body provided with the coatings internally delimits a waterproof conduit. An independent claim is included for an implantable tubular prosthesis comprising a tubular body based on porous material, a reception coating of a bioactive agent comprising a cyclodextrin, a cydodextrin derivative or a complex comprising cyclodextrin and/or cyclodextrin derivatives, a bioactive agent received from the reception coating and an additional seal coating deposited on the tubular body, where the tubular body internally delimits a waterproof conduit.

Description

The present invention relates to a method for preparing a pro-thesis

  tubular implantable from a tubular base body of porous material, the method comprising the following successive steps: a) application on the tubular body of a coating for receiving a bioactive agent, the receiving coating comprising: - at minus one cyclodextrin and / or at least one cydodextrin derivative and / or at least one cyclodextrin inclusion complex and / or cyclodextrin derivatives, at least one polycarboxylic acid, and optionally a catalyst; b) heating the tubular body at a temperature between 100 C and 220 C for a period of 1 to 90 minutes; c) washing the tubular body with water; d) drying the tubular body, then e) impregnating the tubular body in a concentrated solution of at least one bioactive agent. Polyethylene terephthalate vascular tubular prostheses implanted in patients suffering from arterial problems are known. These prostheses are intended in particular to replace clogged or retracted arteries. In this case, a bypass is performed around the blocked artery using a tubular prosthesis of variable diameter. Such vascular prostheses are also used to prevent aneurysm ruptures. A prosthesis is then introduced into the artery itself, opposite the aneurysm, to prevent the aneurysm from evolving.

  Implantation of these prostheses therefore significantly reduces mortality in patients with these arterial problems. However, complications may arise due to the risk of infection per-operative and post-operative respectively before and after implantation of these prostheses. To overcome this problem, the application WO 2006/051227 proposes to bind cyclodextrins on the material constituting an implant intended to be placed in the human body. The implant is then placed in a bath in order to charge the cyclodextrins with molecules of active ingredients for their release into the body after the operation. Such a method is implemented at a laboratory level. However, the implants produced by this method are not satisfactory for their final implantation in the human body, particularly in terms of sealing, haemocompatibility and more generally, to meet the regulatory constraints related to prostheses. An object of the invention is therefore to obtain a process for preparing an implantable tubular prosthesis that makes it possible to obtain prostheses that reduce the risk of post-operative infection while meeting the implantation constraints in the human body. . To this end, the subject of the invention is a process of the aforementioned type, characterized in that the process comprises, after the drying step, a step of depositing an additional sealing coating on the tubular body, the body tubular provided with said coatings internally defining a sealed conduit for circulating a liquid. The process according to the invention may comprise one or more of the following characteristics, taken individually or according to any technically possible combination: the sealing coating is formed based on collagen, gelatin, polyurethane or polyurethane; a polymer capable of sealing the tubular body, or combinations thereof; the step of applying the receiving coating comprises impregnating the tubular body with an aqueous solution comprising: at least one cyclodextrin and / or at least one derivative of cydodextrin and / or at least one inclusion complex of cyclodextrin and / or cyclodextrin derivatives, - at least one poly (carboxylic acid), and optionally a catalyst; It comprises, before the heating step, a precubring step of the tubular body at a temperature between 40 C and 100 C; it comprises, after the drying step, a step of neutralizing the tubular body to bring it to a neutral pH; The tubular body is formed from a braid, a weave or a knit of at least one polymeric yarn, made in particular from a polymer selected from the group consisting of polyethylene terephthalate ( PET), polyethylene terephthalate glycol (PETG), polyurethane (PU) polylactic acid, polyglycolic acid and their copolymers, polyvinylidene fluoride (PVDF), polytetrafluoroethylene (PTFE), polyethylene glycol ( PEG), polyamide-6, polyamide-6,6, polypropylene, polyethylene and their copolymers, or the combination of these polymers; the receiving liner forms between 5% and 7% of the total mass of the prosthesis; said bioactive agent is selected from anticoagulants, antithrombogenic agents, anti-mitotic agents, anti-proliferation, anti-adhesion, anti-migration agents, cell adhesion promoters, growth factors, antiparasitic molecules, anti- inflammatory drugs, angiogenics, angiogenesis inhibitors, vitamins, hormones, proteins, antifungals, antimicrobial molecules, antiseptics or antibiotics; and it comprises, before the step of applying the receiving coating and / or after the washing step, a step of embossing the tubular body.

The invention further relates to an implantable tubular prosthesis comprising: a basic tubular body of porous material; a coating for receiving a bioactive agent applied to the tubular body, the coating comprising at least one cyclodextrin and / or at least one cydodextrin derivative and / or at least one inclusion complex of cyclodextrin and / or derivatives cyclodextrin, - at least one bioactive agent received in the receiving coating; characterized in that the prosthesis comprises an additional sealing coating deposited on the tubular body, the tubular body provided with said coatings internally defining a sealed conduit for circulating a liquid.

The prosthesis according to the invention may comprise one or more of the following characteristics, taken individually or according to any technically possible combination: the tubular body has a chemical structure which comprises a hydroxyl function and / or an amine function, said structure being covalently bonded to at least one cyclodextrin molecule or to a cyclodextrin polymer of the receiving coating, the structure of which comprises the repetition of the unit of general formula: [SB] -X - [-] CO- [Ac] -CO-O- [CD] -O-] n-1 (COOH) xy SB representing the chemical structure of the tubular body made of a polymeric material of natural or artificial origin, X being either a oxygen atom is NH, x> 3, and 2 <y <(x-1) and (xy)> 1, 15 - x being the number of carboxyl functions carried by the poly (carboxylic acid) before reaction is the number of carboxyl functions of the poly (carboxylic acid) e when sterilized or annnidified during the reaction, - (xy) is the number of carboxyl functions of the non-esterified or amidified carboxylic acid (carboxylic acid) after reaction, (COOH) xy 1 [Ac] representing the molecular chain of an acid poly (carboxylic acid) of the formula (COOH) x 1 [Ac] of which at least two carboxyl functions (-COOH) have undergone esterification or esterification and amidification respectively and which carry at least one carboxyl function; has not undergone an esterification or amidation reaction; [CD] representing the molecular structure of the cyclodextrins chosen preferentially from: α-cyclodextrin, [3-cyclodextrin, γ-cyclodextrin and mixtures thereof; their derivatives which are preferably chosen from aminated, methylated, hydroxypropylated, sulphobutylated, carboxymethylated or carboxylic derivatives, and mixtures thereof, said bioactive agent being at least one therapeutic molecule forming a complex with the cyclodextrin molecules and / or cyclodextrin derivatives; the receiving coating is formed by a crosslinked polymer of at least one cyclodextrin and / or at least one cyclodextrin derivative and / or at least one inclusion complex of cyclodextrin or cyclodextrin derivatives and of which the structure comprises the repetition of a unit of general formula: - [CD] -O-CO- [Ac] -CO-O-] n-1 (COOH) x-y with x> 3, and 2 <y (x-1) and (xy) _> 1, where x is the number of carboxyl functions carried by the poly (carboxylic acid) before reaction, y being the number of carboxyl functions of the poly acid ( carboxylic acid) esterified in the reaction, - (xy) being the number of carboxyl functional groups of the non-esterified poly (carboxylic acid) after reaction (COOH) xy 1 [Ac] representing the molecular chain of a poly (carboxylic acid) ) of formula: (COOH) x 1 [Ac] of which at least two carboxyl functions (-COOH) have undergone esterification and which carries at least one carboxyl function which has not undergone a reaction. esterification; [CD] representing the molecular structure of cyclodextrins selected preferentially from: α-cyclodextrin, β-cyclodextrin, γ-cyclodextrin and mixtures thereof; their derivatives which are preferably chosen from aminated, methylated, hydroxypropylated, sulphobutylated, carboxymethylated or carboxylic derivatives, and mixtures thereof, said bioactive agent being a therapeutic molecule forming a complex with the cyclodextrin molecules and / or cyclodextrin derivatives; - the porous material is formed of a braid, a weave, or a knit of at least one polymeric yarn, in particular made from a polymer selected from the group consisting of polyethylene terephthalate (PET), polyethylene terephthalate glycol (PETG), polyurethane (PU) poly-lactic acid, polyglycolic acid and their copolymers, polyvinylidene fluoride (PVDF), polytetrafluoroethylene (PTFE), polyethylene glycol (PEG), polyamide-6, polyamide-6,6, polypropylene, polyethylene and copolymers thereof, or the combination of these polymers; the receiving liner forms between 5% and 7% of the total mass of the prosthesis; the bioactive agent is chosen from anticoagulants, antithrombogenic agents, anti-mitotic agents, anti-proliferation, anti-adhesion, anti-migration agents, cell adhesion promoters, growth factors, antiparasitic, anti- inflammatory, antifungals, antimicrobial molecules, antiseptics and antibiotics; the tubular body is embossed; and the sealing coating is formed from collagen, gelatin, polyurethane or a polymer capable of sealing the tubular body, or combinations thereof. The invention will be better understood on reading the description which follows, given solely by way of example, and with reference to the appended drawings, in which: FIG. 1 is a side perspective view of a first tubular prosthesis according to the invention; FIG. 2 is a schematic view of the first steps of a process for manufacturing a tubular prosthesis according to the invention; Figure 3 is a view similar to Figure 2 of the steps of the manufacturing method subsequent to the steps shown in Figure 2; and FIG. 4 is a view similar to FIG. 1 of a second prosthesis according to the invention. The invention applies in particular to prostheses, stents or stents having a straight or bifurcated tubular body.

A first prosthesis 10 according to the invention is shown in FIG. 1. As illustrated by this FIGURE, this prosthesis comprises a tubular body 12 embossed externally having a coating 14 for receiving a bioactive agent and a coating 16 for sealing. of the prosthesis. The tubular body 12 comprises a substantially cylindrical tubular wall 18 of X-X 'axis having an inner surface 20 delimiting a blood circulation duct 22 and an outer surface 24 intended to be applied at least partially against a human tissue.

The tubular wall 18 is made from interwoven polymer yarns in the form of a braid, weave, or knit. The or each polymeric yarn is made from a polymer selected from the group consisting of polyethylene terephthalate (PET), polyethylene terephthalate glycol (PETG), polyurethane (PU), polylactic acid, polyethylene terephthalate polyglycolic acid and their copolymers, polyvinylidene fluoride (PVDF), polytetrafluoroethylene (PTFE), polyethylene glycol (PEG), polyamide-6, polyamide-6,6, polypropylene, polyethylene and their copolymers, or the combination of these polymers. The or each polymer wire delimits through the wall 18 a plurality of pores extending between the inner surface 20 and the outer surface 24. The tubular wall 18 is therefore porous in the absence of the coatings 14, 16. In the example shown in Figure 1, the wall 18 is embossed or lined. It thus has a plurality of annular ribs 26 projecting outwards.

The coatings 14, 16 are applied to the wires constituting the wall 18 and in the pores delimited between these wires, along the inner surface 20 and the outer surface 24. The coatings 14, 16 cooperate to seal substantially all the pores, so that the tubular body 12 provided with the coatings 14, 16, delimits internally a sealed conduit 22 30 for circulating the blood axis X-X '. The coating 14 for receiving a bioactive agent comprises at least one cyclodextrin and / or a cyclodextrin derivative and / or an inclusion complex of cyclodextrin and / or cyclodextrin derivative. It comprises in addition to a polycarboxylic acid and a catalyst. The coating 14 is bonded to the tubular wall 18 in at least one of the two bonding modes described below. In a first mode of bonding, the tubular wall 18 has a chemical structure which has a hydroxyl function and / or an amine function, said structure being covalently bound to at least one cyclodextrin molecule or a cyclodextrin polymer composed of receiving coating whose structure comprises the repetition of the general formula: 10 - [SB] -X - [- CO- [Ac] -CO-O- [CD] -O-] n-1 (COOH) xy SB representing the chemical structure of the tubular body made of a polymeric material of natural or artificial origin, X being either an oxygen atom or an NH group, x> 3, and 2 <y <(x-1) and (xy)> 1, - x being the number of carboxyl functions carried by the poly (carboxylic acid) before reaction, - y represents the number of carboxyl functions of the poly (carboxylic acid) esterified or amidified during the reaction , 20 - (xy) is the number of carboxyl functions of the unesterified poly (carboxylic acid) or amide after reaction, (COOH) xy 1 [Ac] representing the molecular chain of a poly (carboxylic acid) of formula (COOH) x 1 [Ac] of which at least two carboxyl functions (-COOH) have undergone esterification; Or esterification and amidification, and which carries at least one carboxyl function which has not undergone esterification or amidation reaction; [CD] representing the molecular structure of the cyclodextrins chosen preferentially from: α-cyclodextrin, R-cyclodextrin, γ-cyclodextrin and mixtures thereof; In this case, the coating is obtained by the formation of an anhydrous poly (carboxylic acid) which reacts with the material constituting the tubular wall 18 forming a covalent bond of amide or ester type between this material and the poly (carboxylic acid). Then, in the simplest case, a second anhydride of the poly (carboxylic acid) already bonded to the material is formed, which reacts with a cyclodextrin molecule or a cyclodextrin molecule anchored to an ester bond with the cyclodextrin or cyclodextrin derivative molecule. In a second mode of binding, the receiving coating is formed by a cross-linked polymer of at least one cyclodextrin and / or at least one cyclodextrin derivative and / or at least one cyclodextrin inclusion complex or of cyclodextrin derivatives and whose structure comprises the repetition of a unit of general formula: [CD] -O-CO- [Ac] -CO-O-] n-1 (COOH) xy with x> 3, and 2 <y <_ (x-1) and (xy): where: x is the number of carboxyl functions carried by the poly (carboxylic acid) before reaction, where y is the number of carboxyl functions of the poly (carboxylic) acid esterified in the reaction, - (xy) being the number of carboxyl functional groups of the non-esterified poly (carboxylic acid) after reaction (COOH) xy 1 [Ac] representing the molecular chain of a poly (carboxylic acid) of formula: (COOH) x 1 [Ac] of which at least two carboxyl functions (-COOH) have undergone an esterification and which carries at least one carboxy function having not undergone esterification re-action; [CD] representing the molecular structure of the cyclodextrins chosen preferentially from: α-cyclodextrin, (3-cyclodextrin, γ-cyclodextrin and mixtures thereof, in this second mode, binding of the or each cyclodextrin; and / or cyclodextrin derivatives is produced by the formation of a crosslinked polymer obtained by the exclusive reaction between the cyclodextrin molecules and / or cyclodextrin derivatives and at least one poly (carboxylic acid) .The crosslinked polymer thus formed forms a film or a deposit on the surface of the wires of the tubular wall 18 or is recorded inside its porous structure and remains permanently fixed therein In a variant, the two modes of connection coexist on the wires constituting the wall 18 In this example, the sealing coating 16 is formed by a coating of collagen deposited on the son forming the tubular wall 18, 15 in the pores delimited between the yarns, and on the receiving liner 14. The collagen forms a film sealing the interstices between the inner surface 20 and the outer surface 24 to form the sealed conduit 22 within the tubular body 12. As a variant, the liner sealing 16 is made of gelatin, polyurethane or any other polymer capable of sealing the tubular body 12, or of their mixture. The bioactive agent is received in the hollow molecular structure of each cyclodextrin. It is selected from anticoagulants, antithrombogenic agents, anti-mitotic agents, antiproliferation, antiadhesion, anti-migration agents, cell adhesion promoters, growth factors, antiparasitic molecules, anti-inflammatory drugs, angiogenics, angiogenesis inhibitors, vitamins, hormones, proteins, antifungals, antimicrobial molecules, antiseptics or antibiotics.

The process for preparing the prosthesis 10 according to the invention will now be described, with reference to FIGS. 2 and 3. This process comprises a step 40 of shaping the tubular body 12, a step 42 of applying the coating of 14, a step 43 of neutralization, an application step 44 of the sealing coating 16, then a step 46 of loading the bioactive agent on the prosthesis 10. Initially, in step 40 of implementation In the form, a braided, woven or knitted tubular body 12 made of polymeric yarns is provided. This tubular body 12 initially has an outer surface 24 and a smooth inner surface and a porous tubular wall 18. An embossing of the tubular wall 18 constituting the body is then performed to form the ribs 26.

The step 42 for applying the coating 14 comprises impregnating 50 in a solution 52 of precursor mixture of each shaped body 12, the padding 54 of each body 12 impregnated with the precursor mixture, a precooking 56, a cooking 58 and washing and drying 60 of each body 12.

The precursor mixture 52 is formed by an aqueous solution comprising: at least one cyclodextrin and / or at least one cydodextrin derivative and / or at least one inclusion complex of cyclodextrin and / or cyclodextrin derivatives, at least one poly (carboxylic acid), and optionally a catalyst. The cyclodextrin is preferably chosen from α-cyclodextrin, 13-cyclodextrin and γ-cyclodextrin, and mixtures thereof; their derivatives which are preferably chosen from the amino, methylated, hydroxypropylated, sulphobutylated, carboxymethylated or carboxylic derivatives of these cyclodextrins, and mixtures thereof. The carboxylic acid is chosen from saturated and unsaturated aromatic saturated and unsaturated cyclic saturated acyclic polycarboxylic acids, hydroxypoly (carboxylic) acids, preferably citric acid, polyacrylic acid and poly (methacrylic acid). ), 1, 2, 3, 4-butanetetracarboxylic acid, maleic acid, citraconic acid, itaconic acid, 1,2,3-propanetricarboxylic acid, trans-aconitic acid, all-cis-1,2,3,4-cydopentanetetracarboxylic acid, melititic acid, oxydisuccinic acid, thiodisuccinic acid, or from the anhydrides derived from the aforementioned acids. The catalyst is selected from dihydrogen phosphates, hydrogen phosphates, phosphates, hypophosphites, alkali metal phosphites, alkali metal salts of polyphosphoric acids, carbonates, bicarbonates, acetates, borates and alkali metal hydroxides. aliphatic amines and ammonia, and preferably from sodium hydrogen phosphate, sodium dihydrogen phosphate and sodium phypophosphite.

Preferably, the mixture is made from poly (carboxylic acid), catalyst and cyclodextrin in the following proportions by weight: poly (carboxylic acid): between 2 and 4, catalyst: 1, cyclodextrin: between 2 and 5. The padding 54 is made by passing the tubular bodies 12 impregnated precursor mixture between two rollers 62, and by enclosing the tubular body 12 between the rollers 62. The precooking 56 is preferably carried out in a furnace 64 brought to a temperature between 40 C and 100 C for a period of time between 1 minutes and 30 minutes. The surfaces 20 and 24 of the body 12 are then substantially dry. The heating step is carried out in oven 64 at a temperature of between 100 ° C. and 220 ° C. for a period of 1 to 90 minutes. The retention rate of the receiving coating 14 thus formed is between 5% and 7% relative to the total mass of the prosthesis 10 after drying. This rate preserves the physical and mechanical properties of the prosthesis 10, such as flexibility, piquability and flexibility. In the neutralization step 43, each tubular body 12 is immersed in an aqueous solution of alkali carbonate, for example sodium carbonate. The concentration of this solution is between 1 g / l and 5 g / l. The immersion time of each tubular body 12 in the neutralization solution is for example between 1 minutes and 60 minutes.

Then, a water-soaked washing 72 is performed over three cycles, followed by complete drying of the prostheses 10 provided only with the coating-14 receiving. The pH of the inner surface and the outer surface is then substantially equal to 7.

The step 44 of applying the collagen coating comprises the immersion 74 of the tubular body 12 in an aqueous solution of collagen 76. The collagen is for example chosen from type IV collagens derived from a calf skin. . The concentration of collagen in the solution is between 2% and 4% by weight. The retention rate of collagen on the body 12 is for example between 20% and 30% by weight of the total mass of the body 12 provided with the coatings 14, 16 forming the prosthesis 10 after drying. Collagen is for example provided based on an aqueous solution at acidic pH supplied by the French company SYMATHESE. In the collagen solution, glycerol is added to improve flexibility, and water is added to bring the collagen solution to neutral pH, i.e., about pH 7. of the prosthesis 10 is then performed. Next, the pro-thesis 10 is sterilized using ionizing radiation (3.

The step 46 of loading the active ingredient on the prosthesis 10 is for example performed by the surgeon just before the operation. For this purpose, the prosthesis 10 is immersed in a bath 80 containing the bioactive agent. This bioactive agent is selected from anticoagulants, anti-thrombogenic agents, anti-mitotic agents, anti-proliferation, anti-adhesion, anti-migration agents, cell adhesion promoters, growth factors, antiparasitic molecules, anti-inflammatory drugs, angiogenics, angiogenesis inhibitors, vitamins, hormones, proteins, antifungals, antimicrobial drugs, antiseptics or antibiotics.

The method which has just been described thus makes it possible to obtain prostheses advantageously loaded with a bioactive agent which will be released over time in the body after its implantation in the human body.

The cooperation between a coating 14 for receiving the active ingredient and a sealing coating 16 makes it possible to obtain prostheses which have a very satisfactory seal with a view to their implantation in the human body. Local cooperation between the coatings 14, 16 5 decreases the amount of collagen used while ensuring a good seal, which limits the risks associated with the presence of collagen of animal origin. Surprisingly, the presence of the sealing coating 16 does not affect the ability of the receiving coating 14 to load into bioactive agent, nor its ability to diffuse this agent once implanted into the human body. The amounts of the receiving coating 14 and the sealing coating 16 deposited on the tubular body 12 have been optimized to ensure good physical and mechanical properties (flexibility, piquability, impermeability, flexibility, etc.). the inner surface 20 and the outer surface 24 of the prosthesis 10 ensures the hemocompatibility of the wall 18 coated with the coatings 14, 16 for the subsequent implantation of the prosthesis in the human body and the circulation of the blood within of the pro- The presence of embossings on the prosthesis 10 further improves the grip of the receiving liner 14 on the inner surface 20 and on the outer surface 24 of the prosthesis 14, which decreases the concentration of the precursor mixture solutions 52 and avoids the problems of plication.

A second prosthesis 100 according to the invention is shown in FIG. 4. Unlike the prosthesis 10, it has a single helical groove 110.

Claims (17)

  A method for preparing a tubular prosthesis (10) implantable from a porous material tubular body (12), the method comprising the following successive steps: a) application (50) to the tubular body (12) ) a coating (14) for receiving a bioactive agent, the receiving coating (14) comprising: - at least one cyclodextrin and / or at least one cydodextrin derivative and / or at least one cyclodextrin and / or cyclodextrin derivatives, at least one poly (carboxylic acid), and optionally a catalyst; b) heating (58) the tubular body (12) at a temperature between 100 C and 220 C for a period of 1 to 90 minutes; c) washing (60) with water of the tubular body (12); d) drying (60) the tubular body (12), then e) impregnating (46) the tubular body (12) in a concentrated solution of at least one bioactive agent; characterized in that the method comprises, after the drying step, a step (44) of depositing an additional coating (16) of sealing on the tubular body (12), the tubular body (12) provided with said coatings (14, 16) internally defining a conduit (22) sealed circulation of a liquid.   2. Method according to claim 1, characterized in that the sealing coating (16) is formed based on collagen, gelatin, polyurethane or a polymer capable of sealing the tubular body (12), or their combinations.   3. Method according to one of claims 1 or 2, characterized in that the step (50) for applying the receiving coating (14) comprises impregnating the tubular body with an aqueous solution (52) comprising at least one cyclodextrin and / or at least one derivative of cydodextrin and / or at least one inclusion complex of cyclodextrin and / or cyclodextrin derivatives, at least one polycarboxylic acid, and optionally a catalyst.   4. Method according to any one of claims 1 to 3, characterized in that it comprises, before the heating step (58), a step (56) of precuisson (12) of the tubular body at a temperature of between 40 C and 100 C.   5. Method according to any one of the preceding claims, characterized in that it comprises, after the drying step (60), a step (43) of neutralization of the tubular body (12) to bring it to a pH neutral. 10   6. Method according to any one of the preceding claims, characterized in that the tubular body (12) is formed of a braid, a weave or a knit of at least one polymeric thread, made in particular based on a polymer selected from the group consisting of polyethylene terephthalate (PET), polyethylene terephthalate glycol (PETG), polyurethane (PU) polylactic acid, polyglycolic acid and copolymers thereof, fluoride polyvinylidene (PVDF), polytetrafluoroethylene (PTFE), polyethylene glycol (PEG), polyamide-6, polyamide-6,6, polypropylene, polyethylene and their copolymers, or the combination of these polymers. 20   7. Method according to any one of the preceding claims, characterized in that the receiving coating (14) forms between 5% and 7% of the total mass of the prosthesis (10).   8. Method according to any one of the preceding claims, characterized in that said bioactive agent is selected from anticoagulants, anti-thrombogenic agents, anti-mitotic agents, anti-proliferation, anti-adhesion, anti-migration agents, cell adhesion promoters, growth factors, antiparasitic molecules, anti-inflammatories, angiogenics, angiogenesis inhibitors, vitamins, hormones, proteins, antifungals, anti-microbial molecules, antiseptics or antibiotics.   9. Process according to any one of the preceding claims, characterized in that it comprises, before the step (50) of applying the receiving coating (14) and / or after the washing step. , a step (40) of embossing the tubular body (12).   Implantable tubular prosthesis (10) comprising: - a tubular body (12) of porous material base; A coating (14) for receiving a bioactive agent applied to the tubular body (12), the coating comprising at least one cyclodextrin and / or at least one derivative of cydodextrin and / or at least one inclusion complex of cyclodextrin and / or cyclodextrin derivatives; - at least one bioactive agent received in the receiving coating (14); characterized in that the prosthesis (10) comprises an additional sealing coating (16) deposited on the tubular body (12), the tubular body (12) provided with said coatings (14, 16) internally defining a sealed conduit (22). circulation of a liquid. 15   11. Prosthesis (10) according to claim 10, characterized in that the tubular body (12) has a chemical structure which comprises a hydroxyl function and / or an amine function, said structure being covalently bound to at least one molecule of cyclodextrin or a cyclodextrin compound polymer of the receiving coating, the structure of which is the repetition of the unit of the general formula: - [SB] -X - [- CO- [Ac] -CO-O- [CD] - O-] n-1 (COOH) xy SB representing the chemical structure of the tubular body made of a polymeric material of natural or artificial origin, X being either an oxygen atom or an NH group, x> 3, and 2 <y <(x-1) and (xy)> 1, where x is the number of carboxyl functions carried by the poly (carboxylic acid) before reaction, y represents the number of carboxyl functions of the poly ( carboxylic acid) esterified or arnidified in the reaction, - (xy) is the number of carboxyl functions of the poly (c) acid. arboxylic acid), non-esterified or amidified after reaction, (COOH) xy 1 [Ac] representing the molecular chain of a polycarboxylic acid of formula 5 (COOH) x 1 [Ac] of which at least two carboxyl functions (- COOH) have undergone esterification or esterification and amidification, respectively, and which carry at least one carboxyl group which has not undergone an esterification or amidation reaction; [CD] representing the molecular structure of the cyclodextrins chosen preferentially from: α-cyclodextrin, [3-cyclodextrin, γ-cyclodextrin and mixtures thereof; their derivatives which are preferably chosen from aminated, methylated, hydroxypropylated, sulphobutylated, carboxymethylated or carboxylic derivatives, and mixtures thereof, said bioactive agent being at least one therapeutic molecule forming a complex with the cyclodextrin molecules and / or cyclodextrin derivatives.   12. Prosthesis (10) according to one of claims 10 or 11, characterized in that the receiving coating (14) is formed by a crosslinked polymer of at least one cyclodextrin and / or at least one cyclodextrin derivative and / or at least one inclusion complex of cyclodextrin or of cyclodextrin derivatives and whose structure comprises the repetition of a unit of general formula: 25 - [CD] -O-CO- [Ac] -CO- ## STR5 # carboxylic acid) before reaction, where y is the number of carboxyl functions of the poly (carboxylic acid) esterified in the reaction, where (xy) is the number of carboxyl functions of the poly (carboxylic acid) nonesterified after reaction ( COOH) xy 1 [Ac] 2908047 19 representing the molecular chain of a poly (carboxylic acid) of formula: (COOH): x 1 5 [Ac] of which at least two carboxyl functions (-COOH) have sub an esterification and which carries at least one carboxyl function which has not undergone esterification reaction; [CD] representing the molecular structure of the cyclodextrins selected preferentially from: α-cyclodextrin, R-cyclodextrin, γ-cyclodextrin and mixtures thereof; derivatives thereof which are preferably selected from aminated, methylated, hydroxypropylated, sulfobutylated, carboxymethylated, or carboxylic derivatives, and mixtures thereof, said bioactive agent being a therapeutic molecule complexing with the cyclodextrin molecules and / or cyclodextrin derivatives.   13. Prosthesis (10) according to any one of claims 10 to 12, characterized in that the porous material is formed of a braid, a weave, or a knit of at least one polymeric thread, in particular made from a polymer selected from the group consisting of polyethylene terephthalate (PET), polyethylene terephthalate glycol (PETG), polyurethane (PU) polylactic acid, polyglycolic acid and copolymers thereof, polyvinylidene fluoride (PVDF), polytetrafluoroethylene (PTFE), polyethylene glycol (PEG), polyamide-6, polyamide-6,6, polypropylene, polyethylene and their copolymers, or the combination of these polymers .   14. Prosthesis (10) according to any one of claims 10 to 13, characterized in that the receiving coating (14) forms between 5% and 7% of the total mass of the prosthesis (10).   15. Prosthesis (10) according to any one of claims 10 to 14, characterized in that the bioactive agent is selected from anticoagulants, anti-thrombogenic agents, anti-mitotic agents, antiproliferation agents, anti-adhesion agents. , antimigration, cell adhesion promoters, growth factors, antiparasitic, anti-inflammatory, antifungal, antimicrobial, antiseptic and antibiotic molecules.   16. Prosthesis (10) according to any one of claims 10 to 15, characterized in that the tubular body (12) is embossed. 5   17. Prosthesis (10) according to any one of claims 10 to 16, characterized in that the sealing coating (16) is formed from collagen, gelatin, polyurethane or a polymer capable of sealing the tubular body (12), or combinations thereof.