Method for manufacturing an endoprosthesis in a cavity using a biodegradable sheath

Abstract

The present invention relates to a method for manufacturing an intraluminal endoprosthesis (1), in particular in the form of a stent, the endoprosthesis (1) comprising a support structure (10) and a sheath (3) disposed on the support structure (2), the method comprising the steps of providing a support structure (2) and forming a sheath (3) from polymer fibers on the support structure, a polymer solution being dispensed from a nozzle by electrospinning, the polymer solution (10) comprising at least one biodegradable polymer.

Description

Technical Field

[0001] The present invention relates in particular to a method for manufacturing an endovascular prosthesis in the form of a stent.

Background Art

[0002] Over the past 20 years, the number of interventional vascular (coronary and peripheral) surgeries has been steadily increasing. At the same time, on the one hand, more and more complex and difficult-to-access lesions are being treated, and on the other hand, the number of elderly patients and patients with poor vascular material (e.g., hardened and fragile blood vessels) is increasing. This has led to an increase in the number of patients whose blood vessels are damaged during surgery by the catheters and guidewires used.

[0003] Perforation or rupture of the treated blood vessel can occur. Perforation or rupture is generally a very serious life-threatening complication, especially in the coronary arteries, and must be treated immediately.

[0004] For such treatments, various so-called stent grafts are available, for example in the coronary artery region. Currently available coronary implants consist of a permanent main body made of metal (usually a Co-Cr alloy) and a permanent polymer sheath, preferably made of PTFE or polyurethane, which seals the damage to the blood vessel wall. This sheath can be a simple polymer tube or fabric attached to a stent placed below or above it.

[0005] One drawback of these implants is that they are only needed until the blood vessel wall has healed sufficiently (for about 2 - 3 days) to prevent blood from leaking through the perforated or ruptured area (hemostasis), after which they no longer function.

[0006] However, a permanent polymer sheath (polymer tube or spun cover) can only very slowly and incompletely enable endothelialization inside blood vessels, thereby greatly increasing the overall risk of thrombosis or blood vessel occlusion, which subsequently causes major problems.

[0007] In addition, normal blood vessel peristalsis is hindered by implants that are usually very hard. The main problems or complications are caused by the permanent polymer sheath for the reasons described above. The problems caused by the underlying permanent support structure (such as a stent) are much smaller.

Summary of the Invention

Problems to be Solved by the Invention

[0008] Based on such facts, an object of the present invention is to identify an improved method for manufacturing an endovascular endoprosthesis that is improved with respect to one or more of the above-described problems.

Means for Solving the Problems

[0009] This object is achieved by a method having the features of claim 1. Further aspects of the present invention relate to an endovascular endoprosthesis manufactured by this method.

[0010] Advantageous embodiments of these aspects of the present invention are specified in the corresponding dependent claims and are described below.

[0011] As described in claim 1, a method for manufacturing an endovascular endoprosthesis, particularly in the form of a stent, is disclosed. The endoprosthesis comprises a support structure and a sheath disposed on the support structure. The method comprises: preparing a support structure; and forming a sheath on the support structure by electrospinning a polymer solution containing at least one biodegradable polymer. and

[0012] ​ Preferably, the sheath is strongly spun so that it can seal vascular perforations or ruptures against the blood pressure spreading to the implantation site for at least 48 hours. Support structures (especially stents) and the sheaths disposed thereon are currently divided into two basic types, namely permanent or durable support structures or sheaths and biodegradable support structures or sheaths. Permanent support structures or sheaths are designed so that they can remain indefinitely within blood vessels or at the implantation site in the body of humans or animals. On the other hand, biodegradable support structures or sheaths are decomposed within blood vessels or in the body over a predetermined period. Preferably, the biodegradable support structure is decomposed only after the traumatized tissue of the blood vessel has healed, and the support structure no longer needs to remain in the blood vessel lumen or in the body. Furthermore, it is preferable that the biodegradable sheath is decomposed only when it is no longer necessary to provide a sealing effect.

[0013] According to certain embodiments of the method according to the present invention, at least one biodegradable polymer is selected from the group consisting of polylactide; poly-L-lactide; poly-D,L-lactide; poly-L-lactide-co-D,L-lactide; polyglycolide; polyanhydrides; polyhydroxybutyrate; polyhydroxyvalerate; poly-ε-caprolactone; polydioxanone; poly(lactide-co-glycolide); poly(lactide-co-caprolactone); poly(ethylene glycol-co-caprolactone); poly(glycolide-co-caprolactone); poly(hydroxybutyrate-co-valerate); polytrimethylene carbonate-based polymers; polypropylene succinate; polyphosphazene.

[0014] According to one embodiment of the method, at least one biodegradable polymer may be a copolymer containing two or more different monomers of the polymers of the above group.

[0015] Furthermore, at least one biodegradable polymer may be present in the mixture or blend described in the embodiments of the present method, and the mixture comprises two or more different polymers of the above group. The blend is herein understood to be a macroscopically homogeneous mixture of two or more different polymers.

[0016] Preferably, at least one biodegradable polymer is poly-L-lactide (e.g., Resomer® L210 manufactured by Evonik) or poly-D,L-lactide.

[0017] Furthermore, according to a preferred embodiment of the method according to the present invention, the polymer is poly-D,L-lactide-co-glycolide having a lactide content of 5% to 85% by weight, preferably between 50% and 85% by weight.

[0018] In addition, according to certain embodiments of the present method, at least one biodegradable polymer in the polymer solution is preferably one of the following substances: polyhydroxybutyrate; copolymers containing hydroxybutyrate; polyvalerate; copolymers containing valerate.

[0019] Furthermore, according to certain embodiments of the method according to the present invention, the polymer solution contains at least one additive, and the at least one additive is selected from the group consisting of lactones, citrate esters, glycerol or derivatives thereof, and mixtures thereof. Preferably, the at least one additive is selected from the group consisting of 1,3-dioxan-2-one or 1,4-dioxan-2-one, triethyl citrate, tributyl citrate, glycerol triacetate, n-butyryl tri-n-hexyl citrate, polyethylene glycol, L-α-phosphatidylcholine.

[0020] Generally, the additive(s) substantially affect(s) the mechanical properties (ductility) of the polymer fibers to ensure the required elongation at break. Here, the additives 1,3-dioxan-2-one, triethyl citrate, glycerol triacetate, n-butyryl tri-n-hexyl citrate, and polyethylene glycol all act as plasticizers. Using L-α-phosphatidylcholine can reduce the surface tension and improve the electrospinning process and the hydrophilicity of the cover.

[0021] Endoluminal endoprostheses can assume a compressed state in which they are inserted into the implantation site in the body. At the implantation site, the endoluminal endoprosthesis is expanded and thus left in the implantation site. Therefore, the sheath of the polymer fibers must be able to withstand compression and expansion without impairing the properties of the sheath, especially with regard to permeability. The above additives improve the mechanical properties of the sheath fibers in a beneficial way. The mechanical properties of the sheath of the polymer fibers are maintained even in the case of compression and expansion, especially with regard to permeability. The elongation at break increases or the surface tension decreases so that the fibers are less likely to be damaged during compression or expansion.

[0022] When present as a component of the polymer solution, at least one additive (excluding L-α-phosphatidylcholine) in the polymer solution preferably has a concentration in the range of 5 wt% to 25 wt%, preferably 10 wt% to 20 wt%, and particularly preferably 10 wt% to 15 wt% based on the total mass of the dissolved substances.

[0023] When at least one additive is L-α-phosphatidylcholine, it preferably has a concentration of 1 wt% or less in the polymer solution described in the embodiment.

[0024] According to a preferred embodiment of the method according to the invention, the following is provided: at least one biodegradable polymer is poly-L-lactide (CAS number 26161-42-2), the polymer solution further contains 1,3-dioxan-2-one as an additive, wherein 1,3-dioxan-2-one accounts for 5 wt% to 25 wt%, preferably 10 wt% to 20 wt%, particularly preferably 10 wt% to 15 wt%, preferably 12.5 wt% of the substances dissolved in the polymer solution, and the remaining proportion of the dissolved substances is preferably formed by poly-L-lactide. Other substances dissolved in or otherwise present in the polymer solution may be drugs and / or radiopaque substances.

[0025] Furthermore, according to an embodiment of the method, the polymer solution contains a solvent, and the solvent is selected from the group consisting of chloroform (CHCl 3 ), trifluoroethanol (TFE), and mixtures containing chloroform and trifluoroethanol (TFE), and chloroform and trifluoroethanol are preferably present in a mixing ratio of 1:4 (chloroform:trifluoroethanol).

[0026] Furthermore, according to an embodiment of the method, the following is provided: the polymer solution has a polymer concentration in the range of 1 wt% to 10 wt%, preferably 2 wt% to 8 wt%, particularly preferably 3 wt% to 5 wt%, preferably 4 wt% (based on the mass of the solvent(s) used).

[0027] All additives, drugs and / or radiopaque substances are added (polymer + additives (optional) = total mass of dissolved substances 100%), and the percentage can be between 0 and 20% relative to the total mass of the dissolved substances. The amount of polymer in the solution remains constant.

[0028] Endovascular endoprosthesis is a stent as described in one embodiment, particularly a coronary stent or a peripheral stent.

[0029] The support structure can be, particularly in the case of a stent, a self-expanding support structure or a balloon-expandable support structure. The balloon-expandable support structure may be particularly manufactured, for example, from a tube cut by a laser. In the case of a self-expanding support structure, it may be cut from a tube by laser cutting or may be formed, for example, from a suitable wire.

[0030] The support structure is preferably lattice-shaped and is formed by interconnected bars that define the openings of the support structure. The bars or the openings may be formed from a tube, for example, by laser cutting. A support structure made of wire can also have a grid-like structure.

[0031] Furthermore, a support structure of interconnected bars that define the openings can be formed from a non-metallic material (for example, from a polymer, see also below).

[0032] Furthermore, according to certain embodiments of the method, the support structure is a permanent support structure.

[0033] Such a permanent support structure can consist of, for example, one of the following materials or of the following materials: Co-Cr alloys, Ni alloys, corrosion-resistant stainless steels, Ni-Ti alloys (the atomic ratio of Ni and Ti is approximately equal, for example nitinol), optionally further containing one or more elements Co, Fe, Mn, Ti alloys, Nb alloys, Ta alloys, each in an amount of less than 5%.

[0034] Furthermore, according to another embodiment of the method, the support structure is a biodegradable metal support structure.

[0035] Such a biodegradable metal support structure can consist of, for example, one of the following materials, or the following materials: Mg alloy; Mg-Al-Zn alloy; Mg-Al-Mn alloy; Mg-Al-Zn-Mn alloy; Mg-RE alloy (RE is selected from the rare earth group); Mg-Y-RE alloy (RE is selected from the rare earth group); Mg-RE-Zn alloy (RE is selected from the rare earth group); Mg-Al-Y alloy; Mg-Al-RE alloy (RE is selected from the rare earth group); Mg-Zn-Zr alloy, Mg-Ca-Zn alloy; Mg-Al alloy with an Al content of 3 wt% to 11 wt%; Mg-Ca-Zn alloy with a Zn content of 0.01 wt% to 12 wt%, preferably 0.1 wt% to 5 wt%, and a Ca content of 0.01 wt% to 5 wt%, preferably 0.1 wt% to 1 wt%; Mg-Y-RE- alloy (RE represents other rare earths (not Y), the Y content is 0.1 wt% to 5 wt%, the Nd content is 0.01 wt% to 5 wt%, the Gd content is 0.01 wt% to 3 wt%, the Dy content is 0.01 wt% to 3 wt%, and the alloy may optionally contain 0.1 wt% to 1 wt% of Zr and other rare earths).

[0036] According to another embodiment of the method according to the invention, the support structure is a biodegradable polymer support structure. Here, the balloon-expandable biodegradable polymer stent scaffold or support structure provided by the present invention with a biodegradable sheath may have the stent design described in DE102016117398.

[0037] Furthermore, according to one embodiment of the present method, the polymer support structure comprises one of the following materials or the following materials: biodegradable polymers; poly-L-lactide; poly-D,L-lactide; poly-L-lactide-co-D,L-lactide; polyglycolide; polyanhydrides; polyhydroxybutyrate; polyhydroxyvalerate; poly-ε-caprolactone; polydioxanone; poly(lactide-co-glycolide); poly(lactide-co-caprolactone); poly(ethylene glycol-co-caprolactone); poly(glycolide-co-caprolactone); poly(hydroxybutyrate-co-valerate); polytrimethylene carbonate-based polymers; polypropylene succinate; polyphosphazene; poly-D,L-lactide-co-glycolide having a lactide content of 5 wt% to 85 wt%, preferably 50 wt% to 85 wt%, is provided.

[0038] According to certain embodiments of the present method, the material from which the support structure is formed or the material contained in the support structure may also be a copolymer containing two or more different monomers of the polymers in the above material group.

[0039] Furthermore, according to certain embodiments, the material from which the support structure is formed or the material contained in the support structure may be a copolymer or blend of the above polymers, and the blend contains two or more different polymers of the above support structure material group.

[0040] Furthermore, the support structure may also comprise one of the following materials or may be formed from one of the following materials: copolymers containing hydroxybutyrate; copolymers containing valerate.

[0041] Furthermore, according to certain embodiments of the present method, during electrospinning, it is provided that the polymer solution is applied from the nozzle to the fibrous support structure.

[0042] The polymer solution is preferably dispensed from the nozzle at a volumetric flow rate in the range of 0.1 ml / h [milliliters per hour] to 2 ml / h, preferably in the range of 0.5 ml / h to 0.9 ml / h, and preferably 0.7 ml / h, according to an embodiment of the method.

[0043] According to an embodiment of the method, the nozzle preferably has a distance to the support structure in the range of 50 mm to 200 mm, preferably in the range of 70 mm to 110 mm, and preferably 90 mm.

[0044] Furthermore, according to an embodiment of the method, a voltage in the range of at least 1 kV, preferably 1 kV to 20 kV, particularly preferably 2 kV to 10 kV, and preferably 4 kV is provided to be applied between the nozzle (emitter) and the collector (mandrel) on which the support structure is arranged.

[0045] It is advantageous to place an endoprosthesis in the cavity on the mandrel during electrospinning and to weave a sheath beyond the actual end of the support structure consisting of individual connected bars. The longitudinal extent of the sheath spun from the polymer fibers thus exceeds the longitudinal extent (length) of the support structure. An endoprosthesis having an overly long polymer fiber sheath is then transferred to a suitable mandrel and trimmed by a laser. By doing so, at most half of the width of the outer ring segment of the support structure is no longer covered by the polymer fiber sheath. Such laser trimming of the polymer sheath prevents the detachment of individual fibers or fiber flaps from the endoprosthesis.

[0046] Furthermore, according to an embodiment of the method, the electrospun sheath is exposed to a predetermined temperature for a predetermined time after electrospinning, the time is preferably in the range of 10 hours to 15 hours, the time is preferably 13.5 hours, and the temperature is preferably in the range of 70 °C to 90 °C, and preferably 80 °C.

[0047] According to one embodiment of the method, the polymer solution may contain at least one drug such that the electrospinning sheath contains at least one drug and can release at least one drug.

[0048] According to one embodiment of the method, the support structure, particularly the coating of the support structure, may contain or incorporate a drug such that the drug can be released from the support structure / coating.

[0049] Such drugs incorporated into the polymer sheath or support structure can preferably elute from the polymer or carrier material (e.g., the coating of the support structure) over a period of 7 days to 4 years and help achieve a supportive effect for treatment. Such effects can include, inter alia, - suppression of inflammatory processes that can occur particularly during the degradation of bioresorbable materials, - suppression of proliferative processes that can occur as a result of vascular injury, - support for endothelialization, and - an antithrombotic effect and can be.

[0050] At least one drug of the sheath and / or support structure can be one of the following drugs according to certain embodiments of the invention: drugs having anti-proliferative activity, drugs having anti-inflammatory activity, drugs having antithrombotic activity, paclitaxel, everolimus, mycophenolic acid, angiotensin, enoxaparin, hirudin, acetylsalicylic acid, dexamethasone, rifampicin, minocycline, budesonide, desonide, corticosterone, cortisone, hydrocortisone, prednisolone, heparin, heparin derivatives, urokinase, PPACK.

[0051] Furthermore, according to one embodiment of the method, the polymer solution contains a substance that can be visualized under X-rays.

[0052] A further aspect of the invention relates to endovascular prostheses, particularly in the form of stents (e.g., coronary stents or peripheral stents), produced by the method according to the invention.

[0053] Embodiments of the present invention, as well as further features and advantages, will be described below with reference to the drawings.

Brief Description of the Drawings

[0054]

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

Figure 6

Figure 7

Figure 8

Figure 9

Mode for Carrying Out the Invention

[0055] Figure 1 shows an embodiment of a method according to the present invention for manufacturing an endoprosthesis 1 in the form of a stent (stent graft) in particular, the endoprosthesis 1 having a support structure 2 and a sheath 3 disposed on the support structure 2, the method including the step of providing the support structure 2 and the step of forming the sheath 3 from polymer fibers 30 on the outside of the support structure 2, the polymer solution 10 being dispensed from a nozzle 101 by electrospinning, the polymer solution 10 containing at least one biodegradable polymer.

[0056] In electrospinning, the polymer solution 10 is dispensed from a nozzle (for example, the end of a capillary), which is fluidly connected to a reservoir 100 (for example, syringe-shaped) in which the polymer solution 10 is stored.

[0057] Here, a voltage is applied between the nozzle 101, also known as the emitter, and the collector 200, the voltage being able to be in the range of, for example, 4 kV to 8 kV. The support structure 2 is disposed on the collector 200 and can be rotated (for example, by the collector 200) about the longitudinal axis z, and in particular can be moved along the longitudinal axis z in order to distribute the polymer solution 10 in fiber form on the outside of the support structure 2.

[0058] In electrospinning, the polymer solution forms a so-called Taylor cone T due to the voltage at the nozzle 101 or the capillary opening (see Fig. 1). As a result, the polymer solution 10 is similarly subjected to a high voltage and is irregularly deposited as longitudinally extended fibers 30 on a rotating support structure 2. After evaporation of the solvent (leakage of the solvent), a sheath 3 of the fibers 30 is formed on the support structure 2, and these are bonded (adhered) to each other, forming a non-woven structure as a result of a time-resolved curing process.

[0059] Fig. 2 shows an image recorded by a scanning electron microscope of an endoprosthesis 1 produced by the method according to the invention. This endoprosthesis has a support structure (stent) 2 made of Co-Cr alloy (L605) and a biodegradable electrospun polymer sheath 3.

[0060] Fig. 3 shows a further example according to the invention in the form of a poly-L-lactide-based support structure or stent of a biodegradable polymer, which is covered by a sheath 3 in the form of a fibrous non-woven structure made of poly-L-lactide by electrospinning by the method according to the invention. Thereby, the sheath 3 is applied to the support structure 2 in the non-expanded state of the support structure 2. The desired layer thickness of the sheath 3 can advantageously be made thin and is in the range of 10 μm to 100 μm, preferably 40 μm to 80 μm, and particularly preferably 50 μm to 70 μm.

[0061] Due to a special form of the fibrous non-woven structure, an increase in the elongation at break of the polymer material is achieved, and as a result, the range of polymers that can be used is advantageously increased. In this regard, Fig. 4 shows the elongation at break of an electrospun fleece made of poly-L-lactide (left) compared to a poly-L-lactide foil (right).

[0062] As a further example of an endoprosthesis produced according to the invention, Fig. 5 shows a biodegradable metal Mg-based support structure (high-purity Mg-6.25% Al alloy) having a fibrous non-woven cover of a biodegradable polymer made of poly-L-lactide produced by electrospinning.

[0063] The covering of the support structure 2 with the polymer solution 10 is carried out in the non-expanded state of the support structure 2. The achievable layer thickness can also advantageously be made thin (see above).

[0064] Furthermore, the invention also advantageously enables the use of polymers that allow for high diffusion of water into the polymer material, so that a thin layer thickness of the sheath can be achieved while having a sufficient sealing effect. FIG. 6 shows the integral water permeability over time of five electrospun degradable polymer sheaths made of poly-L-lactide L210 (+12.5% dioxanone) with different layer thicknesses. The integral water permeability first decreases and converges to a value of less than 2 ml×min -1 ×cm -2 after 5 minutes for all layer thicknesses. This shows that in the present invention, the desired low permeability can also be achieved with a thin layer thickness of the polymer fiber sheath.

[0065] Figs. 7 to 9D show further examples of the endoprosthesis 1 in the cavity manufactured according to the invention, where the support structure (not shown) is made of a Co-Cr alloy, and the polymer solution 10 is used as a biodegradable polymer or the dissolved substance poly-L-lactide (PLLA L210, CAS number 26161-42-2) and 12.5 wt% 1,3-dioxan-2-one (based on the total of the dissolved substances), and the polymer in the solvent (CHCl3:TFE, 1:4) has a concentration of 4%.

[0066] In these endoprostheses 1, the electrospinning process takes about 10 minutes per sheath 3. Each support structure is arranged centrally on a mandrel about 10 cm in length forming the collector 200, and the collector has a travel distance of about 6 cm. The distance A between the nozzle 101 and the support structure 2 is 90 mm, and the polymer solution 10 is dispensed through the nozzle 101 at a volume flow rate of 0.7 ml / h [milliliter per hour] and accelerated onto the support structure by a voltage (for example, the nozzle / emitter 101 can be at a potential of 8 kV and the collector 200 can be at a potential of 4 kV). During electrospinning, the temperature, air humidity, exhaust, mass, and layer thickness (e.g., by REM) are recorded for comparison purposes. As a post-treatment, each prosthesis 1 is subjected to tempering (e.g., at 80 °C for 13.5 hours). The produced sheath 3 is trimmed using a CO 2 laser. The cut edges (see FIGS. 7 and 8) show only small fusions and do not show the following support framework. Further, there is no two-dimensional fusion along the circumferential cut of a particular sheath 3.

[0067] FIGS. 9A - 9D show exemplary diameters of the fibers 30 obtained by electrospinning of the sheath 3. The average values of the diameters of the fibers 30 are 785 nm (FIG. 9A), 469 nm (FIG. 9B), 441 nm (FIG. 9C), and 419 nm (FIG. 9D).

[0068] Finally, a measurement report of the endoprosthesis 1 manufactured as described above is given as an example. The support structure 2 (stent) made of Co - Cr alloy (L605) was weighed in a clean room before spinning (according to FIG. 1) (mass m Stent,uncovered = 10.28 μg). Then, the stent 2 was tested on a Diames test bench of IIB e.V. (test laboratory, Rostock - Warnemunde) using a laser to obtain the diameter; the diameter was d Stent,uncovered,mean value = 1.74 mm. Then, the stent 2 was electrospun for 10 minutes, and after the electrospinning process, it was tempered at 80 °C for 13.5 hours in a vacuum drying oven. After tempering, the mass was measured again (m Stent,covered = 11.63 μg). Then, the diameter of the covered stent 2 was measured again (dStent,covered,mean value A cover (sheath) 3 with a layer thickness of 0.07 mm (when = 1.88 mm) was obtained.

[0069] The covered stent 2 was placed on a catheter, shaped into a waveform, then held in tempering water (37 °C) for 30 seconds according to the test instructions, expanded to 3.0 mm within 30 seconds, and further expanded (extended) by leaving it in water for another 30 seconds (holding time). Then, the expanded covered stent was removed from the catheter and dried again at 80 °C for 13.5 hours in a vacuum drying oven. Finally, the covered stent 2 was sputtered onto an SEM slide to determine the fiber diameter (see FIGS. 9A - 9D). Raw data: Mass (m Cover ) of the cover 3: m Stent,uncovered = 10.28 mg, m Stent,covered = 11.63 mg, m Cover = (11.63 - 10.28) mg = 1.35 mg Layer thickness of the cover 3: D Stent,covered -D Stent,uncovered = (1.88 - 1.74) mm = 0.14 mm, layer thickness = (0.14 mm / 2) = 0.07 mm

[0070] The method according to the present invention enables the manufacture of a completely or partially biodegradable implant with an electrospun sheath for treating vascular perforation and vascular rupture.

[0071] The use of biodegradable polymers minimizes potential late - stage effects by using the degradation of the implant. The use of the fibrous non - woven structure created by using electrospinning also offers the advantage that the range of polymers that can be used is increased due to an increase in the elongation at break.

[0072] The present invention further enables the use of a sheath with a reduced layer thickness with sufficient sealing by using a polymer material that allows high diffusion of water into the polymer. Optionally, the polymer sheath may be supported by a hydrogel that can swell rapidly.

[0073] In view of all of the above disclosures, the present invention also provides the following consecutively numbered embodiments.

[0074] 1. A method for manufacturing an endoprosthesis (1) in the form of a stent, in particular, the endoprosthesis (1) comprising a support structure (2) and a sheath (3) disposed on the support structure (2), the method comprising: providing a support structure (2); forming a sheath (3) from polymer fibers (30) on the support structure (2), the forming step comprising dispensing a polymer solution (10) from a nozzle (101) by electrospinning, the polymer solution (10) comprising at least one biodegradable polymer; and a method comprising the above.

[0075] 2. The method according to embodiment 1, characterized in that the at least one biodegradable polymer is selected from the group consisting of polylactide, poly-L-lactide; poly-D,L-lactide; poly-L-lactide-co-D,L-lactide; polyglycolide; polyanhydride; polyhydroxybutyrate; polyhydroxyvalerate; poly-ε-caprolactone; polydioxanone; poly(lactide-co-glycolide); poly(lactide-co-caprolactone); poly(ethylene glycol-co-caprolactone); poly(glycolide-co-caprolactone); poly(hydroxybutyrate-co-valerate); polytrimethylene carbonate-based polymer; polypropylene succinate; polyphosphazene.

[0076] 3. The method according to embodiment 1, characterized in that the polymer is poly-D,L-lactide-co-glycolide having a lactide content of 5% to 85% by weight, preferably 50% to 85% by weight.

[0077] 4. The polymer solution (10) contains at least one additive, and at least one additive is selected from the group consisting of lactones, citrate esters, glycerol or their derivatives, and mixtures thereof, according to the method described in any one of Embodiments 1 to 3.

[0078] 5. At least one additive is selected from the group consisting of 1,3-dioxan-2-one, 1,4-dioxan-2-one, triethyl citrate, glycerol triacetate, n-butyryl tri-n-hexyl citrate, polyethylene glycol, and L-α phosphatidylcholine, according to the method described in Embodiment 4.

[0079] 6. At least one biodegradable polymer is poly-L-lactide, the polymer solution (10) further contains 1,3-dioxan-2-one as an additive, and the proportion of 1,3-dioxan-2-one among the substances dissolved in the polymer solution (10) is in the range of 5% to 25% by weight, preferably 10% to 20% by weight, particularly preferably 10% to 15% by weight, based on the total mass of the dissolved substances, and the remaining proportion of the dissolved substances is preferably formed by poly-L-lactide, according to the method described in any one of Embodiments 1 to 5.

[0080] 7. The substance dissolved in the polymer solution (10) has a concentration in the range of 1% to 10% by weight, preferably 2% to 8% by weight, particularly preferably 3% to 5% by weight, preferably 4% by weight, according to the method described in Embodiment 6.

[0081] 8. The polymer solution (10) contains a solvent, and the solvent is selected from the group consisting of chloroform (CHCl 3 ), trifluoroethanol (TFE), chloroform, and mixtures containing chloroform and trifluoroethanol, and chloroform and trifluoroethanol are preferably present in a mixing ratio of 1:4, according to the method described in any one of Embodiments 1 to 7.

[0082] 9. The method according to any one of Embodiments 1 to 8, characterized in that the support structure (2) is a permanent support structure.

[0083] 10. The method according to any one of Embodiments 1 to 9, characterized in that the support structure (2) consists of one of the following materials or contains at least one of the following materials: Co-Cr alloy, Ni alloy, corrosion-resistant stainless steel, Ni-Ti alloy, Ti alloy, Nb alloy, Ta alloy.

[0084] 11. The method according to any one of Embodiments 1 to 8, characterized in that the support structure (2) is a biodegradable metal support structure.

[0085] 12. The method according to Embodiment 10, characterized in that the support structure (2) contains one of the following materials or is formed from one of the following materials: Mg alloy; Mg-Al-Zn alloy; Mg-Al-Mn alloy; Mg-Al-Zn-Mn alloy; Mg-RE alloy (RE is selected from the rare earth group); Mg-Y-RE alloy (RE is selected from the rare earth group); Mg-RE-Zn alloy (RE is selected from the rare earth group); Mg-Al-Y alloy; Mg-Al-RE alloy (RE is selected from the rare earth group); Mg-Zn-Zr alloy, Mg-Ca-Zn alloy; Mg-Al alloy with an Al content of 0.01 wt% to 12 wt%, preferably 0.1 wt% to 5 wt%, and a Ca content of 0.01 wt% to 5 wt%, preferably 0.1 wt% to 1 wt%; Mg-Y-RE alloy (RE represents another rare earth different from Y, the Y content is 0.1 wt% to 5 wt%, the Nd content is 0.01 wt% to 5 wt%, the Gd content is 0.01 wt% to 3 wt%, the Dy content is 0.01 wt% to 3 wt%, and the alloy optionally contains 0.1 wt% to 1 wt% of Zr and other rare earths).

[0086] 13. The method according to any one of Embodiments 1 to 8, characterized in that the support structure (2) is a biodegradable polymer support structure.

[0087] 14. The support structure (2) comprises one of the following materials or the following materials: biodegradable polymer; poly-L-lactide; poly-D,L-lactide; poly-L-lactide-co-D,L-lactide; polyglycolide; polyanhydride; polyhydroxybutyrate; polyhydroxyvalerate; poly-ε-caprolactone; polydioxanone; poly(lactide-co-glycolide); poly(lactide-co-caprolactone); poly(ethylene glycol-co-caprolactone); poly(glycolide-co-caprolactone); poly(hydroxybutyrate-co-valerate); polytrimethylene carbonate-based polymer; polypropylene succinate; polyphosphazene; poly-D,L-lactide-co-glycolide having a lactide content of 5% to 85% by weight, preferably 50% to 85% by weight, and is formed from one of them. The method according to embodiment 13, characterized in that.

[0088] 15. The polymer solution (10) is dispensed from the nozzle (101) onto the support structure (2) in fiber form during electrospinning, preferably in the range of 0.5 mL / h to 0.9 mL / h, preferably at a volume flow rate of the polymer solution (10) of 0.7 mL / h. The nozzle (101) preferably has a distance (A) from the support structure (2) in the range of 70 mm to 110 mm, preferably 90 mm. A voltage of at least 1 kV, preferably 1 kV to 20 kV, particularly preferably 2 kV to 10 kV, preferably 4 kV is preferably applied between the nozzle (2) and the collector (200) on which the support structure (2) is disposed. The method according to any one of embodiments 1 to 14, characterized in that.

[0089] 16. After electrospinning, the sheath (3) is tempered at a predetermined temperature for a predetermined time. The time is preferably in the range of 10 hours to 15 hours, preferably 13.5 hours. The temperature is preferably in the range of 70 °C to 90 °C, preferably 80 °C. The method according to any one of embodiments 1 to 15, characterized in that.

[0090] 17. An endoprosthesis (1) within a cavity manufactured by the method according to any one of Embodiments 1 to 16.

Claims

1. A method for manufacturing an endoprosthesis (1) in a cavity, wherein the endoprosthesis (1) includes a support structure (2) and a sheath (3) disposed on the support structure (2), The method includes the following: Providing the support structure (2), Forming the sheath (3) from polymer fibers (30) on the support structure (2), provided that a polymer solution (10) is dispensed from a nozzle (101) by electrospinning, and the polymer solution (10) includes at least one biodegradable polymer, and a method characterized by the following: The at least one biodegradable polymer is poly-L-lactide, and the polymer solution (10) further includes 1,3-dioxan-2-one as an additive, and the proportion of 1,3-dioxan-2-one among the substances dissolved in the polymer solution (10) is in the range of 5% to 25% by weight based on the total mass of the substances dissolved in the polymer solution (10).

2. The method according to claim 1, characterized in that the remaining part of the dissolved substance is formed by poly-L-lactide.

3. The method according to claim 1, characterized in that the endoprosthesis (1) in the cavity is a stent.

4. The method according to claim 1, characterized in that the substance dissolved in the polymer solution (10) has a concentration of 1% to 10% by weight in total.

5. The polymer solution (10) contains a solvent, and the solvent is selected from the group consisting of chloroform (CHCl ３ ), trifluoroethanol (TFE), and a mixture containing chloroform and trifluoroethanol. The method according to claim 1, characterized in that.

6. The method according to claim 5, characterized in that chloroform and trifluoroethanol are present in a mixing ratio of 1:

4.

7. The method according to claim 1, characterized in that the support structure (2) is a permanent support structure.

8. The method according to claim 7, characterized in that the support structure (2) is made of one of the following materials, or includes at least one of the following materials: Co-Cr alloy, Ni alloy, corrosion-resistant stainless steel, Ni-Ti alloy, Ti alloy, Nb alloy, Ta alloy.

9. The method according to claim 1, characterized in that the support structure (2) is a biodegradable metal support structure.

10. The method according to claim 9, characterized in that the support structure (2) comprises one of the following materials or is formed from one of the following materials: Mg alloy; Mg-Al-Zn alloy; Mg-Al-Mn alloy; Mg-Al-Zn-Mn alloy; Mg-RE alloy (RE is selected from the rare earth group); Mg-Y-RE alloy (RE is selected from the rare earth group); Mg-RE-Zn alloy (RE is selected from the rare earth group); Mg-Al-Y alloy; Mg-Al-RE alloy (RE is selected from the rare earth group); Mg-Zn-Zr alloy, Mg-Ca-Zn alloy; Mg-Al alloy with an Al content of 0.01 wt% to 12 wt% and a Ca content of 0.01 wt% to 5 wt%; Mg-Y-RE alloy (RE represents another rare earth different from Y, the Y content is 0.1 wt% to 5 wt%, the Nd content is 0.01 wt% to 5 wt%, the Gd content is 0.01 wt% to 3 wt%, the Dy content is 0.01 wt% to 3 wt%, and the alloy optionally contains 0.1 wt% to 1 wt% of Zr and other rare earths).

11. The method according to claim 1, characterized in that the support structure (2) is a biodegradable polymer support structure.

12. The method according to claim 11, characterized in that the support structure (2) comprises one of the following materials or is formed from the following materials: poly-L-lactide; poly-D,L-lactide; poly-L-lactide-co-D,L-lactide; polyglycolide; polyanhydride; polyhydroxybutyrate; polyhydroxyvalerate; poly-ε-caprolactone; polydioxanone; poly(lactide-co-glycolide); poly(lactide-co-caprolactone); poly(ethylene glycol-co-caprolactone); poly(glycolide-co-caprolactone); poly(hydroxybutyrate-co-valerate); polytrimethylene carbonate-based polymer; polypropylene succinate; polyphosphazene; one of poly-D,L-lactide-co-glycolide having a lactide content of 5 wt% to 85 wt%.

13. The polymer solution (10) is dispensed from the nozzle (101) onto the support structure (2) in the form of fibers during electrospinning at a volume flow rate of the polymer solution (10) in the range of 0.5 mL / h to 0.9 mL / h, the nozzle (101) having a distance (A) from the support structure (2) in the range of 70 mm to 110 mm, and a voltage of 1 kV to 20 kV being applied between the nozzle (2) and the collector (200) on which the support structure (2) is disposed. The method according to claim 1, characterized in that.

14. The method according to claim 1, characterized in that after electrospinning, the sheath (3) is tempered at a predetermined temperature for a predetermined time.

15. The method according to claim 14, characterized in that after electrospinning, the sheath (3) is tempered at a predetermined temperature for a predetermined time, the time being in the range of 10 hours to 15 hours and the temperature being in the range of 70 °C to 90 °C.

16. An endoprosthesis (1) in a cavity comprising: - a support structure (2), and - a sheath (3) from electrospun polymer fibers (30) on the support structure (2), provided that the polymer fibers (30) contain at least one biodegradable polymer, the at least one biodegradable polymer being poly-L-lactide, the polymer fibers (30) further containing 1,3-dioxan-2-one as an additive, and the proportion of 1,3-dioxan-2-one among the substances in the polymer fibers (30) being in the range of 5% to 25% by weight based on the total mass of the substances.

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