Preparation method and application of a PTFE artificial blood vessel and a covered stent

Abstract

An embodiment of the present invention provides a method for preparing a PTFE artificial blood vessel, comprising: providing a receiving rod, forming a composite electrospun tube on the receiving rod, wherein the receiving rod includes a mandrel and a mesh support, the mesh support is in a fishing net shape, and the composite electrospun tube includes a PET layer and a PTFE / PEO layer; providing a grooved tube, transferring the composite electrospun tube onto the grooved tube, wherein when transferring the composite electrospun tube, by pulling one end of the mesh support, the mesh support moves towards the grooved tube, and during the movement, the mesh support deforms and separates from the composite electrospun tube; sintering the composite electrospun tube at a high temperature; cooling and separating the composite electrospun tube from the grooved tube to form an artificial blood vessel. Through the above preparation method, on the one hand, a pure PTFE small-diameter artificial blood vessel with a grooved structure on the inner surface can be obtained, and on the other hand, the preparation process is very convenient to operate. At the same time, the present invention also provides an artificial blood vessel prepared by the above preparation method, a preparation method for a stent coating, and a coated stent.

Description

Technical Field

[0001] The present invention relates to an artificial blood vessel, in particular to a preparation method of a PTFE small-diameter artificial blood vessel and an artificial blood vessel prepared by using the method, as well as a preparation method of a covered stent and a covered stent. Background Art

[0002] Polytetrafluoroethylene (PTFE) material is non-toxic, harmless, physiologically inert, surface-hydrophobic and aging-resistant, and is an ideal artificial blood vessel material, which has been widely used in clinic. However, when used for small-diameter (diameter < 6 mm) artificial blood vessels, the blood flow velocity is slow, the blood and tissue cell compatibility on the material surface is poor, and thrombosis and excessive proliferation of neointima are extremely likely to occur, resulting in a very low long-term patency rate of the blood vessel. The presence of the endothelial cell layer can prevent the formation of thrombosis and intimal hyperplasia. Therefore, constructing a surface conducive to rapid endothelialization of blood vessels is the key research direction to solve the poor long-term patency rate of small-diameter polytetrafluoroethylene artificial blood vessels at present.

[0003] The rise of the bionic concept provides inspiration for preparing a surface conducive to endothelialization. The inner membrane of natural blood vessels has grooves on the micron scale along the blood flow direction. Imitating the structure of the inner membrane of natural blood vessels is conducive to the rapid growth of endothelial cells along the groove direction, thereby realizing endothelialization of the artificial blood vessel surface. In addition, the structure of the micro-nano fiber membrane prepared by the electrospinning technology is similar to the structure of the natural extracellular matrix, which is conducive to the adhesion and proliferation of endothelial cells. At present, the preparation of artificial blood vessels of various materials by the electrospinning technology has received wide attention. However, since PTFE basically does not flow after being heated above the melting point (it is difficult to achieve melt electrospinning) and there is no solvent that can dissolve it (it is difficult to achieve solution electrospinning), there are few reports on the preparation of PTFE small-diameter artificial blood vessels by the electrospinning technology at present. At present, the PTFE tubular fiber membrane prepared by the electrospinning technology is mainly used in combination with a metal stent and implanted into the body in the form of a covered stent. The surface of the PTFE tubular fiber membrane has no further treatment, and still faces the problems of poor blood and cell compatibility on the inner surface and poor long-term patency rate, and it is difficult to be directly used as a small-diameter artificial blood vessel.

[0004] The traditional preparation technology of PTFE small-diameter artificial blood vessels requires high-speed hot stretching, which has high requirements for equipment, high energy consumption and high cost. Moreover, the prepared PTFE small-diameter artificial blood vessels have poor blood and cell compatibility. In order to improve its biocompatibility, its surface needs to be subjected to secondary treatment, which is complicated, energy-consuming, and may produce toxic waste, and the process is not environmentally friendly. Summary of the Invention

[0005] Therefore, the present invention provides a preparation method of a PTFE artificial blood vessel to solve the above technical problems.

[0006] A preparation method of a PTFE artificial blood vessel, comprising:

[0007] Providing a receiving rod, and forming a composite electrospun tube on the receiving rod. Wherein, the receiving rod includes a mandrel and a mesh bracket sleeved on the mandrel. The mesh bracket is in a fishing net shape. The composite electrospun tube includes a PET layer attached to the receiving rod and a PTFE / PEO layer formed outside the PET layer;

[0008] Providing a grooved tube, and transferring the composite electrospun tube onto the grooved tube. The outer surface of the grooved tube is provided with a plurality of grooves. Wherein, when transferring the composite electrospun tube, by pulling one end of the mesh bracket, the mesh bracket moves along the axial direction of the grooved tube towards the grooved tube. And, the mesh bracket deforms during the movement and separates from the composite electrospun tube. The grooved tube includes a middle hole. When transferring the composite electrospun tube, one end of the mesh bracket is fixed by a traction wire, and the traction wire is pulled through the middle hole of the grooved tube. And, the mesh bracket penetrates into the middle hole of the grooved tube. The outer diameter of the grooved tube is 0.5 - 1 mm smaller than the outer diameter of the mandrel;

[0009] High-temperature sintering the composite electrospun tube;

[0010] Cooling and separating the composite electrospun tube from the grooved tube to form an artificial blood vessel.

[0011] Further, before forming the PET layer, it further includes the step of preparing a PET spinning solution, and before forming the PTFE / PEO layer, it includes the step of preparing a PTFE / PEO spinning solution. Wherein, the solvent of the PET spinning solution is a mixed solution of trifluoroacetic acid / dichloromethane, and the mass fraction of PET in the solution is 8 - 15%. The PTFE / PEO spinning solution includes a PTFE aqueous dispersion, a PEO aqueous solution, and deionized water. Wherein, the solute mass fraction is 24% - 42%, and the viscosity of the PTFE / PEO spinning solution is 800 - 5000 mP.S.

[0012] Further, when forming the composite electrospun tube on the receiving rod, the rotational speed of the receiving rod is 100 - 500 r / min. A spinning nozzle extrudes a spinning solution towards the receiving rod. The spinning nozzle reciprocates along the axial direction of the mandrel, and the speed is 10 - 30 mm / s. The extrusion speed of the spinning solution is 0.1 - 1 mL / h. The distance between the spinning nozzle and the receiving rod is 10 - 20 cm.

[0013] Further, the grooves are straight grooves, and the straight grooves have a depth of 10 - 1000 μm, and the distance between adjacent straight grooves is 10 - 1000 μm.

[0014] Further, when transferring the composite electrospun tube, the mandrel is first withdrawn from the mesh bracket before pulling the mesh bracket.

[0015] Furthermore, the molecular weight of the PTFE is 100-150 Da, and the mass fraction of PTFE in the PTFE aqueous dispersion is 58%-62%.

[0016] Furthermore, the molecular weight of the PEO is 4,000,000-7,000,000 Da, and the mass fraction of PEO in the prepared PEO aqueous solution is 1%-5%.

[0017] Furthermore, the reticular stent includes a first form in a natural state and a second form sleeved on the mandrel. The reticular stent is cylindrical, including an inner diameter and a length. In the first form, the inner diameter of the reticular stent is 0.2-2 mm smaller than the diameter of the mandrel. In the second form, the inner diameter of the reticular stent is equal to the diameter of the mandrel. And, in the second form, the length of the reticular stent is greater than the length of the reticular stent in the first form. At the same time, before providing the receiving rod, an external force is applied to the reticular stent to cause the two ends of the reticular stent to contract and the inner diameter to increase, and then it is sleeved on the mandrel. After that, the external force is removed, and the reticular stent elongates and is fixed on the mandrel.

[0018] Furthermore, the grooved tube includes a side wall, and the side wall of the grooved tube has a thickness of 1-2 mm.

[0019] The present invention also simultaneously provides an artificial blood vessel prepared by using the above preparation method.

[0020] The present application also simultaneously provides a preparation method of a covered stent,

[0021] Provide a receiving rod, and form a composite electrospun tube on the receiving rod. Among them, the receiving rod includes a mandrel and a reticular stent sleeved on the mandrel in a fishing net shape. The composite electrospun tube includes a PET layer attached to the receiving rod and a PTFE / PEO layer formed outside the PET layer;

[0022] Provide a grooved tube, and transfer the composite electrospun tube onto the grooved tube. The outer surface of the grooved tube is provided with a plurality of grooves. Among them, when transferring the composite electrospun tube, by pulling one end of the reticular stent, the reticular stent moves along the axial direction of the grooved tube towards the grooved tube, and the reticular stent deforms and separates from the composite electrospun tube during the movement;

[0023] High-temperature sinter the composite electrospun tube;

[0024] Cool and separate the composite electrospun tube from the grooved tube to form a covered tube;

[0025] Provide an elastic stent, and transfer the covered tube onto the elastic stent.

[0026] And, the present application also simultaneously provides a covered stent prepared by using the above method.

[0027] Beneficial effects: The embodiment of the present invention provides a preparation method of a small-caliber PTFE artificial blood vessel, including: providing a receiving rod, and forming a composite electrospun tube on the receiving rod, wherein the receiving rod includes a mandrel and a net-shaped bracket sleeved on the mandrel, the net-shaped bracket is in a fishing net shape, and the composite electrospun tube includes a PET layer attached to the receiving rod and a PTFE / PEO layer formed outside the PET layer; providing a grooved tube, and transferring the composite electrospun tube onto the grooved tube, wherein a plurality of grooves are provided on the outer surface of the grooved tube. When transferring the composite electrospun tube, by pulling one end of the net-shaped bracket, the net-shaped bracket moves along the axial direction of the mandrel towards the grooved tube, and during the movement, the net-shaped bracket deforms and separates from the composite electrospun tube; sintering the composite electrospun tube at a high temperature; cooling and separating the composite electrospun tube from the grooved tube to form an artificial blood vessel. Through the above preparation method, on the one hand, a small-caliber artificial blood vessel with a grooved structure on the inner surface and made of pure PTFE can be obtained, and on the other hand, the preparation process is very convenient to operate. At the same time, the present invention also provides an artificial blood vessel prepared by the above preparation method, a preparation method of a covered stent, and a covered stent. Description of the drawings

[0028] Figure 1 Schematic diagram of the preparation device in the preparation method of the PTFE artificial blood vessel of the present invention

[0029] Figure 2 is Figure 1 schematic diagram of the mandrel and the net-shaped bracket in

[0030] Figure 3 is a schematic diagram of the grooved tube;

[0031] Figure 4 is a schematic diagram of transferring the composite electrospun tube onto the grooved tube;

[0032] Figure 5 is an enlarged schematic diagram of the surface of the artificial blood vessel.

[0033] Illustration of the components in the drawings:

[0034] Spinning nozzle 10; Net-shaped bracket 20; Mandrel 30; Driving device 40; Grooved tube 50; Composite electrospun tube 60. Detailed implementation manners

[0035] The present invention provides a preparation method of a PTFE artificial blood vessel, specifically including:

[0036] S1: Provide a receiving rod, and form a composite electrospun tube 60 on the receiving rod, wherein the receiving rod includes a mandrel 30 and a net-shaped bracket 20 sleeved on the mandrel 30, the net-shaped bracket 20 is in a fishing net shape, and the composite electrospun tube 60 includes a PET layer attached to the receiving rod and a PTFE / PEO layer formed outside the PET layer.

[0037] Please also refer to Figure 1 and Figure 2 , in Figure 1 a schematic diagram of a preparation device for preparing a PTFE artificial blood vessel is shown, Figure 2 a schematic diagram of a receiving rod is shown, and the preparation method will be described in detail below in conjunction with this preparation device.

[0038] The mesh stent 20 is in a fishing net shape. In this embodiment, the mesh stent 20 includes a number of grid units. Each grid unit is formed by connecting a plurality of filaments and has a hollow mesh hole. The mesh stent 20 is in a cylindrical shape and has elasticity. It can be understood that when an axial traction force towards the outside is applied to one end or both ends of the mesh stent 20, the mesh stent 20 can deform, and the diameter of the cylindrical shape of the mesh stent 20 decreases under this traction force.

[0039] The mandrel 30 is generally in a round rod shape, and its material is preferably a metal material, more preferably stainless steel. Preferably, it has a diameter of 2 - 6 mm. It can be understood that when the mesh stent 20 is in its natural state, that is, when not acted upon by an external force, it is also in a cylindrical shape with a diameter of 2 - 6 mm. That is, the diameter of the mesh stent 20 is the same as or slightly smaller than the diameter of the mandrel 30, so that the mesh stent 20 can just be sleeved on the mandrel 30, and when the mandrel 30 rotates, it can easily rotate along with the mandrel 30.

[0040] Furthermore, the mesh stent 20 includes a spiral warp thread, and this spiral warp thread continuously extends from one end of the mesh stent to the other end.

[0041] In a preferred embodiment, the mesh stent 20 includes a first form, and the first form is the form when no external force acts on the mesh stent 20. In the first form, the mesh stent 20 is in a cylindrical shape, including an inner diameter and a length. And, in the first form, the inner diameter of the mesh stent 20 is less than or equal to the mandrel diameter. Preferably, in the first form, the inner diameter of the mesh stent 20 is 0.2 - 2 mm less than the mandrel diameter. When the mesh stent 20 is sleeved on the mandrel 30, it presents a second form. It can be understood that in the second form, the inner diameter of the mesh stent 20 is equal to the diameter of the mandrel 30, and the mesh stent 20 has a contraction force to stably fix the mesh stent 20 on the mandrel 30. It can be understood that in the second form, the length of the mesh stent 20 is greater than the length of the mesh stent 20 in the first form. Therefore, in this case, before providing the receiving rod, it also includes the step of applying an external force to the mesh stent 20 to cause the two ends of the mesh stent 20 to contract, increase the inner diameter, then sleeve it onto the mandrel 30, and then remove the external force, and the mesh stent 20 elongates and is fixed on the mandrel 30.

[0042] A driving device 40 is connected to the mandrel 30 for driving the mandrel 30 to rotate. In a specific embodiment, the driving device 40 can be a motor. At the same time, in order to facilitate the connection with the mandrel 30 and the installation of the mandrel 30, a coupling is further provided between the mandrel 30 and the driving device 40.

[0043] A spinning nozzle 10 is provided above the receiving rod. When the receiving rod rotates, the spinning solution extruded from the spinning nozzle 10 can be wound around the receiving rod and form a predetermined shape. In this embodiment, the spinning nozzle 10 is a spinning needle. At the same time, the spinning nozzle 10 reciprocates axially along the mandrel 30 to form multiple layers of electrospun fibers on the receiving rod. It can be understood that in the present invention, multiple layers of electrospun fibers with the same material are referred to as one layer, such as the PET layer or the PEO / PTFE layer in the following description.

[0044] In this embodiment, the rotational speed of the receiving rod is 100 - 500 r / min, the reciprocating speed of the spinning nozzle 10 axially along the mandrel 30 is 10 - 30 mm / s, the extrusion speed of the spinning solution is 0.1 - 1 mL / h, the distance between the spinning nozzle 10 and the receiving rod is 10 - 20 cm, the ambient temperature is 20 - 30 °C, the humidity is 10% - 30%, and the voltage is 8 - 15 kV.

[0045] When forming the composite electrospun tube 60 on the receiving rod, first form a PET layer on the receiving rod, and then form a PTFE / PEO layer on the formed PET layer. It can be understood that when forming the PET layer on the receiving rod, the PET layer adheres to the mesh support 20 of the receiving rod. At the same time, first form a PET layer on the mesh support 20. On the one hand, it is used to fill the pores of the mesh support 20 to prevent the pores of the mesh support 20 from affecting the uniformity of the PTFE / PEO layer. On the second hand, directly electrospinning the PTFE / PEO layer on the mesh support 20 is likely to absorb moisture and adhere to the mesh support 20. Electrospinning a hydrophobic PET layer first to cover the mesh support 20 is more conducive to the demolding of the composite electrospun tube 60.

[0046] It can be understood that before forming the PET layer, it also includes the step of preparing the PET spinning solution, and before forming the PTFE / PEO layer, it includes the step of preparing the PTFE / PEO spinning solution. Among them, the solvent of the PET spinning solution is a mixed solution of trifluoroacetic acid / dichloromethane, and the mass fraction of PET in the solution is 8 - 15%. The PTFE / PEO spinning solution includes PTFE aqueous dispersion, PEO aqueous solution, and deionized water, where the solute mass fraction is 24% - 42%, and the viscosity of the PTFE / PEO spinning solution is 800 - 5000 mP.S.

[0047] Further, the molecular weight of PTFE is 100-150 Da, and the mass fraction of PTFE in the PTFE aqueous dispersion is 58%-62%.

[0048] Further, the molecular weight of PEO is 4,000,000-7,000,000 Da, and the mass fraction of PEO in the prepared PEO aqueous solution is 1%-5%.

[0049] In addition, the function of PEO in the PTFE / PEO spinning solution is: to act as a spinning carrier for PTFE and solve the problem that pure PTFE dispersion cannot be spun. Under the action of an electric field, as PEO is stretched into fibers, the PTFE particles loaded on PEO also pile up into a fibrous shape. The decomposition temperature of PEO is lower than the sintering temperature and is removed after sintering. The molten PTFE fills the voids generated after the decomposition of PEO to form PTFE fibers.

[0050] Further, the mesh stent 20 includes side walls, and the thickness of the PET layer is greater than the thickness of the side walls of the mesh stent 20. It can be understood that when the mesh stent is formed by a single wire spirally, the side plate thickness of the mesh stent 20 is the diameter of the single wire. In this case, the PET layer can completely isolate the PTFE / PEO layer from the mesh stent 20.

[0051] It can be understood that after the composite electrospun tube 60 is formed on the mesh stent 20, the mesh stent 20 will be embedded in the PET layer.

[0052] S2: Provide a grooved tube 50 and transfer the composite electrospun tube 60 onto the grooved tube 50. Among them, when transferring the composite electrospun tube 60, by pulling one end of the mesh stent 20, the mesh stent 20 moves axially along the core shaft 30 towards the grooved tube 50. Moreover, the mesh stent 20 deforms during the movement and separates from the composite electrospun tube 60. The grooved tube 50 includes a middle hole. When transferring the composite electrospun tube 60, one end of the mesh stent 20 is fixed by a traction wire, and the traction wire is passed through the middle hole of the grooved tube 50. Moreover, the mesh stent 20 penetrates into the middle hole of the grooved tube 50. The outer diameter of the grooved tube 50 is 0.5-1 mm smaller than the outer diameter of the core shaft.

[0053] Please refer to Figure 3, the groove tube 50 is a hollow tube, including a central hole, and its outer diameter is slightly smaller than the outer diameter of the mandrel 30. Preferably, the outer diameter of the groove tube 50 is 0.5 - 1 mm smaller than the outer diameter of the mandrel 30. In this case, on the one hand, it is convenient to sleave the composite electrospun tube 60 formed in step S1 onto the groove tube 50; on the other hand, because the main component of the composite electrospun tube 60 is PTFE, PTFE has a large linear expansion coefficient and poor thermal conductivity, and is prone to deformation and cracking. Therefore, in order to prepare a thin and non-cracking pure PTFE electrospun tube, it is necessary to ensure that there is a gap between the composite electrospun tube 60 and the groove tube 50, which is convenient for the PTFE electrospun tube to shrink without cracking after subsequent high-temperature sintering.

[0054] The outer surface of the groove tube 50 is provided with grooves, and the grooves are straight grooves. The straight grooves refer to the grooves provided on the outer surface of the groove tube 50 being strip-shaped. Preferably, these straight grooves penetrate the length direction of the groove tube 50.

[0055] Furthermore, the straight grooves have a depth of 10 - 1000 μm, and the distance between adjacent straight grooves is 10 - 1000 μm. At the same time, the groove tube 50 is a metal tube. On the one hand, the hollow metal tube is more conducive to the uniform heating of the supported composite electrospun tube 60. On the other hand, after sintering, the electrospun tube melts and flows, and shrinks inward and adheres tightly to the outer surface of the groove tube 50, so that the inner surface of the composite electrospun tube 60 also generates a longitudinal groove structure. Furthermore, the groove tube 50 is an aluminum tube or a metal tube with a thermal conductivity greater than or equal to that of aluminum. In addition, when the straight grooves have a depth of 10 - 1000 μm and the distance between adjacent straight grooves is 10 - 1000 μm, it can just make the PTFE fill into the straight grooves after sintering, without pores or excessive filling of PTFE resulting in fiber deformation extrusion and the difference in fiber distribution between the inner and outer layers becoming larger.

[0056] Please refer to Figure 4 , Figure 4 which shows a schematic diagram of transferring the composite electrospun tube 60. When transferring the composite electrospun tube 60, at least one end of the mesh support 20 is fixed with a traction wire, and the traction wire passes through the central hole of the groove tube 50. When a traction force is applied to the traction wire, while the diameter of the mesh support 20 becomes smaller, it penetrates into the central hole of the groove tube 50, so that the mesh support 20 moves along the axial direction of the mandrel 30 towards the groove tube 50. Moreover, the mesh support 20 deforms during the movement and separates from the composite electrospun tube 60. It can be understood that due to a traction force along the axial direction acting on the mesh support 20, the diameter of the mesh support 20 decreases, so that it naturally falls off from the inner wall of the composite electrospun tube 60, that is, the mesh support 20 drives the composite electrospun tube 60 to move onto the groove tube 50 and separates from the groove tube 50, that is, the process of separation and transfer is completed simultaneously.

[0057] Furthermore, the side wall of the groove tube 50 has a thickness of 1-2 mm. In this thickness case, the mesh bracket 20 can easily drive the composite electrospun tube 60 to move on the groove tube 50 and separate from the groove tube 50. At the same time, the side wall is not too thin to form an edge, causing damage to the composite electrospun tube 60, nor is the side wall of the groove tube 50 too thick, resulting in the need for the mesh bracket 20 to generate a large deformation to detach from the composite electrospun tube 60 during separation, or the mesh bracket 20 cannot easily move in the middle hole due to being resisted by the side wall.

[0058] It can be understood that the mandrel 30 can be withdrawn from the mesh bracket 20 before pulling the mesh bracket 20.

[0059] Furthermore, at least one end of the mesh bracket 20 can be fixed with a traction wire. The traction wire passes through the middle hole of the groove tube 50. When a traction force is applied to the traction wire, while the diameter of the mesh bracket 20 becomes smaller, it penetrates into the middle hole of the groove tube 50, and the composite electrospun tube 60 maintains its original diameter and moves onto the groove tube 50, making it easier for the composite electrospun tube 60 to drive the composite electrospun tube 60 to be sleeved onto the groove tube 50 while separating from the composite electrospun tube 60.

[0060] S3: High-temperature sintering of the composite electrospun tube 60.

[0061] It can be understood that the groove tube 50 sleeved with the composite electrospun tube 60 is placed on a bracket, heated up to decompose PET and PEO, and PTFE melts and flows to fill the voids generated by the decomposition of PET and PEO and the groove voids. Preferably, a box furnace can be used to perform high-temperature sintering on the composite electrospun tube 60, heating up to 360°C - 400°C at a rate of 4 - 6°C / min and then holding for 8 - 15 min.

[0062] On the one hand, through high-temperature sintering, the PET and PEO components in the composite electrospun tube 60 are removed. The sintering temperature and holding time are sufficient to decompose other components, while PTFE only melts and does not decompose. On the other hand, PTFE melts and flows into the voids. The voids include the voids generated after the decomposition of other components and the voids between the composite electrospun tube 60 and the groove tube 50 itself, especially the straight-groove voids on the groove tube 50, which helps to change the inner surface structure of the composite electrospun tube 60 after cooling and shrinking. On the third hand, the PTFE particles melt and diffuse and bond into a whole, greatly improving the mechanical strength of the pure polytetrafluoroethylene tubular membrane.

[0063] S4: Cool and separate the composite electrospun tube 60 from the groove tube 50 to form an artificial blood vessel.

[0064] Preferably, the composite electrospun tube 60 can be cooled by natural cooling. At the same time, since the mechanical strength of the pure PTFE tube obtained after sintering is good, it can be directly removed from the grooved tube 50, thereby obtaining an artificial blood vessel with a grooved structure on the inner surface.

[0065] The preparation method of the PTFE artificial blood vessel of the present invention will be further described below through a specific embodiment.

[0066] Example 1:

[0067] S11: Prepare a PET spinning solution and a PTFE / PEO spinning solution.

[0068] PET spinning solution: PET is dissolved in a mixed solvent of trifluoroacetic acid and dichloromethane. Among them, the mass ratio of trifluoroacetic acid to dichloromethane is 4:1, and it is magnetically stirred at 25 °C until it is completely dissolved into a transparent solution to prepare a PET spinning solution with a mass fraction of 10%.

[0069] PTFE / PEO spinning solution: Slowly dissolve PEO powder with a molecular weight of 5 million in deionized water, and magnetically stir at 25 °C until it is transparent to prepare a PEO aqueous solution with a solute mass fraction of 4%; Mix the commercially available PTFE concentrated dispersion with a mass fraction of 60% and the 4% PEO aqueous solution according to the mass ratio of PTFE to PEO of 97:3, and then add an appropriate amount of deionized water to prepare a co-blended spinning solution with a total solute mass fraction of 34%, and the viscosity of the spinning solution is 1422 mP.S.

[0070] S12: Prepare a receiving rod. The receiving rod includes a mandrel 30 and a mesh support 20 sleeved on the mandrel 30. Among them, the outer diameter of the mandrel 30 and the inner diameter of the mesh support 20 are both 4 mm.

[0071] With the parameters: electrospinning voltage 15 kV, extrusion speed 1 ml / hr, receiving rod rotation speed 100 rpm, reciprocating movement speed of the spinning nozzle 10 is 20 mm / s, moving amplitude of the spinning nozzle 10 is 60 mm, distance from the tip of the spinning nozzle 10 to the receiving rod is 10 cm, ambient temperature 25 °C, relative humidity 15%, electrospinning time 5 min, electrospin a PET layer on the receiving rod.

[0072] With the parameters: electrospinning voltage 8 kV, extrusion speed 0.1 ml / h, receiving rod rotation speed 400 rpm, reciprocating movement speed of the spinning nozzle 10 is 20 mm / s, moving amplitude of the spinning nozzle 10 is 60 mm, distance between the spinning nozzle 10 and the receiving rod is 15 cm, ambient temperature 25 °C, relative humidity 15%, electrospinning time 4 h, electrospin a PTFE / PEO layer on the PET layer.

[0073] S13: Provide a grooved tube 50 and transfer the composite electrospun tube 60 onto the grooved tube 50.

[0074] Specifically, the outer diameter of the grooved tube 50 is 3 mm, and several straight-grooved grooves with a depth of about 0.1 mm and a width of 0.7 mm are provided on the surface. The grooved tube 50 is an aluminum tube. The mandrel 30 is drawn out from the combination of the composite electrospun tube 60 and the receiving rod, placed vertically, and the upper and lower ends of the mesh bracket 20 are fixed with cotton threads. The cotton thread at the lower end passes through the central hole of the grooved tube 50, and the cotton thread is pulled to deform the mesh bracket 20 under force and reduce its diameter. At the same time, when the composite electrospun tube 60 is separated from the mesh bracket 20, it is sleeved on the outer surface of the grooved tube 50. It can be understood that placing it vertically can utilize the gravity of the composite electrospun tube 60 at the same time, moving downward and thus being more easily sleeved on the grooved tube 50. In addition, the cotton thread can also be other cord-like or thread-like materials as the traction line.

[0075] S14: High-temperature sintering.

[0076] The grooved tube 50 sleeved with the composite electrospun tube 60 is horizontally placed on a metal rack and placed in a box furnace. It is heated to 380 °C at a rate of 5 °C / min and kept warm for 10 min. During the process, PET and PEO decompose, and PTFE melts and flows to fill the voids generated by the decomposition of PET and PEO and the grooved voids.

[0077] S15: Cooling and forming an artificial blood vessel.

[0078] After keeping warm at 380 °C for 10 min, the box furnace is closed, and the formed PTFE tube is naturally cooled to room temperature in the box furnace. The PTFE tube obtained after sintering has good mechanical strength and can be directly removed from the straight-grooved aluminum tube to obtain a pure PTFE small-diameter artificial blood vessel with a grooved structure on the inner surface and a diameter of 3 mm.

[0079] It can be understood that the present invention also provides an artificial blood vessel prepared by the above method. The diameter of the electrospun fiber is between 400 nm and 2500 nm. The tensile fracture strength of the artificial blood vessel is between 1 and 3 MPa, the elongation at break is between 50% and 350%, the thickness is between 60 and 300 microns, and the porosity is between 65% and 85%.

[0080] In addition, the present application also provides a preparation method of a covered stent at the same time, which will be described below with a specific embodiment.

[0081] Example 2:

[0082] S21: Prepare a PET spinning solution and a PTFE / PEO spinning solution.

[0083] PET spinning solution: Among them, the mass fraction of the PET spinning solution is 12%, and the other preparation processes and parameters are the same as those in step S11.

[0084] PTFE / PEO spinning solution: The mass fraction of the blended spinning solution is 40%, the viscosity of the spinning solution is 2587 mP.S, and the other configuration processes and parameters are the same as those in step S11.

[0085] S22: Prepare a receiving rod, which includes a mandrel and a mesh support sleeved on the mandrel. Among them, the outer diameter of the mandrel and the inner diameter of the mesh support are both 6 mm.

[0086] With the parameters: electrospinning voltage 20 kV, extrusion speed 0.8 ml / hr, receiving rod rotation speed 150 rpm, reciprocating movement speed of the spinning nozzle 10 10 mm / s, moving amplitude of the spinning nozzle 10 50 mm, distance from the tip of the spinning nozzle 10 to the receiving rod 15 cm, ambient temperature 25 °C, relative humidity 15%, electrospinning time 8 min, electrospin a PET layer on the receiving rod.

[0087] With the parameters: electrospinning voltage 15 kV, extrusion speed 0.5 ml / h, receiving rod rotation speed 500 rpm, reciprocating movement speed of the spinning nozzle 10 10 mm / s, moving amplitude of the spinning nozzle 10 50 mm, distance between the spinning nozzle 10 and the receiving rod 18 cm, ambient temperature 25 °C, relative humidity 15%, electrospinning time 1.5 h, electrospin a PTFE / PEO layer on the PET layer.

[0088] S23: Provide a grooved tube and transfer the composite electrospun tube onto the grooved tube.

[0089] The outer diameter of the grooved tube is 5 mm, and the surface is provided with several straight grooves about 0.2 mm deep and 1.0 mm wide. Transfer the composite electrospun tube onto the grooved tube according to the steps in S13.

[0090] S24: High-temperature sintering.

[0091] High-temperature sinter with the same parameters as in step 14 to form a PTFE tube.

[0092] S25: Cool and form a stent coating.

[0093] Obtain a pure PTFE coated tube with a grooved structure on the inner surface and a diameter of 5 mm with the same technical parameters and steps as in step S25.

[0094] S26: Provide an elastic stent and transfer the coated tube onto the elastic stent.

[0095] Stretch the elastic stent with an inner diameter of 5.5 mm axially, introduce it into the middle hole of the coated tube. Viscous substances such as sericin and chitosan are pre-coated on the elastic stent, and the coated tube and the elastic stent are compounded together by means of the viscous substances and the expansion of the elastic stent to form a coated stent.

[0096] In addition, this application also provides a covered stent, which is prepared by using the preparation method of the covered stent.

[0097] The above are only the embodiments of the present invention, and thus do not limit the patent scope of the present invention. Any equivalent structure or equivalent process transformation made by using the content of the specification and drawings of the present invention, or directly or indirectly applied in other related technical fields, shall be equally included in the patent protection scope of the present invention.

Claims

1. A preparation method of a PTFE artificial blood vessel, characterized in that, Comprising: Providing a receiving rod, and forming a composite electrospun tube on the receiving rod. The receiving rod includes a mandrel and a net-shaped bracket sleeved on the mandrel in a fishing net shape. The composite electrospun tube includes a PET layer attached to the receiving rod and a PTFE / PEO layer formed outside the PET layer; Providing a grooved tube, and transferring the composite electrospun tube onto the grooved tube. The outer surface of the grooved tube is provided with a plurality of grooves. When transferring the composite electrospun tube, by pulling one end of the net-shaped bracket, the net-shaped bracket moves along the axial direction of the grooved tube towards the grooved tube. And during the movement, the net-shaped bracket deforms and separates from the composite electrospun tube. The grooved tube includes a middle hole. When transferring the composite electrospun tube, one end of the net-shaped bracket is fixed by a traction wire, and the traction wire is passed through the middle hole of the grooved tube. And the net-shaped bracket penetrates into the middle hole of the grooved tube. The outer diameter of the grooved tube is 0.5 - 1 mm smaller than the outer diameter of the mandrel; High-temperature sintering the composite electrospun tube; Cooling and separating the composite electrospun tube from the grooved tube to form an artificial blood vessel.

2. The preparation method of the PTFE artificial blood vessel according to claim 1, characterized in that, Before forming the PET layer, it further includes the step of preparing the PET spinning solution, and before forming the PTFE / PEO layer, it includes the step of preparing the PTFE / PEO spinning solution. The solvent of the PET spinning solution is a mixed solution of trifluoroacetic acid / dichloromethane, and the mass fraction of PET in the solution is 8 - 15%. The PTFE / PEO spinning solution includes a PTFE aqueous dispersion, a PEO aqueous solution, and deionized water, where the solute mass fraction is 24% - 42%, and the viscosity of the PTFE / PEO spinning solution is 800 - 5000 mP.S.

3. The preparation method of the PTFE artificial blood vessel according to claim 2, characterized in that, When forming the composite electrospun tube on the receiving rod, the rotational speed of the receiving rod is 100 - 500 r / min. A spinning nozzle extrudes the spinning solution towards the receiving rod. The spinning nozzle reciprocates along the axial direction of the mandrel, and the speed is 10 - 30 mm / s. The extrusion speed of the spinning solution is 0.1 - 1 mL / h, and the distance between the spinning nozzle and the receiving rod is 10 - 20 cm.

4. The preparation method of the PTFE artificial blood vessel according to claim 3, characterized in that, The groove is a straight-groove. The straight-groove has a depth of 10 - 1000 μm, and the distance between adjacent straight-grooves is 10 - 1000 μm.

5. The preparation method of the PTFE artificial blood vessel according to claim 4, characterized in that, The molecular weight of the PTFE is 100 - 150 Da, the mass fraction of PTFE in the PTFE aqueous dispersion is 58% - 62%, the molecular weight of the PEO is 4,000,000 - 7,000,000 Da, and the mass fraction of PEO in the prepared PEO aqueous solution is 1 - 5%.

6. The preparation method of the PTFE artificial blood vessel according to claim 4, characterized in that, The described mesh stent includes a first form in a natural state and a second form sleeved on a mandrel. The mesh stent is cylindrical and includes an inner diameter and a length. In the first form, the inner diameter of the mesh stent is 0.2 - 2 mm smaller than the diameter of the mandrel. In the second form, the inner diameter of the mesh stent is equal to the diameter of the mandrel. And, in the second form, the length of the mesh stent is greater than the length of the mesh stent in the first form. At the same time, before providing the receiving rod, an external force is applied to the mesh stent to cause the two ends of the mesh stent to contract and the inner diameter to increase, and then it is sleeved on the mandrel, and then the external force is removed, and the mesh stent extends and is fixed on the mandrel.

7. The preparation method of the PTFE artificial blood vessel according to claim 4, characterized in that, The described grooved tube includes a side wall, and the side wall of the grooved tube has a thickness of 1 - 2 mm.

8. An artificial blood vessel, characterized in that, Prepared by using any of the methods as claimed in claims 1 - 7.

9. A method for preparing a covered stent, characterized in that, Provide a receiving rod and form a composite electrospun tube on the receiving rod. Among them, the receiving rod includes a mandrel and a mesh stent in a fishing net shape sleeved on the mandrel. The composite electrospun tube includes a PET layer attached to the receiving rod and a PTFE / PEO layer formed outside the PET layer; Provide a grooved tube and transfer the composite electrospun tube onto the grooved tube. The outer surface of the grooved tube is provided with a number of grooves. Among them, when transferring the composite electrospun tube, by pulling one end of the mesh stent, the mesh stent moves along the axial direction of the grooved tube towards the grooved tube. And, the mesh stent deforms and separates from the composite electrospun tube during the movement. The grooved tube includes a middle hole. When transferring the composite electrospun tube, one end of the mesh stent is fixed by a traction wire, and the traction wire is pulled through the middle hole of the grooved tube. And, the mesh stent penetrates into the middle hole of the grooved tube. The outer diameter of the grooved tube is 0.5 - 1 mm smaller than the outer diameter of the mandrel; High-temperature sinter the composite electrospun tube; Cool and separate the composite electrospun tube from the grooved tube to form a covered tube; Provide an elastic stent and transfer the covered tube onto the elastic stent.

10. A covered stent, characterized in that, Prepared by using the method as claimed in claim 9.

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