A drug-eluting stent with a coating and its preparation method

Abstract

The present invention relates to the technical field of medical devices, and provides a drug-eluting stent with a membrane and a preparation method thereof, including: a stent body; an inner membrane is strip-shaped, and the outer side of the inner membrane is spirally arranged in contact with the inner wall of the stent body; a drug-eluting membrane is strip-shaped, and is correspondingly arranged on the outer side of the stent body with respect to the inner membrane, and the drug-eluting membrane is in contact with the outer side of the stent body and the inner membrane; an outer membrane is arranged on the outermost side of the stent, covering the stent body and the drug-eluting membrane, and is in contact with the part of the inner membrane that is not in contact with the drug-eluting membrane. The outer membrane includes a first region and a second region. The first region includes the part corresponding to the inner membrane, and the second region includes the part corresponding to the spiral gap of the inner membrane; the total endothelialization period of the second region, the corresponding part of the stent body in the second region, and the inner side of the inner membrane is less than the degradation period of the first region and less than the degradation period of the inner membrane. By wrapping the drug-eluting membrane inside the inner membrane and the outer membrane and differentiating different regions of the outer membrane, rapid endothelialization of the stent is achieved and excessive cell proliferation is avoided.

Description

Technical Field

[0001] The present invention relates to the technical field of medical devices, and in particular to a drug-eluting stent with a membrane and a preparation method thereof. Background Art

[0002] In the field of the treatment of cardiovascular diseases, the implantation of vascular stents is a common interventional means. After traditional vascular stents are implanted into the human body, they face two major challenges: one is that the endothelialization process is slow, which is not conducive to the close combination and long-term stability of the stent and the blood vessel wall. The slow process of endothelial cells covering the surface of the stent not only increases the risk of stent displacement, but also may lead to thrombosis, thus affecting the treatment effect and the safety of patients; the other is that after endothelialization is completed, the stent fails to effectively control the proliferation of vascular smooth muscle cells. This uncontrolled cell proliferation may lead to restenosis in the blood vessel, affecting blood flow patency, and patients need to receive additional treatment, increasing the medical cost and the pain of patients.

[0003] The existing designs of vascular stents fail to effectively solve the above problems. The slow endothelialization speed makes the stent prone to displacement under the impact of blood flow in the initial stage of implantation, while the uncontrolled cell proliferation after endothelialization may lead to restenosis of the blood vessel again. Both of these situations seriously affect the treatment effect of the stent and the quality of life of patients.

[0004] In view of this, the present invention aims to provide a novel vascular stent, which can rapidly promote the endothelialization process after implantation, ensure that the stent can quickly and stably fit with the blood vessel wall, and at the same time effectively inhibit the excessive proliferation of cells after endothelialization is completed, so as to ensure the long-term patency of the blood vessel and reduce the risk of restenosis. Summary of the Invention

[0005] The purpose of the present invention is to provide a drug-eluting stent with a membrane and a preparation method thereof, so as to solve the technical problems in the prior art that the endothelialization speed of the stent is slow and the uncontrolled cell proliferation after endothelialization leads to restenosis of the blood vessel.

[0006] In a first aspect, an embodiment of the present invention provides a drug-eluting stent with a coating, comprising: a stent body, which plays a supporting role; an inner membrane, which is strip-shaped, and the outer side of the inner membrane is spirally arranged in contact with the inner wall of the stent body, and there are gaps between the spirals of the inner membrane; a drug-eluting membrane, which is strip-shaped and is correspondingly arranged outside the stent body with the inner membrane, the drug-eluting membrane is in contact with the outer side of the stent body and the inner membrane, and the width of the drug-eluting membrane is smaller than the width of the inner membrane; an outer membrane, which is arranged on the outermost side of the stent, covers the stent body and the drug-eluting membrane, and is in contact with the part of the inner membrane that is not in contact with the drug-eluting membrane, the outer membrane includes a first region and a second region, the first region includes the part corresponding to the inner membrane, and the second region includes the part corresponding to the spiral gap of the inner membrane; the total endothelialization period of the second region, the corresponding part of the stent body of the second region, and the inner side of the inner membrane is less than the degradation period of the first region and less than the degradation period of the inner membrane.

[0007] Further, the fiber porosity of the second region is greater than the fiber porosity of the first region and / or the diameter of the second region is smaller than the fiber diameter of the first region.

[0008] Further, the width of the first region is greater than or equal to the width of the second region, and the width of the drug-eluting membrane is greater than or equal to half of the width of the inner membrane.

[0009] Further, the drug loading amount of the drug-eluting membrane is generated based on the drug loading coefficient, the porosity of the drug-eluting membrane, and the volume of the drug-eluting membrane.

[0010] Further, the thickness of the second region is greater than or equal to the thickness of the first region.

[0011] Further, the materials of the stent body, the inner membrane, the drug-eluting membrane, and the outer membrane include one or a combination of several of polylactic acid, poly(lactic-co-glycolic acid), polycaprolactone, poly(lactic-co-caprolactone), poly(p-dioxanone), polyglycolic acid, and polyhydroxyalkanoates.

[0012] Further, the stent body adopts a mesh structure.

[0013] In a second aspect, an embodiment of the present invention further provides a preparation method of a drug-eluting stent with a coating, comprising the drug-eluting stent with a coating as described in the previous item, and preparing the inner membrane by spraying or blending processes; preparing the stent body by 3D printing process; preparing the drug-eluting membrane by spraying or blending processes; spraying the drug on the drug-eluting membrane; and preparing the outer membrane by spraying or blending processes.

[0014] In a third aspect, an embodiment of the present invention further provides a method for preparing a drug-eluting stent with a film coating, including the drug-eluting stent with a film coating as described in the previous item. An inner film is prepared by spraying or blending processes; a stent body is prepared by a 3D printing process; a drug-loaded film is prepared by a process of mixing and extruding a drug with a polymer material; and an outer film is prepared by spraying or blending processes.

[0015] Further, the drug is at least one of paclitaxel and rapamycin.

[0016] The embodiment of the present invention has at least the following technical effects:

[0017] A drug-eluting stent with a film coating provided by an embodiment of the present invention has an inner film spirally arranged inside the stent body. The drug-loaded film is arranged outside the stent body and its width is smaller than that of the inner film. The outer film covers the stent body and the drug-loaded film and adheres to a part of the inner film that is not adhered to the drug-loaded film. In this way, the drug-loaded film is equivalent to being wrapped inside the inner film and the outer film. The anti-proliferative drug carried on the drug-loaded film cannot be released after the stent starts to be implanted into the human blood vessel, so it will not affect the proliferation of endothelial cells and helps the stent to be endothelialized quickly.

[0018] At the same time, considering that the stent needs to be crimped before implantation and it is more convenient for crimping, both the inner film and the drug-loaded film are set in a spiral shape. To prevent the drug-loaded film from being broken or even falling off during the crimping process, since the only purpose of the drug-loaded film is to carry more drugs, its resistance to falling off and breaking is very poor. The inner film is arranged inside the stent body, and the inner film adheres to the drug-loaded film and the outer film through the hollow part of the stent body, wrapping the drug-loaded film between the inner film and the outer film. In this way, even if the drug-loaded film is broken during the crimping process, it is still wrapped inside, preventing the formation of thrombus due to the broken drug-loaded film. The outer film wrapping outside the drug-loaded film also prevents the drug-loaded film from falling off. At the same time, it can also achieve the purpose of the drug-loaded film carrying more drugs. Through the drug-loaded film wrapped inside, at this time, the drug-loaded film does not need to consider the problem of falling off and breaking, and a material with stronger drug-carrying ability can be selected.

[0019] The outer membrane includes a first region and a second region. The first region corresponds to the inner membrane, and the second region corresponds to the spiral gap of the inner membrane. That is to say, the first region and the inner membrane wrap the drug-loading membrane inside, and the second region adheres to the stent body. The total endothelialization period of the second region, the corresponding part of the stent body of the second region, and the inner side of the inner membrane is less than the degradation period of the first region and the inner membrane. When endothelial cells attach, proliferate, and even cover the second region, the corresponding part of the stent body of the second region, and the inner side of the inner membrane, the endothelialization of the entire stent is completed. The degradation periods of the first region and the inner membrane must be greater than this total endothelialization period to ensure that after the stent is endothelialized, the anti-proliferative drug carried by the drug-loading membrane begins to be released to inhibit the proliferation of vascular smooth muscle cells and avoid vascular restenosis. After the stent is endothelialized, the first region and the inner membrane both degrade, and the drug-loading membrane may lack restraint and fall off or break. However, since the endothelialization has been completed at this time, the stent is covered and fixed by endothelial cells, and the drug-loading membrane is also wrapped by endothelial cells. Therefore, even if the inner and outer membranes degrade, there is no fear of the drug-loading membrane falling off or breaking, and the drug-loading membrane can still play a role in inhibiting the proliferation of vascular smooth muscle cells.

[0020] Therefore, by wrapping the drug-loading membrane inside the inner membrane and the outer membrane, and the total endothelialization period of the second region, the corresponding part of the stent body of the second region, and the inner side of the inner membrane is less than the degradation period of the first region and the inner membrane, the covered drug-eluting stent of the present invention realizes the rapid endothelialization of the stent, avoids vascular restenosis caused by excessive cell proliferation, and the overall design of the stent is also more convenient for intraoperative crimping, reducing the possibility of the outer membrane and the drug-loading membrane falling off. BRIEF DESCRIPTION OF THE DRAWINGS

[0021] In order to more clearly illustrate the specific embodiments of the present invention or the technical solutions in the prior art, the following will briefly introduce the drawings required for the description of the specific embodiments or the prior art. Obviously, the drawings in the following description are some embodiments of the present invention. For those of ordinary skill in the art, without creative efforts, other drawings can also be obtained based on these drawings.

[0022] Figure 1 It is a partial cross-sectional view of a covered drug-eluting stent provided by an embodiment of the present invention;

[0023] Figure 2 is Figure 1 the cross-sectional view at AB in

[0024] Figure 3 It is an overall schematic diagram of a covered drug-eluting stent provided by an embodiment of the present invention.

[0025] Reference numerals: 1 - stent body; 2 - inner membrane; 3 - drug-loading membrane; 4 - outer membrane; 41 - first region; 42 - second region. DETAILED DESCRIPTION OF THE EMBODIMENTS

[0026] The technical solution of the present invention will be clearly and completely described below in conjunction with the embodiments. Obviously, the described embodiments are part of the embodiments of the present invention, rather than all of the embodiments. All other embodiments obtained by those of ordinary skill in the art based on the embodiments of the present invention without creative efforts shall fall within the protection scope of the present invention.

[0027] Those skilled in the art of the present technology can understand that, unless otherwise defined, all terms used herein (including technical terms and scientific terms) have the same meaning as the general understanding of those of ordinary skill in the art to which the present invention belongs. It should also be understood that terms such as those defined in a general dictionary should be understood to have a meaning consistent with the meaning in the context of the prior art, and will not be interpreted in an idealized or overly formal sense unless specifically defined as here.

[0028] Those skilled in the art of the present technology can understand that, unless specifically stated, the singular forms "a", "an", "the" and "said" used herein may also include the plural forms. It should be further understood that the term "comprising" used in the specification of the present invention means the presence of the described features, integers, steps, operations, elements and / or components, but does not exclude the presence or addition of one or more other features, integers, steps, operations, elements, components and / or their combinations. The phrase "and / or" used herein includes all or any unit and all combinations of one or more of the associated listed items.

[0029] In a first aspect, please refer to Figures 1 to 3 , an embodiment of the present invention provides a drug-coated stent, comprising: a stent body 1, which plays a supporting role; an inner membrane 2, the inner membrane 2 is strip-shaped, the outer side of the inner membrane 2 is spirally arranged in contact with the inner wall of the stent body 1, and there is a gap between the spirals of the inner membrane 2; a drug-coated membrane 3, the drug-coated membrane 3 is strip-shaped, and is correspondingly arranged on the outer side of the stent body 1 with the inner membrane 2, the drug-coated membrane 3 is in contact with the outer side of the stent body 1 and the inner membrane 2, and the width of the drug-coated membrane 3 is smaller than the width of the inner membrane 2; an outer membrane 4, the outer membrane 4 is arranged on the outermost side of the stent, covering the stent body 1 and the drug-coated membrane 3, and is in contact with the part of the inner membrane 2 that is not in contact with the drug-coated membrane 3, the outer membrane 4 includes a first region 41 and a second region 42, the first region 41 includes the part corresponding to the inner membrane 2, and the second region 42 includes the part corresponding to the spiral gap of the inner membrane 2; the total endothelialization period of the second region 42, the corresponding part of the stent body 1 of the second region 42, and the inner side of the inner membrane 2 is less than the degradation period of the first region 41 and less than the degradation period of the inner membrane 2.

[0030] In this embodiment, the inner membrane 2 is spirally arranged inside the stent body 1, the drug-loading membrane 3 is arranged outside the stent body 1 and its width is smaller than that of the inner membrane 2, and the outer membrane 4 covers the stent body 1 and the drug-loading membrane 3 and is attached to the part of the inner membrane 2 that is not attached to the drug-loading membrane 3. In this way, the drug-loading membrane 3 is equivalent to being wrapped by the inner membrane 2 and the outer membrane 4. The anti-proliferation drug carried on the drug-loading membrane 3 cannot be released after the stent starts to be implanted into the human blood vessel, so it will not affect the proliferation of endothelial cells and helps the stent to be quickly endothelialized.

[0031] At the same time, considering that the stent needs to be compressed before implantation for easier compression, the inner membrane 2 and the drug-loading membrane 3 are both arranged in a spiral shape. To prevent the drug-loading membrane 3 from being broken or even falling off during the compression process, since the only purpose of the drug-loading membrane 3 is to carry more drugs, its resistance to falling off and breaking is very poor. The inner membrane 2 is arranged inside the stent body 1, and the inner membrane 2 adheres to the drug-loading membrane 3 and the outer membrane 4 through the hollow part of the stent body 1, so that even if the drug-loading membrane 3 is broken during the compression process, it is still wrapped inside, preventing the formation of thrombus due to the broken drug-loading membrane 3. The outer membrane 4 wrapped outside the drug-loading membrane 3 also prevents the drug-loading membrane 3 from falling off, and at the same time can also achieve the purpose of the drug-loading membrane 3 carrying more drugs. Through the drug-loading membrane 3 wrapped inside, at this time, the drug-loading membrane 3 does not need to consider the problem of falling off and breaking, and a material with stronger drug-loading ability can be selected.

[0032] The outer membrane 4 includes a first region 41 and a second region 42. The first region 41 corresponds to the inner membrane 2, and the second region 42 corresponds to the spiral gap of the inner membrane 2. That is to say, the first region 41 and the inner membrane 2 wrap the drug-loading membrane 3 inside, and the second region 42 adheres to the stent body 1; the total endothelialization period of the second region 42, the part of the stent body 1 corresponding to the second region 42, and the inner side of the inner membrane 2 is shorter than the degradation periods of the first region 41 and the inner membrane 2. When endothelial cells attach, proliferate and even cover the second region 42, the part of the stent body 1 corresponding to the second region 42, and the inner side of the inner membrane 2, the endothelialization of the entire stent is completed. The degradation periods of the first region 41 and the inner membrane 2 must be greater than this total endothelialization period to ensure that after the stent is endothelialized, the anti-proliferation drug carried by the drug-loading membrane 3 begins to be released to inhibit the proliferation of vascular smooth muscle cells and avoid vascular restenosis; after the stent is endothelialized, the first region 41 and the inner membrane 2 both degrade, and the drug-loading membrane 3 may fall off and break due to lack of restraint. However, since the endothelialization has been completed at this time, the stent is covered and fixed by endothelial cells, and the drug-loading membrane 3 is also wrapped by endothelial cells. Therefore, even if the inner and outer membranes degrade, the drug-loading membrane is not afraid of falling off and breaking, and the drug-loading membrane 3 can still play a role in inhibiting the proliferation of vascular smooth muscle cells.

[0033] Therefore, the drug-eluting stent with a coating of the present invention wraps the drug-eluting membrane 3 inside the inner membrane 2 and the outer membrane 4, and the total endothelialization period of the second region 42, the corresponding part of the stent body 1 of the second region 42, and the inner side of the inner membrane 2 is less than the degradation period of the first region 41 and the inner membrane 2, achieving rapid endothelialization of the stent, avoiding restenosis caused by excessive cell proliferation, and the overall design of the stent is also more convenient for intraoperative crimping, reducing the possibility of the outer membrane 4 and the drug-eluting membrane 3 falling off.

[0034] Preferably, the total endothelialization period is 30 - 60 days, and the degradation period of the first region 41 or the inner membrane 2 is 60 - 90 days. It should be noted that the degradation period of the first region 41 or the inner membrane 2 here does not mean that the first region 41 or the inner membrane 2 is completely degraded and metabolized in the human body, but refers to the period when the first region 41 or the inner membrane 2 loses its covering and protective effect on the drug-eluting membrane 3, enabling the drug-eluting membrane 3 to contact the human body and release the anti-proliferation drug. For example, the stent completes endothelialization on the 50th day after implantation, and when either the first region 41 or the inner membrane 2 fails on the 70th day, the drug-eluting membrane 3 can contact the human body and start releasing the drug.

[0035] Optionally, the fiber porosity of the second region 42 is greater than the fiber porosity of the first region 41, and / or the diameter of the fibers in the second region 42 is less than the fiber diameter of the first region 41. In this embodiment, if the membrane layer has a suitable fiber porosity and a suitable fiber diameter, it will be more conducive to the adhesion and proliferation of endothelial cells. The fiber porosity of the second region 42 is set within the range suitable for the adhesion and proliferation of endothelial cells, and the fiber diameter of the second region 42 is set within the range suitable for the adhesion and proliferation of endothelial cells. Therefore, the fiber porosity of the second region 42 being greater than the fiber porosity of the first region 41, or the fiber diameter of the second region 42 being less than the fiber diameter of the first region 41 can ensure that endothelial cells cover the second region 42 as quickly as possible and then cover the entire interior of the stent, or the endothelialization speed of the second region 42 can be accelerated by jointly adjusting the fiber porosity and the fiber diameter. Moreover, a small fiber porosity or a large fiber diameter in the first region 41 can slow down the degradation speed of the first region 41, so that before the entire stent is endothelialized, the drug-eluting membrane 3 is still wrapped by the first region 41 and the inner membrane 2, and the anti-proliferation drug has not been released, and the drug will not have a negative impact on the endothelialization speed of the stent. Preferably, the fiber porosity of the second region 42 is 50% - 70%, and the fiber diameter of the second region 42 is 0.4 μm - 4 μm; the fiber porosity of the first region 41 is 10% - 50%, and the fiber diameter of the first region 41 is 1.5 μm - 4 μm.

[0036] Optionally, the width W1 of the first region 41 is greater than or equal to the width W2 of the second region 42, and the width W3 of the drug-loaded film 3 is greater than or equal to half of the width of the inner membrane 2. In this embodiment, the width W1 of the first region 41 is also the width of the inner membrane 2, and the width W2 of the second region 42 is the width of the spiral gap of the inner membrane 2. The width of the inner membrane 2 is greater than or equal to the width of its spiral gap, which can not only ensure that there is enough bonding area between the outer membrane 4 and the inner membrane 2 so that they will not fall off during press-fitting and can wrap the drug-loaded film 3 therein, but also ensure that the drug-loaded film 3 will not have insufficient drug loading due to too narrow a width. Preferably, considering the influence on the endothelialization cycle of the stent, the width W1 of the first region 41 is less than or equal to 2 times the width W2 of the second region 42.

[0037] Optionally, the drug loading of the drug-loaded film 3 is generated based on the drug loading coefficient, the porosity of the drug-loaded film, and the volume of the drug-loaded film. In this embodiment, considering that if the drug-loaded film 3 is prepared by co-extruding the drug and the polymer, there will be fiber loss during the manufacturing process. Therefore, the product of the drug loading coefficient Y, the porosity H of the drug-loaded film, and the volume V of the drug-loaded film is used to calculate the actual drug loading X of the stent, that is, X = YHV, to ensure more accurate mastery of the drug loading data of the stent. Specifically, the drug loading coefficient Y here refers to the percentage of the drug in the polymer, and the product of the porosity H of the drug-loaded film and the volume V of the drug-loaded film is the actual fiber amount of the drug-loaded film 3. The calculation formula for the volume V of the drug-loaded film is

[0038] ,

[0039] where W1 is the width of the first region 41, W2 is the width of the second region 42, W3 is the width of the drug-loaded film 3, T3 is the thickness of the drug-loaded film 3, L is the length of the stent body 1, D is the outer diameter of the stent body 1, and X is the adjustment coefficient (because the helix will cause the film width to be inclined in the length direction). Therefore is the projection of the width of the inner membrane 2 and the width of the inner membrane gap in one spiral period in the length direction of the stent, it can be calculated how many spiral periods of the drug-loaded film 3 the entire stent includes, and is the length of the drug-loaded film 3 in one spiral period.

[0040] Optionally, the thickness T2 of the second region 42 is greater than or equal to the thickness T1 of the first region 41. In this embodiment, the thickness T2 of the second region 42 being greater than or equal to the thickness T1 of the first region 41 helps to improve the endothelialization efficiency. The relatively thicker second region 42 can better contact with vascular endothelial cells, promote the adhesion and proliferation of endothelial cells, and accelerate the endothelialization process of the stent. Preferably, the thickness T2 of the second region 42 is greater than or equal to the sum of the thicknesses of the first region 41 and the drug-loading membrane 3. If the thickness T2 of the second region 42 is equal to the sum of the thicknesses of the first region 41 and the drug-loading membrane 3, the outer surface of the stent will be smoother at this time, enabling the blood vessel to be stressed evenly. If the thickness T2 of the second region 42 is greater than the sum of the thicknesses of the first region 41 and the drug-loading membrane 3, the second region 42 will be closer to the blood vessel at this time, which is beneficial to promoting the adhesion and proliferation of endothelial cells, and the relatively prominent helix formed by the second region 42 can better get stuck in the blood vessel to ensure that the stent does not displace. Which specific thickness combination to adopt can be determined according to needs and in combination with the requirements in actual use.

[0041] It should be noted that Figure 2 the thicknesses of the intima 2, the drug-loading membrane 3, the first region 41, and the second region 42 in are schematically enlarged, mainly to more intuitively reflect their positional and thickness relationships. The wire diameter d of the stent body is only a schematic demonstration. In actual needs, this diameter d may also be larger than the thicknesses of the intima 2, the drug-loading membrane 3, the first region 41, or the second region 42. However, the drug-loading membrane 3 or the outer membrane 4 will cover the outside of the stent body 1, the drug-loading membrane 3 or the outer membrane 4 will also exist in the voids formed by the wire diameter of the stent body 1, and the first region 41 covers the outside of the drug-loading membrane 3 and contacts the intima 2. These relative positional relationships are determined.

[0042] Optionally, the materials of the stent body 1, the inner membrane 2, the drug-loaded membrane 3, and the outer membrane 4 include one or a combination of several of polylactic acid, or poly(lactic-co-glycolic acid), or polycaprolactone, or poly(lactic-co-caprolactone), or poly(p-dioxanone), or polyglycolic acid, or polyhydroxyalkanoates. In this embodiment, these materials are used because, after being implanted into the human body, these materials generally do not cause significant immune responses, such as allergic or rejection reactions, and their degradation products are usually non-toxic and can be safely metabolized and excreted by the human body. For example, polylactic acid and poly(lactic-co-glycolic acid) are degraded into lactic acid and glycolic acid in the body and ultimately converted into carbon dioxide and water. And these materials can promote cell adhesion, proliferation, and differentiation, which is beneficial to tissue repair and regeneration. For example, polycaprolactone has good cell compatibility and can support cell growth. Moreover, they are not likely to cause thrombosis in the blood, reducing the risk of thrombus-related complications after implantation. At the same time, by optimizing the molecular structure and composition of the materials, their biostability and controllability can be improved, reducing inflammatory reactions and vascular restenosis. Specific examples are as follows. The inner membrane 2 can be selected as polycaprolactone or poly(lactic-co-caprolactone) because of its low melting point and good adhesion to the stent body 1. The stent body 1 can be selected as polylactic acid because of its generally higher hardness and better supportability. The drug-loaded membrane 3 can be selected as polycaprolactone with good flexibility. The outer membrane 4 can be selected as polycaprolactone or poly(lactic-co-caprolactone). The above are only examples, and other materials can be used in combination according to actual needs, such as by monitoring and improving the endothelialization cycle and degradation cycle, so as to achieve better effects.

[0043] Optionally, the stent body 1 adopts a grid-like structure. In this embodiment, the stent body 1 adopts a grid-like structure. The grid-like structure endows the stent with good flexibility, enabling it to adapt to the bending and deformation of blood vessels while still having sufficient mechanical strength to support the blood vessels. Moreover, this structure is also convenient for implantation and crimping operations. The grid-like structure makes it easier for the stent to be delivered into the blood vessel through a catheter and is not easily damaged during the implantation process. The grid-like structure with good flexibility has less impact on blood flow, which can reduce the risk of thrombosis and vascular injury. The grid can be a rhombic grid or a parallelogram grid as shown in Figure 1 Figure, and the size and density of the grid can be adjusted according to requirements.

[0044] In a second aspect, the embodiment of the present invention provides a method for preparing a drug-coated stent, including the drug-coated stent as described in the previous item. The inner membrane 2 is prepared by spraying or blending processes; the stent body 1 is prepared by 3D printing technology; the drug-loaded membrane 3 is prepared by spraying or blending processes; the drug is sprayed on the drug-loaded membrane 3; and the outer membrane 4 is prepared by spraying or blending processes.

[0045] In this embodiment, first, the inner membrane 2 is prepared, then the stent body 1 is prepared, then the drug-loaded membrane 3 is prepared, the drug is sprayed on the drug-loaded membrane 3, and finally the outer membrane 4 is prepared. The outer membrane 4 wraps around the outside of the stent body 1 and the drug-loaded membrane 3.

[0046] Specifically, if the spraying process is adopted, it should be noted that the selected membrane layer material needs to be dissolved in an appropriate solvent to form a uniform solution. Using a spraying device, the solution is atomized into tiny droplets through a nozzle. For example, to form the spiral inner membrane 2, drug-loaded membrane 3, first region 41, and second region 42, either the receiving mandrel can rotate or the nozzle of the spraying device can rotate. After spraying, it can be judged according to actual needs whether the membrane layer needs to be dried and cured. For example, after the inner membrane 2 is prepared, it does not need to be completely cured, and directly preparing the stent body 1 can make the inner membrane 2 bond better with the stent body 1. However, if it is the outer membrane 4 after preparation, it must be dried and cured to ensure the stability of the entire stent. If the blending process is adopted, the membrane layer material needs to be melted or dissolved, and using electrospinning technology, the polymer solution is ejected through a spinneret to form fibers. Similarly, it can also be judged according to needs whether heat treatment or other post-treatments are required for the deposited fiber layer.

[0047] Specifically, when spraying the drug on the drug-loaded membrane 3, ultrasonic spraying technology can be adopted, which can break the liquid into uniform micron-sized droplets, spray evenly and with precise dosage. The drug loading amount can be calculated based on the material dosage of the ultrasonic spraying device.

[0048] In the third aspect, the embodiment of the present invention provides a method for preparing a drug-coated stent, including the drug-coated stent described in the previous item. The inner membrane 2 is prepared by spraying or blending processes; the stent body 1 is prepared by 3D printing process; the drug-loaded membrane 3 is prepared by the process of mixing and extruding the drug with a polymer material; the outer membrane 4 is prepared by spraying or blending processes.

[0049] In this embodiment, first, the inner membrane 2 is prepared, then the stent body 1 is prepared, and then the drug-loaded membrane 3 is prepared by the process of mixing and extruding the drug with a polymer material. Finally, the outer membrane 4 is prepared, and the outer membrane 4 wraps around the outside of the stent body 1 and the drug-loaded membrane 3. When preparing the drug-loaded membrane 3 by the process of mixing and extruding the drug with a polymer material, since the drug is mixed with the polymer material, it can effectively ensure that the drug is continuously released as the drug-loaded membrane 3 degrades, and better inhibit cell proliferation during the later degradation of the stent. If the drug-loaded membrane 3 is prepared by the method of co-extruding the drug and the polymer, the actual drug loading amount X of the stent should be calculated according to the product of the drug loading coefficient Y, the porosity H of the drug-loaded membrane, and the volume V of the drug-loaded membrane, that is, X = YHV, to ensure more accurate mastery of the drug loading data of the stent.

[0050] Optionally, the drug is at least one of paclitaxel and rapamycin. In this embodiment, the drug is at least one of paclitaxel and rapamycin, or the two can be used in combination. Both drugs can effectively reduce cell proliferation after stent implantation and reduce the risk of in-stent restenosis.

[0051] Those skilled in the art of the present technology can understand that the steps, measures, and solutions in the various operations, methods, and processes discussed in the present invention can be alternated, changed, combined, or deleted. Further, the other steps, measures, and solutions in the various operations, methods, and processes discussed in the present invention can also be alternated, changed, rearranged, decomposed, combined, or deleted. Further, the steps, measures, and solutions in the prior art that are the same as those disclosed in the various operations, methods, and processes of the present invention can also be alternated, changed, rearranged, decomposed, combined, or deleted.

[0052] In the description of the present invention, it should be understood that the orientation or positional relationship indicated by the terms "center", "upper", "lower", "front", "rear", "left", "right", "vertical", "horizontal", "top", "bottom", "inner", "outer", etc. is based on the orientation or positional relationship shown in the drawings. It is only for the convenience of describing the present invention and simplifying the description, rather than indicating or implying that the device or element referred to must have a specific orientation, be constructed and operated in a specific orientation, and therefore should not be construed as a limitation of the present invention.

[0053] The terms "first" and "second" are only used for descriptive purposes and cannot be understood as indicating or implying relative importance or implicitly specifying the quantity of the indicated technical features. Thus, the features defined with "first" and "second" may explicitly or implicitly include one or more of such features. In the description of the present invention, unless otherwise specified, the meaning of "plurality" is two or more.

[0054] In the description of the present invention, it should be noted that unless otherwise clearly defined and limited, the terms "installed", "connected", and "connected" should be understood in a broad sense. For example, it can be a fixed connection, a detachable connection, or an integral connection; it can be directly connected, or indirectly connected through an intermediate medium, and it can be the communication inside two elements. For those of ordinary skill in the art, the specific meanings of the above terms in the present invention can be understood according to specific situations.

[0055] In the description of this specification, specific features, structures, materials, or characteristics can be combined in a suitable manner in any one or more embodiments or examples.

[0056] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention, rather than to limit it; although the present invention has been described in detail with reference to the foregoing embodiments, those of ordinary skill in the art should understand that they can still modify the technical solutions described in the foregoing embodiments, or perform equivalent replacements on some or all of the technical features; and these modifications or replacements do not cause the essence of the corresponding technical solutions to deviate from the scope of the technical solutions of the embodiments of the present invention.

Claims

1. A drug-eluting stent coated with a film, characterized in that: include: A support body, wherein the support body plays a supporting role; The inner membrane is in a band shape, the outer side of the inner membrane is spirally arranged in contact with the inner wall of the stent body, and there are gaps between the spirals of the inner membrane; The drug-loaded film is in a strip shape and is arranged on the outside of the stent body corresponding to the inner membrane. The drug-loaded film is attached to the outside of the stent body and the inner membrane, and the width of the drug-loaded film is smaller than the width of the inner membrane; The outer membrane is arranged at the outermost side of the stent, covers the stent body and the drug-loaded membrane, and is attached to the portion of the inner membrane that is not attached to the drug-loaded membrane, the outer membrane includes a first area and a second area, the first area includes a portion corresponding to the inner membrane, and the second area includes a portion corresponding to the spiral gap of the inner membrane; The fiber porosity of the second region is greater than the fiber porosity of the first region, and / or the fiber diameter of the second region is smaller than the fiber diameter of the first region, and the total endothelialization period of the second region, the stent body portion corresponding to the second region, and the inner side of the inner membrane is smaller than the degradation period of the first region and smaller than the degradation period of the inner membrane.

2. The drug-eluting stent according to claim 1, characterized in that: The width of the first region is greater than or equal to the width of the second region, and the width of the drug-loaded film is greater than or equal to one half of the width of the inner film.

3. The drug-eluting stent according to claim 2, characterized in that: The drug loading amount of the drug loaded film is generated based on the drug loading coefficient, the porosity of the drug loaded film and the volume of the drug loaded film.

4. The drug-eluting stent according to claim 2, characterized in that: The thickness of the second region is greater than or equal to the thickness of the first region.

5. The drug-eluting stent according to claim 1, characterized in that: The materials of the stent body, the inner membrane, the drug-loaded membrane and the outer membrane include one or a combination of polylactic acid, polylactic acid-glycolic acid copolymer, polycaprolactone, polylactic acid-caprolactone copolymer, polydioxanone, polyglycolic acid, or polyhydroxyalkanoate.

6. The drug-eluting stent according to claim 1, characterized in that: The support body adopts a grid structure.

7. A method for preparing a film-coated drug-eluting stent, comprising the film-coated drug-eluting stent according to any one of claims 1 to 6, characterized in that: The inner membrane is prepared by spraying or blending; The stent body is prepared by 3D printing technology; The drug-loaded film is prepared by spraying or blending technology; spraying the drug onto the drug-carrying film; The outer membrane is prepared by spraying or blending.

8. A method for preparing a film-coated drug-eluting stent, comprising the film-coated drug-eluting stent according to any one of claims 1 to 6, characterized in that: The inner membrane is prepared by spraying or blending; The stent body is prepared by 3D printing technology; The drug-loaded film is prepared by a process of mixing and extruding the drug with a polymer material; The outer membrane is prepared by spraying or blending.

9. The method for preparing a drug-eluting stent according to any one of claims 7 to 8, characterized in that: The drug is at least one of paclitaxel and rapamycin.

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