Film-coated drug-loaded stent and preparation method thereof

Abstract

The invention relates to the technical field of medical apparatus and instruments, and provides a film-covered drug-loaded stent and a preparation method of the film-covered drug-loaded stent. The inner membrane is strip-shaped, and the outer side of the inner membrane is spirally attached to the inner wall of the stent body; the medicine carrying film is in a strip shape, is arranged on the outer side of the stent body corresponding to the inner film, and is attached to the outer side of the stent body and the inner film; the outer membrane is arranged on the outermost side of the stent, covers the stent body and the medicine carrying membrane and is attached to the part, not attached to the medicine carrying membrane, of the inner membrane, the outer membrane comprises a first area and a second area, the first area comprises the part corresponding to the inner membrane, and the second area comprises the part corresponding to the spiral gap of the inner membrane; the total endothelialization cycle of the second area, the stent body part corresponding to the second area and the inner side of the inner membrane is smaller than the degradation cycle of the first area and smaller than the degradation cycle of the inner membrane. The drug-loaded membrane is wrapped in the inner membrane and the outer membrane, and the outer membrane is divided into different areas, so that rapid endothelialization of the stent is realized, 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 film-coated drug-eluting stent and a preparation method thereof. Background Art

[0002] In the field of cardiovascular disease treatment, the implantation of vascular stents is a common interventional method. After being implanted in the human body, traditional vascular stents face two major challenges: first, the slow endothelialization process is not conducive to the close integration and long-term stability of the stent and the vascular wall. The slow process of endothelial cells covering the stent surface not only increases the risk of stent displacement, but may also cause thrombosis, thus affecting the treatment effect and patient safety; second, after endothelialization is completed, the stent fails to effectively control the proliferation of vascular smooth muscle cells. This uncontrolled cell proliferation may cause restenosis in the blood vessel, affecting blood flow, requiring patients to receive additional treatment, increasing medical costs and patient suffering.

[0003] The existing vascular stent design fails to effectively solve the above problems. The slow endothelialization rate makes the stent easily displaced by blood flow impact in the early stage of implantation, and the uncontrolled cell proliferation after endothelialization may cause the blood vessel to narrow again. Both situations seriously affect the therapeutic effect of the stent and the quality of life of the patient.

[0004] In view of this, the present invention aims to provide a new type of vascular stent, which can quickly promote the endothelialization process after implantation, ensure that the stent can quickly and stably fit the blood vessel wall, and effectively inhibit excessive cell proliferation after endothelialization is completed, so as to ensure long-term patency of the blood vessels and reduce the risk of re-stenosis. Summary of the invention

[0005] The purpose of the present invention is to provide a coated drug-eluting stent and a preparation method thereof, so as to solve the technical problems existing in the prior art of slow stent endothelialization and uncontrolled cell proliferation after endothelialization leading to vascular restenosis.

[0006] In the first aspect, an embodiment of the present invention provides a coated drug-eluting stent, comprising: a stent body, which plays a supporting role; an inner membrane, which is in the shape of a band, and the outer side of the inner membrane is spirally attached to the inner wall of the stent body, and there is a gap between the spirals of the inner membrane; a drug-eluting membrane, which is in the shape of a band and is arranged on the outer side of the stent body corresponding to the inner membrane, the drug-eluting membrane is attached to 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 at the outermost side of the stent, covers the stent body and the drug-eluting membrane, and is attached to the part of the inner membrane that is not attached by the drug-eluting membrane, the outer membrane includes a first area and a second area, the first area includes a part corresponding to the inner membrane, and the second area includes a part corresponding to the spiral gap of the inner membrane; the total endothelialization period of the second area, the part of the stent body corresponding to the second area, and the inner side of the inner membrane is smaller than the degradation period of the first area, and smaller than the degradation period of the inner membrane.

[0007] Furthermore, 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.

[0008] Furthermore, 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.

[0009] Furthermore, 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.

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

[0011] Furthermore, 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, or polylactic acid-glycolic acid copolymer, or polycaprolactone, or polylactic acid-caprolactone copolymer, or polydioxanone, or polyglycolic acid, or polyhydroxyalkanoate.

[0012] Furthermore, the support body adopts a grid structure.

[0013] In the second aspect, an embodiment of the present invention also provides a method for preparing a film-coated drug-eluting stent, including the film-coated drug-eluting stent as described in the preceding item, preparing the inner membrane by a spraying or blending process; preparing the stent body by a 3D printing process; preparing the drug-eluting film by a spraying or blending process; spraying the drug on the drug-eluting film; and preparing the outer membrane by a spraying or blending process.

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

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

[0016] The embodiments of the present invention have at least the following technical effects: A coated drug-eluting stent provided in an embodiment of the present invention has an inner membrane spirally arranged inside the stent body, a drug-eluting membrane arranged outside the stent body and having a width smaller than that of the inner membrane, an outer membrane covering the stent body and the drug-eluting membrane, and being adhered to the portion of the inner membrane that is not adhered to the drug-eluting membrane, so that the drug-eluting membrane is equivalent to being wrapped by the inner membrane and the outer membrane, and the anti-proliferative drugs carried on the drug-eluting membrane cannot be released after the stent is initially implanted into a human blood vessel, thus not affecting the proliferation of endothelial cells and contributing to the rapid endothelialization of the stent.

[0017] At the same time, considering that the stent needs to be implanted after being compressed and gripped, in order to facilitate the compression and gripping, the inner membrane and the drug-loaded membrane are both arranged in a spiral shape; in order to prevent the drug-loaded membrane from breaking or even falling off during the compression and gripping process, since the only purpose of the drug-loaded membrane is to carry more drugs, the resistance to falling off and breaking is very poor, and the inner membrane is arranged inside the stent body, and the inner membrane is bonded to the drug-loaded membrane and the outer membrane through the hollow part of the stent body, and the drug-loaded membrane is wrapped between the inner membrane and the outer membrane, so that even if the drug-loaded membrane 3 is broken during the compression and gripping process, it is still wrapped inside to prevent the formation of thrombus due to the broken drug-loaded membrane 3, and the outer membrane 4 is wrapped on the outside of the drug-loaded membrane 3 to prevent the drug-loaded membrane 3 from falling off, and at the same time, the purpose of the drug-loaded membrane 3 carrying more drugs can be achieved. By wrapping the drug-loaded membrane 3 inside, the drug-loaded membrane 3 does not need to consider the problem of falling off and breaking, and a material with stronger drug loading capacity can be selected.

[0018] 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, the first region and the inner membrane wrap the drug-loaded membrane inside, and the second region is bonded to the stent body; the total endothelialization cycle of the second region, the stent body part corresponding to the second region, and the inner side of the inner membrane is shorter than the degradation cycle of the first region and the inner membrane. When endothelial cells attach, proliferate, and even cover the second region, the stent body part corresponding to the second region, and the inner side of the inner membrane, the endothelialization of the entire stent is completed. The degradation cycle of the first region and the inner membrane is longer. This total endothelialization cycle can ensure that the anti-proliferative drugs carried by the drug-loaded membrane will begin to be released after the stent is endothelialized, thereby inhibiting the proliferation of vascular smooth muscle cells and avoiding restenosis of the blood vessels. After the stent is endothelialized, the first region and the inner membrane are degraded, and the drug-loaded membrane 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-loaded membrane is also wrapped by endothelial cells. Therefore, even if the inner and outer membranes are degraded, there is no need to worry about the drug-loaded membrane falling off and breaking, and the drug-loaded membrane can still play a role in inhibiting the proliferation of vascular smooth muscle cells.

[0019] Therefore, the coated drug-eluting stent of the present invention wraps the drug-eluting film in the inner membrane and the outer membrane, and the total endothelialization cycle of the second region, the stent body corresponding to the second region, and the inner side of the inner membrane is shorter than the degradation cycle of the first region and the inner membrane, thereby achieving rapid endothelialization of the stent and avoiding restenosis of the blood vessels caused by excessive cell proliferation. The overall design of the stent is also more convenient for intraoperative compression and gripping, reducing the possibility of shedding of the outer membrane and the drug-eluting film. BRIEF DESCRIPTION OF THE DRAWINGS

[0020] In order to more clearly illustrate the specific implementation methods of the present invention or the technical solutions in the prior art, the drawings required for use in the specific implementation methods or the description of the prior art will be briefly introduced below. Obviously, the drawings described below are some implementation methods of the present invention. For ordinary technicians in this field, other drawings can be obtained based on these drawings without paying creative work.

[0021] Figure 1 A partial cross-sectional schematic diagram of a drug-eluting stent coated with a membrane provided by an embodiment of the present invention; Figure 2 for Figure 1 The cross-section diagram at AB in the middle; Figure 3 An overall schematic diagram of a film-coated drug-eluting stent provided in an embodiment of the present invention.

[0022] Icon: 1-stent body; 2-inner membrane; 3-drug-loaded membrane; 4-outer membrane; 41-first region; 42-second region. DETAILED DESCRIPTION

[0023] 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. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

[0024] Those skilled in the art will understand that, unless otherwise defined, all terms (including technical and scientific terms) used herein have the same meaning as those generally understood by those skilled in the art in the field to which the present invention belongs. It should also be understood that terms such as those defined in common dictionaries should be understood to have meanings consistent with the meanings in the context of the prior art, and will not be interpreted with idealized or overly formal meanings unless specifically defined as here.

[0025] Those skilled in the art will appreciate that, unless otherwise stated, the singular forms "a", "an", "said" and "the" used herein may also include plural forms. It should be further understood that the term "comprising" used in the specification of the present invention refers to the presence of the 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 combinations thereof. The term "and / or" used herein includes all or any unit and all combinations of one or more associated listed items.

[0026] For the first aspect, see Figures 1 to 3 The embodiment of the present invention provides a coated drug-eluting stent, comprising: a stent body 1, which plays a supporting role; an inner membrane 2, which is in a strip shape, and the outer side of the inner membrane 2 is spirally attached to the inner wall of the stent body 1, and there is a gap between the spirals of the inner membrane 2; a drug-eluting membrane 3, which is in a strip shape and is arranged on the outer side of the stent body 1 corresponding to the inner membrane 2, the drug-eluting membrane 3 is attached to the outer side of the stent body 1 and the inner membrane 2, and the width of the drug-eluting membrane 3 is smaller than the width of the inner membrane 2; an outer membrane 4, which is arranged on the outermost side of the stent, covers the stent body 1 and the drug-eluting membrane 3, and is attached to the part of the inner membrane 2 that is not attached by the drug-eluting membrane 3, the outer membrane 4 includes a first area 41 and a second area 42, the first area 41 includes a part corresponding to the inner membrane 2, and the second area 42 includes a part corresponding to the spiral gap of the inner membrane 2; the total endothelialization period of the second area 42, the part of the stent body 1 corresponding to the second area 42, and the inner side of the inner membrane 2 is less than the degradation period of the first area 41, and less than the degradation period of the inner membrane 2.

[0027] In this embodiment, the inner membrane 2 is spirally arranged inside the stent body 1, the drug-loaded membrane 3 is arranged outside the stent body 1 and its width is smaller than the width of the inner membrane 2, the outer membrane 4 covers the stent body 1 and the drug-loaded membrane 3, and is adhered to the part of the inner membrane 2 that is not adhered to the drug-loaded membrane 3, so that the drug-loaded membrane 3 is equivalent to being wrapped by the inner membrane 2 and the outer membrane 4. The anti-proliferative drugs carried on the drug-loaded membrane 3 cannot be released after the stent is implanted into the human blood vessel, so it will not affect the proliferation of endothelial cells, which helps the stent to quickly endothelialize.

[0028] At the same time, considering that the stent needs to be implanted after being compressed and gripped, in order to facilitate the compression and gripping, the inner membrane 2 and the drug-loaded membrane 3 are both arranged in a spiral shape; in order to prevent the drug-loaded membrane 3 from being broken or even falling off during the compression and gripping process, since the only purpose of the drug-loaded membrane 3 is to carry more drugs, the resistance to falling off and breaking is very poor, and the inner membrane 2 is arranged inside the stent body 1. The inner membrane 2 is bonded to the drug-loaded membrane 3 and the outer membrane 4 through the hollow part of the stent body 1, so that even if the drug-loaded membrane 3 is broken during the compression and gripping process, it is wrapped inside to prevent the formation of thrombus due to the broken drug-loaded membrane 3. The outer membrane 4 is wrapped on the outside of the drug-loaded membrane 3 to prevent the drug-loaded membrane 3 from falling off, and at the same time, the purpose of carrying more drugs by the drug-loaded membrane 3 can be achieved. By wrapping the drug-loaded membrane 3 inside, the drug-loaded membrane 3 does not need to consider the problem of falling off and breaking, and a material with stronger drug loading capacity can be selected.

[0029] 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, the first region 41 and the inner membrane 2 wrap the drug-loaded film 3 inside, and the second region 42 is bonded to the stent body 1; the total endothelialization cycle 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 less than the degradation cycle 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, and the first region The degradation cycle of region 41 and inner membrane 2 must be greater than the total endothelialization cycle to ensure that the anti-proliferative drugs carried by drug-loaded membrane 3 begin to be released after the stent is endothelialized, thereby inhibiting the proliferation of vascular smooth muscle cells and avoiding restenosis of the blood vessels. After the stent is endothelialized, the first region 41 and inner membrane 2 are both degraded, and the drug-loaded membrane 3 lacks restraint and may fall off and break. However, since the endothelialization has been completed at this time, the stent is covered and fixed by endothelial cells, and the drug-loaded membrane 3 is also wrapped by endothelial cells. Therefore, even if the inner and outer membranes are degraded, there is no need to worry about the drug-loaded membrane falling off and breaking, and the drug-loaded membrane 3 can still play the role of inhibiting the proliferation of vascular smooth muscle cells.

[0030] Therefore, the coated drug-eluting stent of the present invention wraps the drug-eluting film 3 in the inner membrane 2 and the outer membrane 4, and 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 period of the first region 41 and the inner membrane 2, thereby achieving rapid endothelialization of the stent and avoiding restenosis of the blood vessels caused by excessive cell proliferation. The overall design of the stent is also more convenient for intraoperative compression and gripping, reducing the possibility of falling off of the outer membrane 4 and the drug-eluting film 3.

[0031] Preferably, the total endothelialization cycle is 30-60 days, and the degradation cycle of the first region 41 or the inner membrane 2 is 60-90 days. It is worth noting that the degradation cycle 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 and disappears in the human body, but refers to the period in which the first region 41 or the inner membrane 2 loses its covering and protective effect on the drug-loaded film 3, so that the drug-loaded film 3 can contact the human body and release anti-proliferative drugs. For example, the stent completes endothelialization on the 50th day after implantation. On the 70th day, any one of the first region 41 or the inner membrane 2 fails, and the drug-loaded film 3 can contact the human body and start to release drugs.

[0032] Optionally, the fiber porosity of the second region 42 is greater than the fiber porosity of the first region 41 , and / or the fiber diameter of the second region 42 is smaller 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 attachment and proliferation of endothelial cells. The fiber porosity of the second region 42 is set to a fiber porosity range suitable for the attachment and proliferation of endothelial cells, and the fiber diameter of the second region 42 is set to a fiber diameter range suitable for the attachment and proliferation of endothelial cells. Therefore, the fiber porosity of the second region 42 is greater than the fiber porosity of the first region 41, or the fiber diameter of the second region 42 is smaller than the fiber diameter of the first region 41. Both can ensure that endothelial cells cover the second region 42 as quickly as possible and even cover the entire stent interior, or the fiber porosity and fiber diameter are jointly adjusted to accelerate the endothelialization speed of the second region 42. Moreover, the small fiber porosity of the first region 41 or the large fiber diameter of 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-loaded 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 0.4um-4um; the fiber porosity of the first region 41 is 10%-50%, and the fiber diameter of the first region 41 is 1.5um-4um.

[0033] Optionally, the width W of the first region 41 is 1 Greater than or equal to the width W of the second region 42 2 , the width W of the drug-loaded film 33 is greater than or equal to half of the width of the inner membrane 2. In this embodiment, the width W of the first region 41 is 1 is also the width of the inner film 2, and the width W of the second region 42 2 That 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, so that it can ensure that the outer membrane 4 and the inner membrane 2 have enough contact area and will not fall off during compression and gripping, and can wrap the drug-loaded film 3 therein, and it can also ensure that the drug-loaded film 3 will not be insufficient in drug loading due to its too narrow width. Preferably, considering the impact on the stent endothelialization cycle, the width W of the first region 41 is 1 Less than or equal to the width W of the second region 42 2 twice.

[0034] Optionally, the drug loading of the drug-loaded membrane 3 is generated based on the drug loading coefficient, the porosity of the drug-loaded membrane and the volume of the drug-loaded membrane. In this embodiment, considering that if the drug-loaded membrane 3 is prepared by co-extrusion of 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 membrane and the volume V of the drug-loaded membrane is used to calculate the actual drug loading X of the stent, that is, X=YHV, to ensure that the drug loading data of the stent is more accurately grasped. 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 membrane and the volume V of the drug-loaded membrane is the actual fiber amount of the drug-loaded membrane 3. The calculation formula of the volume V of the drug-loaded membrane is: , Among them, W 1 is the width of the first region 41, W 2 is the width of the second region 42, W 3 is the width of the drug-loaded film 3, T 3 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 spiral will cause the film width to tilt in the length direction). It is the projection of the width of the inner membrane 2 and the width of the inner membrane gap in the length direction of the stent. It can be calculated how many spiral cycles of drug-loaded membrane 3 the entire stent includes. It is the length of the drug-loaded film 3 of one spiral cycle.

[0035] Optionally, the thickness T of the second region 42 is 2 Greater than or equal to the thickness T of the first region 41 1 In this embodiment, the thickness T of the second region 42 is 2 Greater than or equal to the thickness T of the first region 41 1, which helps to improve the endothelialization efficiency. The second region 42 is thicker, which can better contact with vascular endothelial cells, promote the attachment and proliferation of endothelial cells, and accelerate the endothelialization process of the stent. Preferably, the thickness T of the second region 42 is 2 is greater than or equal to the sum of the thickness of the first region 41 and the drug-loaded film 3. If the thickness T of the second region 42 is 2 is equal to the sum of the thickness of the first region 41 and the drug-loaded film 3. In this case, the stent surface is smoother and the blood vessel can be stressed evenly. If the thickness of the second region 42 is T 2 The thickness of the second region 42 is greater than the sum of the thickness of the first region 41 and the drug-loaded film 3. At this time, the second region 42 is closer to the blood vessel, which is conducive to promoting the attachment and proliferation of endothelial cells, and the more prominent spiral formed by the second region 42 can be better stuck in the blood vessel to ensure that the stent does not move. The specific thickness combination to be used can be determined according to needs and in combination with actual use requirements.

[0036] It is worth mentioning that Figure 2 The thicknesses of the inner membrane 2, the drug-loaded membrane 3, the first region 41 and the second region 42 are schematically enlarged, mainly to more intuitively reflect their position and thickness relationship. The wire diameter d of the stent body is only a schematic demonstration. In actual needs, the diameter d may also be larger than the thickness of the inner membrane 2, the drug-loaded membrane 3, the first region 41 or the second region 42, but the drug-loaded membrane 3 or the outer membrane 4 will be coated on the outside of the stent body 1, the drug-loaded membrane 3 or the outer membrane 4 will also have hollow areas formed by the wire diameter of the stent body 1, and the first region 41 is covered on the outside of the drug-loaded membrane 3 and in contact with the inner membrane 2. These relative positional relationships are determined.

[0037] Optionally, the materials of the stent body 1, the inner membrane 2, the drug-loaded film 3 and the outer membrane 4 include one or more combinations of polylactic acid, or polylactic acid-glycolic acid copolymer, or polycaprolactone, or polylactic acid-caprolactone copolymer, or polydioxanone, or polyglycolic acid, or polyhydroxyalkanoate. In this embodiment, the above-mentioned materials are used because these materials usually do not cause significant immune reactions, such as allergic or rejection reactions, after being implanted in the human body, and their degradation products are usually non-toxic and can be safely metabolized and discharged by the human body. For example, polylactic acid and polylactic acid-glycolic acid copolymer degrade into lactic acid and glycolic acid in the body, and finally convert into carbon dioxide and water. And these materials can promote cell adhesion, proliferation and differentiation, which is conducive to tissue repair and regeneration. For example, polycaprolactone has good cell compatibility and can support cell growth. And they are not easy to cause thrombosis in the blood, reducing the risk of thrombosis-related complications after implantation. At the same time, by optimizing the molecular structure and composition of the material, its biological stability and controllability can be improved, and inflammatory reactions and vascular restenosis can be reduced. Specific examples are as follows: the inner membrane 2 can be selected as polycaprolactone or polylactic acid-caprolactone copolymer, because it has a low melting point and can be well bonded to the stent body 1. The stent body 1 can be selected as polylactic acid, because it is usually hard and has better support. The drug-loaded membrane 3 can be selected as polycaprolactone, which has better softness. The outer membrane 4 can be selected as polycaprolactone or polylactic acid-caprolactone copolymer. The above are just examples. According to actual needs, for example, by monitoring and improving the endothelialization cycle and the degradation cycle, other materials can be used to achieve better results.

[0038] Optionally, the stent body 1 adopts a grid structure. In this embodiment, the stent body 1 adopts a grid structure. The grid structure makes the stent have good flexibility and can adapt to the bending and deformation of the blood vessel while still having sufficient mechanical strength to support the blood vessel. Moreover, this structure is also convenient for implantation and compression and gripping operations. The grid 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 flexible grid structure has little effect on blood flow and can reduce the risk of thrombosis and vascular damage. The grid can be a diamond grid or a grid-shaped grid. Figure 1 The parallelogram grid shown, the size and density of the grid can be adjusted as needed.

[0039] In the second aspect, an embodiment of the present invention provides a method for preparing a film-coated drug-eluting stent, including the film-coated drug-eluting stent as described in the preceding item, preparing the inner membrane 2 by a spraying or blending process; preparing the stent body 1 by a 3D printing process; preparing the drug-eluting film 3 by a spraying or blending process; spraying the drug on the drug-eluting film 3; and preparing the outer membrane 4 by a spraying or blending process.

[0040] In this embodiment, the inner membrane 2 is prepared first, then the stent body 1 is prepared, and 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 is wrapped around the outside of the stent body 1 and the drug-loaded membrane 3.

[0041] Specifically, if a spraying process is used, it should be noted that the selected membrane material should be dissolved in an appropriate solvent to form a uniform solution, and the solution should be atomized into tiny droplets through a spray nozzle using a spraying device. For example, a spiral inner membrane 2, a drug-loaded membrane 3, a first region 41, and a second region 42 need to be formed. Here, the receiving mandrel can be rotated or the nozzle of the spraying device can be rotated. After the spraying is completed, it can be determined whether the membrane layer needs to be dried and cured according to actual needs. For example, after the inner membrane 2 is prepared, it is not necessary to completely cure it. Directly preparing the stent body 1 can make the inner membrane 2 and the stent body 1 bond better. However, if the outer membrane 4 is prepared, it must be dried and cured to ensure the stability of the entire stent. If a blending process is used, the membrane material needs to be melted or dissolved, and the polymer solution is sprayed through a spinneret using electrostatic spinning technology to form fibers. Similarly, it can also be determined whether the deposited fiber layer needs to be heat treated or otherwise post-treated as needed.

[0042] Specifically, the drug is sprayed on the drug-carrying film 3 by using ultrasonic spraying technology, which can break the liquid into uniform micron-sized droplets, spray evenly and accurately, and the drug loading amount can be calculated by the material consumption of the ultrasonic spraying equipment.

[0043] In the third aspect, an embodiment of the present invention provides a method for preparing a film-coated drug-eluting stent, including the film-coated drug-eluting stent as described in the preceding item, preparing the inner membrane 2 by a spraying or blending process; preparing the stent body 1 by a 3D printing process; preparing the drug-eluting membrane 3 by a process of mixing and extruding the drug and the polymer material; and preparing the outer membrane 4 by a spraying or blending process.

[0044] In this embodiment, the inner membrane 2 is first prepared, and then the stent body 1 is prepared, and then the drug-loaded membrane 3 is prepared by a process of mixing and extruding the drug with the polymer material, and finally the outer membrane 4 is prepared, and the outer membrane 4 is wrapped around the outside of the stent body 1 and the drug-loaded membrane 3. The drug-loaded membrane 3 is prepared by a process of mixing and extruding the drug with the 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 late degradation of the stent. If the drug-loaded membrane 3 is prepared by co-extrusion of the drug and the polymer, the actual drug loading X of the stent should be calculated based on 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 that the drug loading data of the stent is more accurately grasped.

[0045] 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 both drugs can be used together. Both drugs can effectively reduce cell proliferation after stent implantation and reduce the risk of restenosis in the stent.

[0046] Those skilled in the art will appreciate that the various operations, methods, steps, measures, and schemes discussed in the present invention may be alternated, modified, combined, or deleted. Further, other steps, measures, and schemes in the various operations, methods, and schemes discussed in the present invention may also be alternated, modified, rearranged, decomposed, combined, or deleted. Further, the steps, measures, and schemes in the prior art that are similar to those disclosed in the present invention may also be alternated, modified, rearranged, decomposed, combined, or deleted.

[0047] In the description of the present invention, it should be understood that the terms "center", "up", "down", "front", "back", "left", "right", "vertical", "horizontal", "top", "bottom", "inside", "outside", etc., indicating the orientation or position relationship are based on the orientation or position relationship shown in the drawings, and are 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 cannot be understood as a limitation on the present invention.

[0048] The terms "first" and "second" are used for descriptive purposes only and should not be understood as indicating or implying relative importance or implicitly indicating the number of the indicated technical features. Thus, a feature defined as "first" or "second" may explicitly or implicitly include one or more of the features. In the description of the present invention, unless otherwise specified, "plurality" means two or more.

[0049] In the description of the present invention, it should be noted that, unless otherwise clearly specified 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 a direct connection, or an indirect connection through an intermediate medium, or it can be the internal communication of two components. For ordinary technicians in this field, the specific meanings of the above terms in the present invention can be understood according to specific conditions.

[0050] In the description of this specification, specific features, structures, materials or characteristics may be combined in an appropriate manner in any one or more embodiments or examples.

[0051] 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 aforementioned embodiments, those skilled in the art should understand that they can still modify the technical solutions described in the aforementioned embodiments, or replace some or all of the technical features therein with equivalents. However, 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 total endothelialization period of the second region, the stent body portion corresponding to the second region, and the inner side of the endothelium is shorter than the degradation period of the first region and shorter than the degradation period of the endothelium.

2. The drug-eluting stent according to claim 1, characterized in that: 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.

3. 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.

4. The drug-eluting stent according to claim 3, 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.

5. The drug-eluting stent according to claim 3, characterized in that: The thickness of the second region is greater than or equal to the thickness of the first region.

6. 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.

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

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 7, 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.

9. 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 7, 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.

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

Images