Intracranial drug eluting stent with gradient drug release function

Abstract

The application provides an intracranial drug eluting stent with gradient drug release function, and belongs to the technical field of vascular interventional medical devices; the stent comprises a stent body, a drug coating and a slow-release layer; the stent body is a tubular structure with a net shape, and the outer surface of the net rod of the tubular structure is provided with accommodating grooves; the drug coating is filled in at least part of the accommodating grooves; the slow-release layer is arranged in at least half of the accommodating grooves filled with the drug coating to cover the drug coating; the slow-release layer is composed of biodegradable high molecular materials, and is used for controlling the release time of the underlying drug coating by gradually degrading; the slow-release layer has multiple thicknesses to form differentiated drug release rates between different accommodating grooves, so that gradient drug release is realized; and the technical problem that the drug release rate of the drug eluting stent in the prior art cannot meet the actual treatment requirements is mainly solved.

Description

Technical Field

[0001] This invention belongs to the field of vascular interventional medical device technology, specifically relating to an intracranial drug-eluting stent with gradient drug release function. Background Technology

[0002] Vascular stenting is currently the primary treatment for coronary artery and peripheral vascular stenosis. However, stent implantation can lead to intimal damage, inflammatory responses, and excessive proliferation of smooth muscle cells, resulting in in-stent restenosis. To address this issue, drug-eluting stents have become widely used. By loading anti-proliferative drugs such as paclitaxel, rapamycin, and their derivatives onto the stent surface, the sustained action of these drugs inhibits excessive smooth muscle cell proliferation, effectively reducing the probability of restenosis.

[0003] Existing drug-eluting stents typically employ a coating structure where drugs are uniformly coated with a mixture of drugs and polymers. This structure allows for a natural decay-based drug release pattern: the surface drug is rapidly released within the initial 24-48 hours after stent implantation, and over time, the drug within the coating must gradually diffuse to the surface for release. However, inflammation of the vascular intima typically begins 24-72 hours after stent implantation, requiring rapid anti-inflammatory action with high-concentration drugs. However, the drug in the coating of existing stents has already passed its peak release period, making it difficult to provide sufficient drug during the inflammatory window. Furthermore, after four weeks post-procedure, the primary issue shifts to smooth muscle cell proliferation, requiring sustained low-concentration drug action. At this point, the drug release rate of existing stents has significantly decreased, often failing to maintain effective therapeutic concentrations and unable to continuously release the required concentration of drug.

[0004] Therefore, there is a need to provide an improved technical solution that addresses the shortcomings of the existing technology. Summary of the Invention

[0005] The purpose of this invention is to provide an intracranial drug-eluting stent with gradient drug release function, so as to solve the technical problem that the drug release rate of existing drug-eluting stents cannot meet the actual treatment needs.

[0006] To achieve the above objectives, the intracranial drug-eluting stent with gradient drug release function of the present invention provides the following technical solution: An intracranial drug-eluting stent with gradient drug release function, comprising: The support body is a mesh-like tubular structure, and the outer surface of the mesh rods of the tubular structure has receiving grooves. A drug coating, the drug coating filling at least partially a receiving groove; and A sustained-release layer is disposed in at least half of the receiving slots filled with drug coatings to cover the drug coatings. The sustained-release layer is composed of a biodegradable polymer material that is gradually degraded to control the timing of the release of the drug coating below. The sustained-release layer has various thicknesses to create differentiated drug release rates between different containment chambers, thereby achieving gradient drug release.

[0007] As a further optimized technical solution, the receiving grooves are evenly distributed along the axial and circumferential directions of the support body, and the slow-release layer in the receiving grooves at different axial or circumferential positions has different thicknesses.

[0008] As a further optimized technical solution, the depth of the receiving groove is 20%-80% of the thickness of the mesh pole.

[0009] As a further optimized technical solution, the width of the receiving groove is 30%-70% of the width of the mesh pole, and the length of the receiving groove is 50%-90% of the width of the mesh pole.

[0010] As a further optimized technical solution, the thickness of the drug coating or the drug coating and the top sustained-release layer is equal to or slightly less than the depth of the receiving groove.

[0011] As a further optimized technical solution, the biodegradable polymer material of the sustained-release layer is selected from at least one of polylactic acid, polylactic acid-glycolic acid copolymer, polycaprolactone, polyglycolic acid, and polyethylene glycol.

[0012] As a further optimized technical solution, the drug in the drug coating is selected from at least one of paclitaxel, rapamycin and its derivatives.

[0013] As a further optimized technical solution, the drug coating is composed of at least two sub-coatings stacked together, with the drug ratio of different sub-coatings increasing sequentially from the inner layer close to the scaffold substrate to the outer layer far from the scaffold substrate.

[0014] As a further optimized technical solution, the drug coating includes a polymer carrier, wherein the binding force of the groups of the polymer carrier to the drug decreases sequentially from the inner layer near the scaffold matrix to the outer layer far away from the scaffold matrix.

[0015] As a further optimized technical solution, the drug coating includes a polymer carrier, wherein the crystallinity of the polymer carrier gradually decreases or the looseness of the molecular chain arrangement gradually increases from the inner layer near the scaffold matrix to the outer layer far away from the scaffold matrix.

[0016] Beneficial effects: First, this invention creates receiving grooves on the mesh rods of the stent body, and sets sustained-release layers of varying thicknesses in at least half of the receiving grooves filled with drug coatings. In this way, the drug coating in the receiving grooves without buffer layers releases the drug first. During drug release, some of the thinner sustained-release layers gradually dissolve, and the underlying sustained-release layers begin to release a large amount of drug. This allows for rapid release of high-concentration drugs within 24-72 hours post-surgery, ensuring sufficient drug supply during the inflammatory window to treat acute inflammation. Subsequently, when it is necessary to inhibit smooth muscle cell proliferation, the thicker portions of the sustained-release layers dissolve sequentially, continuously releasing drug concentrations that meet therapeutic requirements and continuously inhibiting smooth muscle cell proliferation. This achieves a gradient drug release that meets therapeutic requirements.

[0017] Secondly, this invention addresses the issue by creating a receiving groove on the outer surface of the stent body's mesh and filling the groove with a drug-eluting coating. A sustained-release layer of varying thickness is then placed on top of the drug-eluting coating. In contrast, existing drug-eluting stents typically have the drug coating directly applied to the outer surface of the stent body. During stent clamping and delivery, mechanical contact and friction occur between the drug coating and the delivery system and vessel wall, easily leading to coating detachment, cracking, or delamination. This not only results in drug loss but also risks the detached coating particles entering distal vessels with the bloodstream, increasing the risk of embolism. In this invention, the drug coating is positioned inside the receiving groove, with the sidewalls of the groove providing physical protection. During stent clamping and delivery, the opening of the receiving groove is covered by a protective sheath from the delivery system, preventing the drug coating from being directly exposed to the friction interface. Even in cases of partial contact, the sidewalls of the receiving groove can withstand the main mechanical stress, thereby reducing the risk of drug coating detachment, cracking, and delamination.

[0018] Furthermore, by arranging a receiving tank, placing a drug coating at the bottom of the tank, and then placing a sustained-release layer on top of the drug coating, the boundaries of the receiving tank naturally form a constraint, ensuring that the sustained-release layer is accurately positioned above the drug coating that needs to be covered. This avoids premature release of the drug coating due to positioning deviations that may result in some parts of the drug coating not being covered. In other words, the sidewalls of the receiving tank provide a space for the sustained-release layer material, allowing the sustained-release solution to spread evenly during the filling process through surface tension and capillary action, completely covering the underlying drug coating without leaving any dead corners. Compared to directly coating the sustained-release layer on a flat surface, the receiving tank structure effectively avoids problems such as uneven coating, missed coating, or thinning at the edges, ensuring the integrity and density of the sustained-release layer. At the same time, the depth of the receiving tank provides a reference benchmark for controlling the thickness of the sustained-release layer. By controlling the sustained-release layer to be filled to be flush with or slightly higher than the opening of the receiving tank, the thickness of the sustained-release layer can be accurately reproduced, ensuring that the thickness difference between different receiving tanks meets the design expectations. This allows the sustained-release layer to stably and continuously block drug diffusion over a long period, keeping the drug release rate within a controllable range, resulting in a more stable and lasting gradient drug release effect. Attached Figure Description

[0019] The accompanying drawings, which form part of this application, are used to provide a further understanding of the invention. The illustrative embodiments of the invention and their descriptions are used to explain the invention and do not constitute an undue limitation of the invention. Wherein: Figure 1 This is a schematic diagram of the unfolded stent body of the intracranial drug-eluting stent with gradient drug release function according to Embodiment 1 of the present invention. Figure 2 This is a schematic cross-sectional view of a portion of the receiving groove of the intracranial drug-eluting stent with gradient drug release function in Embodiment 1 of the present invention. At this time, only the drug coating is present in the receiving groove of this portion. Figure 3 This is a schematic cross-sectional view of another part of the receiving groove of the intracranial drug-eluting stent with gradient drug release function in Embodiment 1 of the present invention. In this case, the top of the drug coating of this part of the receiving groove has a thinner sustained-release layer. Figure 4 This is a schematic cross-sectional view of another portion of the receiving tank of the intracranial drug-eluting stent with gradient drug release function according to Embodiment 1 of the present invention. In this case, the top of the drug coating of this portion of the receiving tank has a thicker sustained-release layer.

[0020] In the diagram: 1. Stent body; 2. Mesh pole; 3. Receiving groove; 4. Drug coating; 5. Sustained-release layer. Detailed Implementation

[0021] The technical solutions in the embodiments of the present invention will be clearly and completely described below. Obviously, the described embodiments are only a part of the embodiments of the present invention, and not all of them. All other embodiments obtained by those skilled in the art based on the embodiments of the present invention are within the scope of protection of the present invention.

[0022] In the description of this invention, the terms "longitudinal," "lateral," "upper," "lower," "front," "rear," "left," "right," "vertical," "horizontal," "top," and "bottom," etc., indicate the orientation or positional relationship based on the orientation or positional relationship shown in the accompanying drawings. They are used only for the convenience of describing the invention and do not require the invention to be constructed and operated in a specific orientation; therefore, they should not be construed as limitations on the invention. The terms "connected" and "linked" used in this invention should be interpreted broadly. For example, they can refer to a fixed connection or a detachable connection; they can refer to a direct connection or an indirect connection through intermediate components. Those skilled in the art can understand the specific meaning of the above terms according to the specific circumstances. Furthermore, the term "proximal end" uniformly refers to the end closer to the operator, while "distal end" refers to the end farther from the operator.

[0023] The present invention will now be described in detail with reference to the accompanying drawings and embodiments. It should be noted that, unless otherwise specified, the embodiments and features described herein can be combined with each other.

[0024] The shapes and sizes of the components in the accompanying drawings do not reflect the actual proportions of the product; they are only intended to illustrate the content of the invention.

[0025] To address the technical problem that existing drug-eluting stents cannot achieve drug release rates sufficient for practical treatment needs. For example... Figure 1-4 As shown, this invention provides an intracranial drug-eluting stent with gradient drug release function. It involves setting receiving grooves 3 on the outer surface of the stent body 1 and mesh rods 2, and filling at least a portion of these grooves 3 with a drug coating 4. Then, in at least half of the receiving grooves 3 filled with the drug coating 1, a sustained-release layer 5 made of biodegradable polymer material is placed, with different thicknesses of the sustained-release layer 5 in different receiving grooves. Based on the characteristic that the degradation time of the biodegradable polymer material is positively correlated with its thickness, the relatively thinner sustained-release layer 5 degrades faster, thus exposing the underlying drug coating 4 earlier; the relatively thicker sustained-release layer degrades slower, exposing the underlying drug coating later. Therefore, the receiving grooves 3 without a sustained-release layer 5 release the drug first, followed by those covered by a thinner sustained-release layer 5, and finally those covered by a thicker sustained-release layer 5, thus forming a gradient release curve in the time series, accurately matching the clinical needs of high-concentration drugs during the inflammatory window period and low-concentration continuous drugs during the proliferative phase after stent implantation.

[0026] Based on this, the present invention further proposes three optional gradient designs for drug coating structures: multilayer sub-coating ratio gradient, functional group difference gradient, and aggregated state structure gradient, which can be used in conjunction with the above-mentioned sustained-release layer thickness gradient design.

[0027] This invention constructs a gradient drug release system by synergistically combining a receiving groove with biodegradable sustained-release layers of varying thicknesses, and optionally incorporating a gradient design within a multi-layered drug coating. This system enables rapid drug release in the early postoperative period to suppress acute inflammation, followed by sustained low-rate drug release to inhibit excessive proliferation of vascular smooth muscle cells. This effectively adjusts the drug release curve, ensuring a high degree of match between the drug release curve and the pathological process following vascular injury, thereby significantly improving drug utilization.

[0028] The present invention will be described in detail below through specific embodiments.

[0029] Example 1

[0030] like Figure 1-4 As shown, the intracranial drug-eluting stent with gradient drug release function includes a stent body 1, a drug coating 4, and a sustained-release layer 5.

[0031] The stent body 1 is made of cobalt-chromium alloy and has a mesh-like tubular structure. The outer surface of the mesh rods 2 of the tubular structure has receiving grooves 3, which are evenly distributed along the axial and circumferential directions of the stent body 1. The depth of the receiving grooves 3 is 20%-80% of the thickness of the mesh rods 2, the width of the receiving grooves 3 is 30%-70% of the width of the mesh rods 2, and the length of the receiving grooves 3 is 50%-90% of the width of the mesh rods 2. A drug coating 4 fills all the receiving grooves 3, and the drug in the drug coating 4 is selected from at least one of paclitaxel, rapamycin, and their derivatives.

[0032] In all the receiving tanks 3 where the drug coating 4 is arranged, at least half of the receiving tanks 3 have a sustained-release layer 5 arranged on top of the drug coating 4. The sustained-release layer 5 fully covers the drug coating 4. The sustained-release layer 5 is composed of a biodegradable polymer material. Specifically, the biodegradable polymer material of the sustained-release layer 5 is selected from at least one of polylactic acid, polylactic acid-glycolic acid copolymer, polycaprolactone, polyglycolic acid, and polyethylene glycol. The sustained-release layer 5 has a variety of thicknesses. Through sequential degradation, it forms a differentiated drug release rate between different receiving tanks 3, effectively controlling the release timing of the drug coating 4 below, thereby achieving gradient drug release.

[0033] In this embodiment, the sustained-release layer 5 divides all the receiving slots 3 into two categories: rapid-release receiving slots 3 and sustained-release receiving slots 3. That is, the sustained-release layer 5 in the receiving slots 3 at different axial or circumferential positions has different thicknesses. The rapid-release receiving slots 3 and the sustained-release receiving slots 3 are arranged alternately and crosswise on the support, specifically including at least one of the following arrangements: The first type involves alternating rapid-release drug-containing grooves 3 and sustained-release drug-containing grooves 3 along the axial direction of the support body 1. That is, on each row of mesh rods 2, among two adjacent grooves 3, one is a rapid-release drug-containing groove 3 and the other is a sustained-release drug-containing groove 3, and so on, forming an alternating sequence.

[0034] The second type involves alternating rapid-release drug-containing grooves 3 and sustained-release drug-containing grooves 3 along the circumferential direction of the stent body 1. That is, on each row of mesh rods 2, among two adjacent grooves 3, one is a rapid-release drug-containing groove and the other is a sustained-release drug-containing groove, forming an alternating sequence in the circumferential direction.

[0035] The third method combines axial and circumferential staggered arrangement, so that the rapid drug release reservoir 3 and the sustained drug release reservoir 3 are distributed in a checkerboard pattern on the entire surface of the support body 1, that is, each rapid drug release reservoir 3 is surrounded by a sustained drug release reservoir 3, and each sustained drug release reservoir 3 is surrounded by a rapid drug release reservoir 3.

[0036] The fourth method involves arranging several fast-release drug-containing containers 3 around each sustained-release drug-containing container 3 as the center; or arranging several sustained-release drug-containing containers 3 of different gradients around each fast-release drug-containing container 3 as the center.

[0037] The purpose of designing the rapid-release and sustained-release drug-receiving reservoirs 3 is as follows: If the rapid-release reservoirs 3 are concentrated in one area of ​​the stent (e.g., all in the proximal region), while the sustained-release reservoirs 3 are concentrated in another area (e.g., all in the distal region), it will lead to excessively large differences in drug release characteristics between different areas of the stent. The rapid-release area will have excessively high drug concentrations and rapid decay, while the sustained-release area will have no drug release initially. This may create treatment blind spots in the diseased vessel segment covered by the stent, meaning that the drug concentration is insufficient in certain locations, failing to effectively inhibit intimal hyperplasia.

[0038] By employing a staggered and cross-arranged design, the rapid-release drug-receiving channels 3 and the sustained-release drug-receiving channels 3 are mixed and distributed on the stent surface, ensuring that every local area of ​​the stent simultaneously has both rapid-release and sustained-release sources. In this way, at any point after stent implantation, all parts of the vessel wall can receive drug supply from adjacent channels 3, thereby achieving a relatively uniform drug concentration distribution throughout the diseased vessel segment and avoiding local restenosis caused by uneven drug distribution.

[0039] Of these, sustained-release drug-containing reservoirs 3 account for 70% of the total number of reservoirs 3. Multiple gradient reservoirs 3 can be configured by adjusting the thickness of the sustained-release layer 5 according to actual needs. For example, the first gradient of sustained-release drug-containing reservoirs 3 is used to extend the release time of the rapid-release drug-containing reservoirs 3, and its total number accounts for 50% of the total number of sustained-release drug-containing reservoirs 3. The thickness of the sustained-release layer 5 of this type of reservoir is specifically designed in conjunction with the degradation rate of its material, ensuring a smooth transition in drug release rhythm between the rapid-release drug-containing reservoirs 3 and the initial drug efficacy, achieving a smooth transition in release rate for rapid anti-inflammatory effects. The second gradient of sustained-release drug-containing reservoirs 3 is used to address smooth muscle cell proliferation approximately 4 weeks after stent implantation, and its total number accounts for 50% of the total number of sustained-release drug-containing reservoirs 3. During this stage, vascular smooth muscle cells enter a period of high proliferation. This type of reservoir is equipped with a thick sustained-release layer 5, significantly slowing down drug diffusion and release rates, allowing low-concentration drugs to act on the lesion site for a long time, continuously inhibiting abnormal smooth muscle cell proliferation, thereby significantly reducing the risk of in-stent restenosis.

[0040] Furthermore, in order to ensure the stability of the drug coating 4 during delivery and treatment, the thickness of the drug coating 4 or the drug coating 4 and the top sustained-release layer 5 is equal to or slightly less than the depth of the receiving groove 3.

[0041] Specifically, in this embodiment, the preparation of drug coating 4 involves mixing rapamycin and PLGA (50:50, molecular weight 50,000) at a mass ratio of 1:4, dissolving them in acetone, and preparing a 2% (w / v) coating solution.

[0042] The above solution was filled into each of the receiving tanks 3 using micro-jet technology. After filling, the solution was vacuum dried at 40°C for 30 minutes.

[0043] Sustained-release layer preparation: PLGA (50:50, molecular weight 50,000) was dissolved in acetone to prepare a 1.5% (w / v) sustained-release layer solution. The sustained-release layer 5 was then printed on top of the drug coating 4 in the partial containment tank 3 using 3D printing technology.

[0044] Example 2

[0045] The difference between this embodiment and Embodiment 1 is that the drug coating 4 is made of at least two sub-coatings stacked together, with the drug ratio of different sub-coatings increasing sequentially from the inner layer close to the stent body 1 to the outer layer far away from the stent body 1.

[0046] Specifically, in this embodiment, the drug coating 4 adopts a three-layer sub-coating stack structure, wherein: Solution preparation for the inner sub-coating: Rapamycin and PLGA (50:50, molecular weight 50,000) were dissolved in acetone at a mass ratio of 1:8 to prepare a 2% (w / v) solution.

[0047] Solution preparation for intermediate layer coating: Rapamycin and PLGA (50:50, molecular weight 50,000) were dissolved in acetone at a mass ratio of 1:4 to prepare a 2% (w / v) solution.

[0048] Solution preparation for the outer sub-coating: Rapamycin and PLGA (50:50, molecular weight 50,000) were dissolved in acetone at a mass ratio of 1:2 to prepare a 2% (w / v) solution.

[0049] In preparing the drug coating, an ultrasonic spraying device is used to spray the inner layer, the intermediate layer and the outer layer in sequence.

[0050] Because the inner layer has the lowest drug ratio and the outer layer has the highest drug ratio, and the lower the drug load, the more stable the drug and polymer binding is, the drug release rate of the bottom layer is significantly slower than that of the top layer.

[0051] Example 3

[0052] The difference between this embodiment and Embodiment 1 is that the drug coating 4 includes a polymer carrier, and the binding force of the groups of the polymer carrier to the drug decreases sequentially from the inner layer close to the scaffold body 1 to the outer layer far away from the scaffold body 1.

[0053] Specifically, in this embodiment, ring-opening polymerization was used to synthesize two materials: PLGA-COOH (terminated carboxyl group) and PLGA (non-functional group). GPC measurements showed that the molecular weight of both was approximately 50,000. Among them: Base layer: PLGA-COOH and rapamycin are mixed at a ratio of 4:1 to prepare a 2% acetone solution, which is then sprayed to form a 5μm coating.

[0054] Top layer: PLGA and rapamycin are mixed in a 4:1 ratio to prepare a 2% acetone solution, which is then sprayed to form a 5μm coating.

[0055] Due to the hydrogen bonding between the carboxyl group and rapamycin, the drug release rate in the lower layer is significantly slower than in the upper layer.

[0056] Example 4

[0057] The difference between this embodiment and Embodiment 1 is that the drug coating 4 includes a polymer carrier, and the crystallinity of the polymer carrier gradually decreases or the looseness of the molecular chain arrangement gradually increases from the inner layer near the scaffold substrate to the outer layer far away from the scaffold substrate.

[0058] Specifically, in this embodiment, the drug coating 4 has a two-layer stacked structure, wherein: Outer spray liquid: PLGA (molecular weight 30,000) and rapamycin are mixed at a ratio of 4:1 and dissolved in acetone (concentration 3%).

[0059] Inner spray solution: PLGA (molecular weight 100,000) and rapamycin are mixed at a ratio of 4:1 and dissolved in chloroform (concentration 3%).

[0060] The outer layer of PLGA (low molecular weight) has a lower glass transition temperature, stronger molecular chain mobility, and an amorphous state; the inner layer of PLGA (high molecular weight) has higher crystallinity and a more compact molecular chain arrangement. This difference in aggregate structure results in a significantly faster drug diffusion and release rate from the outer layer compared to the inner layer.

[0061] Example 5

[0062] The difference between this embodiment and embodiment 1 is that the number of sustained-release layers 5 arranged in the receiving groove 3 is different. In this embodiment, the sustained-release drug receiving groove 3 accounts for 50% of the total number of grooves.

[0063] Example 6

[0064] The difference between this embodiment and Embodiment 1 lies in the number of drug coatings 4 arranged. In this embodiment, the drug coatings 4 are arranged in some, but not all, of the receiving tanks 3. For example, the receiving tanks 3 in which the drug coatings 4 are arranged account for 95% of the total number of receiving tanks.

[0065] In summary, this invention establishes receiving grooves on the outer surface of the stent body's mesh, fills these grooves with a drug coating, and incorporates biodegradable sustained-release layers of varying thicknesses in at least half of the grooves. Utilizing the positive correlation between sustained-release layer thickness and degradation time, a temporal gradient release of the drug is achieved in different receiving grooves: grooves without a sustained-release layer release the drug first, followed by those with a thin sustained-release layer, and finally those with a thick sustained-release layer. This design accurately matches the drug release curve with the pathological process following vascular injury (high drug concentrations are required during the inflammatory window, and low-concentration continuous drug concentrations are required during the proliferative phase). Furthermore, this invention can combine the sustained-release layer thickness gradient with the internal gradient of the drug coating (gradient of multilayer sub-coating ratios, gradient of functional group differences, and gradient of aggregated structure) to achieve a composite gradient release in both temporal and spatial dimensions. This invention features an adjustable release curve, high drug utilization efficiency, and effectively solves the technical problem of the mismatch between the release rate of existing drug-eluting stents and clinical needs.

[0066] It is understood that the above description is merely exemplary and the embodiments of this application do not limit the scope of the application.

[0067] The above are merely preferred embodiments of the present invention and are not intended to limit the present invention. Any modifications, equivalent substitutions, improvements, etc., made within the spirit and principles of the present invention are within the protection scope of the present invention.

Claims

1. An intracranial drug-eluting stent with gradient drug release function, characterized in that, include: The support body (1) is a mesh tube structure, and the outer surface of the mesh rod (2) of the tube structure has a receiving groove (3). A drug coating (4) is filled in at least part of the receiving groove (3); as well as A sustained-release layer (5) is disposed in at least half of the receiving grooves (3) filled with drug coatings (4) to cover the drug coatings (4). The sustained-release layer (5) is composed of a biodegradable polymer material and is used to control the release timing of the drug coatings (4) below by gradual degradation. The sustained-release layer (5) has multiple thicknesses to create differentiated drug release rates between different containment tanks (3), thereby achieving gradient drug release.

2. The intracranial drug-eluting stent with gradient drug release function according to claim 1, characterized in that, The receiving groove (3) is evenly distributed along the axial and circumferential directions of the support body (1), and the slow-release layer (5) in the receiving groove (3) at different axial or circumferential positions has different thicknesses.

3. The intracranial drug-eluting stent with gradient drug release function according to claim 1, characterized in that, The depth of the receiving groove (3) is 20%-80% of the thickness of the wire rod (2).

4. The intracranial drug-eluting stent with gradient drug release function according to claim 3, characterized in that, The width of the receiving groove (3) is 30%-70% of the width of the net rod (2), and the length of the receiving groove (3) is 50%-90% of the width of the net rod (2).

5. The intracranial drug-eluting stent with gradient drug release function according to claim 1, characterized in that, The thickness of the drug coating (4) or the drug coating (4) and the top sustained-release layer (5) is equal to or slightly less than the depth of the receiving groove (3).

6. The intracranial drug-eluting stent with gradient drug release function according to claim 1, characterized in that, The biodegradable polymer material of the sustained-release layer (5) is selected from at least one of polylactic acid, polylactic acid-glycolic acid copolymer, polycaprolactone, polyglycolic acid, and polyethylene glycol.

7. The intracranial drug-eluting stent with gradient drug release function according to claim 1, characterized in that, The drug in the drug coating (4) is selected from at least one of paclitaxel, rapamycin and its derivatives.

8. The intracranial drug-eluting stent with gradient drug release function according to any one of claims 1-7, characterized in that, The drug coating (4) is composed of at least two sub-coatings stacked together, with the drug ratio of different sub-coatings increasing sequentially from the inner layer close to the scaffold substrate to the outer layer far from the scaffold substrate.

9. The intracranial drug-eluting stent with gradient drug release function according to any one of claims 1-7, characterized in that, The drug coating (4) includes a polymer carrier, wherein the binding force of the polymer carrier groups to the drug decreases sequentially from the inner layer near the scaffold matrix to the outer layer far away from the scaffold matrix.

10. The intracranial drug-eluting stent with gradient drug release function according to any one of claims 1-7, characterized in that, The drug coating (4) includes a polymer carrier, the crystallinity of which gradually decreases or the looseness of the molecular chain arrangement gradually increases from the inner layer near the scaffold matrix to the outer layer far away from the scaffold matrix.

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