Full-groove drug-loading coating stent, clamp and preparation method of stent

Abstract

The invention provides a full-groove drug-loading coating stent, a clamp and a preparation method of the stent, and belongs to the technical field of medical instruments. The support comprises a support base body, matrix grooves are formed in the support base body, and the matrix grooves are evenly distributed in the surface of the support base body in the circumferential direction of the support base body. A plurality of matrix grooves are formed in the support base body in the axis direction of the support base body. The medicine carrying coating comprises an active medicine, nano particles and a degradable polymer, the degradable polymer is arranged on the bottom layer of the matrix groove, and the active medicine and the nano particles are arranged on the top of the degradable polymer. The stent can avoid explosive release at the initial stage of the medicine, realizes stable, lasting and uniform release of the medicine, can reduce toxic stimulation to vascular endothelium, and ensures a long-term treatment effect.

Description

Technical Field

[0001] This invention relates to the field of medical device technology, and in particular to a fully grooved drug-loaded coating stent, a clamp, and a method for preparing the stent. Background Technology

[0002] Drug-eluting stents (DES) are important medical devices that effectively inhibit intimal hyperplasia and prevent in-stent restenosis by loading anti-intima-proliferative drugs onto the surface of a metallic stent platform and releasing the drugs in a controlled manner locally within the blood vessel. The widespread clinical application of this type of stent has significantly reduced the incidence of restenosis and the need for repeat interventional procedures, playing a particularly important role in the treatment of vertebral artery atherosclerosis.

[0003] Currently, most common stent designs employ either overall surface drug coating or localized groove drug loading, making it difficult to precisely control the contact area between the drug coating and the blood vessel wall, as well as the release behavior. This can easily lead to a "burst release" phenomenon in the initial stage of drug release, where the drug concentration is too high in a short period of time. This can not only damage the vascular endothelium and affect the endothelialization process, but also result in insufficient drug concentration in some areas due to uneven drug distribution, failing to effectively inhibit intimal hyperplasia.

[0004] Therefore, existing drug-eluting stents need to be improved to overcome the shortcomings of the current technology. Summary of the Invention

[0005] To overcome the problems existing in related technologies, one of the objectives of this invention is to provide a fully grooved drug-loaded coating stent that can avoid the initial explosive release of drugs, achieve stable, sustained and uniform drug release, reduce toxic stimulation to vascular endothelium, and ensure long-term therapeutic effects.

[0006] A fully grooved drug-loaded stent, comprising: A support substrate, wherein a matrix of grooves is provided on the support substrate, the matrix of grooves being evenly distributed along the circumference of the support substrate on the surface of the support substrate; and multiple matrix grooves are provided along the axial direction of the support substrate. A drug-loaded coating comprising an active drug, nanoparticles, and a biodegradable polymer, wherein the biodegradable polymer is disposed at the bottom layer of the matrix groove, and the active drug and the nanoparticles are disposed on top of the biodegradable polymer.

[0007] In a preferred embodiment of the present invention, the nanoparticles are biodegradable polymer particles or liposome particles, and the particle size of the nanoparticles is 50nm-200nm. The nanoparticles form a shell that encapsulates the active drug inside the shell.

[0008] In a preferred embodiment of the present invention, each of the matrix grooves is formed by connecting multiple S-shaped grooves end to end, and the cross-section of the S-shaped grooves is trapezoidal or rectangular.

[0009] In a preferred embodiment of the present invention, the distance between the inner wall of the S-shaped groove and the outer wall of the S-shaped groove is greater than 0.01 mm.

[0010] In a preferred embodiment of the present invention, the biodegradable polymer is any one of polyurethane, polylactic acid, or polylactic acid-glycolic acid copolymer; The active drug is mixed with the nanoparticles to form a composite sustained-release agent, which is disposed on the top layer of the biodegradable polymer.

[0011] In a preferred embodiment of the present invention, the support substrate is made of any one of cobalt-based alloys, stainless steel, or nickel-based alloys; The matrix grooves are engraved on the support substrate using laser cutting technology; and an S-shaped connecting rod is provided between two adjacent matrix grooves.

[0012] A second objective of this invention is to provide a clamp for spraying drugs onto the fully grooved drug-loaded coating stent as described above. The clamp includes a thin-walled tube, the inner wall of which is adapted to the outer wall of the support base, and the surface of the thin-walled tube is provided with a hollowed-out position, which corresponds to the matrix groove.

[0013] In a preferred embodiment of the present invention, a positioning rod is further included, wherein a positioning boss is provided on the positioning rod; a first positioning groove is provided on the support base, and a second positioning groove is provided on the thin-walled tube. The first positioning groove and the second positioning groove are both adapted to the positioning boss, so that the positioning rod can position the support base and the thin-walled tube through the positioning boss.

[0014] The third objective of this invention is to provide a method for preparing a fully grooved drug-loaded coated stent, which is used to prepare the fully grooved drug-loaded coated stent as described above. The preparation method includes: Fabrication of the scaffold substrate: A scaffold substrate with a matrix of grooves is formed by laser engraving of metal tubing; Fixture assembly: The prepared support base is fitted onto the positioning rod, and the thin-walled tube is fitted onto the support base, so that the hollowed-out part of the thin-walled tube corresponds to the matrix groove; Drug spraying: The drug coating slurry is sprayed into the exposed matrix grooves through the hollowed-out parts of the thin-walled tube, depositing the drug coating slurry into the matrix grooves; Post-processing: Remove the clamps, dry and cure the sprayed bracket to form a composite sustained-release drug-loaded coating.

[0015] In a preferred embodiment of the present invention, during the drug spraying process, a layer of biodegradable polymer is first sprayed as a base layer, and then a mixed drug layer containing active drugs and nanoparticles is sprayed.

[0016] The beneficial effects of this invention are as follows: This invention provides a fully grooved drug-loaded scaffold, comprising a scaffold substrate with a matrix of grooves evenly distributed circumferentially along the surface of the substrate; and multiple matrix grooves arranged along the axial direction of the substrate. The drug-loaded coating comprises an active drug, nanoparticles, and a biodegradable polymer, with the biodegradable polymer disposed at the bottom layer of the matrix grooves, and the active drug and nanoparticles disposed on top of the biodegradable polymer. This scaffold encapsulates the active drug within the nanoparticles of the biodegradable polymer, allowing drug release kinetics to be dominated by the degradation rate of the nanoparticle shell, rather than simple diffusion. Nanoparticles and biodegradable polymers form a dual sustained-release barrier, which can avoid the explosive release of drugs in the early stage and achieve a stable and sustained release of drugs. The matrix groove design provides a standardized storage space for drugs, ensuring that the distribution of drugs on the stent surface is quantitative, localized and highly uniform. This can avoid the problems of uneven coating and edge thickening caused by the complex structure of traditional spraying stents. It makes the drug dose received by all parts of the blood vessel wall consistent, which can effectively inhibit the intimal hyperplasia of the whole area and avoid the toxicity caused by local drug overdose, thus helping to ensure long-term treatment effect.

[0017] This application also provides a fixture for preparing the above-mentioned fully grooved drug-loaded stent and a method for preparing the stent. The method ensures that the drug slurry can only be completely filled into the preset groove during spraying through the precise shielding effect of the fixture, ensuring that the drug distribution on the stent surface is quantitative, positional and highly uniform, thereby ensuring uniform drug distribution and improving treatment safety and effectiveness. Attached Figure Description

[0018] Figure 1 This is a schematic diagram of a fully grooved drug-loaded coating stent provided in an embodiment of the present invention; Figure 2 yes Figure 1 Sectional view at point AA; Figure 3 This is a schematic diagram of the clamp provided in an embodiment of the present invention; Figure 4 This is a flowchart of a method for preparing a stent provided in an embodiment of the present invention.

[0019] Figure label: 1. Support base; 2. Matrix groove; 3. S-shaped connecting rod; 4. Support groove; 5. Hollowed-out position; 6. Thin-walled tube; 7. Positioning boss; 8. Positioning rod. Detailed Implementation

[0020] Preferred embodiments of the invention will now be described in more detail with reference to the accompanying drawings. While preferred embodiments of the invention are shown in the drawings, it should be understood that the invention can be implemented in various forms and should not be limited to the embodiments set forth herein. Rather, these embodiments are provided so that the invention will be thorough and complete, and will fully convey the scope of the invention to those skilled in the art.

[0021] Drug-eluting stents (DES) are important medical devices that effectively inhibit intimal hyperplasia and prevent in-stent restenosis by loading anti-intima-proliferative drugs onto the surface of a metallic stent platform and releasing the drugs in a controlled manner locally within the blood vessel. The widespread clinical application of this type of stent has significantly reduced the incidence of restenosis and the need for repeat interventional procedures, playing a particularly important role in the treatment of vertebral artery atherosclerosis.

[0022] Currently, most common stent designs employ either overall surface drug coating or localized groove drug loading, making it difficult to precisely control the contact area between the drug coating and the blood vessel wall, as well as the release behavior. This can easily lead to a "burst release" phenomenon in the initial stage of drug release, where the drug concentration is too high in a short period of time. This can not only damage the vascular endothelium and affect the endothelialization process, but also result in insufficient drug concentration in some areas due to uneven drug distribution, failing to effectively inhibit intimal hyperplasia.

[0023] Based on this, this application provides a fully grooved drug-loaded coating stent.

[0024] Example 1 like Figures 1-2 As shown, this embodiment provides a fully grooved drug-loaded coating stent, comprising: A support base 1 is provided with a matrix groove 2, which is evenly distributed on the surface of the support base 1 along the circumference of the support base 1; and multiple matrix grooves 2 are provided on the support base 1 along the axial direction of the support base 1. A drug-loaded coating comprising an active drug, nanoparticles, and a biodegradable polymer, wherein the biodegradable polymer is disposed at the bottom layer of the matrix groove 2, and the active drug and the nanoparticles are disposed on top of the biodegradable polymer.

[0025] Specifically, the support substrate 1 is made of any one of cobalt-based alloys, stainless steel, or nickel-based alloys; The matrix groove 2 is engraved on the support base 1 using laser cutting technology; and an S-shaped connecting rod 3 is provided between two adjacent matrix grooves 2.

[0026] In practical applications, the stent substrate 1 is made of biocompatible cobalt-chromium alloy tubing (in other embodiments, 316L stainless steel or nickel-titanium alloy can also be used), formed by precision laser cutting and engraving. The substrate has a mesh-like perforated structure, characterized by a matrix of grooves on its outer surface. These grooves are evenly distributed circumferentially along the stent substrate 1 and arranged in multiple rings along its axial direction, thus forming a fully covered, regular drug reservoir matrix on the outer surface of the stent. Specifically, adjacent matrix grooves 2 are connected by S-shaped connecting rods 3, a structure that provides excellent flexibility while ensuring the overall structural strength of the stent.

[0027] The arc-shaped structure of the S-shaped connecting rod has a natural elastic deformation capability. When the stent is implanted in a curved blood vessel, the arc-shaped segment of the S-shape can "deform with the deformation of the blood vessel" through slight stretching, compression or torsion, avoiding continuous mechanical pressure or friction on the blood vessel wall due to excessive rigidity of the stent, and reducing the risk of endothelial damage. The mesh hollow design of the stent base 1 in this application can reduce the overall weight of the stent and reduce the pushing resistance to the blood vessel during implantation. The arc-shaped structure of the S-shaped connecting rod can disperse the radial pressure in the blood vessel (such as the pressure generated by blood flow and the contraction force of the blood vessel itself), avoiding stent deformation or breakage caused by local stress concentration.

[0028] The aforementioned fully grooved drug-eluting stent encapsulates active drugs within biodegradable polymer nanoparticles. Drug release kinetics are dominated by the degradation rate of the nanoparticle shell, rather than simple diffusion. The nanoparticles and biodegradable polymer form a dual sustained-release barrier, preventing initial explosive drug release and achieving stable and sustained drug release. The matrix groove design provides standardized storage space for the drug, ensuring quantitative, targeted, and highly uniform drug distribution on the stent surface. This avoids problems such as uneven coating and edge thickening caused by the complex stent structure in traditional spraying, resulting in consistent drug dosage received throughout the blood vessel wall. This effectively inhibits global intimal hyperplasia while avoiding the toxicity caused by local drug overdose, contributing to long-term therapeutic efficacy.

[0029] Specifically, the nanoparticles are biodegradable polymer particles or liposome particles, and the particle size of the nanoparticles is 50nm-200nm. The nanoparticles form a shell that encapsulates the active drug inside the shell.

[0030] Degradable shells (degradable polymers or liposomes) release drugs through "stepwise hydrolysis / enzymatic hydrolysis". For example, polylactic acid polymer shells have a degradation cycle of 2-3 months in vivo, while liposome shells can slowly release drugs through membrane fusion, avoiding the burst release phenomenon of more than 60% of drugs being released within 12 hours after traditional "naked drugs" come into contact with the blood.

[0031] The "composite sustained-release body" formed by mixing nanoparticles with active drugs has a porous structure between particles that can further slow down the drug diffusion rate, so that the drug release curve shows a trend of "smooth rise - plateau maintenance - slow decline", which can avoid the problem of "high concentration in the early stage damaging blood vessels and low concentration in the later stage being ineffective".

[0032] In one embodiment, each of the matrix grooves 2 is formed by connecting multiple S-shaped grooves end to end, and the cross-section of the S-shaped grooves is trapezoidal or rectangular. A rectangular cross-section provides the maximum drug-loading volume, suitable for complex vascular lesions requiring high drug loading (such as severe vertebral artery stenosis), and the straight walls of the rectangle facilitate uniform drug accumulation during spraying, avoiding coating thickness deviations. Furthermore, the distance between the inner wall of the S-shaped groove and the outer wall of the S-shaped groove is greater than 0.01 mm.

[0033] The S-shaped grooves, connected end to end, form a "continuous drug release zone," achieving "no dead-angle coverage" along the stent's circumference and axis, thus preventing localized intimal hyperplasia. The arc-shaped trajectory of the S-shaped grooves aligns with the direction of blood flow, reducing direct erosion of the drug coating by blood flow and lowering the coating detachment rate.

[0034] Furthermore, the biodegradable polymer is any one of polyurethane, polylactic acid, or polylactic acid-glycolic acid copolymer; The active drug is mixed with the nanoparticles to form a composite sustained-release agent, which is disposed on the top layer of the biodegradable polymer.

[0035] The degradation rate of the bottom polymer and the top nanoparticles form a "gradient match". When the bottom layer degrades slowly, it can gradually "push" the upper composite sustained-release body to release the drug, forming a "stepped controlled release" and further prolonging the drug's action time.

[0036] Example 2 like Figures 1-3 As shown, this embodiment provides a clamp for spraying drugs onto the fully grooved drug-loaded coating stent as described above; The clamp includes a thin-walled tube 6, the inner wall of which is adapted to the outer wall of the support base 1, and the surface of the thin-walled tube 6 is provided with a hollow position 5, which corresponds to the matrix groove 2.

[0037] Furthermore, it also includes a positioning rod 8, on which a positioning boss 7 is provided; a first positioning groove is provided on the support base 1, and a second positioning groove is provided on the thin-walled tube 6. The first positioning groove and the second positioning groove are both adapted to the positioning boss 7, so that the positioning rod 8 can position the support base 1 and the thin-walled tube 6 through the positioning boss 7.

[0038] In this embodiment, the clamp with the hollowed-out portion 5 of the thin-walled tube 6 is perfectly matched in size and position to the groove 2 of the stent matrix. During spraying, only the groove is exposed, while non-drug-loaded areas (such as the outer wall of the S-shaped connecting rod and the end faces of the stent) are completely covered by the PTFE thin-walled tube 6. This effectively avoids the problem of drug solution being accidentally applied to non-drug-loaded areas in traditional "clamp-free spraying". There is no drug residue in the non-drug-loaded areas, which reduces drug waste and avoids direct contact between the drug in the non-drug-loaded areas and the vascular endothelium, reducing the risk of local inflammatory reactions.

[0039] The V-shaped protrusion of the positioning rod 8 simultaneously engages the first positioning groove of the bracket and the second positioning groove of the thin-walled tube 6, forcing the three to be coaxial, thus avoiding "insufficient spraying of local grooves" or "drug accumulation in local grooves" caused by the bracket or thin-walled tube 6 shifting during spraying.

[0040] Example 3 like Figures 1-4 As shown, this embodiment provides a method for preparing a fully grooved drug-loaded coated stent, which is used to prepare the fully grooved drug-loaded coated stent as described above. The preparation method includes: S100, Preparation of scaffold substrate 1: A scaffold substrate 1 with matrix grooves 2 is formed by laser engraving of a metal tube; S200, Fixture assembly: The prepared bracket base 1 is fitted onto the positioning rod 8, and the thin-walled tube 6 is fitted onto the bracket base 1, so that the hollow position 5 of the thin-walled tube 6 corresponds to the matrix groove 2. S300, Drug spraying: Through the hollowed-out position 5 of the thin-walled tube 6, the drug coating slurry is sprayed into the exposed matrix groove 2 to deposit the drug coating slurry into the matrix groove 2; specifically, during the drug spraying process, a layer of biodegradable polymer is first sprayed as the base layer, and then a mixed drug layer containing active drugs and nanoparticles is sprayed.

[0041] S400, Post-processing: Remove the fixture, dry and cure the sprayed bracket to form a composite sustained-release drug-loaded coating.

[0042] This method ensures that the drug slurry can only be completely filled into the preset groove during spraying through the precise shielding effect of the clamp, thus ensuring that the drug distribution on the surface of the stent is quantitative, precise and highly uniform, thereby ensuring uniform drug distribution and improving the safety and effectiveness of treatment.

[0043] Unless otherwise specifically stated, the relative arrangement, numerical expressions, and values ​​of the components and steps described in these embodiments do not limit the scope of this application. It should also be understood that, for ease of description, the dimensions of the various parts shown in the drawings are not drawn to actual scale. Techniques, methods, and devices known to those skilled in the art may not be discussed in detail, but where appropriate, such techniques, methods, and devices should be considered part of the specification. In all examples shown and discussed herein, any specific values ​​should be interpreted as merely exemplary and not as limitations. Therefore, other examples of exemplary embodiments may have different values. It should be noted that similar reference numerals and letters in the following drawings denote similar items; therefore, once an item is defined in one drawing, it need not be further discussed in subsequent drawings. In the description of this application, it should be understood that the orientation or positional relationship indicated by directional terms such as "front, back, up, down, left, right", "horizontal, vertical, horizontal" and "top, bottom" is usually based on the orientation or positional relationship shown in the accompanying drawings, and is only for the convenience of describing this application and simplifying the description. Unless otherwise stated, these directional terms do not indicate or imply that the device or element referred to must have a specific orientation or be constructed and operated in a specific orientation, and therefore should not be construed as a limitation on the scope of protection of this application; the directional terms "inner" and "outer" refer to the inner and outer contours relative to the outline of each component itself.

[0044] For ease of description, spatial relative terms such as "above," "on top of," "on the upper surface of," "above," etc., are used herein to describe the spatial positional relationship of a device or feature as shown in the figures to other devices or features. It should be understood that spatial relative terms are intended to encompass different orientations in use or operation beyond the orientation of the device as described in the figures. For example, if the device in the figures were inverted, a device described as "above" or "on top of" other devices or structures would subsequently be positioned as "below" or "under" other devices or structures. Thus, the exemplary term "above" can include both "above" and "below." The device may also be positioned in other different ways (rotated 90 degrees or in other orientations), and the spatial relative descriptions used herein will be interpreted accordingly.

[0045] Furthermore, it should be noted that the use of terms such as "first" and "second" to define components is merely for the purpose of distinguishing the corresponding components. Unless otherwise stated, these terms have no special meaning and therefore should not be construed as limiting the scope of protection of this application. The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. For those skilled in the art, the present invention can have various modifications and variations. Any modifications, equivalent substitutions, improvements, etc., made within the spirit and principles of the present invention should be included within the scope of protection of the present invention.

Claims

1. A fully grooved drug-loaded stent, characterized in that: The support includes a support base, on which a matrix of grooves is provided. The matrix of grooves is evenly distributed along the circumference of the support base on the surface of the support base; and multiple matrix grooves are provided along the axial direction of the support base. A drug-loaded coating comprising an active drug, nanoparticles, and a biodegradable polymer, wherein the biodegradable polymer is disposed at the bottom layer of the matrix groove, and the active drug and the nanoparticles are disposed on top of the biodegradable polymer.

2. The fully grooved drug-loaded stent according to claim 1, characterized in that: The nanoparticles are biodegradable polymer particles or liposome particles, and the particle size of the nanoparticles is 50nm-200nm. The nanoparticles form a shell that encapsulates the active drug inside the shell.

3. The fully grooved drug-loaded stent according to claim 1, characterized in that: Each of the matrix grooves is formed by connecting multiple S-shaped grooves end to end, and the cross-section of the S-shaped grooves is trapezoidal or rectangular.

4. The fully grooved drug-loaded stent according to claim 3, characterized in that: The distance between the inner wall of the S-shaped groove and the outer wall of the S-shaped groove is greater than 0.01 mm.

5. The fully grooved drug-loaded stent according to any one of claims 1-4, characterized in that: The biodegradable polymer is any one of polyurethane, polylactic acid, or polylactic acid-glycolic acid copolymer; The active drug is mixed with the nanoparticles to form a composite sustained-release agent, which is disposed on the top layer of the biodegradable polymer.

6. The fully grooved drug-loaded stent according to any one of claims 1-4, characterized in that: The support substrate is made of any one of the following materials: cobalt-based alloy, stainless steel, or nickel-based alloy. The matrix grooves are engraved on the support substrate using laser cutting technology; and an S-shaped connecting rod is provided between two adjacent matrix grooves.

7. A clamp, characterized in that, Drug spraying for the fully grooved drug-loaded coating stent as described in any one of claims 1-6; The clamp includes a thin-walled tube, the inner wall of which is adapted to the outer wall of the support base, and the surface of the thin-walled tube is provided with a hollowed-out position, which corresponds to the matrix groove.

8. The clamp according to claim 7, characterized in that: It also includes a positioning rod with a positioning boss; a first positioning groove is provided on the support base, and a second positioning groove is provided on the thin-walled tube. The first positioning groove and the second positioning groove are both adapted to the positioning boss, so that the positioning rod can position the support base and the thin-walled tube through the positioning boss.

9. A method for preparing a fully grooved drug-loaded coated stent, used to prepare the fully grooved drug-loaded coated stent as described in any one of claims 1-6, characterized in that: The preparation method includes: Fabrication of the scaffold substrate: A scaffold substrate with a matrix of grooves is formed by laser engraving of metal tubing; Fixture assembly: The prepared support base is fitted onto the positioning rod, and the thin-walled tube is fitted onto the support base, so that the hollowed-out part of the thin-walled tube corresponds to the matrix groove; Drug spraying: The drug coating slurry is sprayed into the exposed matrix grooves through the hollowed-out parts of the thin-walled tube, depositing the drug coating slurry into the matrix grooves; Post-processing: Remove the clamps, dry and cure the sprayed bracket to form a composite sustained-release drug-loaded coating.

10. The method for preparing a fully grooved drug-loaded scaffold according to claim 9, characterized in that: During the drug spraying process, a layer of biodegradable polymer is first sprayed as the base layer, followed by a mixed drug layer containing active drugs and nanoparticles.

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