Antithrombotic surface modification process and guide double catheter applied to nerve intervention

Abstract

The invention discloses an antithrombotic surface modification process and a guiding double catheter applied to nerve intervention, and belongs to the field of medical instrument surface engineering. The process comprises the following steps: after the catheter is cleaned, coating the far end of the catheter with a hydrophilic lubricating coating and carrying out UV curing; differential click chemical grafting is carried out, specifically, heparin and polysulfobetaine are sequentially grafted to the inner wall of the outer catheter, PEG-liposome is grafted to the outer surface, branched PEG is grafted to the inner wall of the inner catheter, and REDV polypeptide is specifically grafted to the head end; and finally shaping the head end and pairing the inner pipe and the outer pipe. According to the manufactured double-catheter system, the outer catheter has the inner wall long-acting anti-thrombus function and the outer wall super-lubrication function, and the inner catheter achieves the inner cavity anti-adhesion function and the head end endothelialization promoting function. According to the invention, through the precise differentiated surface design, the composite requirements on the super-strong tracking property of the catheter, the long-time retention antithrombotic property and the head biocompatibility in the nerve interventional operation are synchronously met.

Description

Technical Field

[0001] This invention relates to the field of medical catheter technology, and in particular to an antithrombotic surface modification process and its application in neurointervention as a guiding dual catheter. Background Technology

[0002] In neurointerventional therapy, it is routine to deliver the guiding catheter system to target vessels such as the internal carotid artery or vertebral artery via the femoral artery approach. Due to the tortuous pathways and complex anatomy of the cerebral blood vessels, the catheter system must possess excellent tracking ability, permeability, positioning stability, and biocompatibility for long-term placement. Among these, thrombosis caused by contact between the catheter surface and blood (thrombogenic) is a key risk leading to surgical complications and limiting the long-term placement of catheters.

[0003] Currently, the mainstream technical solutions for improving the thrombogenicity of catheter surfaces mainly include the following two categories, but both have significant limitations: Single-function coating technology: The most common is to coat the catheter surface with a hydrophilic lubricating coating or a heparinized anticoagulant coating.

[0004] Hydrophilic lubricating coatings: Their main function is to reduce the friction coefficient of the catheter surface, improving delivery and permeability within blood vessels. However, such coatings typically lack active antithrombotic bioactivity and cannot effectively inhibit platelet adhesion and fibrinogen adsorption. For catheters requiring long-term indwelling, their antithrombotic effect is limited.

[0005] Heparin and other anticoagulant coatings: Heparin is immobilized on the catheter surface through physical adsorption or chemical grafting, utilizing its biological activity to directly inhibit thrombin formation. However, such coatings often face risks such as easy detachment of the active substance, short duration of action, and potential to cause systemic coagulation dysfunction or heparin-induced thrombocytopenia (HIT). More importantly, a single heparin coating cannot simultaneously meet the combined requirements of lubricity, tracking, and mechanical strength of catheters in complex vascular environments.

[0006] Composite modification techniques based on conventional surface wetting: To simultaneously achieve antibacterial and antithrombotic effects, existing technology (Chinese patent publication number CN120037460A) proposes a scheme to construct a multilayer hydrogel coating on the surface of silicone catheters. This technology achieves anti-protein adhesion and sustained-release antibacterial effects through a dopamine adhesion layer, a zwitterionic hydrogel layer, and an enzyme-encapsulating functional layer. However, such methods typically employ a monolithic, uniform surface treatment strategy, which lacks specificity for dual-catheter systems (such as guide sheaths and microcatheters) with complex structures and vastly different functional requirements for their inner and outer surfaces. For example, the outer surface of the catheter requires an extremely low coefficient of friction to facilitate delivery, while the inner lumen surface requires extremely strong anticoagulant and anti-biofilm formation capabilities. A monolithic coating struggles to achieve this differentiated performance optimization. Furthermore, hydrogel coatings may present a challenge in balancing mechanical strength and lubricity, facing the risk of coating wear and peeling when traversing extremely tortuous cerebral blood vessels.

[0007] Therefore, there is an urgent need to develop a new type of catheter surface modification process based on precise functional design. Summary of the Invention

[0008] In order to solve the above-mentioned technical problems, the present invention provides an antithrombotic surface modification process and its application in neurointervention with a dual-catheter.

[0009] One of the technical solutions of the present invention is as follows: An antithrombotic surface modification process, applied to a guiding dual catheter in neurointervention, the dual catheter comprising an outer catheter and an inner catheter, characterized by comprising the following steps: S1, Clean the bodies of the external and internal catheters; S2, Surface modification treatment is performed on the cleaned pipe body; The surface modification treatment includes a hydrophilic coating treatment, in which the distal end of the tube is immersed in a hydrophilic coating solution, and after a lifting process, it is continuously cured under UV light of a specific intensity to form a lubricating coating. S3, shaping the modified inner catheter tip; S4, insert the inner catheter into the outer catheter to complete the pairing.

[0010] In step S2, the hydrophilic coating solution includes a primer solution and a topcoat solution. The viscosity of the primer solution at 55 RPM is 1.3-6.6 mPa·s, and the viscosity of the topcoat solution at 10 RPM is 16.0-37.0 mPa·s.

[0011] In step S2(A), The concentration of the N3-heparin solution is 3-7 mg / mL, and the perfusion treatment is carried out at 35-39°C for 18-30 hours. The concentration of the N3-polysulfonated betaine solution is 8-12 mg / mL, and the perfusion treatment is carried out at 35-39°C for 8-16 hours. The concentration of the N3-PEG-liposome solution is 1-3 mg / mL, and the immersion treatment is carried out at 23-27°C for 12-24 hours.

[0012] Specifically, step S3 involves inserting a stainless steel core needle into the distal end of the inner catheter, bending it into a predetermined shape, and then shaping it by heating.

[0013] A dual-catheter guide for neurointervention, wherein the outer and inner catheters are obtained by the aforementioned antithrombotic surface modification process.

[0014] The inner wall of the external catheter is grafted with a heparin molecular layer and a polysulfobetaine molecular layer by click chemical grafting, and the outer surface is grafted with a PEG-liposome layer; the inner wall of the internal catheter is grafted with a branched PEG molecular layer, and the tip is grafted with a REDV polypeptide layer.

[0015] The second technical solution of the present invention is a neurointerventional guidance dual catheter, wherein the outer catheter and the inner catheter of the dual catheter are obtained by an antithrombotic surface modification process.

[0016] The inner wall of the external catheter is grafted with a heparin molecular layer and a polysulfobetaine molecular layer by click chemical grafting, and the outer surface is grafted with a PEG-liposome layer; the inner wall of the internal catheter is grafted with a branched PEG molecular layer, and the tip is grafted with a REDV polypeptide layer.

[0017] The external catheter tip has a pre-formed special structure for auxiliary treatment, and the internal catheter tip has a pre-shaped shape. The internal and external catheters work together to provide a stable delivery channel from the femoral artery to the internal carotid artery or vertebral artery.

[0018] The ends of the dual conduits are also connected to a connecting tube, which communicates with the Y-shaped tube.

[0019] Compared with the prior art, the present invention has the following beneficial effects: 1. Significantly enhances the long-term effectiveness and stability of antithrombotic properties. This invention utilizes click chemistry technology to achieve a stable chemical bond between a heparin molecular layer and a polysulfonated betaine molecular layer on the inner wall of the external catheter, constructing a synergistic "active anticoagulation-passive antifouling" system. Heparin molecules specifically inhibit the activation of coagulation factors, exerting an active anticoagulation effect; polysulfonated betaine molecules form a physical barrier through strong hydration, effectively blocking the non-specific adhesion of proteins and platelets, achieving passive antifouling. This chemical bonding method effectively avoids the technical defects of traditional physical adsorption coatings that are prone to detachment and chemically grafted coatings that experience rapid activity decay. It enables the modified layer to form a strong interfacial bond with the catheter body, providing long-lasting and stable antithrombotic protection for prolonged catheter placement. Its antithrombotic duration and stability are significantly superior to existing single heparin coatings or hydrophilic lubricating coatings.

[0020] 2. Optimized lubrication and biocompatibility: The PEG-liposome layer grafted onto the outer surface of the external catheter forms a synergistic lubrication structure with the hydrophilic coating at the distal end of the catheter, significantly reducing the coefficient of friction between the catheter and the vessel wall. This imparts a super-lubricating surface to the catheter, effectively improving its tracking performance in extremely tortuous cerebral blood vessels, reducing the risk of vessel wall damage, and ensuring smooth surgical procedures. On the other hand, the branched PEG layer grafted onto the inner wall of the inner catheter effectively inhibits the non-specific adsorption of blood components on the luminal surface, maintaining luminal patency and preventing luminal blockage caused by blood component adhesion. Furthermore, all grafted molecules possess excellent biocompatibility, significantly reducing the body's foreign body reaction to the catheter and the risk of inflammatory stress, thus improving the safety of clinical applications.

[0021] 3. Enhanced delivery stability and positioning accuracy: The synergistic effect of the ultra-lubricated outer surface of the external catheter and the auxiliary structure at the tip, combined with the pre-shaping design of the inner catheter tip, effectively improves the propulsion stability, tracking accuracy, and positioning precision of the entire catheter system in complex cerebrovascular anatomy. It can achieve smooth delivery and precise positioning in tortuous vascular pathways, providing a stable and reliable pathway for the precise release of subsequent interventional devices, reducing the risk of surgical deviations caused by catheter displacement and shaking, and improving the reliability of neurointerventional surgery. Attached Figure Description

[0022] Figure 1 This is a flowchart illustrating the antithrombotic surface modification process of the present invention.

[0023] Figure 2 This is a schematic diagram of the overall structure of an antithrombotic surface modification process according to the present invention.

[0024] Figure 3 This is a schematic diagram of the structure of the neurointerventional guidance dual catheter of the present invention.

[0025] 1-External catheter; 2-Internal catheter; 3-Double catheter; 4-Connecting tube; 5-Y-type tube. Detailed Implementation

[0026] The present invention will be further described in detail below with reference to specific embodiments, which is intended to provide a basis for understanding the present invention and is not intended to limit the scope of protection of the present invention.

[0027] Example 1 like Figure 1 As shown, the present invention provides an antithrombotic surface modification process, comprising the following steps: S1. The outer and inner conduits are sequentially immersed in anhydrous ethanol and deionized water for ultrasonic cleaning, each cleaning time being 20 minutes and the cleaning temperature being 25℃, to remove oil, dust, and processing residues from the surface of the conduits. After cleaning, they are placed in a vacuum drying oven and dried at 60℃ for 2 hours until no moisture remains on the surface of the conduits. After removal, they are placed in a vacuum drying oven. S2. The cleaned conduits are then subjected to surface modification treatment. The outer conduit is modified first by performing plasma pretreatment (100W power, argon atmosphere, treatment time 3 minutes) to improve the surface activity and coating adhesion. Then, a hydrophilic coating treatment is performed by immersing the distal end of the outer conduit into the primer solution using a pull-coating machine at a pull-coating speed of 2mm / s. After removal, it is air-dried at room temperature for 15 minutes and then immersed in the topcoat solution at the same pull-coating speed to complete the coating. It is then placed in a UV curing machine and continuously irradiated at a wavelength of 365nm for 300s to cure and form a uniform lubricating coating with a thickness controlled at 5-8μm.

[0028] After the lubricating coating cured, functional molecules were grafted onto it. A 5 mg / mL N3-heparin solution was infused into the inner wall of the inner catheter via perfusion, and the chamber was incubated at 37°C for 24 hours to allow heparin molecules to be initially fixed through physical adsorption. The heparin solution was then drained, and the tube was rinsed three times with pH 7.4 phosphate-buffered saline (PBS). A 10 mg / mL N3-polysulfobetaine solution was then infused, and the chamber was incubated at 37°C for 12 hours to complete the initial loading of the bilayer molecules. Finally, a CuBr / PMDETA catalyst solution was added to initiate a click chemistry reaction, which was carried out at room temperature for 6 hours, allowing heparin and polysulfobetaine to be chemically bonded and firmly grafted onto the inner wall. The outer surface of the outer catheter was immersed in a 2 mg / mL N3-PEG-liposome solution at 25°C for 18 hours, and fixed through a click chemistry reaction to form a PEG-liposome lubricating layer.

[0029] The inner catheter was then modified. The distal end of the inner catheter was treated with the same hydrophilic coating process as the outer catheter to form a basic lubricating coating. The inner wall was infused with a branched PEG solution at a concentration of 8 mg / mL and kept at 37°C for 20 h. A branched PEG molecular layer was formed by click chemical grafting. Ungrafted free molecules were removed by rinsing with PBS buffer. The tip of the inner catheter (5 cm in length) was additionally grafted with REDV peptide. The tip was immersed in a REDV peptide solution (0.5 mg / mL) containing EDC / NHS activator and reacted at 25°C for 8 h. This allowed the REDV peptide to be grafted onto the tip surface via amide bonds. After the reaction was completed, the tip was rinsed with deionized water and vacuum dried for later use.

[0030] S3. A 1.2mm diameter medical stainless steel needle is slowly inserted into the distal end of the inner catheter. Based on the anatomical characteristics of cerebral blood vessels, the needle is bent into a predetermined shape at a 15° angle. The shaped inner catheter tip is then placed in a heating and shaping instrument, set to 80°C, and heated at a constant temperature for 15 minutes. After shaping, the tip is removed and allowed to cool naturally to room temperature. The stainless steel needle is then slowly withdrawn to obtain an inner catheter tip with a fixed bending angle, ensuring that the tip is free from cracking and deformation after shaping and that its flexibility meets the standards.

[0031] S4. On a sterile operating table, slowly insert the shaped inner catheter into the modified outer catheter, ensuring that the tip of the inner catheter extends 2cm beyond the tip of the outer catheter and that the tube is free from twisting or jamming. After assembly, check the smoothness of the inner catheter sliding within the outer catheter, ensuring that the pushing and pulling resistance is ≤0.5N. Finally, perform an airtightness test by introducing sterile air at a pressure of 0.3MPa into the lumen and maintaining it for 30 seconds without leakage. This completes the pairing and assembly of the two catheters.

[0032] The performance of the guided dual catheters prepared in the above embodiments was tested, with an unmodified dual catheter of the same specification used as a control group. The test results are as follows. (1) Antithrombotic properties: In an in vitro coagulation test, the coagulation time of the inner wall of the external catheter in the experimental group was 3.2 times longer than that in the control group, and the platelet adhesion rate dropped to below 8% (65% in the control group). In the long-term indwelling simulation test (72h), there was no obvious thrombus formation on the surface of the catheter in the experimental group, while a large number of platelets aggregated and fibrin deposited in the control group.

[0033] (2) Lubrication performance: The friction coefficient test showed that the friction coefficient of the outer surface of the external catheter in the experimental group was 0.03 (0.18 in the control group). In the simulated tortuous blood vessel model, the crossing resistance was reduced by 68%, and the tracking passability was significantly better than that of the control group.

[0034] (3) Coating stability: After 1000 repeated friction tests, the wear rate of the coating in the experimental group was ≤5%, and HPLC detection showed no loss of heparin, polysulfobetaine and other molecules. The physical coating in the control group showed obvious peeling.

[0035] (4) Biocompatibility and cytotoxicity experiments showed that the cell survival rate of the experimental group was ≥95% and there was no obvious inflammatory response; the grafting end of the REDV polypeptide can promote the adhesion and spread of endothelial cells, and the endothelial cell coverage rate reached more than 70% in 72h, which has the potential for rapid endothelialization.

[0036]

[0037] Table 1 is a comparison table of performance verification results for Example 1.

[0038] Example 2 This embodiment is based on the general process framework of Embodiment 1, and optimizes and adapts key process parameters to achieve the best balance of performance of each functional layer. The specific implementation details are as follows. Steps not explicitly described shall be performed in accordance with the operating specifications of Embodiment 1.

[0039] The external catheter underwent surface modification treatment, and an antithrombotic layer was grafted onto the inner wall. A dedicated pressure perfusion device was used to fix the external catheter, and a 5 mg / mL N3-heparin solution (dissolved in pH 7.4 PBS buffer) was selected. The perfusion pressure was set at 1.2 bar, and the temperature at 37°C, with continuous perfusion for 24 hours to ensure that heparin molecules were uniformly grafted onto the inner wall through click chemistry to form a dense molecular layer. After perfusion, the inner wall was flushed four times with sterile PBS buffer at the same pressure, with each flush volume being 8 times the lumen volume, to thoroughly remove physically adsorbed free heparin molecules and avoid interference from subsequent functional layers. After flushing, the solution was replaced with a 10 mg / mL N3-polysulfobetaine solution, and perfusion was maintained at 37°C for 12 hours to form a uniform second functional layer on the heparin layer surface, constructing a synergistic system of "active anticoagulation-passive antifouling". The outer surface lubricating layer was grafted; simultaneous treatment of the outer surface was initiated after 12 hours of heparin solution perfusion on the inner wall of the external catheter to improve process efficiency. The entire outer catheter was immersed in a 2 mg / mL N3-PEG-liposome solution and placed in a 25°C constant temperature shaker. It was shaken at a low speed of 45 RPM for 18 hours to allow PEG-liposome molecules to be firmly grafted onto the outer surface through click chemical reaction, forming a uniform lubricating layer that balances coating adhesion and lubrication performance.

[0040] The inner catheter underwent surface modification treatment, and an anti-adhesion layer was grafted onto the inner wall. The inner catheter was connected to a microfluidic pump system, and a 15 mg / mL N3-branched PEG solution was used. The flow rate was set at 12 mL / min, and the temperature at 37°C. The lumen was circulated for 24 hours to ensure that the branched PEG molecules completely covered the inner wall and formed a dense anti-adhesion layer, effectively preventing non-specific adhesion of blood components. For the tip bioactive layer grafting, a specially positioned clamp was used to hold the distal 20 mm area of ​​the inner catheter, ensuring complete isolation of the rest of the catheter. The clamped tip was then vertically immersed in a 1 mg / mL N3-REDV peptide solution at 25°C for 30 minutes under static conditions, allowing the REDV peptide to specifically graft onto the tip surface via amide bonds. After immersion, the tip was immediately rinsed three times with sterile deionized water to remove residual solution and prevent non-specific adsorption of peptide molecules.

[0041] The optimized parameter combination in this embodiment ensures uniform thickness of each functional layer (coating thickness controlled at 6-7 μm, with a uniformity error of ≤10% for molecular grafting layer thickness) and tight interlayer bonding. Preliminary testing shows that the catheter prepared under these parameters achieves an optimal overall balance in terms of lubricity, resistance to protein adsorption, resistance to platelet adhesion, and biocompatibility, fully meeting the stringent clinical requirements for catheters in neurointerventional surgery.

[0042] To systematically verify the modification effect of the process of the present invention, the catheter samples prepared in Example 2 were used as the experimental group, and the unmodified double catheters of the same specification were used as the control group. The following performance tests were conducted in a simulated clinical environment, and the test results are as follows. (1) Lubricity test: The friction coefficient tester was used to measure the dynamic friction coefficient of the catheter outer surface in a simulated body fluid (composition close to human blood plasma) environment. The results showed that the friction coefficient of the catheter outer surface in the experimental group was reduced by 72% compared with the control group. In the simulated tortuous cerebral blood vessel model, the catheter pushing force was reduced by 69% compared with the control group, which significantly improved the smoothness and passability of the surgical operation.

[0043] (2) Anti-protein adsorption test: The catheter sample was immersed in PBS buffer containing fluorescently labeled fibrinogen and incubated at 37°C for 2 hours. The samples were then observed and quantitatively analyzed by fluorescence microscopy. The results showed that the fluorescence signal intensity of the inner wall of the inner catheter and the inner wall of the outer catheter in the experimental group decreased by 93% compared with the control group, confirming that the branched PEG layer and polysulfonated betaine layer can effectively block protein molecule adhesion and avoid the risk of lumen blockage.

[0044] (3) Antiplatelet adhesion / activation test: The sample was incubated with platelet-rich plasma at 37°C for 1 hour, and the results were observed by scanning electron microscopy and quantitatively detected by lactate dehydrogenase method. The results showed that a large number of platelets aggregated on the surface of the bare catheter in the control group and were in an activated state, while the number of platelets adhering to the surface of the catheter in the experimental group was very small, and more than 95% of them were inactive normal morphology, showing excellent antithrombotic performance.

[0045] (4) REDV peptide activity verification: In an in vitro endothelial cell adhesion experiment, human umbilical vein endothelial cells were co-cultured with the catheter tip for 24 hours, and the cell coverage was counted. The results showed that the endothelial cell coverage in the catheter tip region grafted with REDV peptide was increased by 85% compared with the unmodified region, and the cells spread out well, exhibiting specific endothelialization-promoting biological activity, thus optimizing the long-term implantation safety from the root.

[0046] The performance of the guided dual catheters prepared in the above embodiments was tested, with an unmodified dual catheter of the same specification used as a control group. The test results are as follows. (1) Antithrombotic properties: In an in vitro coagulation test, the coagulation time of the inner wall of the external catheter in the experimental group was 3.2 times longer than that in the control group, and the platelet adhesion rate dropped to below 8% (65% in the control group). In the long-term indwelling simulation test (72h), there was no obvious thrombus formation on the surface of the catheter in the experimental group, while a large number of platelets aggregated and fibrin deposited in the control group.

[0047] (2) Lubrication performance: The friction coefficient test showed that the friction coefficient of the outer surface of the external catheter in the experimental group was 0.03 (0.18 in the control group). In the simulated tortuous blood vessel model, the crossing resistance was reduced by 68%, and the tracking passability was significantly better than that of the control group.

[0048] (3) Coating stability: After 1000 repeated friction tests, the wear rate of the coating in the experimental group was ≤5%, and HPLC detection showed no loss of heparin, polysulfobetaine and other molecules. The physical coating in the control group showed obvious peeling.

[0049] (4) Biocompatibility and cytotoxicity experiments showed that the cell survival rate of the experimental group was ≥95% and there was no obvious inflammatory response; the grafting end of the REDV polypeptide can promote the adhesion and spread of endothelial cells, and the endothelial cell coverage rate reached more than 70% in 72h, which has the potential for rapid endothelialization.

[0050]

[0051] Table 2 is a comparison table of performance verification results for Example 2.

[0052] Example 3 This embodiment details a neurointerventional guiding dual catheter prepared by the process described in Embodiment 1 or 2, comprising an outer catheter and an inner catheter; The external catheter comprises a body and a lumen. The body is made of a biocompatible polymer material and has a total length of approximately 90-110 cm, suitable for access via the femoral artery. The lumen has a single main lumen with an inner diameter of approximately 2.3-2.8 mm, capable of accommodating the internal catheter and allowing the passage of therapeutic instruments.

[0053] The distal end of the tube, approximately 3-5 cm in diameter, is pre-formed to have a specific compliant bend and a gradually thinning wall thickness, providing excellent vascular tracking and support for superselective entry into the openings of the internal carotid artery or vertebral artery.

[0054] The inner catheter includes a body and a lumen. The body is made of a polymer material and its total length is typically 20-30 cm longer than the outer catheter, approximately 115-130 cm. The lumen has a single microlumen with an inner diameter of approximately 0.40-0.70 mm, used to deliver embolic materials or drugs.

[0055] The distal tip of the inner catheter can be steam-shaped intraoperatively according to the anatomical morphology of the target lesion to form a personalized, predetermined curved shape, thereby achieving precise placement.

[0056] Example 4 like Figure 2-3 As shown, the present invention provides a neurointerventional guidance dual catheter, wherein the outer and inner catheters of the dual catheter are obtained by an antithrombotic surface modification process.

[0057] The inner wall of the external catheter is grafted with a heparin molecular layer and a polysulfobetaine molecular layer by click chemical grafting, and the outer surface is grafted with a PEG-liposome layer; the inner wall of the internal catheter is grafted with a branched PEG molecular layer, and the tip is grafted with a REDV polypeptide layer.

[0058] The external catheter tip has a pre-formed special structure for auxiliary treatment, and the internal catheter tip has a pre-shaped shape. The internal and external catheters work together to provide a stable delivery channel from the femoral artery to the internal carotid artery or vertebral artery.

[0059] The ends of the dual conduits are also connected to a connecting tube, which communicates with the Y-shaped tube.

[0060] The above description is merely a preferred embodiment of the present invention and is not intended to limit the present invention in any way. Although the present invention has been disclosed above with reference to preferred embodiments, it is not intended to limit the present invention. Any person skilled in the art can make some modifications or alterations to the above-disclosed technical content to create equivalent embodiments without departing from the scope of the present invention. Any simple modifications, equivalent changes and alterations made to the above embodiments based on the technical essence of the present invention without departing from the scope of the present invention shall still fall within the scope of the present invention.

Claims

1. An antithrombotic surface modification process applied to a dual-catheter guide in neurointervention, wherein the dual-catheter comprises an outer catheter and an inner catheter, characterized in that, Includes the following steps, Step S1: Clean the bodies of the external and internal catheters; Step S2: Perform surface modification treatment on the cleaned pipe body; The surface modification treatment includes a hydrophilic coating treatment, in which the distal end of the tube is immersed in a hydrophilic coating solution, and after a lifting process, it is continuously cured under UV light of a specific intensity to form a lubricating coating. The surface modification treatment also includes differentiated click grafting treatment. First, the outer catheter is treated by using a pressure infusion device to sequentially infuse N3-heparin solution and N3-polysulfonated betaine solution into the inner wall of the outer catheter for grafting. At the same time, the outer surface of the outer catheter is immersed in N3-PEG-liposome solution for grafting. Then, the inner catheter is treated by using a microfluidic pump to circulate and infuse N3-branched PEG solution into the inner wall of the inner catheter for grafting. A segmented immersion method is used, immersing only the tip of the inner catheter in N3-REDV solution for grafting. Step S3: Shape the modified inner catheter tip; Step S4: Insert the inner catheter into the outer catheter to complete the pairing.

2. The antithrombotic surface modification process according to claim 1, characterized in that, In step S2, the hydrophilic coating solution includes a primer solution and a topcoat solution. The viscosity of the primer solution at 55 RPM is 1.3-6.6 mPa·s, and the viscosity of the topcoat solution at 10 RPM is 16.0-37.0 mPa·s.

3. The antithrombotic surface modification process according to claim 1, characterized in that, In step S2 The concentration of the N3-heparin solution is 3-7 mg / mL, and the perfusion treatment is carried out at 35-39°C for 18-30 hours. The concentration of the N3-polysulfonated betaine solution is 8-12 mg / mL, and the perfusion treatment is carried out at 35-39°C for 8-16 hours. The concentration of the N3-PEG-liposome solution is 1-3 mg / mL, and the immersion treatment is carried out at 23-27°C for 12-24 hours.

4. The antithrombotic surface modification process according to claim 1, characterized in that, In step S2 The concentration of the N3-branched PEG solution is 10-20 mg / mL, and the cyclic perfusion treatment is carried out at 35-39°C for 18-30 hours. The concentration of the N3-REDV solution is 0.5-2.0 mg / mL, and the immersion treatment is carried out at 23-27°C for 15-60 minutes.

5. The antithrombotic surface modification process according to claim 1, characterized in that, In step S2, between the infusion of N3-heparin solution and N3-polysulfonated betaine solution into the inner wall of the outer catheter, the inner wall of the outer catheter needs to be thoroughly cleaned; in step S2, before the N3-REDV solution grafting treatment is performed on the tip of the inner catheter, the inner catheter body is not treated with this solution.

6. The antithrombotic surface modification process according to claim 1, characterized in that, Specifically, step S3 involves inserting a stainless steel core needle into the distal end of the inner catheter, bending it into a predetermined shape, and then shaping it by heating.

7. A neurointerventional guidance dual-catheter, characterized in that, The outer and inner catheters in the dual catheters are obtained by the antithrombotic surface modification process as described in any one of claims 1 to 6.

8. The neurointerventional guidance dual catheter according to claim 7, characterized in that, The inner wall of the external catheter is grafted with a heparin molecular layer and a polysulfobetaine molecular layer by click chemical grafting, and the outer surface is grafted with a PEG-liposome layer; the inner wall of the internal catheter is grafted with a branched PEG molecular layer, and the tip is grafted with a REDV polypeptide layer.

9. The neurointerventional guidance dual catheter according to claim 7, characterized in that, The external catheter tip has a pre-formed special structure for auxiliary treatment, and the internal catheter tip has a pre-shaped shape. The internal and external catheters work together to provide a stable delivery channel from the femoral artery to the internal carotid artery or vertebral artery.

10. The neurointerventional guidance dual catheter according to claim 7, characterized in that, The ends of the dual conduits are also connected to a connecting tube, which communicates with the Y-shaped tube.

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