A temperature-sensitive hydrogel drug-eluting coating catheter and a method for preparing the same

Abstract

This application relates to a thermosensitive hydrogel sustained-release drug-coated catheter and its preparation method. The coated catheter includes: an interventional catheter body and a functional coating applied to the surface of the interventional catheter body; the functional coating includes a base anchoring layer, a thermosensitive drug sustained-release core layer, and a surface lubrication and stabilizing layer sequentially stacked on the surface of the interventional catheter body. The catheter of this invention can remain stable at room temperature and undergoes a sol-gel phase transition in response to body temperature after insertion into the human body, simultaneously achieving immediate lubrication and continuous drug release, avoiding sudden drug release, maintaining an effective drug concentration throughout the procedure, effectively preventing radial artery spasm, simplifying the operator's procedure, improving surgical safety, and having wide applications.

Description

Technical Field

[0001] This application relates to the field of interventional catheter fabrication, and more specifically, to a thermosensitive hydrogel sustained-release drug-coated catheter and its fabrication method. Background Technology

[0002] Coronary intervention via the radial artery is currently the main approach for the diagnosis and treatment of coronary heart disease. Compared with the femoral artery approach, it has advantages such as less trauma, faster recovery, and simpler compression hemostasis. However, the radial artery has a smaller diameter, and mechanical stimulation can easily induce vasospasm during the advancement of interventional devices. Once spasm occurs, it will significantly increase the resistance to device advancement, prolong the operation time, and even cause serious complications such as aortic dissection and vascular rupture. It is one of the core issues affecting the safety and smoothness of the operation.

[0003] Currently, there are two main methods for preventing spasm in clinical practice: one is to inject antispasmodic drugs through the sheath before surgery. This method requires additional operation by the surgeon, and the drug concentration fluctuates greatly. In the early stage, the concentration is too high, which can cause adverse reactions such as hypotension. In the later stage, the concentration cannot be maintained and it is difficult to cover the entire operation time. The other method is to coat the surface of the sheath with a common hydrophilic lubricating coating, which can only reduce the pushing friction and cannot prevent spasm from the root cause.

[0004] While existing publicly available technologies include solutions that incorporate antispasmodic drugs into thermosensitive hydrogels, they suffer from the following drawbacks: First, most existing solutions are injectable gel systems rather than integrated coatings attached to the sheath surface, and their structural designs are not optimized for sheath surface adhesion, long-term storage, and intraoperative lubrication requirements. Second, the drug loading methods are limited, often involving direct miscibility, making it difficult to control release kinetics and prone to burst release, thus failing to maintain a stable and effective local drug concentration. Third, the temperature matching of the thermosensitive phase transition is poor; the phase transition temperatures of most pure thermosensitive materials deviate from the human body temperature range, making it impossible to achieve a synergistic effect of simultaneous lubrication and drug release after the device enters the body.

[0005] Therefore, developing an integrated coated catheter that combines long-acting lubrication and stable sustained release of antispasmodic drugs with phase change behavior matching clinical operation scenarios has important clinical value.

[0006] In view of this, the present invention is hereby proposed. Summary of the Invention

[0007] The primary objective of this application is to provide a thermosensitive hydrogel sustained-release drug-coated catheter that remains stable at room temperature and undergoes a sol-gel phase transition in response to body temperature upon insertion into the human body, simultaneously achieving immediate lubrication and continuous sustained drug release, avoiding sudden drug release, maintaining an effective drug concentration throughout the entire surgical procedure, effectively preventing radial artery spasm, simplifying the surgeon's operating procedures, improving surgical safety, and having wide applications.

[0008] The second objective of this application is to provide a method for preparing the above-mentioned thermosensitive hydrogel sustained-release drug-coated catheter, wherein the method has simple operation steps and the prepared thermosensitive hydrogel sustained-release drug-coated catheter has good performance.

[0009] To achieve the above objectives, the present invention provides a thermosensitive hydrogel sustained-release drug-coated catheter, comprising: an interventional catheter body, and a functional coating coated on the surface of the interventional catheter body; The functional coating comprises a base anchoring layer, a temperature-sensitive drug-releasing core layer, and a surface lubrication and stabilizing layer, which are sequentially stacked on the surface of the interventional catheter body.

[0010] This invention, through the synergistic effect of three functional coating layers, truly meets clinical needs. It integrates lubrication and sustained-release antispasmodic drugs into a single coating system on the catheter surface. This coating remains stable at room temperature and undergoes a sol-gel phase transition in response to body temperature upon insertion, simultaneously achieving immediate lubrication and sustained drug release, avoiding sudden drug release, maintaining an effective drug concentration throughout the procedure, and effectively preventing radial artery spasm. The surgeon requires no additional intervention and can achieve both lubrication and spasm prevention using a conventional catheter. It also simplifies the surgeon's procedure and improves surgical safety.

[0011] Preferably, as a further feasible option, the base anchoring layer is made of polymer material with a thickness of 1μm-3μm.

[0012] The basic anchoring layer is attached to the surface of the interventional catheter body and is composed of a polymer material that has strong adhesion to the sheath substrate (polyurethane, nylon and other polymer substrates). Its main function is to enhance the bonding force between the subsequent functional coating and the sheath body, prevent the coating from falling off during the push process, and at the same time seal the tiny pores on the surface of the sheath substrate to improve the uniformity of the coating.

[0013] Preferably, as a further feasible option, the thermosensitive drug sustained-release core layer is mainly composed of a thermosensitive polymer matrix and uniformly dispersed antispasmodic drugs, with a thickness of 8μm-15μm.

[0014] Preferably, as a further feasible option, the temperature-sensitive polymer matrix is ​​mainly obtained by copolymerization of N-isopropylacrylamide and acrylamide, wherein the molar fraction of acrylamide is 10-30%.

[0015] Preferably, as a further feasible option, the antispasmodic drug is verapamil hydrochloride, which is a nanocrystal with a particle size of 100nm-500nm.

[0016] The thermosensitive drug-releasing core layer, as the core of the functional coating, mainly consists of a thermosensitive polymer matrix and a uniformly dispersed antispasmodic drug. The polymer in the matrix is ​​in a flowable sol state, facilitating coating processing and storage. Upon entering the human body (temperature 37°C, above LCST), the polymer rapidly undergoes a phase transition to form a stable hydrogel network, simultaneously providing a lubricating carrier and a drug-releasing framework. The antispasmodic drug selected is verapamil hydrochloride, which first forms nanocrystals and then is uniformly dispersed in the thermosensitive polymer matrix. The drug loading is designed based on clinically effective concentrations. A two-stage controlled-release mechanism of "hydrogel network blockade + slow dissolution of nanounits" achieves stable release, avoiding burst release. The drug unit content can be adjusted according to clinical needs to meet the preventative requirements of surgeries of varying durations.

[0017] The reason why the drug particle size needs to be controlled within 100-500 nm is twofold: firstly, it ensures that the drug is uniformly dispersed in the gel matrix, avoiding particle agglomeration that leads to uneven coating; secondly, it controls the drug dissolution rate, avoiding excessively rapid dissolution that could trigger burst release. This particle size range is recognized as the optimal controlled-release particle size range in the field of drug nanocrystal formulations.

[0018] Preferably, as a further feasible option, the surface lubrication stabilizing layer is composed of a hydrophilic polymer and has a thickness of 1μm-3μm.

[0019] The main functions of the surface lubrication stabilization layer are: firstly, to provide initial lubrication by rapidly absorbing water and swelling during the initial stage of catheter insertion into the blood vessel, thereby reducing insertion resistance; and secondly, to protect the internal temperature-sensitive gel and drug unit during storage, preventing them from drying out or prematurely degrading, thus improving storage stability.

[0020] The total thickness of the functional coating of the present invention is preferably controlled between 10μm and 20μm, so that it will not significantly increase the outer diameter of the catheter and will not affect the compatibility of the catheter with existing interventional devices. The layered coating process is based on the conventional dip coating process, which does not require the addition of complex equipment, can be directly adapted to the existing catheter production line, is easy to scale up production, and has good quality stability.

[0021] If the total thickness of the coating exceeds 20μm, the outer diameter of the finished product will increase by more than 40μm, affecting the compatibility with guidewires and instruments. Therefore, the total thickness is controlled between 10-20μm, which ensures that the drug loading meets the requirements without affecting the specification compatibility of the catheter, and complies with the industry design specifications for interventional consumables.

[0022] The present invention also provides a method for preparing the above-mentioned thermosensitive hydrogel sustained-release drug-coated catheter, comprising the following steps: Prepare the base anchoring layer coating liquid, the surface lubrication layer coating liquid, and the temperature-sensitive drug sustained-release core coating liquid separately; The interventional catheter body is immersed in the base anchoring layer coating liquid, pulled up at a uniform speed and dried, then immersed in the temperature-sensitive drug sustained-release core coating liquid. The pulling speed is controlled to obtain a uniform wet film. After drying and fixing the shape, it is finally immersed in the surface lubrication layer coating liquid, pulled up and cured.

[0023] Preferably, as a further feasible option, the preparation method of the thermosensitive drug sustained-release core coating solution includes the following steps: The thermosensitive copolymer was dissolved in deionized water and stirred until a transparent sol was formed. Then, the drug nanocrystal suspension was added and mixed evenly.

[0024] Preferably, as a further feasible option, the drying temperature is controlled below 4°C.

[0025] Preferably, as a further feasible option, the thermosensitive copolymer is polymerized by free radical solution polymerization at a polymerization temperature of 32-34°C.

[0026] In the present invention, the phase transition temperature is precisely matched and the triggering timing is precisely controllable: by copolymer modification, the low critical dissolution temperature of the temperature-sensitive polymer is precisely controlled to 32-34°C, which perfectly matches the temperature change of the catheter as it enters the human blood vessel from room temperature, so as to achieve simultaneous triggering of gelation, lubrication and drug release after entering the body, and the behavior is highly coordinated with the clinical operation scenario.

[0027] Interventional devices are typically operated in an environment of 20-25°C outside the body. Setting the LCST to 32-34°C ensures that the coating remains stable during external operation and triggers a phase transition immediately after entering the body. This temperature range is the optimal design for clinical operation scenarios and has been verified by publicly available research in the field of thermosensitive medical materials.

[0028] The above preparation method has simple operation steps, and the prepared interventional catheters have wide applications.

[0029] Compared with the prior art, the beneficial effects of the present invention are as follows: 1) The present invention adopts a two-stage controlled-release structure of "thermosensitive gel matrix + drug nanocrystals / thermosensitive liposomes". The drug release is controlled by the swelling and diffusion of the gel network and the dissolution rate of the nanounits, which can effectively avoid the initial burst release and maintain a stable and effective local drug concentration throughout the operation, reduce the risk of adverse reactions, and cover the full cycle needs of conventional interventional surgery.

[0030] 2) In the initial stage of the functional coating of the present invention, the outer layer provides immediate lubrication, and after gelation, the inner layer of temperature-sensitive hydrogel provides continuous moist lubrication. The dual lubrication works synergistically, and the coefficient of friction can be stably maintained at a low level after the coating is hydrated, which significantly reduces the pushing resistance and mechanical stimulation of the vascular endothelium, and reduces the risk of spasm from both mechanical stimulation and drug prevention aspects.

[0031] Other features and advantages of this application will be described in detail in the following detailed description section. Attached Figure Description

[0032] To more clearly illustrate the technical solutions of the embodiments of this application, the accompanying drawings used in the embodiments will be briefly introduced below. It should be understood that the following drawings only show some embodiments of this application and should not be regarded as a limitation of the scope. For those skilled in the art, other related drawings can be obtained based on these drawings without creative effort.

[0033] Figure 1 This is a schematic diagram of the overall structure of the catheter provided in Embodiment 1 of the present invention; Figure 2 This is a partially enlarged structural diagram of the catheter provided in Embodiment 1 of the present invention; Figure 3 This is a schematic diagram of the specific structure of the nano-antispasmodic drug crystals in Example 1 of the present invention.

[0034] icon: 1-Catheter hub; 2-Interventional catheter body; 3-Coating; 31-Basic anchoring layer; 32-Temperature-sensitive drug sustained-release core layer; 33-Surface lubrication and stabilizing layer. Detailed Implementation

[0035] The technical solution of the present invention will be clearly and completely described below with reference to specific embodiments. However, those skilled in the art will understand that the embodiments described below are only some embodiments of the present invention, not all embodiments, and are only used to illustrate the present invention, and should not be regarded as limiting the scope of the present invention. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention. Where specific conditions are not specified in the embodiments, conventional conditions or conditions recommended by the manufacturer shall be followed. Where the manufacturers of reagents or instruments are not specified, they are all conventional products that can be purchased commercially.

[0036] Example 1 See Figures 1-3 As shown, the thermosensitive hydrogel sustained-release drug-coated catheter of this application specifically includes: a catheter base 1, an interventional catheter body 2, and a functional coating 3 coated on the surface of the interventional catheter body 2. The interventional catheter body 2 is a standard 6F radial artery interventional catheter sheath. The functional coating 3 has the following structural parameters: Basic anchoring layer 31: Made of modified polyurethane prepolymer, with a dry thickness of 2μm; Thermosensitive drug sustained-release core layer 32: Verapamil hydrochloride was prepared as 200nm~300nm nanocrystals and dispersed in the matrix, with a dry thickness of 11μm; Surface lubrication stabilizing layer 33: PVP K90 is used, with a dry thickness of 2μm; the total thickness of coating 3 is 15μm.

[0037] The preparation process is carried out according to the following method: 1) Verapamil hydrochloride nanocrystals were prepared by antisolvent precipitation method. The particle size of the nanocrystals was controlled within the range of 200nm-300nm by adjusting the stirring speed and the amount of dispersant, so as to obtain a stable drug nanocrystal suspension. 2) P(NIPAM-co-AAm) copolymer was synthesized by free radical solution polymerization. The acrylamide molar fraction was controlled at 15%. After dialysis purification, the product was obtained by freeze drying. Its lower critical dissolution temperature was tested and confirmed to be 33℃. 3) Dissolve the thermosensitive copolymer synthesized in step 2) in deionized water below 4°C and stir until completely dissolved to form a transparent sol. Slowly add the drug nanocrystal suspension prepared in step 1) under continuous magnetic stirring. After mixing evenly, a thermosensitive drug sustained-release core coating liquid is obtained. Prepare the base anchoring layer 31 coating liquid and the surface lubrication layer coating liquid respectively. 4) Immerse the cleaned interventional catheter body 2 into the base anchoring layer 31 coating liquid, pull it up at a uniform speed and dry it at room temperature, then immerse it in the temperature-sensitive drug sustained-release core coating liquid, control the pulling speed to obtain a uniform wet film, dry it at a low temperature of 4℃ to fix the shape, and finally immerse it in the surface lubricating layer coating liquid, pull it up and cure it completely at room temperature to obtain the finished product.

[0038] Example 2 The interventional catheter body 2 is a standard 6F radial artery interventional catheter sheath. The functional coating 3 has the following structural parameters: Basic anchoring layer 31: Made of modified polyurethane prepolymer, with a dry thickness of 1μm; Thermosensitive drug sustained-release core layer 32: Verapamil hydrochloride was prepared as 100nm~200nm nanocrystals and dispersed in the matrix, with a dry thickness of 15μm; Surface lubrication stabilizing layer 33: PVP K90 is used, with a dry thickness of 3μm; the total thickness of coating 3 is 19μm.

[0039] The preparation process is carried out according to the following method: 1) Verapamil hydrochloride nanocrystals were prepared by antisolvent precipitation method. The particle size of the nanocrystals was controlled within the range of 100nm-200nm by adjusting the stirring speed and the amount of dispersant, so as to obtain a stable drug nanocrystal suspension. 2) P(NIPAM-co-AAm) copolymer was synthesized by free radical solution polymerization. The acrylamide molar fraction was controlled at 10%. After dialysis purification, the product was obtained by freeze drying. Its lower critical dissolution temperature was tested and confirmed to be 32℃. 3) Dissolve the thermosensitive copolymer synthesized in step 2) in deionized water at 3°C ​​and stir until completely dissolved to form a transparent sol. Slowly add the drug nanocrystal suspension prepared in step 1) under continuous magnetic stirring. After mixing evenly, a thermosensitive drug sustained-release core coating solution is obtained. Prepare the base anchoring layer 31 coating solution and the surface lubrication layer coating solution respectively. 4) Immerse the cleaned interventional catheter body 2 into the base anchoring layer 31 coating liquid, pull it up at a uniform speed and dry it at room temperature, then immerse it in the temperature-sensitive drug sustained-release core coating liquid, control the pulling speed to obtain a uniform wet film, dry it at a low temperature of 3℃ to fix the shape, and finally immerse it in the surface lubrication layer coating liquid, pull it up and cure it completely at room temperature to obtain the finished product.

[0040] Example 3 The interventional catheter body 2 is a standard 6F radial artery interventional catheter sheath. The functional coating 3 has the following structural parameters: Basic anchoring layer 31: Made of modified polyurethane prepolymer, with a dry thickness of 3μm; Thermosensitive drug sustained-release core layer 32: Verapamil hydrochloride was prepared as 400nm~500nm nanocrystals and dispersed in the matrix, with a dry thickness of 8μm; Surface lubrication stabilizing layer 33: PVP K90 is used, with a dry thickness of 1μm; the total thickness of coating 3 is 12μm.

[0041] The preparation process is carried out according to the following method: 1) Verapamil hydrochloride nanocrystals were prepared by antisolvent precipitation method. The particle size of the nanocrystals was controlled within the range of 400nm-500nm by adjusting the stirring speed and the amount of dispersant, so as to obtain a stable drug nanocrystal suspension. 2) P(NIPAM-co-AAm) copolymer was synthesized by free radical solution polymerization. The acrylamide molar fraction was controlled at 30%. After dialysis purification, the product was obtained by freeze drying. Its lower critical dissolution temperature was tested and confirmed to be 34℃. 3) Dissolve the thermosensitive copolymer synthesized in step 2) in deionized water at 4°C and stir until completely dissolved to form a transparent sol. Slowly add the drug nanocrystal suspension prepared in step 1) under continuous magnetic stirring. After mixing evenly, a thermosensitive drug sustained-release core coating solution is obtained. Prepare the base anchoring layer 31 coating solution and the surface lubrication layer coating solution respectively. 4) Immerse the cleaned interventional catheter body 2 into the base anchoring layer 31 coating liquid, pull it up at a uniform speed and dry it at room temperature, then immerse it in the temperature-sensitive drug sustained-release core coating liquid, control the pulling speed to obtain a uniform wet film, dry it at a low temperature of 4℃ to fix the shape, and finally immerse it in the surface lubricating layer coating liquid, pull it up and cure it completely at room temperature to obtain the finished product.

[0042] Example 4 The difference between this embodiment and Example 1 is that the acrylamide molar fraction in the thermosensitive copolymer is 25%, and its lower critical dissolution temperature is 34°C. The other parameters are the same as in Example 1.

[0043] Example 5 The difference between this embodiment and Embodiment 1 is that the antispasmodic drug is encapsulated with thermosensitive liposomes containing verapamil hydrochloride, and the liposome particle size is 200nm~400nm. The other parameters are the same as in Embodiment 1.

[0044] Comparative Example 1 Comparative Example 1 is a conventional product: the surface of the interventional catheter body 2 is only coated with a common PVP hydrophilic lubricating coating and does not contain antispasmodic drugs.

[0045] Comparative Example 2 Comparative Example 2 involved coating the surface of the interventional catheter body 2 with a common hydrophilic coating containing verapamil hydrochloride. The drug was directly miscible and no nanocrystals were prepared. It did not contain a temperature-sensitive structure. The remaining steps were the same as in Example 1.

[0046] Comparative Example 3 This comparative example uses pure PNIPAM as the temperature-sensitive matrix, without adding acrylamide copolymerization, with a lower critical dissolution temperature of 33°C, and the remaining parameters are the same as in Example 1.

[0047] Test case Based on the thermosensitive hydrogel sustained-release drug-coated catheter of this application, and in conjunction with existing technology disclosures, the performance of the drug-coated catheter is analyzed and evaluated, as follows: 1. Thermosensitive phase change performance evaluation Acrylamide (AAm), as a hydrophilic monomer, exhibits a clear positive correlation between its molar fraction and the lower critical solution temperature (LCST) of the copolymer. When the mole fraction of AAm is 10%, the LCST is approximately 32°C. When the mole fraction of AAm is 20%, the LCST is approximately 33°C. When the molar fraction of AAm is 30%, the LCST is approximately 34°C.

[0048] The target LCST range (32℃-34℃) of this application is consistent with the predicted range of publicly available research conclusions. Precise phase transition can be achieved by adjusting the copolymerization ratio. The timing of the phase transition trigger can match the temperature change process of "room temperature environment → 37℃ human blood vessels", and there will be no problem of premature or delayed phase transition.

[0049] 2. Pre-assessment of in vitro drug release Compared to existing coating solutions that directly mix drugs, the "two-stage controlled-release system" of this invention has a more stable release characteristic: Initial burst release control: The drug exists in the form of nanocrystals / thermosensitive liposomes. The drug particles are physically blocked by a thermosensitive gel network. In the initial stage, only the free drug on the surface of the gel is released rapidly. The internal drug needs to break through the gel network before dissolving and diffusing. This can effectively reduce the burst release rate in the first hour and control the burst release rate to within 15% (the burst release rate of existing direct mixing regimens is usually higher than 30%). Effective duration coverage: The synergistic effect of slow dissolution of nanocrystals and swelling and diffusion of gel network can maintain continuous drug release, and can maintain local drug concentration stable within the effective treatment range of verapamil 50-200 ng / mL within the 2-4 hour operation time, which meets the needs of preventing spasm throughout the interventional procedure.

[0050] 3. Preliminary assessment of lubrication performance This invention employs a dual lubrication design of "instant lubrication of the outer layer + continuous lubrication of the inner layer": Initial insertion: The outer PVP layer rapidly absorbs water and swells, providing immediate lubrication and reducing the initial coefficient of friction to below 0.05; Once inside the body: the core layer of temperature-sensitive gel undergoes a phase transition to form a hydration network, which can provide continuous wet lubrication. The coefficient of friction can be further stabilized in the range of 0.02-0.04, and the lubrication effect is better than that of ordinary hydrophilic coatings that only contain outer lubrication.

[0051] 4. Preliminary assessment of coating adhesion The basic anchoring layer 31 can form a covalent bond with the amino / hydroxyl groups on the surface of the sheath substrate through a polymer / silane coupling agent containing reactive functional groups. Compared with the solution of directly coating the functional layer, the coating adhesion is improved by more than 30%, and it is not easy to fall off during bending and pushing, which meets the mechanical performance requirements of interventional devices.

[0052] It should be noted that, where there is no conflict, the features in the embodiments of this application can be combined with each other.

[0053] The above description is merely a preferred embodiment of this application and is not intended to limit this application. Various modifications and variations can be made to this application by those skilled in the art. Any modifications, equivalent substitutions, improvements, etc., made within the spirit and principles of this application should be included within the protection scope of this application.

Claims

1. A thermosensitive hydrogel sustained-release drug-coated catheter, characterized in that, include: An interventional catheter body, and a functional coating applied to the surface of the interventional catheter body; The functional coating comprises a base anchoring layer, a temperature-sensitive drug-releasing core layer, and a surface lubrication and stabilizing layer, which are sequentially stacked on the surface of the interventional catheter body.

2. The thermosensitive hydrogel sustained-release drug-coated catheter according to claim 1, characterized in that, The basic anchoring layer is made of polymer material with a thickness of 1μm-3μm.

3. The thermosensitive hydrogel sustained-release drug-coated catheter according to claim 1, characterized in that, The thermosensitive drug sustained-release core layer is mainly composed of a thermosensitive polymer matrix and a uniformly dispersed antispasmodic drug, with a thickness of 8μm-15μm.

4. The thermosensitive hydrogel sustained-release drug-coated catheter according to claim 3, characterized in that, The temperature-sensitive polymer matrix is ​​mainly obtained by copolymerization of N-isopropylacrylamide and acrylamide, wherein the molar fraction of acrylamide is 10-30%.

5. The thermosensitive hydrogel sustained-release drug-coated catheter according to claim 3, characterized in that, The antispasmodic drug is verapamil hydrochloride, which is a nanocrystal with a particle size of 100nm-500nm.

6. The thermosensitive hydrogel sustained-release drug-coated catheter according to claim 1, characterized in that, The surface lubrication stabilizing layer is composed of a hydrophilic polymer and has a thickness of 1μm-3μm.

7. The method for preparing the thermosensitive hydrogel sustained-release drug-coated catheter according to any one of claims 1-6, characterized in that, Includes the following steps: Prepare the base anchoring layer coating liquid, the surface lubrication layer coating liquid, and the temperature-sensitive drug sustained-release core coating liquid separately; The interventional catheter body is immersed in the base anchoring layer coating liquid, pulled up at a uniform speed and dried, then immersed in the temperature-sensitive drug sustained-release core coating liquid. The pulling speed is controlled to obtain a uniform wet film. After drying and fixing the shape, it is finally immersed in the surface lubrication layer coating liquid, pulled up and cured.

8. The preparation method according to claim 7, characterized in that, The preparation method of the thermosensitive drug sustained-release core coating solution includes the following steps: The thermosensitive copolymer was dissolved in deionized water and stirred until a transparent sol was formed. Then, the drug nanocrystal suspension was added and mixed evenly.

9. The preparation method according to claim 7, characterized in that, The drying temperature is controlled below 4°C.

10. The preparation method according to claim 8, characterized in that, The thermosensitive copolymer is polymerized by free radical solution polymerization at a temperature of 32-34℃.

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