Spring ring for embolism and preparation method

Abstract

The invention discloses a spring ring for embolism and a preparation method, and relates to the technical field of medical spring rings. The spring ring for embolism is a three-dimensional spring ring, and the three-dimensional spring ring is a spindle variable-diameter spring; the drug-loaded coating is arranged on the surface of the ring body of the spring ring for embolism, the filling stability in a blood vessel is enhanced through a spindle variable diameter structure, gradient slow release of drugs is achieved in combination with a dual drug-loaded mode, and meanwhile the bonding strength of the coating is improved through pretreatment of dopamine and tannic acid; the preparation method has the advantages that the filling stability of the spring ring in the blood vessel is improved, the drug slow release effect is enhanced, and the bonding strength of the coating and the matrix is improved.

Description

Technical Field

[0001] This invention relates to the field of medical coil technology, and in particular to a spring coil for embolization and its preparation method. Background Technology

[0002] Embolization therapy involves the controlled injection of a thrombus into the blood vessel supplying the diseased organ via an arterial or venous catheter, causing occlusion and interrupting blood supply to control bleeding, treat tumors, and vascular lesions. Coil embolization is the mainstream method of embolization therapy. After the coil is inserted into the aneurysm cavity, it induces thrombus formation. To effectively avoid vascular damage and reduce unnecessary pain and harm to the patient when the coil moves within the blood vessel, a hydrophilic coating needs to be applied to the surface of the coil. Related technologies use a single-layer coating method for coating preparation; however, the connection between the single hydrophilic polymer chain and the substrate is often weak, resulting in insufficient coating adhesion and easy frictional detachment, exposing the substrate surface and causing the entire coating to lose its lubricity. Another related technology uses a double-layer coating, but the resulting hydrophilic coating is relatively thick, affecting the use of the coil, and the entire coating preparation cycle is long. Furthermore, existing coils are mostly of uniform diameter, making it difficult to form a stable three-dimensional filling effect within the blood vessel, and drug release control is poor, failing to achieve a sustained and effective thrombolytic effect. These problems seriously affect the efficacy and safety of embolization therapy. To address the aforementioned issues, existing technologies urgently need improvement. Summary of the Invention

[0003] The main objective of this invention is to develop an embolization coil and its preparation method, which enables the coil to have good filling stability in blood vessels, and the coating on the surface of the coil has good bonding stability and lubricity, making it less likely to damage blood vessels during use.

[0004] To achieve the above objectives, the present invention proposes a spring coil for embolization, wherein the spring coil for embolization is a three-dimensional spring coil, and the three-dimensional spring coil is a spindle-shaped variable diameter spring; the surface of the spring coil for embolization is provided with a drug-loaded coating.

[0005] In one embodiment, the embolization spring coil includes a helical secondary coil, and the diameter of the secondary coil increases continuously from both ends of the three-dimensional spring coil toward the middle.

[0006] In one embodiment, the diameter of the secondary coil is 0.5 mm to 10 mm.

[0007] In one embodiment, the free length of the three-dimensional spring coil is 0.8 mm to 4 mm.

[0008] In one embodiment, the secondary coil includes a helical primary coil of equal diameter; the primary coil is wound with a metal wire of equal diameter; wherein the diameter of the primary coil is 0.1 mm to 0.8 mm; and / or the diameter of the metal wire is 0.05 mm to 0.2 mm; and / or the metal wire is made of platinum-tungsten alloy, and the mass percentage of platinum to tungsten is (85 to 92): (8 to 15).

[0009] In one embodiment, the drug-loaded coating includes a hydrogel base layer; the hydrogel includes at least one of sodium carboxymethyl cellulose, hyaluronic acid, polyvinylpyrrolidone, and polyethylene glycol; the hydrogel base layer further includes a first thrombotic agent selected from any one of snake venom hemocoagulase, human prothrombin complex, vitamin K, tranexamic acid, protamine sulfate, aminocaproic acid, ethamsylate, and benifen.

[0010] In one embodiment, the drug-loaded coating further includes drug-loaded microspheres, the drug-loaded microspheres including a second thromboplastin drug, the second thromboplastin drug being selected from any one of snake venom hemocoagulase, human prothrombin complex, vitamin K, tranexamic acid, protamine sulfate, aminocaproic acid, ethamsylate, and benifen; and the second thromboplastin drug is a different type of thromboplastin drug from the first thromboplastin drug.

[0011] The present invention also proposes a method for preparing the above-mentioned embolization spring coil, comprising the following steps: S1. Platinum and tungsten are melted according to the ratio to obtain a platinum-tungsten alloy, which is then straightened to obtain a platinum-tungsten alloy wire; the platinum-tungsten alloy wire is wound to obtain a primary coil, and the primary coil is wound on a spindle-shaped mold to obtain a secondary coil. The coil is then heat-treated to set the shape and obtain a spring coil substrate. S2. The spring coil substrate is immersed in anhydrous ethanol for ultrasonic cleaning, dried, and then immersed in a buffer solution containing dopamine hydrochloride and tannic acid. The mixture is stirred and reacted, then removed and dried to obtain the first spring coil. S3. Disperse drug-loaded microspheres in mannitol solution, coat them onto the surface of the first spring coil by electrostatic spraying, and then cure them by hot air to obtain the second spring coil. S4. Prepare the coating base solution and add the first thrombolytic drug, stir, let stand, immerse the second spring coil in the coating base solution, lift, freeze dry under vacuum, spray calcium chloride atomized liquid to form a hydrogel base layer, and obtain the embolization spring coil.

[0012] In one embodiment, during step S1, the gap between the sub-coils of the primary coil is 0.01mm to 0.2mm during the winding process of the platinum-tungsten alloy wire.

[0013] In one embodiment, during step S1, the gap between the sub-coils of the secondary coil is 0.1mm to 0.5mm during the winding process of the primary coil.

[0014] In one embodiment, during step S1, the heat setting temperature range is 430℃~600℃, and the heat setting time is 10min~50min.

[0015] In one embodiment, step S3, the method for preparing the drug-loaded microspheres includes the following steps: Polyglycolic acid fiber was dispersed in sodium alginate solution and stirred. A second thrombotic drug was added and stirred. Calcium chloride solution was added dropwise and stirred. The mixture was centrifuged, the precipitate was collected, washed, and drug-loaded microspheres were obtained. The polyglycolic acid fiber has a diameter of 0.5μm to 10μm and a length of 0.1mm to 1mm.

[0016] In one embodiment, in step S4, the coating base liquid comprises the following raw materials by weight percentage Sodium carboxymethyl cellulose: 2wt%~4wt%; hyaluronic acid: 3wt%~4wt%; polyvinylpyrrolidone: 2wt%~5wt%; polyethylene glycol-400: 4wt%~8wt%; and the balance being water.

[0017] The technical solution of this invention designs an embolization spring coil and its preparation method. The embolization spring coil is a three-dimensional spring coil, and the three-dimensional spring coil is a spindle-shaped variable diameter spring. The surface of the embolization spring coil is provided with a gel drug-loaded coating. The spindle-shaped variable diameter structure enhances the filling stability in the blood vessel. Combined with the double-layer drug-loaded coating, it realizes the gradient sustained release of drugs. At the same time, the coating bonding strength is improved by pretreatment with dopamine and tannic acid. It has the advantages of improving the filling stability of the spring coil in the blood vessel, enhancing the sustained release effect of drugs, and improving the bonding strength between the coating and the substrate. Attached Figure Description

[0018] To more clearly illustrate the technical solutions in the embodiments of the present invention or the prior art, the drawings used in the description of the embodiments or the prior art will be briefly introduced below. Obviously, the drawings described below are only some embodiments of the present invention. For those skilled in the art, other drawings can be obtained based on the structures shown in these drawings without creative effort.

[0019] Figure 1 This is a schematic diagram of the structure of the spring coil base of the embolization spring coil in Example 1; Figure 2 This is a schematic diagram of the spindle-shaped mold in Example 1; The realization of the objective, functional features and advantages of the present invention will be further explained in conjunction with the embodiments and with reference to the accompanying drawings. Detailed Implementation

[0020] The technical solutions of the embodiments of the present invention will be clearly and completely described below with reference to the accompanying drawings. Obviously, the described embodiments are only a part of the embodiments of the present invention, and not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those of ordinary skill in the art without creative effort are within the scope of protection of the present invention.

[0021] It should be noted that if the embodiments of the present invention involve directional indicators (such as up, down, left, right, front, back, etc.), the directional indicators are only used to explain the relative positional relationship and movement of the components in a specific posture. If the specific posture changes, the directional indicators will also change accordingly.

[0022] Furthermore, if the embodiments of this invention involve descriptions such as "first" or "second," these descriptions are for descriptive purposes only and should not be construed as indicating or implying their relative importance or implicitly specifying the number of technical features indicated. Thus, a feature defined with "first" or "second" may explicitly or implicitly include at least one of those features. Additionally, the use of "and / or" or "and / or" throughout the text includes three parallel solutions. For example, "A and / or B" includes solution A, solution B, or a solution where both A and B are satisfied simultaneously. Furthermore, the technical solutions of the various embodiments can be combined with each other, but this must be based on the ability of those skilled in the art to implement them. When the combination of technical solutions is contradictory or impossible to implement, it should be considered that such a combination of technical solutions does not exist and is not within the scope of protection claimed by this invention.

[0023] The technical problem addressed by this application is that, in related technologies, the coils used in embolization therapy often fail to lubricate due to insufficient adhesion of the surface coating, and the single-coating structure is prone to frictional detachment, making it difficult to sustain drug release. Traditional coils use an equal-diameter helical structure, which is easily displaced by blood flow impact during endovascular embolization, and the coating has weak adhesion to the metal substrate, making it impossible to precisely control the drug release rate and affecting thrombus formation efficiency.

[0024] To address the aforementioned technical challenges, the applicant discovered a correlation between coating detachment and insufficient substrate surface treatment during the research and development process. This necessitates a synergistic approach of material modification and structural design to enhance interfacial adhesion. Further analysis revealed that the variable-diameter structure enhances the morphological adaptability of the coil within the blood vessel, reducing the risk of displacement. Simultaneously, multilayer loading of the hydrogel material can prolong the drug release period. Based on this, a three-dimensional spindle-shaped variable-diameter structure is combined with a gel-loaded drug coating to optimize the embolization effect through the synergistic effect of mechanical support and bioactivity.

[0025] This invention proposes a spring coil for embolization, which is a three-dimensional spring coil and is a spindle-shaped variable diameter spring; the surface of the spring coil for embolization is provided with a drug-loaded coating.

[0026] It should be noted that the three-dimensional spring coil is a spindle-shaped variable-diameter spring. Specifically, it can be formed by winding coils of different diameters, resulting in a shape that is thin at both ends and thick in the middle. This structure can adapt to changes in the lumen diameter when deployed within the blood vessel, improving embolization stability. Specifically, the spindle-shaped variable-diameter structure forms multiple points of contact with the vessel wall after implantation through diameter changes, reducing displacement caused by blood flow impact. It should also be noted that the drug-loaded coating forms an interface layer through a combination of polydopamine and tannic acid. The phenolic hydroxyl groups in tannic acid form strong coordination bonds with the metal surface. The interface layer obtained by the stable accumulation of polydopamine and tannic acid can stably bond with the surface of the spring coil substrate, thus preventing coating detachment. Drug-loaded microspheres are located between the interface layer and the hydrogel matrix layer. On the one hand, when the hydrogel matrix layer outside the drug-loaded coating of the embolization spring coil detaches due to friction or degradation, the second thrombolytic drug in the drug-loaded microspheres can continue to exert an embolic effect; on the other hand, the sustained release of the drug by the microspheres maintains the drug concentration and improves occlusion efficiency.

[0027] Through the above technical solution, this application solves the problem of lubrication failure caused by easy coating peeling, enhances the stability of the spring coil in the blood vessel, realizes the staged release of thrombolytic drugs, thereby improving the embolization treatment effect and reducing the risk of complications.

[0028] In one embodiment, the embolization spring coil includes a helical secondary coil, the diameter of which increases continuously from both ends of the three-dimensional spring coil toward the middle.

[0029] It should be noted that the spiral secondary coil refers to a higher-order spiral structure formed by winding the primary coil. Specifically, this can be achieved by winding the primary coil onto a spindle-shaped mold with a preset pitch. This structure enhances the spatial support capability of the spring coil. The diameter continuously increasing from both ends to the middle means that the radial dimension of the secondary coil smoothly increases along the axial direction. This can be achieved by controlling the winding process with the spindle-shaped contour of the mold. This design allows the middle section of the spring coil to form a larger radial support surface.

[0030] Specifically, the spiral-shaped secondary coils form a three-dimensional structure through multiple layers of spiral stacking, generating multi-directional support when deployed within the blood vessel. The continuously increasing diameter structure increases the contact area between the middle section of the coil and the aneurysm cavity wall, creating a progressive pressure distribution during packing. When the coil is released into the aneurysm cavity, the larger diameter of the middle section preferentially contacts the center of the cavity to form an anchoring point, while the smaller diameters at both ends gradually expand to fill the surrounding space. This continuously varying diameter design avoids localized stress concentration, while the physical blocking effect of the middle section limits the overall displacement of the coil.

[0031] In one embodiment, the diameter of the secondary coil is 0.5 mm to 10 mm. It should be noted that the diameter of the secondary coil refers to the radial dimension of the helical structure formed by winding metal wire. This can be achieved by adjusting the dimensional parameters of the winding die. This dimensional range balances the supporting force of the coil within the blood vessel with the contact pressure against the blood vessel wall. Specifically, the lower limit of the secondary coil diameter is set to 0.5 mm to ensure sufficient radial supporting force after the coil is unwound, preventing displacement under the impact of blood flow; the upper limit of the diameter is controlled within 2 mm to avoid mechanical damage to the vascular endothelium.

[0032] In one embodiment, the free length of the three-dimensional spring coil is 0.8 mm to 4 mm. It should be noted that the free length of the three-dimensional spring coil refers to the maximum length of the spring coil when it extends axially without constraint. Specifically, this can be achieved by controlling the coil's shrinkage rate through a heat treatment shaping process. This length range can accommodate aneurysm cavities of different volumes. Specifically, the lower limit of the free length of the three-dimensional spring coil is set at 0.8 mm to accommodate the anatomical structure of small blood vessels and reduce the operational difficulty during interventional catheter delivery; the upper limit of the free length is extended to 4 mm to meet the filling requirements of larger aneurysm cavities, forming a dense three-dimensional mesh structure through multiple coils stacked together.

[0033] In one embodiment, the secondary coil includes a helical primary coil of equal diameter; the primary coil is wound with a metal wire of equal diameter; wherein the diameter of the primary coil is 0.1 mm to 0.8 mm; and / or the diameter of the metal wire is 0.05 mm to 0.2 mm; and / or the metal wire is made of platinum-tungsten alloy, and the mass percentage of platinum to tungsten is (85 to 92): (8 to 15).

[0034] It should be noted that a spiral-shaped equal-diameter primary coil refers to a spiral structure formed by winding metal wires of uniform diameter with a constant pitch. Equal-diameter metal wires refer to metal wires that maintain a consistent diameter in the axial direction.

[0035] Specifically, a primary coil formed by winding metal wires of equal diameter creates a uniform helical support structure within the secondary coil. When the spring coil unfolds inside the blood vessel, the equal diameter of each sub-coil of the primary coil ensures a uniform distribution of radial support force, preventing excessive local deformation that could damage the blood vessel wall. The platinum component in the platinum-tungsten alloy imparts excellent X-ray radiolucency, while the solid solution strengthening effect of tungsten enhances the alloy's yield strength. This specific ratio solves the problem of insufficient mechanical strength in traditional platinum-iridium alloys.

[0036] In one embodiment, the drug-loaded coating includes a hydrogel base layer; the hydrogel includes at least one of sodium carboxymethyl cellulose, hyaluronic acid, polyvinylpyrrolidone, and polyethylene glycol; the hydrogel base layer further includes a first thrombotic agent selected from any one of snake venom hemocoagulase, human prothrombin complex, vitamin K, tranexamic acid, protamine sulfate, aminocaproic acid, ethamsylate, and benifen.

[0037] It should be noted that the hydrogel base layer refers to a three-dimensional network structure coating formed by hydrophilic polymer materials. Specifically, it can be achieved using a composite system of sodium carboxymethyl cellulose and hyaluronic acid. Sodium carboxymethyl cellulose provides the cross-linking framework, hyaluronic acid enhances biocompatibility, and polyvinylpyrrolidone and polyethylene glycol adjust the coating's flexibility and lubricity. Through physical entanglement and hydrogen bonding, it bonds with the spring coil matrix, effectively preventing the coating from detaching due to mechanical friction or blood flushing. The first thrombolytic drug refers to a coagulation-active substance directly dispersed in the hydrogel base layer. Specifically, it can be achieved using snake venom thrombin or tranexamic acid. Snake venom thrombin promotes coagulation by hydrolyzing fibrinogen to generate fibrin monomers, while tranexamic acid reduces fibrinolysis by inhibiting plasminogen activator. Different drugs are released slowly through the hydrogel network, prolonging the local action time.

[0038] In one embodiment, the drug-loaded coating further includes drug-loaded microspheres, which include a second thrombotic drug selected from any one of snake venom hemocoagulase, human prothrombin complex, vitamin K, tranexamic acid, protamine sulfate, aminocaproic acid, ethamsylate, and benifen; and the second thrombotic drug is a different type of thrombotic drug from the first thrombotic drug.

[0039] It should be noted that drug-loaded microspheres refer to sustained-release carriers composed of polyglycolic acid fibers and sodium alginate. Specifically, polyglycolic acid fibers are dispersed in a sodium alginate solution, and a second thrombolytic drug is added. Calcium ion cross-linking then forms a microsphere structure, achieving drug encapsulation and controlled release. The selection of different types of the second and first thrombolytic drugs significantly improves the reliability and persistence of thrombus formation through synergistic effects. The interlocking structure between the drug-loaded microspheres and the hydrogel matrix layer effectively enhances the coating bonding strength, preventing coating detachment due to friction or blood flow impact, and ensuring stable drug release performance and surface lubrication of the coil during implantation.

[0040] This invention also proposes a method for preparing an embolic spring coil, comprising the following steps: S1. Platinum and tungsten are melted according to the ratio to obtain a platinum-tungsten alloy, which is then straightened to obtain a platinum-tungsten alloy wire; the platinum-tungsten alloy wire is wound to obtain a primary coil, and the primary coil is wound on a spindle-shaped mold to obtain a secondary coil. The coil is then heat-treated to set the shape and obtain a spring coil substrate. S2. The spring coil substrate is immersed in anhydrous ethanol for ultrasonic cleaning, dried, and then immersed in a buffer solution containing dopamine hydrochloride and tannic acid. The mixture is stirred and reacted, then removed and dried to obtain the first spring coil. S3. Disperse drug-loaded microspheres in mannitol solution, coat them onto the surface of the first spring coil by electrostatic spraying, and then cure them by hot air to obtain the second spring coil. S4. Prepare the coating base solution and add the first thrombolytic drug, stir, let stand, immerse the second spring coil in the coating base solution, lift, freeze dry under vacuum, spray calcium chloride atomized liquid to form a hydrogel base layer, and obtain the embolization spring coil.

[0041] It should be noted that the buffer solution for dopamine hydrochloride and tannic acid refers to a mixed solution containing both substances. Specifically, a Tris buffer solution with a pH of approximately 8-9 can be used as the reaction medium. An interfacial layer is formed through oxidative self-polymerization to enhance the adhesion between the coating and the metal substrate. Electrostatic spraying of drug-loaded microspheres involves using an electrostatic field to uniformly disperse and deposit microspheres onto the surface of a spring coil. Specifically, an electric field parameter of 10-20 kV can be used to achieve this, avoiding the microsphere aggregation problem caused by traditional impregnation methods.

[0042] Specifically, in the preparation process of the embolization spring coil, this invention sequentially employs substrate treatment, interface strengthening, microsphere loading, and hydrogel curing to reduce coating thickness while improving bonding stability and coating lubrication performance. Through the above technical solution, this application solves the problem of coating detachment due to insufficient adhesion on the spring coil surface, achieving a stable bond with the substrate through an intermediate adhesion layer. The defect of excessive coating thickness is suppressed, and electrostatic spraying and freeze-drying work together to achieve uniform thin-layer coating. Staged process optimization shortens the preparation cycle and avoids the repeated curing steps of traditional multi-layer coatings.

[0043] In one embodiment, during step S1, the gap between the sub-coils of the primary coil is 0.01mm to 0.2mm during the winding process of the platinum-tungsten alloy wire.

[0044] In one embodiment, during step S1, the gap between the sub-coils of the secondary coil is 0.1mm to 0.5mm during the winding of the primary coil.

[0045] In one embodiment, during step S1, the heat setting temperature range is 430℃~600℃, and the heat setting time is 10min~50min.

[0046] It is understandable that the sub-coil gap of the primary coil refers to the distance between the helical structures formed by adjacent metal wires, and this parameter range can balance winding accuracy and stress distribution. The sub-coil gap of the secondary coil refers to the distance between the secondary helical structures formed by the primary coil, and this parameter range can maintain the morphological stability of the three-dimensional structure.

[0047] In one embodiment, step S3, the method for preparing the drug-loaded microspheres includes the following steps: Polyglycolic acid fibers were dispersed in sodium alginate solution and stirred. A second thrombolytic drug was added and stirred. Calcium chloride solution was added dropwise and stirred. The mixture was centrifuged, the precipitate was collected, washed, and drug-loaded microspheres were obtained. The diameter of the polyglycolic acid fibers was 0.5 μm to 10 μm, and the length of the polyglycolic acid fibers was 0.1 mm to 1 mm.

[0048] It should be noted that polyglycolic acid (PGA) fibers refer to fibrous structures made of PGA material, specifically achievable through melt spinning or electrospinning processes, and possess excellent biodegradability. In some specific embodiments, PGA fibers can be prepared using electrospinning, with the fiber diameter controlled by adjusting the spinning voltage and receiving distance. The concentration of sodium alginate solution can be set to 2wt%~4wt%, and the concentration of calcium chloride solution can be controlled to 5wt%~10wt%. The particle size of the drug-loaded microspheres can be controlled within the range of 50μm~200μm by adjusting the stirring speed.

[0049] In one embodiment, in step S4, the coating base liquid comprises the following raw materials by weight percentage Sodium carboxymethyl cellulose: 2wt%~4wt%; hyaluronic acid: 3wt%~4wt%; polyvinylpyrrolidone: 2wt%~5wt%; polyethylene glycol-400: 4wt%~8wt%; and the balance being water.

[0050] It should be noted that, compared with existing technologies, traditional single-layer coatings rely solely on the physical adsorption of a single polymer chain, while this solution achieves a dual combination mechanism of chemical bonding and physical entanglement through the synergistic effect of sodium carboxymethyl cellulose, hyaluronic acid, and polyvinylpyrrolidone. Sodium carboxymethyl cellulose, as the main framework of the three-dimensional cross-linked structure, can rapidly expand and absorb water. The active groups of hyaluronic acid, polyvinylpyrrolidone, and polyethylene glycol-400 can bind with the active groups of sodium carboxymethyl cellulose, further strengthening the framework. Furthermore, hyaluronic acid has a good lubricating effect on the drug-loaded coating surface, reducing damage during implantation; polyethylene glycol-400 can reduce the contact angle of the formed hydrogel surface, further promoting the water absorption and expansion of the drug-loaded coating.

[0051] The present invention will be further illustrated below through specific embodiments: All raw materials used in the embodiments of this invention are commercially available, and this invention does not impose any restrictions on the source of raw materials.

[0052] Example 1 The preparation method of the embolic spring coil in Example 1 includes the following steps: S1. Platinum powder and tungsten powder are mixed and melted at a mass ratio of 92:8, cooled and shaped to obtain a platinum-tungsten alloy. The alloy wire is straightened to obtain a platinum-tungsten alloy wire with a diameter of about 0.15 mm. The platinum-tungsten alloy wire is wound on a constant diameter die to obtain a primary coil with a diameter of about 0.7 mm. The primary coil is wound on a spindle-shaped die to obtain a secondary coil with a diameter range of 1.5 mm to 2.5 mm and a free length of about 2.9 mm. The coil is then heat-treated at 470°C for 50 minutes to obtain the spring coil matrix. S2. Immerse the spring coil substrate in anhydrous ethanol and ultrasonically clean for 10 min, dry it, and then immerse it in a Tris-HCl buffer solution containing approximately 1 mg / mL dopamine hydrochloride and 0.5 mg / mL tannic acid. React at 40°C with stirring for 30 min, remove it, and blow it dry with nitrogen to obtain the first spring coil. S3. Disperse the drug-loaded microspheres in a 5 wt% mannitol aqueous solution (weight ratio 1:15), and coat them onto the surface of the first spring coil by electrostatic spraying (voltage 15 kV, flow rate 2 mL / min). The spraying amount is controlled to be approximately 2.5 mg / cm³. 2Then, it is cured under hot air at 60℃ for 5 minutes to obtain the second spring coil; S4. Prepare a coating base solution by mixing 3.5 wt% sodium carboxymethyl cellulose, 3 wt% hyaluronic acid, 2 wt% polyvinylpyrrolidone, 7 wt% polyethylene glycol-400, and the balance water. Add the first thrombolytic drug (the mass concentration of the first thrombolytic drug in the coating base solution is about 0.2 wt%), stir for 20 min, let stand for 1 h, immerse the second spring coil in the coating base solution, lift it, freeze dry it at 0.1 mbar pressure and -10℃ for 5 h, spray with calcium chloride atomized solution with a concentration of about 3 wt%, about 2 mL / each second spring coil, blow dry with nitrogen to form a hydrogel base layer, and obtain the embolization spring coil.

[0053] The preparation process of drug-loaded microspheres includes the following steps: 1.5 g of polyglycolic acid (average filament diameter of about 5 μm and length of 0.5 mm to 1 mm) fibers were dispersed in 100 mL of sodium alginate solution with a concentration of about 3 wt%. The solution was stirred at 60 °C for 2 h. A second thrombotic drug was added to a concentration of about 0.2 mg / mL. The solution was stirred at 5 °C for 2 h. 15 mL of calcium chloride solution with a concentration of about 3 wt% was added dropwise while stirring. The solution was centrifuged, the precipitate was collected, washed, and drug-loaded microspheres were obtained.

[0054] The first thrombolytic drug used is tranexamic acid, also known as Transamin, manufactured by Yangtze River Pharmaceutical Group; the second thrombolytic drug used is hetrombopag, manufactured by Hengrui Medicine.

[0055] The structural schematic diagram of the spring coil substrate obtained in step S1 is shown below. Figure 1 The schematic diagram of the spindle-shaped mold in step S1 is shown below. Figure 2 .

[0056] The cytotoxicity of the drug-loaded coating on the surface of the embolization spring coil prepared in Example 1 was determined according to standard GB / T 16886.5-2017. Ten samples were tested, and the results were all grade 0, indicating that they are suitable for clinical use. The contact angle of the drug-loaded coating on the surface of the embolization spring coil prepared in Example 1 was measured, and the average result was 19°, indicating that the surface of the embolization spring coil prepared in this invention has good hydrophilicity.

[0057] The above description is merely an exemplary embodiment of the present invention and does not limit the patent scope of the present invention. Any equivalent structural transformations made using the contents of the present invention specification and drawings under the technical concept of the present invention, or direct / indirect applications in other related technical fields, are included within the patent protection scope of the present invention.

Claims

1. A spring coil for embolization, characterized in that, The embolization spring coil is a three-dimensional spring coil, and the three-dimensional spring coil is a spindle-shaped variable diameter spring; The surface of the embolization spring coil is coated with a drug-loaded coating.

2. The embolization spring coil as described in claim 1, characterized in that, The embolization spring coil includes a helical secondary coil, and the diameter of the secondary coil increases continuously from both ends of the three-dimensional spring coil toward the middle.

3. The embolic spring coil as described in claim 1, characterized in that, The diameter of the secondary coil is 0.5mm to 10mm; And / or, the free length of the three-dimensional spring coil is 0.8mm to 4mm.

4. The embolic spring coil as described in claim 1, characterized in that, The secondary coil includes a helical primary coil of equal diameter; the primary coil is made of metal wire of equal diameter. Wherein, the diameter of the primary coil is 0.1mm~0.8mm; and / or, the wire diameter of the metal wire is 0.05mm~0.2mm; and / or, the metal wire is made of platinum-tungsten alloy, and the mass percentage of platinum to tungsten is (85~92):(8~15).

5. The embolization spring coil as described in claim 1, characterized in that, The drug-loaded coating includes a hydrogel base layer; the hydrogel includes at least one of sodium carboxymethyl cellulose, hyaluronic acid, polyvinylpyrrolidone, and polyethylene glycol; The hydrogel base layer further includes a first thrombotic drug, which is selected from any one of snake venom hemocoagulase, human prothrombin complex, vitamin K, tranexamic acid, protamine sulfate, aminocaproic acid, ethamsylate, and benifen.

6. The embolization spring coil as described in claim 1, characterized in that, The drug-loaded coating further includes drug-loaded microspheres, which include a second thrombotic drug selected from any one of snake venom hemocoagulase, human prothrombin complex, vitamin K, tranexamic acid, protamine sulfate, aminocaproic acid, ethamsylate, and benifen; and the second thrombotic drug is a different type of thrombotic drug from the first thrombotic drug.

7. A method for preparing an embolic spring coil as described in any one of claims 1 to 6, characterized in that, The method for preparing the embolization spring coil includes the following steps: S1. Platinum and tungsten are melted according to the ratio to obtain a platinum-tungsten alloy, which is then straightened to obtain a platinum-tungsten alloy wire; the platinum-tungsten alloy wire is wound to obtain a primary coil, and the primary coil is wound on a spindle-shaped mold to obtain a secondary coil. The coil is then heat-treated to set the shape and obtain a spring coil substrate. S2. The spring coil substrate is immersed in anhydrous ethanol for ultrasonic cleaning, dried, and then immersed in a buffer solution containing dopamine hydrochloride and tannic acid. The mixture is stirred and reacted, then removed and dried to obtain the first spring coil. S3. Disperse drug-loaded microspheres in mannitol solution, coat them onto the surface of the first spring coil by electrostatic spraying, and then cure them by hot air to obtain the second spring coil. S4. Prepare the coating base solution and add the first thrombolytic drug, stir, let stand, immerse the second spring coil in the coating base solution, lift, freeze dry under vacuum, spray calcium chloride atomized liquid to form a hydrogel base layer, and obtain the embolization spring coil.

8. The method for preparing the embolic spring coil as described in claim 7, characterized in that, In step S1, during the winding of the platinum-tungsten alloy wire, the gap between the sub-coils of the primary coil is 0.01mm~0.2mm; And / or, in step S1, during the winding of the primary coil, the gap between the sub-coils of the secondary coil is 0.1mm~0.5mm; And / or, in step S1, during the heat treatment and setting process, the heat setting temperature range is 430℃~600℃, and the heat setting time is 10min~50min.

9. The method for preparing the embolic spring coil as described in claim 7, characterized in that, In step S3, the method for preparing the drug-loaded microspheres includes the following steps: Polyglycolic acid fiber was dispersed in sodium alginate solution and stirred. A second thrombotic drug was added and stirred. Calcium chloride solution was added dropwise and stirred. The mixture was centrifuged, the precipitate was collected, washed, and drug-loaded microspheres were obtained. The polyglycolic acid fiber has a diameter of 0.5μm to 10μm and a length of 0.1mm to 1mm.

10. The method for preparing the embolic spring coil as described in claim 7, characterized in that, In step S4, the coating base liquid comprises the following raw materials by weight percentage. Sodium carboxymethyl cellulose: 2wt%~4wt%; hyaluronic acid: 3wt%~4wt%; polyvinylpyrrolidone: 2wt%~5wt%; polyethylene glycol-400: 4wt%~8wt%; and the balance being water.

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