A partially degradable hydrogel-coated coil and its preparation method

Abstract

The present invention discloses a partially degradable hydrogel-coated coil and a preparation method thereof. The degradable hydrogel-coated coil comprises a coil body, wherein a hydrogel drug-loading coating is coated on the surface of the coil body, an anti-unwinding wire is arranged inside the coil body, the coil body comprises a degradable coil body and a non-degradable coil body which are spliced and connected, and the proportion of the volume of the degradable coil body in the volume of the whole coil is between 65% and 95%. The partially degradable hydrogel-coated coil and the preparation method thereof provided by the present invention have the characteristics of degradability, good biocompatibility, dense packing property, good imaging property, and safety and reliability.

Description

Technical Field

[0001] The present invention relates to a minimally invasive interventional medical device and a preparation method thereof, and particularly relates to a partially degradable hydrogel-coated coil and a preparation method thereof. Background Art

[0002] Aneurysm, gastrointestinal bleeding, tumors, hypervascular tumors, etc. are common hemorrhagic diseases of arteries. Taking aneurysm as an example, if the aneurysm ruptures, the patient's life may be endangered. In the past, the treatment of such diseases often required surgical methods, which had relatively high risks and traumas, especially for elderly patients. With the progress and development of medical technology, endovascular interventional therapy has become the preferred treatment option for such diseases. Among many options, coil embolization therapy has stood out due to its advantages such as safety, reliability, stable implantation, and convenient delivery, and has been favored by doctors and researchers.

[0003] Currently, coil embolization devices can be classified into bare metal coils and surface-modified coils according to materials and structures. The bare metal coil is the coil with the longest development history and the most commonly used in clinics. Its coil body material is platinum-tungsten alloy, which has a self-metal imaging function and good biocompatibility. After being implanted into the lesion, it occludes the lesion site through the thrombus mechanism to achieve the treatment effect. The surface-modified coils are further divided into bioactive surface-coated coils, hydrogel coils, and coils with fiber hairs. The bioactive surface-coated coil refers to coating a drug coating with thrombus-promoting effects, such as prothrombin complex, vitamin K, reptilase, and protamine sulfate, on the surface of the bare metal coil; the hydrogel coil refers to having a hydrogel filament core in the coil or a hydrogel coating on the surface of the coil body. After contacting with blood, it expands, increasing the packing property of the device. At the same time, the additional expansion of the hydrogel volume increases the filling rate of the lesion, reducing the number of coils to be implanted, thereby reducing the economic burden on patients and the perioperative time; the coil with fiber hairs refers to having high-molecular materials such as nylon, polypropylene, polytetrafluoroethylene, and poly(glycolide-lactide) copolymer (PGLA) embedded outside the coil body. It builds a dense network at the lesion site through the mechanical overlap of microfibers, changing the hemodynamics to achieve the effect of rapid and stable thrombosis. Currently, the coil body materials of all coils used clinically are 100% platinum-tungsten alloy and do not have degradable properties. After the implant reaches the lesion, blood supply is inhibited due to mechanical occlusion or thrombus mechanism, but the implant will remain in the body permanently. For aneurysms, the implantation of metal coils cannot shrink the aneurysm body, so it will continuously compress the nerve tissue outside the aneurysm, unable to eliminate the mass effect. The long-term implantation of metal materials may also produce metal toxicity, causing certain damage to the human body, and its long-term safety still needs to be investigated. In addition, the metal artifacts will also affect the image quality during postoperative follow-up, bringing some inconvenience to clinicians.

[0004] At present, there are patent documents mentioning the use of magnesium-based alloys to prepare degradable coils. However, the degradation rate of magnesium alloys in the body is too fast, and they may have been completely degraded before the embolization treatment effect is achieved at the lesion site. There are also patent documents mentioning the use of poly-L-lactic acid (PLLA) sutures to wind and prepare degradable coils, but the physical strength of this kind of coil needs to be investigated, and it is still unknown whether it can have good imaging effects.

[0005] Therefore, to solve the above problems, it is of great significance to develop a medical coil with degradable performance, good biocompatibility, dense packing property, good imaging performance and safety and reliability. Summary of the Invention

[0006] The technical problem to be solved by the present invention is to provide a partially degradable hydrogel-coated coil and its preparation method, which has degradable performance, good biocompatibility, dense packing property, good imaging performance and safety and reliability.

[0007] The technical solution adopted by the present invention to solve the above technical problems is to provide a partially degradable hydrogel-coated coil, including a coil body. Among them, a hydrogel drug-loading coating is coated on the surface of the coil body, an anti-unwinding wire is arranged inside the coil body, the coil body includes a degradable coil body and a non-degradable coil body connected by splicing, and the volume ratio of the degradable coil body to the overall volume of the coil is between 65% and 95%.

[0008] Furthermore, the material of the degradable coil body is a degradable substrate containing a developing material, and the degradable substrate is any one or a combination of poly-lactic acid, poly-L-lactic acid, poly-glycolic acid, poly-glycolide-lactide copolymer, polyethylene glycol, poly-p-dioxanone, polycaprolactone, etc.; the developing material is any one or a combination of barium sulfate, tungsten powder, tantalum powder, bismuth phosphate, hydroxyapatite, triiodophenol or other iodine-containing substances.

[0009] Furthermore, the degradable substrate is a poly-glycolide-lactide copolymer with a molecular weight of 10,000 - 66,000.

[0010] Furthermore, the non-degradable coil body is a platinum-tungsten alloy coil, located at the head, tail and / or middle section of the overall coil; the wire diameter of the platinum-tungsten alloy coil is the same as that of the degradable coil body, and the wire diameter ranges from 0.02 to 0.2 mm, the diameter of the first-level coil ranges from 0.05 to 1 mm, the diameter of the second-level spiral coil ranges from 0.2 to 5 mm, and the K value range of the spliced overall coil is between 0.15 and 0.4.

[0011] Further, the platinum-tungsten alloy coils are located at the head, middle section, and tail of the overall coil. The volume ratios of the platinum-tungsten alloy coils at the head, middle section, and tail are 10%, 5%, 10% or 8%, 6%, 4% or 6%, 5%, 9%. The degradable coil bodies on both sides of the platinum-tungsten alloy coil in the middle section are made of materials with different degradation rates.

[0012] Further, the overall length of the anti-uncoiling wire does not exceed the length of the overall coil, and the diameter is between 0.01 - 0.3 mm. The head and tail ends of the anti-uncoiling wire are connected to the head and tail ends of the coil in a welded form or using an adhesive to form an integral body.

[0013] Further, the material of the anti-uncoiling wire is any one of polypropylene, polyethylene, polyisoprene, nitinol alloy, magnesium alloy, poly-p-dioxanone. The thickness of the hydrogel drug-loading coating is 0.01 - 1 mm. The hydrogel drug-loading coating is any one of polyacrylate gel coatings, polyacrylamide gel coatings, polycarbonate gel coatings, polyurethane gel coatings, amphiphilic block copolymer gel coatings, transparent acetate gel coatings, chitosan gel coatings, alginate gel coatings, polyethylene glycol gel coatings, polyvinyl alcohol gel coatings, carrageenan gel coatings.

[0014] The present invention also provides a preparation method of the above-mentioned partially degradable hydrogel-coated coil to solve the above technical problems. The method includes the following steps: Step S1: Directly blend, graft, or deposit the degradable substrate and the imaging material, then make fine filaments through electrospinning technology, and then wind and entangle the fine filaments through a mandrel mold. Finally, put the mandrel and the fine filaments into a precision temperature-controlled heat-setting oven for heat setting. Anneal at room temperature to prepare a degradable coil with imaging performance; Step S2: Stretch the tungsten alloy material into a metal wire, then wind it into the initial shape of the coil by a wire winding machine, and finally perform high-temperature heat setting by a heat treatment device. After annealing, a platinum-tungsten alloy coil is obtained; Step S3: Use the platinum-tungsten alloy coil as the head, tail, and / or middle section of the overall coil, and adhere it to the degradable coil with an adhesive to form an overall coil; Step S4: Place the head and tail ends of the anti-uncoiling wire into the overall coil body, and connect them to the head and tail ends of the coil through a welding process or an adhesive method to form an integral body; Step S5: Prepare a hydrogel drug-loading solution, coat the hydrogel drug-loading solution on the surface of the coil body, dry it to form a film, and form a hydrogel drug-loading coating on the surface of the coil body.

[0015] Further, in the step S1, the mandrel is a stainless steel rod with a diameter between 0.05 - 1 mm. When winding the fine filaments, the gap width between the coils is 0.0005 inches - 0.01 inches, and the winding angle is 60° - 90°. The range of the heat-setting temperature is 60°C - 350°C, and the heat-setting time is 3 - 60 minutes.

[0016] Further, in step S2, the mass percentages of platinum and tungsten are 92:8, and the heat setting temperature range is 450°C - 650°C.

[0017] Further, before adhesion in step S3, use sandpaper or a polishing machine to polish and flatten the surface of the spring coil that needs to be bonded, then wipe its surface with a lint-free cloth, and then apply an adhesive to the metal coil surface or the biodegradable coil surface and hold it for 3 - 5 minutes to make the bond firm; the adhesive is any one or more of polyester, polyurethane, polyamide, and α-cyanoacrylate adhesives.

[0018] Further, step S5 includes: dissolving a certain mass of sodium alginate in physiological saline to obtain solution A;

[0019] Dissolve a certain mass of acrylamide-based substance in deionized water, then sequentially add a certain mass of calcium carbonate and a thrombus-promoting drug and mix them evenly to obtain solution B; mix solution A and solution B, stir and heat them evenly, and then add an initiator to carry out a polymerization reaction to obtain solution C; after solution C is naturally cooled, a hydrogel solution can be obtained.

[0020] Further, in the mixed solution C, the mass concentration of sodium alginate is 0.1 - 3%; the mass concentration of the acrylamide-based substance is 5 - 40%; the mass concentration of calcium carbonate is 2 - 6%; the mass concentration of the thrombus-promoting drug is 0.1 - 1.5%; the mass concentration of the initiator is 2 - 8%; the acrylamide-based substance is any one of N-isopropylacrylamide and 2-acrylamido-2-methylpropanesulfonic acid; the thrombus-promoting drug is any one or more of vitamin K, aminomethylbenzoic acid, reptilase, prothrombin complex, aminocaproic acid, thrombin, freeze-dried human fibrinogen, adoniside, etamsylate, benyfin, and alpha 9SD coagulation factor; the initiator is any one of ammonium persulfate, hydrogen peroxide, potassium persulfate, benzoyl peroxide, methyl ethyl ketone peroxide, and tert-butyl benzoyl peroxide; the temperature range of the heating reaction is 30 - 80°C, and the polymerization reaction time is 1 - 5h.

[0021] Further, the coating method in step S5 is spraying, brushing, electrostatic coating, dip coating, spin coating, or flow coating; after coating, the drying temperature range is 20 - 230°C, the pressure range is 0.001 - 3 bar, and the drying time is 2 - 256h.

[0022] Compared with the prior art, the present invention has the following beneficial effects: the partially degradable hydrogel-coated spring coil provided by the present invention has high embolic density, good biocompatibility, excellent development performance and certain degradability, thereby solving the current problems of low spring coil embolic filling rate, non-degradable metal implants and space-occupying effect, and at the same time, meets the development function of the spring coil during the pushing process. It has the following advantages:

[0023] 1. The degradable part of the spring coil of the present invention will eventually degrade completely and will not remain in the human body for a long time; and the degradable spring coil containing developing substances such as barium sulfate or iodine will not produce metal artifacts in the body, which is convenient for doctors to observe during or after surgery;

[0024] 2. The head end, tail end or middle section of the spring coil of the present invention is made of platinum-tungsten alloy, which provides good development performance while increasing the overall mechanical strength of the spring coil. The proportion of the metal spring coil is relatively small, and no serious artifact interference will be generated.

[0025] 3. The coil body of the present invention is mostly made of degradable materials, and the coil will gradually degrade after the lesion is completely filled. For aneurysms, the space-occupying effect caused by non-degradable materials can be reduced or completely eliminated, alleviating the pain of patients.

[0026] 4. The hydrogel drug-loaded coating on the surface of the spring coil of the present invention can expand rapidly when it comes into contact with water or blood, and the final volume can reach 3-5 times that before expansion, which greatly increases the embolization density and reduces the number of coils implanted, thereby reducing the economic burden on patients and the perioperative time of doctors.

[0027] 5. The hydrogel drug-loaded coating on the surface of the spring coil of the present invention contains a thrombogenic drug, which can react with the blood after being implanted into the lesion area, quickly induce thrombosis, and increase the embolism density and occlusion success rate.

[0028] 6. Compared with the spring coil containing a gel core, the spring coil containing a hydrogel drug-loaded coating of the present invention will not be restricted in the coil body when expanding, and thus has a larger expansion volume, and the thrombogenic drug in the coating can also respond more quickly. BRIEF DESCRIPTION OF THE DRAWINGS

[0029] Figure 1 This is a schematic diagram of the spring coil structure in which the non-degradable coil body is located at the head and tail of the present invention;

[0030] Figure 2 for Figure 1 A schematic cross-sectional structure diagram of ;

[0031] Figure 3 This is a schematic diagram of the spring coil structure of the present invention in which the non-degradable coil body is located at the head, tail and middle sections;

[0032] Figure 4 Schematic diagram of using the coil of the present invention to treat aneurysms;

[0033] Figure 5 Schematic cross-sectional structure diagram of the coil of the present invention. Detailed implementation manners

[0034] The present invention will be further described below in conjunction with the accompanying drawings and embodiments.

[0035] The partially degradable hydrogel-coated coil provided by the present invention mainly consists of a coil body, a hydrogel drug-loading coating, and an anti-unwinding wire.

[0036] The coil body is composed of two parts. One part is a degradable material with X-ray imaging effect. The degradable material can be any one or a combination of poly(lactic acid) (PLA), poly(L-lactic acid) (PLLA), poly(glycolic acid) (PGA), poly(glycolide-co-lactide) copolymer (PGLA), polyethylene glycol (PEG), poly(p-dioxanone) (PDO), polycaprolactone (PCL), etc. The imaging material can be any one or a combination of barium sulfate (BaSO4), tungsten powder (W), tantalum powder (Ta), bismuth phosphate (BiPO4), hydroxyapatite (HAP), triiodophenol, or other iodine-containing substances, etc. Iodine-containing substances are preferred, such as iohexol, iodized oil, etc. After directly blending, grafting, or depositing the degradable substrate and the imaging material, they are made into filaments by electrospinning technology. Then, the filaments are wound and entangled through a mandrel die. Finally, the mandrel and the filaments are placed in a precision temperature-controlled heat-setting oven for heat setting. The mandrel can be a stainless steel rod with a diameter between 0.05 - 1 mm, and the preferred diameter range is 0.1 - 0.5 mm. When winding the filaments, the gap width between the coils can be 0.0005 inches - 0.01 inches, and the winding angle can be 60° - 90°. The preferred gap width range is 0.0008 inches - 0.008 inches, and the preferred winding angle range is 65° - 80°. The range of the heat-setting temperature can be 60°C - 350°C, and the preferred temperature range is 120°C - 250°C. The range of the heat-setting time can be 3 - 60 minutes, and the preferred time range is 5 - 45 minutes. After completion, the equipment is taken out and annealed at room temperature to prepare a degradable coil with imaging performance. The other part of the coil body is made of a platinum-tungsten alloy wire material that does not have degradation performance. The platinum-tungsten alloy material with an alloy material percentage of 92:8 (92 for platinum and 8 for tungsten) is stretched into a metal wire by a special stretching machine, and then wound into the initial shape of a coil by a wire winding machine. Finally, it is heat-set at a high temperature by a heat treatment device. After annealing, the coil can be obtained. The processes and preparation methods such as winding and heat treatment are similar to those of the degradable coil. The preferred heat-setting temperature range is 450°C - 650°C.

[0037] The platinum-tungsten alloy spring coil is used as the head or tail of the whole spring coil, or the head and tail, or the middle section, and is bonded with the biodegradable material through an adhesive to form the whole spring coil. Figure 1 and 2 As shown, the head and tail ends are platinum-tungsten alloy coils, wherein 10 is a degradable spring coil body, 20 is a platinum-tungsten alloy coil body, 30 is an anti-untwisting wire, and 40 is a developable particle. Figure 3 The platinum-tungsten alloy coil body 20 serves as the head and tail ends and the middle section of the overall spring coil. Figure 4 In the middle, 15 is the aneurysm, 25 is the coil, and 35 is the blood vessel; Figure 5 In the middle, 45 is the coil body, and 55 is the hydrogel drug-loaded coating.

[0038] Before bonding, the side of the spring coil to be bonded needs to be polished and leveled with sandpaper or a polishing machine, and then the surface is wiped with a dust-free cloth to ensure cleanliness, and then the adhesive is applied to the metal ring surface or the degradable ring surface, and pressed for 3-5 minutes to make it firmly bonded. The adhesive can be any one or more of polyester, polyurethane, polyamide, α-cyanoacrylate and other adhesives. The wire diameter of the degradable material spring coil and the platinum tungsten alloy spring coil is consistent, and the diameter range is between 0.02-0.2mm, the diameter of the primary coil is between 0.05-1mm, and the diameter of the secondary spiral coil is between 0.2-5mm. The proportion of the degradable material spring coil to the total spring coil volume is about 65%-95%, and the degradable material will be completely degraded in the human body in about 3-24 months. Generally, the proportion of degradable spring coils cannot be less than 65%, otherwise the proportion of platinum tungsten alloy coils is too high, which will lead to a large number of non-degradable metal coils in the lesion after surgery, so that the space-occupying effect still exists and a good prognosis cannot be achieved. Preferably, the proportion of degradable coils ranges from 80-90%. The platinum tungsten alloy coils at the head end, tail end or middle section of the spring coil in the whole spring coil provide good support and development for the whole spring coil, and the basket-forming performance and basket-forming performance are also improved after implantation. Compared with the fully degradable coils, the overall performance and development are also improved. The molecular weight of the degradable material determines its degradation performance and mechanical properties. The material with high molecular weight also has great mechanical strength, but the degradation performance will be reduced. For example, polycaprolactone (PCL) with a molecular weight greater than 66,000 can exist intact in the body for two years, while those with a molecular weight of less than 10,000 can only exist for a few months before being completely degraded. The properties of degradable materials formed by the polymerization of a single monomer are relatively simple, so multiple monomers are often mixed and polymerized into copolymers to achieve the desired effect. For example, polyglycolide (PGA) with a faster degradation rate and polylactide (PLA) with a slower degradation rate are copolymerized to obtain PGLA, which neutralizes its degradation properties, and then its physical properties are changed by adjusting the molecular weight.

[0039] The softness or flexibility of the coil is determined by the K-factor of the spring, which is in proportion to the thickness of the primary wire of the spring and the tightness of winding. The smaller the K-value, the better the flexibility of the coil. By adjusting the formulation or proportion of the degradable polymer material, filaments with different wire diameters and physical strengths can be spun, and thus coils with different flexibilities can be prepared. Generally, the K-value of the coil ranges between 0.1 and 0.35. Due to the presence of the platinum-tungsten coil in this solution, the K-value will be slightly larger, and its range is about between 0.15 and 0.4. Generally, the K-value of the coil will not exceed 0.5. If it exceeds 0.5, its flexibility may become poor, making it unsuitable for the treatment of diseases such as aneurysms and likely to cause rupture at the lesion site. Generally, the K-value of the coil will not be lower than 0.1. If it is lower than 0.1, it may be too soft and result in insufficient physical strength to achieve the treatment effect. The platinum-tungsten alloy coil in the overall coil itself has X-ray impermeability and does not require the addition of an extra contrast agent, which improves the imaging effect of the overall coil.

[0040] The material of the anti-unwinding wire can be any one of polypropylene (PP), polyethylene (PE), polyisoprene (PI), nitinol alloy, magnesium alloy, etc. The anti-unwinding wire is preferably made of polydioxanone (PDO). The ether bond in the PDO material endows it with good flexibility and tensile strength, and it has good anti-bending fatigue performance and can be bent multiple times at room temperature without deformation or damage. Selecting high-molecular-weight PDO as the anti-unwinding wire, the tensile force it can withstand can be greater than 1 N, and it is less likely to unwind during the operation. The PDO material also has good biocompatibility and biodegradability, can be naturally degraded in the body, and the PDO material is stable and will not react incompatibly with other component materials of the coil. The overall length of the anti-unwinding wire does not exceed the length of the coil, and its diameter is between 0.01 and 0.3 mm. The head and tail ends of the anti-unwinding wire are connected to the head and tail ends of the coil in a welding form or using an adhesive to form an integral body.

[0041] The material of the hydrogel drug-loading coating can be any one of polyacrylic acid gel coatings, polyacrylamide gel coatings, polycarbonate gel coatings, polyurethane gel coatings, amphiphilic block copolymer gel coatings, transparent acetate gel coatings, chitosan gel coatings, alginate gel coatings, polyethylene glycol gel coatings, polyvinyl alcohol gel coatings, carrageenan gel coatings, etc. Any raw material that can make the hydrogel have water-swellable and drug-loading properties can be applicable here. The raw material of the hydrogel coating is preferably an acrylamide-based raw material because its structural unit contains an amide group, which is easy to form hydrogen bonds, thus having better water solubility and chemical activity. Dissolve a certain mass of sodium alginate in physiological saline to obtain solution A; dissolve a certain mass of acrylamide-based substance in deionized water, and then sequentially add a certain mass of calcium carbonate and antithrombotic drugs for uniform mixing to obtain solution B. Mix solution A and solution B, stir and heat uniformly, and then add an initiator for polymerization reaction to obtain solution C. The hydrogel solution can be obtained after the solution C is naturally cooled. In the overall mixed solution, the mass concentration of sodium alginate is 0.1-3%, preferably 0.1-1.5%; the mass concentration of acrylamide-based substance is 5-40%, preferably 10-30%; the mass concentration of calcium carbonate in the overall mixed solution is 2-6%, preferably 3.5-5%; the mass concentration of antithrombotic drug in the overall mixed solution is 0.1-1.5%, preferably 0.5-1%; the mass concentration of initiator is 2-8%, preferably 3-5%. The acrylamide-based substance can be any one of N-isopropylacrylamide and 2-acrylamido-2-methylpropanesulfonic acid. The antithrombotic drug can be any one or more of vitamin K, aminomethylbenzoic acid, hemocoagulase, prothrombin complex, aminocaproic acid, thrombin and freeze-dried human fibrinogen, adoniside, etamsylate, benyfin, alpha 9SD coagulation factor, etc. The initiator can be any one of ammonium persulfate, hydrogen peroxide, potassium persulfate, benzoyl peroxide, methyl ethyl ketone peroxide, tert-butyl benzoyl peroxide, etc. The temperature range of the heating reaction is 30-80°C, preferably 40-55°C; the polymerization reaction time is 1-5 h, preferably 1.5-3 h.

[0042] Place the head and tail ends of the anti-unwinding wire into the spring coil body, and connect them with the head and tail ends of the spring coil through welding process or adhesive technology to form an integral body. Specifically, the anti-unwinding wire is at the central position of the spring coil, so that the force is more uniform during the delivery stage. Then, coat the surface of the spring coil body with the hydrogel drug-loading solution. The coating method can be spraying, brushing, electrostatic coating, dip coating, spin coating or flow coating, etc., and spraying is preferred, because the coating is more uniform and the thickness is controllable by this method. The thickness range of the coating is between 0.01 - 1 mm, preferably 0.01 - 0.5 mm, and more preferably 0.01 - 0.1 mm. After coating, dry the coating to form a film, the temperature range is 20 - 230 °C, preferably 30 - 120 °C; the pressure range is 0.001 - 3 bar, preferably 0.002 - 1 bar; the drying time is 2 - 256 h, preferably 6 - 96 h. After the film formation is completed, cool it naturally to obtain the final spring coil product.

[0043] Example 1

[0044] The head and tail ends of the coil in this embodiment are both coils made of platinum-tungsten alloy wire, each accounting for 2.5% of the volume of the overall coil body. The middle section of the coil is a coil body made of a degradable material, and the material can be any one or more of polylactic acid (PLA), poly-L-lactic acid (PLLA), polyglycolic acid (PGA), polyglycolide-lactide copolymer (PGLA), polyethylene glycol (PEG), polydioxanone (PDO), polycaprolactone (PCL), etc. The imaging agent can be any one of iodine-containing substances, barium sulfate (BaSO4), etc. The degradable material and the iodine-containing substance are directly grafted or deposited with barium sulfate, or blended with tungsten powder (W), tantalum powder (Ta), bismuth phosphate (BiPO4), hydroxyapatite (HAP), etc., and then made into a degradable coil material with imaging performance through precision processes such as spinning, winding, and heat setting. Finally, its head and tail ends are adhered to the platinum-tungsten alloy coil with an adhesive, and the adhesive can be any one or more of polyester, polyurethane, polyamide, α-cyanoacrylate adhesives, etc. The wire diameters of the degradable coil and the platinum-tungsten alloy coil range from 0.02 to 0.2 mm, the diameter of the first-level coil is between 0.05 and 1 mm, and the diameter of the second-level spiral coil is between 0.2 and 5 mm. An anti-unwinding wire is placed into the coil body, and its head and tail ends are connected to the head and tail ends of the coil in the form of welding or gluing. Finally, a hydrogel drug-loading solution is coated on the surface of the coil body. The diameter range of the anti-unwinding wire is between 0.01 and 0.3 mm. The material of the anti-unwinding wire can be any one of polypropylene (PP), polyethylene (PE), polyisoprene (PI), nitinol alloy, magnesium alloy, etc. The hydrogel drug-loading coating is a material based on acrylamide. A certain amount of sodium alginate is dissolved in physiological saline to obtain solution A; a certain amount of acrylamide-based substance is dissolved in deionized water, and then a certain amount of calcium carbonate and a thrombus-promoting drug are added in sequence and uniformly mixed to obtain solution B. Solution A and solution B are mixed, stirred evenly and heated, and then an initiator is added for polymerization reaction to obtain solution C. The hydrogel solution can be obtained after solution C is naturally cooled. The mass concentration of sodium alginate is 0.5%; the mass concentration of acrylamide-based substance is 20%; the mass concentration of calcium carbonate is 4%; the mass concentration of thrombus-promoting drug is 0.5%; the mass concentration of initiator is 4%. The acrylamide-based substance can be any one of N-isopropylacrylamide, 2-acrylamido-2-methylpropanesulfonic acid. The thrombus-promoting drug can be any one or more of vitamin K, aminomethylbenzoic acid, reptilase, prothrombin complex, aminocaproic acid, thrombin, freeze-dried human fibrinogen, adrenergic, etamsylate, benyfin, alpha 9SD coagulation factor, etc. The initiator can be any one of ammonium persulfate, hydrogen peroxide, potassium persulfate, benzoyl peroxide, methyl ethyl ketone peroxide, tert-butyl benzoyl peroxide, etc. The temperature range of the heating reaction is 50 °C; the polymerization reaction time is 2 h.After the hydrogel solution was prepared, it was coated on the surface of the coil body by spraying. The thickness was 0.05 mm, the drying temperature was 70 °C, the pressure was 0.5 bar, and the drying time was 24 h.

[0045] Example 2

[0046] The overall implementation process of this example is generally the same as that of Example 1. The difference from Example 1 is the proportion of the platinum-tungsten alloy coils at both ends of the coil. It can be 5%, 7.5%, 10%, 12.5%, 15%, etc. at both ends. It can also be that the content of the platinum-tungsten alloy coils is unevenly distributed at both ends, but the total content does not exceed 35% of the volume of the entire coil body.

[0047] Example 3

[0048] The overall implementation process of this example is generally the same as that of Example 1. The difference from Example 1 is that the platinum-tungsten alloy coils not only exist at both ends of the coil, but also the middle section of the coil body contains platinum-tungsten alloy coils. The biodegradable coils of the same material are respectively adhered to both ends of the middle metal coil, and then the metal coils at both ends are adhered to form a complete coil. The content of the platinum-tungsten alloy coils in the middle section is always less than or equal to the content of the platinum-tungsten alloy coils at both ends, but the content of the overall metal coils does not exceed 35% of the volume of the entire coil body. For example, the content of the platinum-tungsten alloy coils at the head end, middle section and tail end can be 10%, 5%, 10% or 8%, 6%, 4% or 6%, 5%, 9%, etc.

[0049] Example 4

[0050] The overall implementation process of this example is generally the same as that of Example 3. The difference from Example 3 is that the two biodegradable coils are made of different materials, aiming to regulate the overall degradation rate of the coil. The materials can be low molecular weight polycaprolactone (PCL) with a complete degradation time of 12 - 24 months; it can be poly(p-dioxanone) (PDO) with a complete degradation time of 6 - 8 months; it can be poly(glycolide-lactide) copolymer (PGLA) with a complete degradation time of 1 - 3 months; it can be polyethylene glycol (PEG) with a complete degradation time of 3 - 18 months. It can also be other biodegradable medical polymer materials, and the materials of the biodegradable coil are a combination of any two of the above materials.

[0051] Although the present invention has been disclosed above with preferred embodiments, it is not intended to limit the present invention. Any person skilled in the art can make some modifications and improvements without departing from the spirit and scope of the present invention. Therefore, the protection scope of the present invention shall be defined by the claims.

Claims

1. A partially degradable hydrogel-coated coil, comprising a coil body, characterized in that, The surface of the spring coil body is coated with a hydrogel drug-loading coating. An anti-unwinding wire is arranged inside the spring coil body. The spring coil body includes a degradable coil body and a non-degradable coil body that are spliced and connected. The volume ratio of the degradable coil body to the overall volume of the spring coil is between 65% and 95%. The material of the degradable coil body is a degradable substrate containing a developing material. The degradable substrate is a polyglycolide-lactide copolymer with a molecular weight ranging from 10,000 to 66,000. The non-degradable coil body is a platinum-tungsten alloy spring coil, located at the head, tail, and / or middle section of the overall spring coil. The wire diameter of the platinum-tungsten alloy spring coil is the same as that of the degradable coil body, with the wire diameter ranging from 0.02 to 0.2 mm, the diameter of the first-level coil ranging from 0.05 to 1 mm, the diameter of the second-level spiral coil ranging from 0.2 to 5 mm, and the K value range of the overall spring coil after splicing being between 0.15 and 0.

4.

2. The partially degradable hydrogel-coated coil as claimed in claim 1, wherein The developing material is any one or a combination of barium sulfate, tungsten powder, tantalum powder, bismuth phosphate, hydroxyapatite, triiodophenol, or other iodine-containing substances.

3. The partially degradable hydrogel-coated coil as claimed in claim 1, wherein The platinum-tungsten alloy spring coil is located at the head, middle section, and tail of the overall spring coil. The volume ratios of the platinum-tungsten alloy coils at the head, middle section, and tail are 10%, 5%, 10% or 8%, 6%, 4% or 6%, 5%, 9%. The materials of the degradable coil bodies on both sides of the platinum-tungsten alloy coil in the middle section are materials with different degradation rates.

4. The partially degradable hydrogel-coated coil according to claim 1, wherein The overall length of the anti-unwinding wire does not exceed the length of the overall spring coil, and the diameter is between 0.01 and 0.3 mm. The head and tail ends of the anti-unwinding wire are connected to the head and tail ends of the spring coil in a welded form or using an adhesive to form an integral body.

5. The partially degradable hydrogel-coated detachable coil according to claim 1, wherein The material of the anti-unwinding wire is any one of polypropylene, polyethylene, polyisoprene, nitinol alloy, magnesium alloy, and poly-p-dioxanone. The thickness of the hydrogel drug-loading coating is between 0.01 and 1 mm. The hydrogel drug-loading coating is any one of polyacrylic acid gel coatings, polyacrylamide gel coatings, polycarbonate gel coatings, polyurethane gel coatings, amphiphilic block copolymer gel coatings, hyaluronic acid gel coatings, chitosan gel coatings, alginate gel coatings, polyethylene glycol gel coatings, polyvinyl alcohol gel coatings, and carrageenan gel coatings.

6. A method for preparing a partially degradable hydrogel-coated coil as described in any one of claims 1-5, characterized in that, It includes the following steps: Step S1: After directly blending, grafting, or depositing the degradable substrate and the developing material, make fine filaments through electrospinning technology, then wind and entangle the fine filaments through a mandrel mold, and finally put the mandrel and the fine filaments into a precision temperature-controlled heat-setting oven for setting. Anneal at room temperature to prepare a degradable spring coil with developing performance. Step S2: Stretch the tungsten alloy material into a metal wire, then wind it into the initial shape of a spring coil by a wire winding machine, and finally perform high-temperature setting by a heat treatment device. After annealing, a platinum-tungsten alloy spring coil is obtained. Step S3: Use the platinum-tungsten alloy spring coil as the head, tail, and / or middle section of the overall spring coil, and adhere it to the degradable spring coil with an adhesive to form the overall spring coil. Step S4: Place the head and tail ends of the anti-unwinding wire into the overall spring coil body, and connect them with the head and tail ends of the spring coil by welding or gluing to form an integral body. Step S5: Prepare a hydrogel drug-loading solution, coat the hydrogel drug-loading solution on the surface of the spring coil body, and dry it to form a film, so as to form a hydrogel drug-loading coating on the surface of the spring coil body.

7. The preparation method of the partially degradable hydrogel-coated coil according to claim 6, characterized in that, In the step S1, the mandrel is a stainless steel rod with a diameter between 0.05 mm and 1 mm; when the fine wire is wound, the gap width between the coils is 0.0005 inches - 0.01 inches, and the winding angle is 60° - 90°; the range of the heat setting temperature is 60°C - 350°C, and the heat setting time is 3 - 60 minutes.

8. The preparation method of the partially degradable hydrogel-coated coil according to claim 6, characterized in that, In the step S2, the mass percentage of platinum and tungsten is 92:8, and the range of the heat setting temperature is 450°C - 650°C.

9. The preparation method of the partially degradable hydrogel-coated coil according to claim 6, characterized in that, Before the adhesion in the step S3, use sandpaper or a polishing machine to polish and flatten the surface of the spring coil that needs to be adhered, then wipe its surface with a lint-free cloth, and then apply an adhesive to the metal coil surface or the biodegradable coil surface, and hold it for 3 - 5 minutes to make the adhesion firm; the adhesive is any one or more of polyester, polyurethane, polyamide, and α-cyanoacrylate adhesives.

10. The preparation method of the partially degradable hydrogel-coated coil according to claim 6, characterized in that, The step S5 includes: Dissolve a certain mass of sodium alginate in physiological saline to obtain solution A; Dissolve a certain mass of acrylamide-based substance in deionized water, and then sequentially add a certain mass of calcium carbonate and a thrombus-promoting drug for uniform mixing to obtain solution B; Mix solution A and solution B, stir and heat them evenly, and then add an initiator for polymerization reaction to obtain solution C; After the solution C is naturally cooled, a hydrogel solution can be obtained.

11. The preparation method of the partially degradable hydrogel-coated detachable coil according to claim 10, wherein In the mixed solution C, the mass concentration of the sodium alginate is 0.1 - 3%; the mass concentration of the acrylamide-based substance is 5 - 40%; the mass concentration of the calcium carbonate is 2 - 6%; the mass concentration of the thrombus-promoting drug is 0.1 - 1.5%; the mass concentration of the initiator is 2 - 8%; the acrylamide-based substance is any one of N-isopropylacrylamide and 2-acrylamido-2-methylpropanesulfonic acid; the thrombus-promoting drug is any one or more of vitamin K, aminomethylbenzoic acid, hemocoagulase, prothrombin complex, aminocaproic acid, thrombin, freeze-dried human fibrinogen, adoniside, etamsylate, benifene, and alpha 9SD coagulation factor; the initiator is any one of ammonium persulfate, hydrogen peroxide, potassium persulfate, benzoyl peroxide, methyl ethyl ketone peroxide, and tert-butyl benzoyl peroxide; the temperature range of the heating reaction is 30 - 80°C, and the polymerization reaction time is 1 - 5 h.

12. The preparation method of the partially degradable hydrogel-coated coil according to claim 6, characterized in that, In the step S5, the coating method is spraying, brushing, electrostatic coating, dip coating, spin coating or flow coating; after the coating is completed, the drying temperature range is 20 - 230°C, the pressure range is 0.001 - 3 bar, and the drying time is 2 - 256 h.

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