A Degradable Hydrogel Coil Based on Zinc-Iron-Copper Alloy and Its Preparation Method

Abstract

The present invention discloses a degradable hydrogel coil based on a zinc-iron-copper alloy and a preparation method thereof. The degradable hydrogel coil includes a coil body. Among them, a hydrogel filament core and an anti-unwinding wire are arranged in the coil body. The material of the coil body contains the following components by mass percentage: 58.5%-90.25% of zinc element; 1.9%-7.6% of iron element; 0.65%-1.9% of copper element; 5%-35% of platinum-tungsten powder. The degradable hydrogel coil based on a zinc-iron-copper alloy and the preparation method thereof provided by the present invention have the properties of complete 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 degradable hydrogel coil based on a zinc-iron-copper alloy 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. For the treatment of such diseases, surgical methods were often required in the past, with 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 treatment 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 divided into bare metal coils and surface-modified coils according to materials and structures. Bare metal coils are the coils with the longest development history and the most commonly used clinically. The 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 therapeutic effect. Surface-modified coils are further divided into bioactive surface-coated coils, hydrogel coils, and coils with fiber tufts. Bioactive surface-coated coils refer to coating the surface of bare metal coils with drug coatings having a thrombus-promoting effect, such as prothrombin complex, vitamin K, reptilase, and protamine sulfate, etc.; hydrogel coils refer to having a hydrogel filament core inside the coil or a hydrogel coating on the surface of the coil body, which expands when encountering blood, 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, and can reduce the implantation amount of the coil; coils with fiber tufts refer to having high-molecular materials such as nylon, polypropylene, polytetrafluoroethylene, and poly(glycolide-co-lactide) (PGLA) embedded outside the coil body. Through the mechanical overlap of microfibers, a dense network is built at the lesion site to change the hemodynamics and achieve the effect of rapid and stable thrombosis. The coil body materials of all coils currently 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 and cannot eliminate the mass effect. The long-term implantation of metal materials may also produce metal toxicity and cause 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] Currently, 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 preparation of degradable coils by winding poly-L-lactic acid (PLLA) sutures, but the physical strength of this kind of coil needs to be investigated and whether it has good imaging effect is still unknown.

[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 degradable hydrogel coil based on zinc-iron-copper alloy 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 degradable hydrogel coil based on zinc-iron-copper alloy, including a coil body. Among them, a hydrogel filament core and an anti-unwinding wire are arranged in the coil body of the coil, and the material of the coil body of the coil contains the following components by mass percentage:

[0008] Zinc element: 58.5% - 90.25%;

[0009] Iron element: 1.9% - 7.6%;

[0010] Copper element: 0.65% - 1.9%;

[0011] Platinum-tungsten powder: 5% - 35%.

[0012] Further, the material of the coil body of the coil contains the following components by mass percentage:

[0013] Zinc element: 68.5% - 85%;

[0014] Iron element: 3% - 5.8%;

[0015] Copper element: 0.8% - 1.55%;

[0016] Platinum-tungsten powder: 10% - 25%.

[0017] Further, in the platinum-tungsten powder, platinum accounts for 92% of the total mass percentage, and tungsten accounts for 8%.

[0018] Further, the wire diameter range of the coil body of the coil is between 0.02 - 0.2 mm, the diameter of the first-level coil is between 0.05 - 1 mm, and the diameter of the second-level spiral coil is between 0.2 - 5 mm.

[0019] Furthermore, the material of the anti-unwinding wire is any one of polypropylene, polyethylene, polyisoprene, nitinol alloy, magnesium alloy, and poly-p-dioxanone.

[0020] Furthermore, the material of the hydrogel wire core is any one of polyacrylic acid gels, polyacrylamide gels, polycarbonate gels, amphiphilic block copolymer gels, transparent acetate gels, chitosan gels, alginate gels, polyethylene glycol gels and their modified products.

[0021] The present invention also provides a preparation method of the above-mentioned degradable hydrogel coil based on zinc-iron-copper alloy to solve the above technical problems. The method includes the following steps: Step S1: Melt the zinc-iron-copper raw materials, add platinum-tungsten powder and mix evenly, stretch them into filamentous materials by a machine, then wind the metal wire into the initial shape of a coil by a winding machine or a mandrel die, and finally perform high-temperature shaping through a heat treatment device. After annealing, a degradable coil can be obtained; Step S2: Place the head and tail ends of the anti-unwinding wire into the degradable coil, and connect them with the head and tail ends of the coil by welding process or gluing method to form an integral body; Step S3: Form a hydrogel by condensation polymerization or free radical polymerization of different types of gel monomers, then stretch the hydrogel fiber into a filament by centrifugal spinning method, wet spinning technology or rod die, then immerse the filamentous hydrogel in purified water or injection water for soaking and passivation, and finally air dry naturally to obtain a hydrogel wire, and embed the hydrogel wire into the coil body of the coil.

[0022] Furthermore, in the step S1, the mandrel is a stainless steel rod with a diameter between 0.1 - 0.5 mm; when winding the thin wire, the gap width between the coils is 0.0008 inches - 0.008 inches, and the winding angle is 65° - 80°; the range of the heat setting temperature is 120°C - 250°C, and the heat setting time is 5 - 45 minutes.

[0023] Furthermore, the adhesive used in the step S2 is any one or more of adhesives such as polyester, polyurethane, polyamide, α-cyanoacrylate, etc.

[0024] Furthermore, in the step S3, immerse the filamentous hydrogel in purified water or injection water for soaking and passivation for 18 - 48 hours; when soaking, the volume ratio of the hydrogel wire to the soaking solution volume is 5 - 10, the diameter of the filamentous hydrogel is between 0.01 - 0.3 mm; the length of the hydrogel wire is less than the overall length of the coil, and both the head and tail ends are placed inside the coil body, and the diameter after complete expansion does not exceed the diameter of the first-level coil of the coil.

[0025] Compared with the prior art, the present invention has the following beneficial effects: the degradable hydrogel coil based on zinc-iron-copper alloy provided by the present invention has high embolic density, good biocompatibility, excellent development performance and is completely degradable, thereby solving the current problems of low coil embolic filling rate, non-degradable metal implants and the space-occupying effect, while satisfying the development function of the coil during the pushing process. The specific advantages are as follows:

[0026] 1. The spring coil of the present invention overcomes technical prejudice and uses zinc alloy as the main material of the spring coil, which can be degraded in the body, and the degraded elements can be used by the human body.

[0027] 2. The zinc alloy coil of the present invention is uniformly mixed with platinum tungsten powder to provide good X-ray development; at the same time, the high hardness tungsten can increase the physical properties of the coil and better form a basket in the aneurysm cavity.

[0028] 3. The main material of the spring coil of the present invention is a degradable zinc alloy, and the spring 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.

[0029] 4. The hydrogel silk in the spring coil of the present invention can expand rapidly in the coil when it meets water or blood, but will not expand beyond the coil gap, thereby increasing the density of the embolization without affecting the doctor's pushing during the operation. BRIEF DESCRIPTION OF THE DRAWINGS

[0030] Figure 1 A schematic diagram of the spring coil structure of an embodiment of the present invention;

[0031] Figure 2 for Figure 1 A schematic cross-sectional structure diagram of ;

[0032] Figure 3 This is a schematic diagram of treating an aneurysm with a coil of the present invention. DETAILED DESCRIPTION

[0033] The present invention will be further described below in conjunction with the accompanying drawings and embodiments.

[0034] Figure 1 A schematic diagram of the spring coil structure of an embodiment of the present invention; Figure 2 for Figure 1 Schematic diagram of the cross-sectional structure.

[0035] See also Figure 1 and Figure 2 The degradable hydrogel spring coil based on zinc-iron-copper alloy provided by the present invention mainly consists of a spring coil body 10, a hydrogel silk core 20 and an anti-untwisting silk 30, wherein the spring coil body 10 is a completely degradable spring coil body and has developable microparticle platinum tungsten powder 40.

[0036] The spring coil body is made of a zinc-iron-copper alloy material with zinc as the main element. Zinc is an essential trace element in the human body. It participates in cell division and differentiation, promotes human growth and development, regulates the body's immune system, etc., and plays an important role in maintaining health; iron can help the human body maintain the normal function of the immune system and participate in the metabolism of vitamin A and other trace elements; copper can promote the development of human bones and internal organs and maintain the normal blood concentration in the human body. The zinc-iron-copper alloy can be completely degraded in the human body and the degradation products are non-toxic.

[0037] After melting the zinc-iron-copper raw materials, platinum-tungsten powder is added and mixed evenly, and then drawn into a filamentous material by a precision machine, with its diameter ranging from 0.02 to 0.2 mm. Then the metal wire is wound into the initial shape of a spring coil by a wire winding machine or a mandrel die, and finally heat-set at a high temperature by a heat treatment device. After annealing, the spring coil can be obtained. The mandrel can be a stainless steel rod with a diameter ranging from 0.05 to 1 mm, and the preferred diameter range is 0.1 to 0.5 mm; when the metal wire is wound, the gap width between the coils can be 0.0005 inches to 0.01 inches, and the winding angle can be 60° to 90°, preferably the gap width range is 0.0008 inches to 0.008 inches, and the preferred winding angle range is 65° to 80°; the range of the heat-setting temperature can be 60°C to 800°C, and the preferred temperature range is 250°C to 400°C; the range of the heat-setting time can be 3 to 60 minutes, and the preferred time range is 5 to 45 minutes. At this time, the platinum-tungsten powder is evenly distributed on the surface layer or the coil wire of the spring coil. The diameter of its 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. By adjusting the proportions of zinc, iron, and copper elements, the flexibility, degradability, mechanical properties, etc. of the spring coil body can be adjusted. After research, the zinc element should account for 58.5% to 90.25% of the total mass percentage of the spring coil, the iron element should account for 1.9% to 7.6% of the total mass percentage of the spring coil, the copper element should account for 0.65% to 1.9% of the total mass percentage of the spring coil, and the platinum-tungsten powder should account for 5% to 35% of the total mass percentage of the spring coil. Preferably, the mass percentage range of the zinc element is 68.5% to 85%, the mass percentage range of the iron element is 3% to 5.8%, the mass percentage range of the copper element is 0.8% to 1.55%, and the mass percentage range of the platinum-tungsten powder is 10% to 25%. The degradation rate of the spring coil will increase with the increase of the mass percentage of the zinc element. In this preferred range, the spring coil is completely degraded in about 3 to 9 months. In the platinum-tungsten powder, platinum accounts for 92% of the total mass percentage, and tungsten accounts for 8%. In this formula, the mass percentage of the zinc element shall not exceed 90.25%. If the content of the zinc element is too high, it will affect the overall degradation performance of the spring coil, and the spring coil will be completely degraded in the body due to too fast degradation before it reaches the treatment effect; if the content of the platinum-tungsten powder is too high, there will be more non-degradable metal elements in the whole spring coil, and the occupation effect may not be eliminated or reduced; if the content of the platinum-tungsten powder is too low, the overall spring coil will have poor imaging properties under X-rays. The addition of an appropriate amount of platinum-tungsten metal can improve the mechanical strength of the spring coil and also enhance its imaging properties.

[0038] 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 good anti-bending fatigue property. It can be bent multiple times at room temperature without deformation or damage. Using high molecular weight PDO as the anti-unwinding wire, the tensile force it can withstand is greater than 1N, 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 the diameter is between 0.01 - 0.3mm. 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. The adhesive can be any one or more of adhesives such as polyester, polyurethane, polyamide, α-cyanoacrylate, etc.

[0039] The hydrogel material can be any one of polyacrylic acid gels, polyacrylamide gels, polycarbonate gels, amphiphilic block copolymer gels, transparent acetate gels, chitosan gels, alginate gels, polyethylene glycol gels, etc. and their modified products. Different types of gel-forming monomers form hydrogels through condensation polymerization, radical polymerization and other reactions, and then through centrifugal spinning method, wet spinning technology or other spinning technologies, or rod-shaped molds, the hydrogel fibers are stretched into filaments. Then the filamentous hydrogel is immersed in purified water or injection water for soaking and passivation for 18 - 48 hours, and finally dried naturally under sterile conditions to obtain hydrogel expanded filaments. When soaking, the volume ratio of the hydrogel filaments to the soaking solution volume ranges from 2 - 15, and the preferred range is 5 - 10. The diameter of the filamentous hydrogel is between 0.01 - 0.3mm. There is a direct relationship between the diameter of the hydrogel filaments, the diameter of the primary coil of the coil, and the volume ratio of the soaking solution, that is, the maximum diameter of the hydrogel filaments after expansion shall not exceed the diameter of the primary coil to prevent it from expanding out of the primary coil gap.

[0040] Place the head and tail ends of the anti-unwinding wire into the coil body of the coil, and connect them to the head and tail ends of the coil through a welding process or adhesive technology to form an integral body. Specifically, the anti-unwinding wire is connected at a position close to the edge inside the coil, rather than the center. Finally, embed the hydrogel filaments into the coil body of the coil. The length of the hydrogel filaments is less than the overall length of the coil, and both the head and tail ends are placed inside the coil body. The hydrogel filaments are placed in a straight line on the side with a larger space of the anti-unwinding wire and do not wind around the anti-unwinding wire. When the hydrogel filaments encounter water or blood, they can quickly expand inside the coil body, but the diameter after complete expansion does not exceed the diameter of the primary coil of the coil. As Figure 3 shown, 15 is the aneurysm sac, 25 is the coil, 35 is the blood vessel, and the expanded coil 25 almost fills the aneurysm sac 15.

[0041] Example 1

[0042] The degradable hydrogel coil based on zinc-iron-copper alloy in this example, where zinc accounts for 90.25% of the total mass of the coil, iron is 3.75%, copper is 1%, and platinum-tungsten powder is 5%. After melting the raw materials of zinc alloy elements and uniformly blending them with platinum-tungsten powder, it is drawn into wires with a diameter ranging from 0.02 to 0.2 mm by a machine. Subsequently, the metal wires are wound into the initial shape of the coil by a wire winding machine, and finally, it is heat-set at a high temperature by a heat treatment device and annealed to obtain the coil. Among them, the diameter of the primary coil is between 0.05 and 1 mm, and the diameter of the secondary helical coil is between 0.2 and 5 mm. The 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, the hydrogel wire core is placed on the side with a larger space for the anti-unwinding wire inside the coil. The diameter range of the anti-unwinding wire and the hydrogel wire is between 0.01 and 0.3 mm. The adhesive can be any one or more of adhesives such as polyester, polyurethane, polyamide, α-cyanoacrylate, etc. 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 material can be any one of polyacrylic acid gels, polyacrylamide gels, polycarbonate gels, amphiphilic block copolymer gels, transparent acetate gels, chitosan gels, alginate gels, etc.

[0043] Example 2

[0044] The overall implementation process of this example is generally the same as that of Example 1. The difference from Example 1 is the mass percentage of different elements in the coil. In this coil, zinc accounts for 86% of the total mass of the coil, iron is 2.5%, copper is 1.5%, and platinum-tungsten powder is 10%.

[0045] Example 3

[0046] The overall implementation process of this example is generally the same as that of Example 1. The difference from Example 1 is the mass percentage of different elements in the coil. In this coil, zinc accounts for 80% of the total mass of the coil, iron is 3.6%, copper is 1.4%, and platinum-tungsten powder is 15%.

[0047] Example 4

[0048] The overall implementation process of this example is generally the same as that of Example 1. The difference from Example 1 is the mass percentage of different elements in the coil. In this coil, zinc accounts for 72% of the total mass of the coil, iron is 6.8%, copper is 1.2%, and platinum-tungsten powder is 20%.

[0049] Although the present invention has been disclosed above in 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 subject to that defined by the claims.

Claims

1. A degradable hydrogel coil based on zinc-iron-copper alloy, comprising a coil body, characterized in that, The interior of the spring coil body is provided with hydrogel filaments and anti-unwinding filaments. The length of the hydrogel filaments is less than the overall length of the spring coil, and both the head and tail ends are placed inside the coil body. The diameter after complete expansion does not exceed the diameter of the primary coil of the spring coil. The material of the spring coil body contains the following components by mass percentage: Zinc element: 58.5% - 90.25%; Iron element: 1.9% - 7.6%; Copper element: 0.65% - 1.9%; Platinum-tungsten powder: 5% - 35%; The wire diameter range of the spring coil body is between 0.02 - 0.2 mm, the diameter of the primary coil is between 0.05 - 1 mm, and the diameter of the secondary spiral coil is between 0.2 - 5 mm; The material of the anti-unwinding filament is any one of polypropylene, polyethylene, polyisoprene, nickel-titanium alloy, magnesium alloy, and poly(p-dioxanone); The material of the hydrogel filament is any one of polyacrylic acid gels, polyacrylamide gels, polycarbonate gels, amphiphilic block copolymer gels, hyaluronic acid gels, chitosan gels, alginate gels, polyethylene glycol gels and their modified products; 2. The degradable hydrogel coil based on zinc-iron-copper alloy according to claim 1, wherein The material of the spring coil body contains the following components by mass percentage: Zinc element: 68.5% - 85%; Iron element: 3% - 5.8%; Copper element: 0.8% - 1.55%; Platinum-tungsten powder: 10% - 25%.

3. The degradable hydrogel coil based on zinc-iron-copper alloy according to claim 1, characterized in that, In the platinum-tungsten powder, platinum accounts for 92% of the total mass percentage, and tungsten accounts for 8%.

4. A preparation method of a degradable hydrogel coil based on zinc-iron-copper alloy according to any one of claims 1-3, characterized in that, It includes the following steps: Step S1: Melt the zinc, iron, and copper raw materials, add platinum-tungsten powder and mix evenly, then stretch them into filamentous materials by a machine, wind the metal wires into the initial shape of the spring coil by a winding machine or a mandrel die, and finally perform high-temperature shaping by a heat treatment device. After annealing, a degradable spring coil can be obtained; Step S2: Place the head and tail ends of the anti-unwinding filament into the degradable spring coil, and connect them with the head and tail ends of the spring coil by welding process or gluing method to form an integral body; Step S3: Form a hydrogel by condensation polymerization or free radical polymerization of different types of gel monomers, then stretch the hydrogel fibers into filaments by centrifugal spinning method, wet spinning technology or rod-shaped die, then immerse the filamentous hydrogel in purified water or injection water for soaking and passivation, and finally air dry naturally to obtain hydrogel filaments, and embed the hydrogel filaments into the spring coil body.

5. The preparation method of the degradable hydrogel coil based on zinc-iron-copper alloy according to claim 4, characterized in that, In Step S1, the mandrel is a stainless steel rod with a diameter between 0.1 - 0.5 mm; when winding the filaments, the gap width between the coils is 0.0008 inches - 0.008 inches, and the winding angle is 65° - 80°; the range of the heat setting temperature is 120°C - 250°C, and the heat setting time is 5 - 45 minutes.

6. The preparation method of the degradable hydrogel coil based on zinc-iron-copper alloy according to claim 4, wherein, The adhesive used in Step S2 is any one or more of polyester, polyurethane, polyamide, and α-cyanoacrylate adhesives; 7. The preparation method of the degradable hydrogel coil based on zinc-iron-copper alloy according to claim 4, characterized in that, In Step S3, immerse the filamentous hydrogel in purified water or injection water for soaking and passivation for 18 - 48 hours; when soaking, the volume ratio of the hydrogel filaments to the soaking liquid volume is 5 - 10, and the diameter of the filamentous hydrogel is between 0.01 - 0.3 mm.

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