Magnetic hydrogel as well as preparation method and application thereof

Abstract

The invention discloses magnetic hydrogel as well as a preparation method and application thereof, and relates to the technical field of hydrogel. The magnetic hydrogel is prepared from the following raw materials: a component A, a component B and a component C, the component A comprises a magnetic functional component, a hydrophilic polymer dispersion liquid and a material containing ortho-hydroxybenzene; the component B comprises a material containing an aldehyde group; and the component C comprises a material with oxidizing property. The magnetic hydrogel disclosed by the invention has injectability, can realize directional accurate delivery under the action of an external directional magnetic field, and can be efficiently adhered to the tissue surface in a dynamic water environment, so that the stability and lasting plugging capacity of an embolism material at a target part in a blood vessel are greatly improved.

Description

Technical Field

[0001] This invention relates to the field of hydrogel technology, and in particular to a magnetic hydrogel, its preparation method, and its applications. Background Technology

[0002] Endovascular embolization is an important minimally invasive interventional treatment widely used to treat various vascular diseases such as aneurysms and tumor-related vascular abnormalities. Currently, commonly used embolization materials include metal spring coils, granular embolic agents, and liquid embolic agents. Although all demonstrate embolization effectiveness at the target site, each still has significant limitations. Metal spring coil embolization relies on coagulation, resulting in insufficient embolization density and a tendency to induce vessel wall damage and inflammation. Granular embolic agents lack good controllability and carry the risk of off-target embolization. While liquid embolic agents possess cavity adaptability, their lack of interaction with tissue surfaces results in insufficient stabilization. Current vascular embolization materials still face two main challenges: first, the lack of effective positioning and control methods leads to insufficient embolization precision, and the material is prone to displacement due to blood flow impact and the complexity of anatomical structures, resulting in off-target embolization and even serious complications; second, poor adhesion to vascular tissue can lead to embolization material detachment or displacement, resulting in incomplete embolization and an increased risk of recanalization. Therefore, developing a novel embolic material that is injectable, precisely delivered, and provides stable embolization remains a research hotspot and technical challenge in the field of endovascular embolization in medicine. Summary of the Invention

[0003] The present invention aims to at least solve one of the aforementioned technical problems existing in the prior art. Therefore, the object of the present invention is to provide a magnetic hydrogel that can be rapidly gelled by mixing three components, and possesses underwater injectability, magnetic field-responsive directional movement, tissue adhesion, and embolic stabilization capabilities.

[0004] A second aspect of the present invention is to provide a method for preparing a magnetic hydrogel.

[0005] A third aspect of the present invention is to provide an intravascular embolization system.

[0006] To achieve the above objectives, the technical solution adopted by the present invention is as follows: A first aspect of the present invention provides a magnetic hydrogel, wherein the raw materials for preparing the magnetic hydrogel include component A, component B and component C; component A includes a magnetic functional component, a hydrophilic polymer dispersion and a material containing ortho-hydroxybenzene; component B includes a material containing an aldehyde group; and component C includes a material with oxidizing properties.

[0007] Hydrogels are a class of soft materials formed by the physical or chemical cross-linking of polymer chains to create a three-dimensional network structure. They possess excellent biocompatibility, tunable physicochemical properties, and biodegradability, demonstrating broad application potential in biomedical fields such as tissue engineering, drug delivery, and interventional therapy. By rationally selecting and controlling the types of polymers, functional components, and cross-linking methods, hydrogels can be endowed with different properties to adapt to specific medical applications.

[0008] To address the challenges faced by vascular embolization materials, this invention designs a magnetic hydrogel for intravascular embolization, composed of three components, possessing injectability and tissue adhesion capabilities. Specifically, component A of the magnetic hydrogel contains a magnetic functional component, which is stably introduced into the hydrogel using a hydrophilic polymer dispersion, thereby achieving responsive and precise delivery of the hydrogel under the influence of an applied directional magnetic field. The three components of the magnetic hydrogel can be delivered separately to ensure injectability, and upon delivery to the target site, the components come into contact and rapidly crosslink to form the hydrogel. During deposition, the wettable adhesive components (e.g., materials containing ortho-hydroxybenzene) in the magnetic hydrogel enhance the interaction between the material and the tissue surface, thereby enhancing the embolization stability of the magnetic hydrogel. Through the design of different components, this magnetic hydrogel exhibits excellent injectability, rapid crosslinking capability in a liquid environment, magnetically responsive directional delivery capability, tissue adhesion capability, and stable embolization capability as an embolization material.

[0009] Preferably, the magnetic functional component is a magnetic material with a hydrophilic surface modification. This hydrophilic surface modification improves the dispersibility of the magnetic material.

[0010] More preferably, the magnetic material includes at least one of metallic magnetic materials, iron oxide magnetic materials, ferrite magnetic materials, and rare earth magnetic materials. Specifically, the metallic magnetic material includes at least one of Fe, Ni, Co, iron-containing alloys, nickel-containing alloys, and cobalt-containing alloys; the iron oxide magnetic material includes at least one of Fe3O4 and γ-Fe2O3; the ferrite magnetic material includes at least one of CoFe2O4, MnFe2O4, and ZnFe2O4; and the rare earth magnetic material includes at least one of NdFeB and SmCo. The iron-containing alloys, nickel-containing alloys, and cobalt-containing alloys can be independently selected from iron-nickel alloys, iron-cobalt alloys, or iron-nickel-cobalt alloys.

[0011] Furthermore, the magnetic material described in this invention can also be an inorganic or organic composite material of the aforementioned magnetic material, such as a composite material of Fe3O4 and SiO2, or a composite material of Fe3O4 and polydopamine (PDA).

[0012] More preferably, the magnetic material is magnetic nanoparticles.

[0013] More preferably, the surface hydrophilicity modification includes at least one of chemical bonding modification and physical adsorption modification. Specifically, the chemical bonding modification includes at least one of silane coupling modification, dopamine self-polymerization modification, small molecule ligand coordination modification, small molecule ligand exchange modification, in-situ polymerization grafting modification, and inorganic coating layer modification; the physical adsorption modification includes at least one of polymer adsorption modification, surfactant modification, self-assembly modification, and electrostatic composite modification.

[0014] More preferably, the surface hydrophilic modification is a dopamine self-polymerization modification; then, the magnetic functional component is a magnetic material modified with polydopamine.

[0015] More preferably, the preparation process of polydopamine-modified magnetic materials includes the following steps: The magnetic material was dispersed in Tris-HCl buffer solution, and dopamine was added to react, resulting in a magnetic material with surface modification by polydopamine, i.e., a magnetic functional component.

[0016] Specifically, the surface of the magnetic material modified with polydopamine contains a polydopamine coating. The reaction is carried out at room temperature for 20-50 minutes; the reaction is followed by solid-liquid separation and drying steps; the mass ratio of the magnetic material to the dopamine is 1:(0.01-0.5); preferably, the mass ratio of the magnetic material to the dopamine is 1:(0.05-0.15); more preferably, the mass ratio of the magnetic material to the dopamine is 1:(0.08-0.12).

[0017] Preferably, the concentration of the magnetic functional component in component A is 1~1000 mg / mL.

[0018] It should be understood that the magnetic functional component is dispersed in the hydrophilic polymer dispersion. Since the volume of the dispersion remains essentially constant, the concentration of the magnetic functional component in the dispersion is 1~1000 mg / mL.

[0019] More preferably, the concentration of the magnetic functional component in component A is 0.1~0.8 g / mL, i.e., 100~800 mg / mL. More preferably, the concentration of the magnetic functional component in component A is 0.1~0.5 g / mL, i.e., 100~500 mg / mL. Even more preferably, the concentration of the magnetic functional component in component A is 0.2~0.4 g / mL, i.e., 200~400 mg / mL.

[0020] Preferably, the hydrophilic polymer dispersion contains at least one of polysaccharide polymers, protein polymers, polypeptide polymers, and synthetic polymers.

[0021] More preferably, the polysaccharide polymer includes at least one of chitosan, chitosan derivatives, hyaluronic acid, hyaluronic acid salts, sodium alginate, dextran, starch, starch derivatives, cellulose, and cellulose derivatives. Specifically, the chitosan derivative includes at least one of chitosan quaternary ammonium salt and carboxymethyl chitosan; the starch derivative includes at least one of hydroxypropyl starch and carboxymethyl starch; and the cellulose derivative includes at least one of hydroxypropyl cellulose and carboxymethyl cellulose.

[0022] More preferably, the protein-based polymer includes at least one selected from gelatin, collagen, silk fibroin, elastin, and albumin; the polypeptide-based polymer includes at least one selected from polylysine and polyglutamic acid; and the synthetic polymer includes at least one selected from polyethylene glycol, polyvinyl alcohol, polyvinylpyrrolidone, polyacrylic acid, sodium polyacrylate, polyacrylamide, polyacrylamide derivatives, polyethylene oxide, polyhydroxyethyl methacrylate, and zwitterionic polymers. Among these, polyacrylamide derivatives include, for example, hydroxypropyl and carboxypropyl derivatives of polyacrylamide; and zwitterionic polymers include, for example, methacryloyl ethyl sulfobetaine.

[0023] Preferably, the hydrophilic polymer dispersion is prepared by dispersing or dissolving the hydrophilic polymer in a PBS solution.

[0024] Preferably, the mass-volume concentration of the hydrophilic polymer in the hydrophilic polymer dispersion is 0.1~10% (0.001~0.1g / mL).

[0025] More preferably, the mass-volume concentration of the hydrophilic polymer in the hydrophilic polymer dispersion is 1-5% (0.01-0.05 g / mL).

[0026] More preferably, the mass-volume concentration of the hydrophilic polymer in the hydrophilic polymer dispersion is 2-4% (0.02-0.04 g / mL).

[0027] Specifically, in this invention, the mass volume concentration of a solution / dispersion refers to the mass of solute contained in a unit volume of solution / dispersion, and its unit is mass (g) / volume (mL). For example, a mass volume concentration of 10% is 0.1 g / mL.

[0028] Preferably, the material containing ortho-hydroxybenzene includes at least one of catechol, dopamine, dopa, tannic acid, gallic acid, caffeic acid, or derivatives thereof, or includes a polymeric material containing at least one structural unit of catechol, dopamine, dopa, tannic acid, gallic acid, or caffeic acid, such as polydopamine, dopa-grafted chitosan, dopa-grafted gelatin, dopa-grafted polyethylene glycol, or hyperbranched aminoethyl gelatin material with catechol at the end.

[0029] More preferably, the material containing ortho-hydroxybenzene includes hyperbranched aminoethyl gelatin material with terminal catechol.

[0030] Specifically, catechol is also known as catechol, gelatin is a polymer, and the hyperbranched aminoethyl gelatin material with catechol at the end is a polymer material containing catechol structural units.

[0031] Preferably, the concentration of the material containing ortho-hydroxybenzene in component A is 0.01~1 g / mL.

[0032] More preferably, the concentration of the material containing ortho-hydroxybenzene in component A is 0.1~1.5 g / mL.

[0033] More preferably, the concentration of the material containing ortho-hydroxybenzene in component A is 0.1~1 g / mL.

[0034] More preferably, the concentration of the material containing ortho-hydroxybenzene in component A is 0.3 to 0.7 g / mL. For example, this concentration is preferably 0.3 g / mL, 0.4 g / mL, 0.5 g / mL, 0.6 g / mL or 0.7 g / mL, or other ranges of these values, such as 0.4 to 0.6 g / mL.

[0035] Preferably, the aldehyde-containing material includes at least one of glutaraldehyde, formaldehyde, adipaldehyde, malondialdehyde, succinal, glyoxal, acetaldehyde, propionaldehyde, oxidized hyaluronic acid, oxidized sodium hyaluronate, oxidized alginate, oxidized sodium alginate, oxidized chitosan, oxidized dextran, aldehyde derivatives of proteins, aldehyde derivatives of peptides, and aldehyde derivatives of synthetic polymers. Among these, aldehyde derivatives of synthetic polymers include, for example, aldehyde-based polyethylene glycol and aldehyde-based polyacrylic acid.

[0036] Preferably, the concentration of the aldehyde-containing material in component B is 0.03~0.5 g / mL.

[0037] More preferably, the concentration of the aldehyde-containing material in component B is 0.03~0.1 g / mL.

[0038] More preferably, the concentration of the aldehyde-containing material in component B is 0.04~0.06 g / mL.

[0039] Preferably, the oxidizing material includes at least one selected from periodate oxidants, peroxide oxidants, high-valence metal oxidants, quinone oxidants, persulfate oxidants, and polymeric oxidants. The periodate oxidants include at least one selected from sodium periodate and potassium periodate.

[0040] More preferably, the oxidizing material includes sodium periodate and / or potassium periodate.

[0041] In addition, the oxidizing material can also be a composite material loaded with an oxidant.

[0042] Preferably, the concentration of the oxidizing material in component C is 0.01~0.15 g / mL.

[0043] More preferably, the concentration of the oxidizing material in component C is 0.05~0.15 g / mL.

[0044] More preferably, the concentration of the oxidizing material in component C is 0.075~0.15 g / mL.

[0045] More preferably, the concentration of the oxidizing material in component C is 0.08~0.12 g / mL.

[0046] Preferably, component A further includes a CT contrast agent.

[0047] More preferably, the CT contrast agent includes at least one of iodine-containing contrast agents, metal contrast agents, and oxidizing contrast agents. Iodine-containing contrast agents include at least one of metal iodides and lipid-soluble iodides; metal contrast agents include at least one of metal nanoparticles, such as silver nanoparticles, tantalum nanoparticles, bismuth nanoparticles, strontium nanoparticles, or composite nanoparticles of the above; oxidizing contrast agents include sodium periodate and potassium periodate. Additionally, functionalized or targeted nanoparticles can also be used as CT contrast agents.

[0048] More preferably, the CT contrast agent includes at least one of silver nanoparticles, tantalum nanoparticles, bismuth nanoparticles, and strontium nanoparticles. Specifically, tantalum nanoparticles with polydopamine surface modification are used as the CT contrast agent.

[0049] More preferably, the preparation process of polydopamine-modified tantalum nanoparticles includes the following steps: The tantalum nanoparticles were dispersed in Tris-HCl buffer solution, and dopamine was added to react, resulting in tantalum nanoparticles with polydopamine surface modification.

[0050] Specifically, the tantalum nanoparticles, after surface modification with polydopamine, have a polydopamine coating on their surface. The reaction is carried out at room temperature for 20-50 minutes; the reaction is followed by solid-liquid separation and drying steps; the mass ratio of the tantalum nanoparticles to the dopamine is 1:(0.01-0.5); preferably, the mass ratio of the tantalum nanoparticles to the dopamine is 1:(0.08-0.12).

[0051] Preferably, the volume ratio of component A, component B and component C is 1:(0.1~2):(0.1~2).

[0052] More preferably, the volume ratio of component A, component B and component C is 1: (0.2~1): (0.2~0.8).

[0053] More preferably, the volume ratio of component A, component B and component C is 1: (0.4~0.8): (0.2~0.6).

[0054] More preferably, the volume ratio of component A, component B and component C is 1: (0.5~0.7): (0.3~0.5).

[0055] A second aspect of the present invention provides a method for preparing the magnetic hydrogel described in the first aspect of the present invention, comprising the following steps: Component A is obtained by dispersing the magnetic functional component and the material containing ortho-hydroxybenzene in a hydrophilic polymer dispersion; component B is obtained by dissolving the aldehyde-containing material in PBS solution; and component C is obtained by dissolving the oxidizing material in water. Component A, component B, and component C are mixed to obtain the magnetic hydrogel.

[0056] Preferably, the preparation method includes the following steps: Component A is obtained by dispersing a magnetic functional component (e.g., polydopamine-modified γ-Fe2O3 nanoparticles), a material containing ortho-hydroxybenzene (e.g., hyperbranched aminoethyl gelatin material with terminal catechol enrichment), and a CT contrast agent (e.g., polydopamine-modified tantalum nanoparticles) in a hydrophilic polymer (e.g., chitosan quaternary ammonium salt) dispersion; component B is obtained by dissolving an aldehyde-containing material (e.g., oxidized hyaluronic acid) in PBS solution; and component C is obtained by dissolving an oxidizing material (e.g., sodium periodate) in water; and component C is obtained by mixing components A, B, and C in water for use.

[0057] A third aspect of the present invention provides a directional embolization system comprising the magnetic hydrogel described in the first aspect of the present invention.

[0058] Specifically, the qualitative embolization system is an intravascular directional embolization system.

[0059] The magnetic hydrogel of this invention contains three components, which can be used as an embolic material in a targeted embolization system. During use, the three components are delivered separately and injected simultaneously. Upon reaching the target site, they cross-link to form a hydrogel. Therefore, the magnetic hydrogel of this invention, when used as an embolic material, possesses injectability and tissue adhesion capabilities. Under the guidance of an external magnetic field, it can achieve precise intravascular targeted delivery. Simultaneously, the specific chemical design of the magnetic hydrogel endows the material with excellent tissue adhesion properties, thereby significantly improving the stability and long-lasting occlusion capability of the embolic material at the target site while effectively avoiding off-target embolization. It can be used to construct a targeted embolization system based on magnetic field response control, achieving precise material positioning via magnetic navigation and rapid gelation at the target tissue, providing a safer and more efficient solution for intravascular embolization treatment.

[0060] Specifically, the magnetic hydrogel of the present invention can be used as an embolization material for a directional embolization system, and can be used for embolization treatment of abnormal arteriovenous structures such as aneurysms, arteriovenous malformations (AVMs), and hemangiomas, to prevent endoleak after endovascular stent transplantation repair of abdominal aortic aneurysms, and for embolization of tumor-feeding arteries in interventional tumor therapy.

[0061] Compared with the prior art, the beneficial effects of the present invention are: This invention provides a magnetic hydrogel. By introducing magnetic functional components, it achieves directional traction and embolization of the hydrogel under the control of an external magnetic field, enabling precise directional delivery of the hydrogel under the influence of an applied directional magnetic field. The presence of ortho-hydroxybenzene in the magnetic hydrogel acts as a wet adhesion component, enhancing the interaction between the material and the tissue surface. This allows for efficient adhesion to the tissue surface in a dynamic aqueous environment, thereby enhancing the embolization stability of the magnetic hydrogel and significantly improving the stability and long-term occlusion capability of the embolic material at the target site. Furthermore, the three components of the magnetic hydrogel can be delivered separately to ensure injectability. Due to the rational design of each component, they rapidly cross-link upon contact at the target site to form a hydrogel. Therefore, the magnetic hydrogel of this invention, as an embolization material for a directional embolization system, exhibits excellent injectability, rapid cross-linking capability in a liquid environment, magnetically responsive directional delivery capability, tissue adhesion capability, and stable embolization capability. Moreover, its preparation method is simple and low-cost, providing a safer and more efficient solution for endovascular embolization therapy. Attached Figure Description

[0062] Figure 1Transmission electron microscopy (TEM) images of the magnetic materials prepared in Example 1 before and after polydopamine modification; wherein, Figure 1 Figures a and b in the diagram represent transmission electron microscopy (TEM) images of the magnetic material before and after modification, respectively.

[0063] Figure 2 The images show the magnetic materials before and after polydopamine modification in Example 1, dispersed in a hydrophilic polymer dispersion; wherein, Figure 2 Figures a and b in the image represent the dispersion photographs of the magnetic material before and after modification, respectively.

[0064] Figure 3 The graph shows the change in modulus over time after the three components of the magnetic hydrogel in Example 1 are mixed.

[0065] Figure 4 The graphs show the adhesion strength of the magnetic hydrogels in Examples 2-4; where, Figure 4 Figures a, b, and c in the diagram represent the adhesion strength of the magnetic hydrogels in Examples 2, 3, and 4, respectively.

[0066] Figure 5 The three-channel injection catheter used for simultaneous injection of the three components of the magnetic hydrogel in Test Example 1.

[0067] Figure 6 This is a diagram showing the state of the hydrogel injected during the injection process in Test Example 1 when the catheter was swung.

[0068] Figure 7 This is a diagram showing the adhesion effect of the three components of the magnetic hydrogel injected into blood-covered vascular tissue in Test Example 1.

[0069] Figure 8 This is an image showing the underwater directional magnetic guidance effect of the magnetic hydrogel in Test Example 2; where, Figure 8 Figures a, b, and c in the diagram show the effects of no magnetic field, a horizontal magnetic field, and a vertical magnetic field, respectively.

[0070] Figure 9 This is a schematic diagram illustrating the underwater directional embolization effect of the magnetic hydrogel in Test Example 3.

[0071] Figure 10 The image shows the effect of magnetic hydrogel on directional embolization in an in vitro simulated aneurysm model, as shown in Test Example 3. Detailed Implementation

[0072] The present invention will be further described in detail below through specific embodiments. Unless otherwise specified, the raw materials, reagents, or apparatus used in the embodiments and comparative examples are all available from conventional commercial sources or can be obtained by existing technical methods. Unless otherwise specified, the test or experimental methods are conventional methods in the art.

[0073] Preparation Example 1 Preparation of polydopamine-modified γ-Fe2O3 magnetic materials: 0.1 g of magnetic nanoparticles γ-Fe2O3 were added to 50 mL of Tris-HCl buffer (10 mmol / L, pH=8.5). Then, under mechanical stirring and a room temperature water bath, 0.01 g of dopamine was added to the suspension and the mixture was reacted at room temperature for 30 minutes to ensure that the dopamine was fully polymerized on the surface of the magnetic nanoparticles. After the reaction was completed, the magnetic nanoparticles were collected by filtration and washed five times alternately with deionized water and anhydrous ethanol to remove unreacted dopamine and its polymers. Finally, the product was vacuum dried at 50 °C for 12 hours to obtain γ-Fe2O3 magnetic nanoparticles with a polydopamine coating on the surface.

[0074] like Figure 1 As shown, Figure 1 These are transmission electron microscopy images of the magnetic material before and after polydopamine modification. The presence of the polydopamine coating on the surface after modification can be observed.

[0075] The magnetic materials prepared in this example, before and after surface modification of polydopamine, were dispersed in a hydrophilic polymer dispersion or pure water, and their dispersion effect was observed. The specific process is as follows: 0.03 g of chitosan quaternary ammonium salt was dissolved in 1 mL of PBS solution to prepare a hydrophilic polymer dispersion (hydrophilic polymer mass-volume concentration 3%). 0.3 g of γ-Fe₂O₃ magnetic material before and after polydopamine surface modification was added to the 3% (w / v) hydrophilic polymer dispersion, and an equal volume was added to pure water. After ultrasonic treatment for 30 minutes, a dispersion containing magnetic functional components was obtained. Figure 2 As shown, it can be observed that the modified magnetic material (i.e., the magnetic functional component) can be stably dispersed in the hydrophilic polymer dispersion.

[0076] Example 1 A magnetic hydrogel comprises component A, component B, and component C. Component A contains a magnetic functional component (γ-Fe2O3 magnetic material with polydopamine surface modification as described in Preparation Example 1), a material containing ortho-hydroxybenzene (hyperbranched aminoethyl gelatin material with terminal catechol richness (Gel-AE-Ca)), a hydrophilic polymer dispersion (PBS solution dispersion of chitosan quaternary ammonium salt (purchased from Shanghai Maclean Biochemical Technology Co., Ltd., catalog number 850125, degree of substitution 95%)), and a CT contrast agent (tantalum nanoparticles with polydopamine surface modification). Component B is a PBS solution containing oxidized hyaluronic acid. Component C is an aqueous solution of sodium periodate. The preparation method of this magnetic hydrogel is as follows: Preparation of Component A: 0.03 g of chitosan quaternary ammonium salt was dissolved in 1 mL of PBS solution as a hydrophilic polymer dispersion. 0.3 g of polydopamine-modified γ-Fe2O3 magnetic material and 0.2 g of polydopamine-modified tantalum nanoparticles were added and dispersed thoroughly. Subsequently, 0.4 g of hyperbranched aminoethyl gelatin material (Gel-AE-Ca) with catechol-rich ends was dissolved to obtain Component A. The volume of the PBS solution remained essentially unchanged after dissolving the raw materials in Component A. Preparation of component B: 0.05 g of oxidized hyaluronic acid was dissolved in 1 mL of PBS solution to obtain component B; Preparation of component C: Dissolve 0.1 g of sodium periodate in 1 mL of deionized water to obtain component C; Components A, B, and C were mixed at a volume ratio of A:B:C = 1:0.6:0.4. The gel-forming behavior of the mixture was evaluated using a rheometer. The test was conducted using a parallel plate rheometer; the relative motion of the upper and lower parallel plates generated shear force. The test was performed at 37°C, a frequency of 1 Hz, and a strain of 1%, to detect the changes in the storage modulus (G') and loss modulus (G'') of the magnetic hydrogel over time. Figure 3 As shown, it is easy to see that the three components of the magnetic hydrogel can undergo rapid gelation within 2 seconds after mixing, which shows that the magnetic hydrogel of the present invention has rapid gelation ability.

[0077] The preparation method of polydopamine-modified tantalum nanoparticles is the same as that of polydopamine-modified γ-Fe2O3 magnetic nanoparticles in Preparation Example 1, except that γ-Fe2O3 magnetic nanoparticles are replaced with tantalum nanoparticles.

[0078] Hyperbranched aminoethyl gelatin material containing terminal catechol-rich gelatin (Gel-AE-Ca) is obtained by reacting gelatin with 2-chloroethylamine hydrochloride, and the terminal catechol groups are grafted by EDC (1-ethyl-3-(3-dimethylaminopropyl)carbodiimide) / NHS (N-hydroxysuccinimide) chemical modification (for specific preparation methods, refer to “Acatechol bioadhesive for rapid hemostasis and healing of traumatic internalorgans and major arteries, Biomaterials, Volume 291, December 2022, 121908”, 4.2. Synthesis of Gel-AE-Ca).

[0079] Example 2 The difference between this embodiment and Example 1 is that different concentrations of Gel-AE-Ca were included in component A to illustrate the effect of different concentrations of Gel-AE-Ca on the adhesion strength of the magnetic hydrogel to the tissue surface after gelation. The mass concentrations of Gel-AE-Ca in component A were: 0%, 10% (0.1 g / mL), 20% (0.2 g / mL), 30% (0.3 g / mL), 40% (0.4 g / mL), and 50% (0.5 g / mL).

[0080] The preparation method of the magnetic hydrogel differs from that of Example 1 only in the amount of Gel-AE-Ca added, which are 0g, 0.1g, 0.2g, 0.3g, 0.4g, and 0.5g, respectively; the volume ratio of the three components is the same as that of Example 1.

[0081] Example 3 The difference between this embodiment and Example 1 is that component C contains sodium periodate aqueous solutions of different concentrations to illustrate the effect of different concentrations of sodium periodate on the adhesion strength of the magnetic hydrogel to the tissue surface after gelation. The mass concentrations of sodium periodate are 0%, 2.5% (0.025 g / mL), 5% (0.05 g / mL), 7.5% (0.075 g / mL), and 10% (0.1 g / mL).

[0082] The preparation method of the magnetic hydrogel differs from that of Example 1 only in the amount of sodium periodate added; the volume ratio of the three components is the same as that of Example 1.

[0083] Example 4 The difference between this embodiment and Example 1 is that component B contains PBS solutions of oxidized hyaluronic acid at different concentrations to illustrate the effect of different concentrations of oxidized hyaluronic acid on the adhesion strength of the magnetic hydrogel to the tissue surface after gelation. The mass concentrations of oxidized hyaluronic acid are: 0%, 5% (0.05 g / mL), 10% (0.1 g / mL), 15% (0.15 g / mL), 20% (0.2 g / mL), and 25% (0.25 g / mL).

[0084] The preparation method of the magnetic hydrogel differs from that of Example 1 only in the amount of oxidized hyaluronic acid added; the volume ratio of the three components is the same as that of Example 1.

[0085] The adhesion strength of the magnetic hydrogels obtained in Examples 2-4 is as follows: Figure 5As shown. The adhesion strength of the magnetic hydrogel to the tissue surface was tested using a universal testing machine through a tensile adhesion test on pigskin. During the test, fresh pigskin was cut into 1cm wide strips, and the magnetic hydrogel was used to adhere two pieces of pigskin together, with the adhesion area controlled to be 1cm × 1cm. After the three components of the magnetic hydrogel were mixed and fully gelled at 37℃, a tensile test was performed (loading speed 5mm / min). The adhesion strength was determined based on the maximum stress obtained during the tensile process. From... Figure 4 It can be seen that different concentrations of Gel-AE-Ca, oxidized hyaluronic acid, and sodium periodate have a significant impact on the adhesion strength of the magnetic hydrogel.

[0086] Test Example 1: Underwater injectability and adhesion of magnetic hydrogels This test example uses the magnetic hydrogel obtained in Example 1 as an example to test its underwater injectability and adhesion effect.

[0087] Simulated blood: Artificial synthetic blood (Phygene, PH1899) is used only to simulate the surface tension and viscosity of blood. It contains a mixture of gentian red dye, surfactant, thickener, inorganic salt and distilled water.

[0088] The underwater injectability of hydrogels is illustrated using an example simulating the injection behavior of hydrogels in blood. During the injection process, through methods such as... Figure 5 The three-channel catheter shown injects the three components of the magnetic hydrogel into simulated blood in the proportions corresponding to Example 1. During injection, the total injection rate of the three channels is controlled at 200 μL / min. By oscillating the catheter during injection, it can be clearly observed that the magnetic hydrogel exiting from the catheter tip maintains a continuous linear shape, such as... Figure 6 As shown.

[0089] The magnetically guided deposition behavior of magnetic hydrogels in a blood environment is used as an example to illustrate their adhesion effect. During injection... Figure 5 The three-channel injection catheter shown was placed 2 mm above the blood vessel tissue (New Zealand rabbit aorta) covered with blood (New Zealand rabbit blood). The total injection rate was 200 μL / min. Magnetic guidance was applied below the blood vessel tissue during injection. After injection, strong adhesion of the magnetic hydrogel to the tissue surface was observed. Figure 7 As shown.

[0090] Test Example 2: Underwater Directional Magnetic Guidance Effect of Magnetic Hydrogel This test example uses the magnetic hydrogel in Example 1 as an example to conduct underwater directional magnetic guidance tests.

[0091] pass Figure 5The three-channel catheter shown simultaneously injected the three components of the magnetic hydrogel into a simulated blood environment (same as Test Example 1) at the proportions specified in Example 1, with a total injection rate of 200 μL / min. During the injection process, no magnetic field, a horizontal magnetic field, or a vertical magnetic field were applied, respectively. Figure 8 The underwater directional magnetic guidance effect of the magnetic hydrogel is shown. From the response state of the magnetic hydrogel in the magnetic field, it can be seen that the magnetic hydrogel of the present invention can effectively respond to the magnetic field and achieve directional guidance movement that overcomes the influence of gravity.

[0092] Test Example 3: Underwater Directional Embolization Effect of Magnetic Hydrogel This test example uses the magnetic hydrogel in Example 1 as an example to conduct an underwater directional embolism test.

[0093] The underwater directional magnetic guidance effect of the magnetic hydrogel was further illustrated using an in vitro simulated aneurysm model. The aneurysm model was constructed using 3D printing technology; the arterial lumen diameter was 6 mm, and the aneurysm spherical structure had an inner diameter of 10 mm. A peristaltic pump was used to establish continuous flow of simulated blood inside (same as in Test Case 1). Figure 5 The tip of the three-channel injection catheter shown is positioned at the opening of the aneurysm structure, and an external magnetic field is applied during injection. Figure 9 and Figure 10 As shown, the magnetic hydrogel of the present invention can be effectively pulled into the aneurysm sac to achieve targeted embolization.

[0094] In summary, the magnetic hydrogel of this invention is injectable, enabling precise directional delivery under the influence of an applied directional magnetic field. Furthermore, it exhibits efficient adhesion to tissue surfaces in dynamic aqueous environments, significantly improving the stability and long-lasting occlusion capability of the embolic material at the target site. Therefore, when used as an embolic material in a directional embolization system, the magnetic hydrogel of this invention demonstrates excellent injectability, rapid cross-linking capability in a liquid environment, magnetically responsive directional delivery capability, tissue adhesion capability, and stable embolization capability. Moreover, its preparation method is simple and cost-effective, providing a safer and more efficient solution for endovascular embolization therapy.

[0095] The above embodiments are preferred embodiments of the present invention, but the embodiments of the present invention are not limited to the above embodiments. Any changes, modifications, substitutions, combinations, or simplifications made without departing from the spirit and principle of the present invention shall be considered equivalent substitutions and shall be included within the protection scope of the present invention.

Claims

1. A magnetic hydrogel, characterized in that, The raw materials for preparing the magnetic hydrogel include component A, component B, and component C; component A includes a magnetic functional component, a hydrophilic polymer dispersion, and a material containing ortho-hydroxybenzene; component B includes a material containing an aldehyde group; and component C includes an oxidizing material.

2. The magnetic hydrogel according to claim 1, characterized in that, The magnetic functional component is a magnetic material with a surface modified for hydrophilicity; And / or, the magnetic material includes at least one of metallic magnetic materials, iron oxide magnetic materials, ferrite magnetic materials, and rare earth magnetic materials; And / or, the concentration of the magnetic functional component in component A is 1~1000 mg / mL.

3. The magnetic hydrogel according to claim 1, characterized in that, The hydrophilic polymer dispersion contains at least one of the following: polysaccharide polymers, protein polymers, polypeptide polymers, and synthetic polymers. And / or, the polysaccharide polymer includes at least one of chitosan, chitosan derivatives, hyaluronic acid, hyaluronic acid salts, sodium alginate, dextran, starch, starch derivatives, cellulose, and cellulose derivatives; And / or, in the hydrophilic polymer dispersion, the mass-volume concentration of the hydrophilic polymer is 0.1~10%.

4. The magnetic hydrogel according to claim 1, characterized in that, The material containing ortho-hydroxybenzene includes at least one of catechol, dopamine, dopa, tannic acid, gallic acid, caffeic acid or its derivatives, or a polymeric material containing at least one structural unit of catechol, dopamine, dopa, tannic acid, gallic acid or caffeic acid. And / or, the concentration of the material containing ortho-hydroxybenzene in component A is 0.01~1 g / mL.

5. The magnetic hydrogel according to claim 1, characterized in that, The aldehyde-containing materials include at least one of glutaraldehyde, formaldehyde, adipaldehyde, malondialdehyde, succinate, glyoxal, acetaldehyde, propionaldehyde, oxidized hyaluronic acid, oxidized sodium hyaluronate, oxidized alginate, oxidized sodium alginate, oxidized chitosan, oxidized dextran, protein aldehyde derivatives, polypeptide aldehyde derivatives, and aldehyde derivatives of synthetic polymers. And / or, the concentration of the aldehyde-containing material in component B is 0.03~0.5 g / mL.

6. The magnetic hydrogel according to claim 1, characterized in that, The oxidizing material includes at least one of periodate oxidants, peroxide oxidants, high-valence metal oxidants, quinone oxidants, persulfate oxidants, and polymeric oxidants; And / or, the concentration of the oxidizing material in component C is 0.01~0.15 g / mL.

7. The magnetic hydrogel according to claim 1, characterized in that, Component A also includes a CT contrast agent; And / or, the CT contrast agent includes at least one of iodine-containing contrast agents, metal contrast agents, and oxidizing contrast agents.

8. The magnetic hydrogel according to any one of claims 1 to 7, characterized in that, The volume ratio of component A, component B and component C is 1: (0.1~2): (0.1~2).

9. A method for preparing the magnetic hydrogel according to any one of claims 1 to 8, characterized in that, Includes the following steps: The magnetic functional component and the material containing ortho-hydroxybenzene are dispersed in a hydrophilic polymer dispersion to obtain component A; the aldehyde-containing material is dissolved in PBS solution to obtain component B; the oxidizing material is dissolved in water to obtain component C; and the magnetic hydrogel is obtained by mixing the components A, B, and C.

10. A directional embolization system, characterized in that, The directional embolization system contains the magnetic hydrogel according to any one of claims 1 to 8.

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