Temperature-responsive magnetic emulsion embolization agent containing triptolide, and preparation method and application thereof

Abstract

The invention provides a temperature response type magnetic emulsion embolization agent containing triptolide as well as a preparation method and application of the temperature response type magnetic emulsion embolization agent, and belongs to the technical field of biological medicines. The triptolide temperature response type magnetic emulsion embolization agent comprises triptolide, a temperature-sensitive polymer, iodized oil and magnetic nanoparticles, and the temperature-sensitive polymer can be subjected to phase change at 32 DEG C or above to be gelated. The triptolide temperature response type magnetic emulsion embolism agent provided by the invention can continuously release triptolide and has excellent mechanical properties to realize long-acting tumor vascular embolism, and the magnetic nanoparticles can effectively exert magnetocaloric properties to realize an anti-tumor effect; the iodinated oil has X-ray opaqueness and can be visualized in an embolism operation, the safety in the using process is improved, and then the triple synergistic anti-tumor effect of embolism, chemotherapy and magnetic hyperthermia is achieved.

Description

Technical Field

[0001] This invention relates to the field of biomedicine, and in particular to a temperature-responsive magnetic emulsion embolizer containing triptolide, its preparation method and application. Background Technology

[0002] Hepatocellular carcinoma (HCC) is a common cancer, and its clinical treatment has long relied on chemotherapy and immunotherapy, but these often face challenges such as limited efficacy, easy acquisition of drug resistance, and significant systemic toxicity. Tripterygium wilfordii, a natural active compound extracted from the traditional Chinese medicine Tripterygium wilfordii, possesses multiple broad-spectrum anti-tumor effects, including inducing apoptosis, arresting the cell cycle, and inhibiting angiogenesis, showing significant potential in HCC treatment. However, the inherent limitations of triptopterygium wilfordii, such as poor water solubility, narrow therapeutic window, and high systemic toxicity, severely restrict its direct clinical application. Although nano-targeted delivery strategies offer the possibility of improving its bioavailability, they are still limited by complex biological barriers in vivo and the potential toxicity of the carrier. Therefore, developing a local drug delivery system that can achieve precise and sustained release of triptopterygium wilfordii at the tumor site has become the key to overcoming its clinical translation bottleneck. Summary of the Invention

[0003] In view of the above, in order to at least partially solve at least one of the aforementioned technical problems, the present invention provides a temperature-responsive magnetic emulsion embolizing agent containing triptolide, its preparation method and application.

[0004] According to one embodiment of the present invention, a temperature-responsive magnetic emulsion embolizing agent is provided, comprising: triptolide, a thermosensitive polymer, iodized oil, and magnetic nanoparticles, wherein the thermosensitive polymer is capable of undergoing a phase transition and gelling at temperatures above 32°C.

[0005] According to another embodiment of the present invention, a method for preparing a temperature-responsive magnetic emulsion embolizer is provided, comprising:

[0006] Tripterygium wilfordii, magnetic nanoparticles, and a thermosensitive polymer were dissolved in a deionized aqueous solution to form a mixed solution.

[0007] The mixed solution was thoroughly mixed with iodized oil to prepare a temperature-responsive magnetic emulsion embolizer.

[0008] According to another embodiment of the present invention, a temperature-responsive magnetic emulsion embolizer is provided for use in the preparation of anticancer drugs.

[0009] According to an embodiment of the present invention, the temperature-responsive magnetic emulsion embolization agent containing triptolide provided by the present invention utilizes the amphiphilic stable water-oil interface of the thermosensitive polymer to enable the entire system to have long-term stability, continuously release triptolide, and possess excellent mechanical properties to achieve long-term tumor vascular embolization. This overcomes the problems of unstable drug loading in iodized oil, violent burst release, and easy recanalization of embolization. Simultaneously, the thermosensitive polymer undergoes a phase transition at body temperature to form a stable gel network, exhibiting excellent injection performance at room temperature. When it enters the human body and responds to body temperature (37°C), the thermosensitive polymer undergoes a hydrophilic-hydrophobic phase transition crosslinking to form an oil-in-water gel network structure, significantly enhancing the stability and mechanical strength of the system. This meets the performance requirements of clinical vascular embolization agents and also achieves long-term sustained release of triptolide at the tumor site (avoiding systemic toxicity caused by burst release). Furthermore, its in-situ enhanced mechanical strength effectively resists arterial blood flow erosion, ensuring persistent and stable vascular embolization to block tumor blood supply and achieve anti-tumor effects. The magnetic nanoparticles can effectively exert magnetothermal properties to achieve anti-tumor effects; the iodized oil is X-ray impermeable, which can be visualized during embolization surgery, increasing the safety during use, thereby achieving a triple synergistic anti-tumor effect of embolization, chemotherapy and magnetothermal therapy. Moreover, this embolization agent has the advantages of being pollution-free, biocompatible, low cytotoxic, structurally stable and highly practical, and has high potential for clinical and market applications. Attached Figure Description

[0010] The above and other objects, features and advantages of the present invention will become more apparent from the following description of embodiments of the invention with reference to the accompanying drawings, in which:

[0011] Figure 1 The above is the 1H NMR spectrum of the embolic agent prepared in Example 1 of this invention;

[0012] Figure 2 The image shows a scanning electron microscope (SEM) image of the internal structure of the embolic agent prepared in Example 1 of this invention.

[0013] Figure 3 This is a transmission electron microscope (TEM) image of the magnetic nanoparticles prepared in Example 1 of the present invention.

[0014] Figure 4 The images shown are actual photos and fluorescence microscope photographs of emulsions 1 to 5 of this invention after being placed in a room temperature environment for 14 days.

[0015] Figure 5 These are photographs and infrared thermal images of emulsion 2 in this embodiment of the invention under conditions of 25°C and 37°C.

[0016] Figure 6 This is a modulus-temperature curve diagram of emulsions 1 to 5 in embodiments of the present invention;

[0017] Figure 7 This is a viscosity-shear rate curve of emulsions 1 to 5 in the embodiments of the present invention;

[0018] Figure 8 This is a yield resistance-stress curve of emulsion 2 in an embodiment of the present invention;

[0019] Figure 9 This is a bar chart showing the injection force of emulsion 2 through different types of cannulas according to an embodiment of the present invention;

[0020] Figure 10 This is a schematic diagram of the embolization pressure testing device for the embolization agent according to an embodiment of the present invention;

[0021] Figure 11 This is a bar chart showing the embolic pressure of emulsion 2 at different temperatures according to an embodiment of the present invention;

[0022] Figure 12 Infrared thermal images (A) and real-time temperature rise curves (B) of emulsions 2, 6 and 7 under the action of an alternating magnetic field in embodiments of the present invention.

[0023] Figure 13 The cumulative release rate curves of triptolide from emulsions 2, 8, and oil solution 1 in an environment of 37°C are shown in the embodiments of the present invention.

[0024] Figure 14 A comparison (n=3) of the CT values ​​of air, water, iodized oil, and emulsion 2 of the present invention in an embodiment of the present invention;

[0025] Figure 15 This is a schematic diagram of the in vitro vascular embolization model device according to an embodiment of the present invention;

[0026] Figure 16 Images and corresponding UV 365 nm fluorescence images of the embolization simulation process of emulsion 2 and iodized oil prepared in Example 1 of this invention in an intravascular simulator;

[0027] Figure 17 This is a distribution diagram of emulsion 2 in a rat decellularized liver model according to an embodiment of the present invention;

[0028] Figure 18 This is a CT contrast imaging image of emulsion 2 in a rat decellularized liver model according to an embodiment of the present invention;

[0029] Figure 19 The images and thermal images of the New Zealand rabbit ear before and after embolization of the ear artery with emulsion 2 and iodized oil in this embodiment of the invention are shown in (A), and the tumor volume change curve over time is shown in (B).

[0030] Figure 20Infrared thermal imaging (A) and heating curve (B) of New Zealand rabbit ears embolized with emulsion 2 in an alternating magnetic field according to an embodiment of the present invention;

[0031] Figure 21 Image of hematoxylin-eosin (H&E) staining of New Zealand rabbit ear tissue 14 days after embolization with emulsion 2 and iodized oil according to an embodiment of the present invention;

[0032] Figure 22 This is a Prussian blue staining (PB) image of a New Zealand rabbit ear tissue 14 days after embolization with emulsion 2 and iodized oil, according to an embodiment of the present invention.

[0033] Figure 23 Digital subtraction angiography (DSA) images of the renal artery and renal branches of rabbits before and after embolization of emulsion 2 prepared in Example 1 of this invention;

[0034] Figure 24 The image shows an X-ray fluoroscopic image of emulsion 2 prepared in Example 1 of this invention in an embolized kidney;

[0035] Figure 25 Cross-sectional images of rabbit kidney CT scans before and 28 days after embolization of emulsion 2 prepared in Example 1 of this invention.

[0036] Figure 26 These are actual images of the rabbit kidney embolism before and after the emulsion 2 prepared in Example 1 of this invention;

[0037] Figure 27 Images of hematoxylin and eosin (H&E) staining of tissue sections from rabbit embolized kidneys after applying emulsion 2 prepared in Example 1 of this invention;

[0038] Figure 28 Prussian blue (PB) staining image of a tissue section of rabbit embolized kidney prepared by emulsion 2 in Example 1 of this invention. Detailed Implementation

[0039] Hereinafter, embodiments of the present invention will be described with reference to the accompanying drawings. However, it should be understood that these descriptions are exemplary only and are not intended to limit the scope of the invention. In the following detailed description, numerous specific details are set forth to provide a thorough understanding of the embodiments of the invention for ease of explanation. However, it will be apparent that one or more embodiments may be practiced without these specific details. Furthermore, descriptions of well-known structures and techniques are omitted in the following description to avoid unnecessarily obscuring the concept of the invention.

[0040] The terminology used herein is for the purpose of describing particular embodiments only and is not intended to limit the invention. The term "comprising" as used herein indicates the presence of features, steps, or operations, but does not exclude the presence or addition of one or more other features.

[0041] When using expressions such as "at least one of A, B and C", they should generally be interpreted in accordance with the meaning that is commonly understood by those skilled in the art (e.g., "a system having at least one of A, B and C" should include, but is not limited to, a system having A alone, a system having B alone, a system having C alone, a system having A and B, a system having A and C, a system having B and C, and / or a system having A, B and C, etc.).

[0042] The term "treatment" refers to exposing a subject to (e.g., administering medication) a drug, composition, or the like based on the present invention after the subject has contracted a disease, thereby reducing the symptoms of the disease compared to when the subject has not been exposed, and does not imply the necessity of completely suppressing the symptoms of the disease. Contracting a disease means the appearance of symptoms of a disease in the body.

[0043] The term "prevention" refers to the reduction of symptoms after contracting a disease by exposing (e.g., administering medication) a subject to a drug, composition, or the like based on the present invention before the onset of the disease, compared to the absence of exposure, and does not imply the necessity of completely suppressing the disease.

[0044] In realizing the concept of this invention, it was discovered that transarterial embolization (TAE), as an image-guided minimally invasive interventional therapy, induces ischemic necrosis of tumors by blocking their blood supply. The embolic agent not only performs the function of vascular occlusion but also often serves as a delivery carrier for local chemotherapy drugs, and its performance directly affects the treatment effect. Currently, commonly used embolic agents are mainly divided into two categories: solid and liquid. However, both have significant limitations when used to load triptolide. Solid embolic agents, represented by polyvinyl alcohol (PVA) microspheres, have good embolic stability but low loading efficiency for hydrophobic triptolide. Furthermore, due to their lack of visibility and uneven size distribution, they are prone to incomplete vascular filling, catheter blockage, and collateral circulation formation. Liquid embolic agents, represented by iodized oil, have good tissue permeability and X-ray visibility, but their physical stability is poor after loading triptolide. They are prone to drug burst release and phase separation, making it difficult to achieve controlled sustained drug release. At the same time, they are easily washed away by blood flow, leading to vascular recanalization and a high risk of tumor recurrence. Therefore, there is an urgent need to develop a novel embolizing agent that can combine efficient drug delivery, stable embolization, controlled drug release, and good visibility, so as to achieve the safe and synergistic effect of triptolide in HCC interventional treatment.

[0045] Specifically, according to one embodiment of the present invention, a temperature-responsive magnetic emulsion embolizing agent is provided, comprising: triptolide, a thermosensitive polymer, iodized oil, and magnetic nanoparticles, wherein the thermosensitive polymer is capable of undergoing a phase transition and gelling at temperatures above 32°C.

[0046] According to an embodiment of the present invention, the triptolide temperature-responsive magnetic emulsion embolization agent provided by the present invention utilizes the amphiphilic stable water-oil interface of the thermosensitive polymer, enabling the entire system to have long-term stability, continuously release triptolide, and possess excellent mechanical properties to achieve long-term tumor vascular embolization. This overcomes problems such as unstable drug loading, uncontrolled release, and easy recanalization of embolization agents. Simultaneously, the thermosensitive polymer undergoes a phase transition at body temperature to form a stable gel network, exhibiting excellent injection performance at room temperature. When it enters the human body and responds to body temperature (37°C), the thermosensitive polymer undergoes a hydrophilic-hydrophobic phase transition crosslinking to form an oil-in-water gel network structure, significantly enhancing the stability and mechanical strength of the system. This meets the performance requirements of clinical vascular embolization agents and also achieves long-term sustained release of triptolide at the tumor site (avoiding systemic toxicity caused by sudden release). Furthermore, its in-situ enhanced mechanical strength effectively resists arterial blood flow erosion, ensuring persistent and stable vascular embolization to block tumor blood supply and achieve anti-tumor effects. The magnetic nanoparticles can effectively exert magnetothermal properties to achieve anti-tumor effects; the iodized oil is X-ray impermeable, which can be visualized during embolization surgery, increasing the safety during use, thereby achieving a triple synergistic anti-tumor effect of embolization, chemotherapy and magnetothermal therapy. Moreover, this embolization agent has the advantages of being pollution-free, biocompatible, low cytotoxic, structurally stable and highly practical, and has high potential for clinical and market applications.

[0047] According to an embodiment of the present invention, the emulsion embolizing agent comprises water, and the mass ratio of water to iodized oil is (1~3):1, preferably (1.3~2.3):1.

[0048] According to embodiments of the present invention, the mass ratio of water to iodized oil can be 1:1, 1.3:1, 1.5:1, 1.95:1, 2:1, 2.5:1, or 3:1, but is not limited to the listed values; other unlisted values ​​within this range are also applicable. Alternatively, it can be within a range consisting of any two values, such as (1~2):1, (1.5~2.5):1, etc.

[0049] According to an embodiment of the present invention, water and iodized oil in the embolic agent form the basis of the continuous and dispersed phases of the emulsion. An appropriate water-to-oil ratio ensures that the embolic agent has good fluidity at room temperature before injection, i.e., shear-thinning properties and physical stability, avoiding oil-water separation, stratification, or blockage of the microcatheter in the syringe or during delivery. If the oil ratio is too high, the embolic agent will rapidly stratify and fail; if the water ratio is too low, the thermosensitive polymer will not have enough aqueous environment to fully dissolve and exhibit its thermosensitive properties, resulting in incomplete phase transition, insufficient gel strength, and inability to effectively embolize blood vessels. An appropriate water-to-oil ratio can provide a stable oil-in-water structure that can encapsulate the iodized oil's imaging function, magnetic particles, and active drug, and achieve overall structural control through the thermosensitive polymer network in the aqueous phase, thereby avoiding component aggregation, functional separation, and drug burst release, and ensuring good pharmacokinetic performance.

[0050] According to an embodiment of the present invention, the mass ratio of magnetic nanoparticles to water is (0.0015~0.003):1.

[0051] According to embodiments of the present invention, the mass ratio of magnetic nanoparticles to water can be 0.0015:1, 0.002:1, 0.0025:1, or 0.003:1, but is not limited to the listed values; other unlisted values ​​within this range are also applicable. Alternatively, it can be within a range consisting of any two values, such as (0.0015~0.002):1, (0.002~0.0025):1, etc.

[0052] According to an embodiment of the present invention, an appropriate amount of magnetic nanoparticles can enable the magnetic particles to have sufficient density to rapidly and effectively convert electromagnetic energy into thermal energy under a magnetic field, raising the target area to a therapeutic temperature sufficient to kill tumor cells. Simultaneously, it avoids excessively high particle concentrations that could lead to particle aggregation and sedimentation within the emulsion, disrupting the emulsion's uniformity and stability. Furthermore, excessively high concentrations of magnetic nanoparticles may also pose potential biocompatibility risks in vivo.

[0053] According to an embodiment of the present invention, the mass ratio of water: thermosensitive polymer: triptolide is 100:(10~20):(0.02~0.06).

[0054] According to embodiments of the present invention, the mass ratio of water: iodized oil: thermosensitive polymer: triptolide: magnetic nanoparticles can be 100:15:0.02, 100:18:0.04, or 100:20:0.05, but is not limited to the listed values; other unlisted values ​​within this range are also applicable. Alternatively, it can be within a range consisting of any two values, such as 100:(10~15):(0.02~0.04), 100:(15~20):(0.04~0.06), etc.

[0055] According to the embodiments of the present invention, the mass ratio of water, iodized oil, and thermosensitive polymer can ensure that the emulsion has sufficient fluidity while its oil phase (iodized oil) content is sufficient to provide excellent X-ray imaging effect. The mass ratio of thermosensitive polymer can ensure that the gel strength of the embolization agent is suitable for embolization treatment while avoiding excessive viscosity at room temperature that would affect injectability. The mass ratio of triptolide can ensure a balance between effective therapeutic dose and systemic toxicity, ensuring an effective drug concentration for local chemotherapy while minimizing systemic risks caused by burst release or leakage. The proportion of magnetic nanoparticles can further prevent excessive magnetic nanoparticles from agglomerating and causing emulsion instability or biocompatibility problems, while ensuring an effective magnetocaloric effect.

[0056] According to embodiments of the present invention, the thermosensitive polymer includes poly(N-isopropylacrylamide) (PNIPAM), poly(N-isopropylmethacrylamide) (PNIPMAm) or poly(N-vinylcaprolactam) (PVCL), and the magnetic nanoparticles include Fe3O4.

[0057] According to an embodiment of the present invention, poly(N-isopropylacrylamide) (PNIPAM), as a thermosensitive polymer, has a low critical solution temperature (LCST of approximately 32°C), allowing it to remain in a solution state at room temperature for easy delivery. At body temperature, it spontaneously undergoes a hydrophilic-hydrophobic phase transition to form a gel, requiring no exogenous crosslinking agents or complex triggering conditions. This allows the embolic agent to hydrophilically expand when stored and injected at room temperature, presenting a low-viscosity, flowable solution or emulsion state, making it easy to pass through microcatheters. Upon injection into the body, the temperature rises to 37°C, exceeding its LCST, causing the PNIPAM chains to rapidly transition to a hydrophobic, collapsed state. Hydrophobic association occurs between the molecular chains, driving the entire system to undergo a sol-gel phase transition within seconds, forming a physically crosslinked network structure, thereby achieving precise and stable physical embolization at the target site. Poly(N-isopropylmethacrylamide) (PNIPMAm) and poly(N-vinylcaprolactam) (PVCL) have low critical solution temperatures (LCST) that can be adjusted within the range of 30~35°C, ensuring that the embolic agent is an injectable liquid at room temperature. After being injected into the human body, it can be rapidly and reliably transformed into a solid gel due to body temperature triggering, achieving precise and stable embolization.

[0058] In some specific embodiments of the present invention, one of the above-mentioned temperature-sensitive polymers may be selected, or two or three may be used in combination. The present invention does not limit this.

[0059] Specifically, Fe3O4 has excellent magnetocaloric conversion efficiency, ensuring that the embolic agent can efficiently convert electromagnetic energy into thermal energy when an external magnetic field is applied, thus achieving local hyperthermia.

[0060] According to another embodiment of the present invention, a method for preparing a temperature-responsive magnetic emulsion embolizing agent is provided, comprising the following steps S1 to S2:

[0061] Step S1: Dissolve triptolide, magnetic nanoparticles and thermosensitive polymer in deionized water to form a mixed solution;

[0062] Step S2: Mix the mixed solution with iodized oil until homogeneous to obtain a temperature-responsive magnetic emulsion embolizer.

[0063] According to the embodiments of the present invention, the preparation method of the present invention integrates the complex multi-component system with aqueous premixing and oil emulsification, thereby efficiently and quickly preparing temperature-responsive magnetic emulsion embolizing agents. It is easy to operate in the laboratory and in industry, avoids multi-step complex reactions or harsh conditions, and ensures the feasibility and repeatability of the preparation.

[0064] According to an embodiment of the present invention, the volume ratio of the mixed solution to the iodized oil is (5~7):(3~5).

[0065] According to embodiments of the present invention, the volume ratio of the mixed solution to the iodized oil can be 5:3, 5:4, 5:5, 6:3, or 7:5, but is not limited to the listed values; other unlisted values ​​within this range are also applicable. Alternatively, it can be within a range consisting of any two values, such as (5~6):(3~4), (5~6):(3~4), etc.

[0066] According to embodiments of the present invention, the volume ratio of the mixed solution to the iodized oil within the claimed scope of the invention means that the aqueous phase (mixed solution) is always slightly more than or equal to the oil phase (iodized oil), which can force the formation of an "oil-in-water" emulsion from a process perspective. This structure is the basis for the thermosensitive polymer to perform gelation in the aqueous phase and achieve temperature response. An imbalance in this ratio may lead to the formation of an unstable water-in-oil emulsion or a complex emulsion, which will fail to achieve the corresponding embolizing effect.

[0067] According to an embodiment of the present invention, the concentration of magnetic nanoparticles in the mixed solution is 2 mg / mL to 3 mg / mL; the solid content of the thermosensitive polymer in the mixed solution is 10% (w / v) to 20% (w / v); and the concentration of triptolide in the temperature-responsive magnetic emulsion embolizer is 300 ng / mL to 500 ng / mL.

[0068] According to embodiments of the present invention, the concentration of magnetic nanoparticles in the mixed solution can be 2 mg / mL, 2.2 mg / mL, 2.5 mg / mL, 2.8 mg / mL, or 3 mg / mL, but is not limited to the listed values; other unlisted values ​​within this range are also applicable. Alternatively, it can be within a range consisting of any two values, such as 2 mg / mL to 2.5 mg / mL, 2.5 mg / mL to 3 mg / mL, etc.

[0069] According to embodiments of the present invention, the solid content of the thermosensitive polymer in the mixed solution can be 10% (w / v), 15% (w / v), or 20% (w / v), but is not limited to the listed values; other unlisted values ​​within this range are also applicable. Alternatively, it can be within a range consisting of any two values, such as 10% (w / v) to 15% (w / v), 10% (w / v) to 12% (w / v), etc.

[0070] According to embodiments of the present invention, the concentration of triptolide in the temperature-responsive magnetic emulsion embolizing agent can be 300 ng / mL, 400 ng / mL, or 500 ng / mL, but is not limited to the listed values; other unlisted values ​​within this range are also applicable. Alternatively, it can be within a range consisting of any two values, such as 300 ng / mL to 400 ng / mL, 350 ng / mL to 450 ng / mL, etc.

[0071] According to an embodiment of the present invention, an appropriate concentration of magnetic nanoparticles during the preparation process ensures sufficient density for the nanoparticles to generate effective heat under an alternating magnetic field, achieving an effective thermotherapy effect. The concentration of the thermosensitive polymer ensures sufficient polymer molecular chains to form a dense physical cross-linked network at body temperature, providing sufficient mechanical strength to resist blood flow and achieve stable embolization, while preventing excessively high viscosity of the thermosensitive polymer at room temperature, which would affect its injectability through microcatheters. The concentration of triptolide ensures an effective local anticancer effect, and because it is encapsulated in a thermosensitive gel for sustained release, it minimizes the risk of systemic toxicity associated with sudden release of high concentrations.

[0072] According to another embodiment of the present invention, the application of a temperature-responsive magnetic emulsion embolizer in the preparation of anticancer drugs is also provided.

[0073] According to an embodiment of the present invention, the anticancer drug is an anti-liver cancer drug.

[0074] According to embodiments of the present invention, the responsive magnetic emulsion embolization agent of the present invention can be used in the preparation of a drug for the treatment of liver cancer via transarterial chemoembolization combined with magnetothermal therapy.

[0075] The technical solution of the present invention will be further described below with reference to specific embodiments and accompanying drawings. Unless otherwise stated, the reagents used in the present invention are all commercially available reagents, and the test methods used are all conventional test methods in the relevant fields.

[0076] Example 1: Preparation of Temperature-Responsive Magnetic Emulsion Embolizing Agent

[0077] 1. The preparation of thermosensitive polymers includes the following steps:

[0078] (1) Dissolve 15 g of polyethylene glycol and 1.8 g of triethylamine in 150 mL of dichloromethane, purge with argon gas, add 2 g of 2-bromoisobutyryl bromide dropwise at 0 °C, stir at room temperature for 24 hours, dialyze and freeze dry to obtain the initiator;

[0079] (2) Dissolve 0.16 g of initiator in a mixed solvent of isopropanol and water, then add 2.5 g of N-isopropylacrylamide, 0.21 g of n-butyl acrylate and 28.6 mg of cuprous chloride in sequence. After deoxygenation by three freeze-thaw cycles under argon protection, inject 80.3 mg of tris(2-dimethylaminoethyl)amine and react at room temperature for 72 hours. Separate by neutral alumina column, dialyze, and freeze dry to obtain the thermosensitive polymer.

[0080] 2. The preparation of magnetic nanoparticles includes the following steps:

[0081] (1) Dissolve 2.16 g of ferric chloride hexahydrate (FeCl3·6H2O) in a mixed solvent of 20 mL of ethylene glycol and 60 mL of diethylene glycol, and stir for 30 minutes until completely dissolved; add 0.2 g of polyacrylic acid (PAA) and continue stirring for 30 minutes; then add 12 g of anhydrous sodium acetate and stir for 1 hour;

[0082] (2) Transfer the above mixture to a high-pressure reactor and react at 200 °C for 12 hours;

[0083] (3) After the reaction is complete, the black product is collected by centrifugation and washed several times to obtain spherical magnetic nanoparticles for later use.

[0084] 3. Preparation of thermosensitive emulsion embolizer: Tripterygium wilfordii and magnetic nanoparticles were dissolved in a thermosensitive polymer aqueous solution at a specific ratio, with final concentrations of 400 ng / mL and 2 mg / mL, respectively. The thermosensitive polymer content was 15% (w / v). Subsequently, the mixture was thoroughly mixed with iodized oil at a volume ratio of 4:6 through a three-way valve to obtain a temperature-responsive magnetic emulsion embolizer of triptolide, denoted as emulsion 2. Characterization was performed, and the results are as follows: Figures 1-3 As shown.

[0085] Figure 1The above is the 1H NMR spectrum of the embolic agent prepared in Example 1 of this invention; Figure 2 The image shows a scanning electron microscope (SEM) image of the internal structure of the embolic agent prepared in Example 1 of this invention. Figure 3 This is a transmission electron microscope image of the magnetic nanoparticles prepared in Example 1 of the present invention.

[0086] according to Figures 1-3 It can be seen that, as Figure 1 As shown, the ¹H NMR spectrum of the thermosensitive polymer matches the design expectations, indicating successful synthesis. Figure 2 The porous internal structure of the thermosensitive polymer hydrogel can be observed, which is beneficial for nanoparticle loading and sustained drug release. For example... Figure 3 As shown, the magnetic nanoparticles exhibit a uniform spherical morphology (approximately 100 nm in diameter).

[0087] Example 2

[0088] The same preparation method as in Example 1 was used, except that the volume ratio of the mixed solution to the iodized oil was 5:5, and the resulting triptolide temperature-responsive magnetic emulsion embolizer was designated as Emulsion 1.

[0089] Example 3

[0090] The same preparation method as in Example 1 was used, except that the volume ratio of the mixed solution to the iodized oil was 3:7, and the resulting triptolide temperature-responsive magnetic emulsion embolizer was designated as emulsion 3.

[0091] Example 4

[0092] The same preparation method as in Example 1 was used, except that the concentration of magnetic nanoparticles was 3 mg / mL, and the resulting triptolide temperature-responsive magnetic emulsion embolizer was designated as Emulsion 6.

[0093] Comparative Example 1

[0094] The same preparation method as in Example 1 was used, except that the volume ratio of the mixed solution to the iodized oil was 2:8, and the resulting triptolide temperature-responsive magnetic emulsion embolizer was designated as emulsion 4.

[0095] Comparative Example 2

[0096] The same preparation method as in Example 1 was used, except that the volume ratio of the mixed solution to the iodized oil was 1:9, and the resulting triptolide temperature-responsive magnetic emulsion embolizer was designated as emulsion 5.

[0097] Comparative Example 3

[0098] The same preparation method as in Example 1 was used, except that the concentration of magnetic nanoparticles was 1 mg / mL, and the resulting triptolide temperature-responsive magnetic emulsion embolizer was designated as Emulsion 7.

[0099] Comparative Example 4

[0100] The same preparation method as in Example 1 was used, except that triptolide and magnetic nanoparticles were dissolved in iodized oil and thermosensitive polymer aqueous solution, respectively, with final concentrations of 400 ng / mL and 2 mg / mL, respectively, and the content of thermosensitive polymer was 15% (w / v). Then, the iodized oil solution and the thermosensitive polymer solution were mixed uniformly at a volume ratio of 4:6 through a three-way valve to obtain a temperature-responsive magnetic emulsion embolizer containing triptolide, denoted as emulsion 8.

[0101] Comparative Example 5

[0102] Tripterygium wilfordii was directly dissolved in iodized oil to a final concentration of 400 ng / mL. The resulting material was designated as oil solution 1 (non-magnetic nanoparticles and thermosensitive polymer).

[0103] Test Example 1 Performance Test

[0104] To investigate the effect of the water-oil phase volume ratio on emulsion stability, Rhodamine B was added to the aqueous phase and coumarin-6 was added to the oil phase as fluorescent labels. The results are as follows: Figure 4 As shown.

[0105] Figure 4 The images shown are actual photos and fluorescence microscope photographs of emulsions 1 to 5 of the present invention after being placed in a room temperature environment for 14 days.

[0106] according to Figure 4 It can be seen that the stability of the emulsions significantly improves with the increase of the aqueous phase ratio, specifically manifested in a reduction of macroscopic stratification and a more uniform droplet size distribution under a fluorescence microscope. After 14 days of storage at room temperature, emulsion 2 remained stable, without water-oil phase separation, and the droplet morphology did not show significant changes. Although the aqueous phase ratio in emulsion 1 was higher than that in emulsion 2, its droplets formed a water-in-oil-in-water (W / O / W) complex emulsion structure, leading to reduced stability. After 14 days of storage at room temperature, emulsion 1 maintained a stable state, but the droplet size increased. After 14 days of storage at room temperature, emulsion 3 maintained a stable state. Emulsion 4 showed poor stability after 14 days of storage at room temperature, with increased droplet size and severe water-oil phase separation. Emulsion 5 also showed poor stability after 14 days of storage at room temperature, with increased droplet size and severe water-oil phase separation.

[0107] Emulsion 2 was photographed and subjected to infrared thermal imaging at 25℃ and 37℃, respectively. The results are as follows: Figure 5 As shown.

[0108] Figure 5 These are photographs and infrared thermal images of emulsion 2 in this embodiment of the invention under conditions of 25°C and 37°C.

[0109] according to Figure 5 It can be seen that emulsion 2 is a flowable emulsion at room temperature, but rapidly transforms into a non-flowable gel at body temperature, exhibiting obvious thermosensitive phase transition characteristics.

[0110] The modulus-temperature change, viscosity-shear rate change, and yield resistance-stress change of emulsions 1 through 5 were tested respectively, and the results are as follows: Figures 6-8 As shown.

[0111] Figure 6 This is a modulus-temperature curve diagram of emulsions 1 to 5 in embodiments of the present invention; Figure 7 This is a viscosity-shear rate curve of emulsions 1 to 5 in the embodiments of the present invention; Figure 8 This is a yield resistance-stress curve of emulsion 2 in an embodiment of the present invention.

[0112] according to Figures 6-8 It can be seen that, Figure 6 The results show that the storage modulus and loss modulus of emulsion 2 increase significantly starting at 31℃, with the highest storage modulus and loss modulus reaching 4578.68 Pa and 303.42 Pa, respectively. With increasing temperature, the storage modulus (G′) and loss modulus (G″) of emulsion 1 begin to increase significantly from approximately 31℃, with the highest storage modulus reaching 4640 Pa and the highest loss modulus being 657.7 Pa, indicating that emulsion 1 possesses thermo-sensitive enhancement properties. The storage modulus (G′) and loss modulus (G″) of emulsion 3 also begin to increase from approximately 31℃, with the highest storage modulus reaching 315 Pa and the highest loss modulus being 47.13 Pa, indicating that emulsion 3 possesses thermo-sensitive enhancement properties. The storage modulus (G′) and loss modulus (G″) of emulsion 4 did not increase significantly with increasing temperature, indicating that this sample does not possess temperature-sensitive gelling properties. The storage modulus (G′) and loss modulus (G″) of emulsion 5 did not increase significantly with increasing temperature, indicating that this sample does not possess temperature-sensitive gelling properties.

[0113] Furthermore, from Figure 7It can be seen that at room temperature, the viscosity of emulsion 1 decreases with increasing shear rate, exhibiting a certain shear-thinning characteristic, proving its good injectability. These results indicate that emulsion 1 meets the performance requirements of a vascular embolization agent. At room temperature, the viscosity of emulsion 2 decreases with increasing shear rate, exhibiting a certain shear-thinning characteristic, with a maximum viscosity of only about 0.4 Pa·s, proving the injectability of emulsion 2. At room temperature, the viscosity of emulsion 3 decreases with increasing shear rate, exhibiting a certain shear-thinning characteristic, proving its good injectability, indicating that emulsion 3 meets the performance requirements of a vascular embolization agent. Emulsion 4 maintains a low viscosity with increasing shear rate, proving that it is suitable for injection but cannot meet the performance requirements of a vascular embolization agent for stable embolization. Emulsion 5 maintains a low viscosity with increasing shear rate, proving that it is suitable for injection but cannot meet the performance requirements of a vascular embolization agent for stable embolization.

[0114] like Figure 8 As shown, under body temperature (37℃) and within a stress range of 1–100 Pa, the yield strength of the iodized oil remained consistently low (approximately 0.091 Pa·s), while both the polymer solution and emulsion 2 exhibited higher yield strength (approximately 249858 Pa·s). Notably, under high stress conditions, the polymer solution showed a decrease in yield strength, while emulsion 2 remained stable, indicating that emulsion 2 has a longer-lasting embolic effect in the in vivo environment.

[0115] The performance of emulsion 2 prepared in Example 1 of this invention was tested, and the results are as follows: Figure 9 As shown, the following is adopted Figure 10 The embolism pressure testing device shown impinges an anticoagulant onto a simulated blood vessel with a diameter of 2 mm at a flow rate of 50 mL / min, and monitors upstream pressure changes. The results are as follows: Figure 11 As shown.

[0116] Figure 9 This is a bar chart showing the injection force of emulsion 2 through different types of cannulas according to an embodiment of the present invention; Figure 10 This is a schematic diagram of the embolization pressure testing device for the embolization agent according to an embodiment of the present invention; Figure 11 This is a bar chart showing the embolization pressure of emulsion 2 at different temperatures according to an embodiment of the present invention.

[0117] according to Figures 9-11 It can be seen that the injection force of emulsion 2 is 3.35 N in the 4F catheter and 32.26 N in the 2.6F catheter, both of which are within the range suitable for manual operation. Furthermore, using... Figure 10 The embolism pressure testing device shown impinges an anticoagulant onto a simulated blood vessel with a diameter of 2 mm at a flow rate of 50 mL / min, and monitors upstream pressure changes. Figure 11As shown, the embolic pressure of emulsion 2 at 25°C is lower than the physiological pressure of human arteries (16 kPa), while it increases to 48.03 kPa at 37°C, indicating that it can effectively resist blood flow impact and achieve stable embolization under body temperature conditions. These results demonstrate that emulsion 2 meets the performance requirements as a vascular embolizing agent.

[0118] Figure 12 The images show infrared thermal images (A) and real-time temperature rise curves (B) of emulsions 2, 6 and 7 under the action of an alternating magnetic field in this embodiment of the invention.

[0119] according to Figure 12 It can be seen that the introduction of magnetic nanoparticles endows the material with magnetothermal heating capability. Under the action of an alternating magnetic field (20 kA / m), emulsion 2 can respond to the magnetic field and rapidly heat up and maintain at 45°C, which can effectively kill tumor cells without causing unnecessary damage to normal tissues. Under the action of an alternating magnetic field of 20 kA / m, emulsion 6 can respond to the magnetic field and heat up, and its final temperature is maintained at about 56°C, which can effectively kill tumor cells. The rheological properties and injection performance of emulsion 6 are similar to those of emulsion 2 in Example 1, indicating that emulsion 6 meets the performance requirements of a vascular embolizing agent. Under the action of an alternating magnetic field of 20 kA / m, emulsion 7 can respond to the magnetic field and heat up, but its final temperature is only maintained at about 35°C, which cannot reach the temperature conditions required for effective killing of tumor cells.

[0120] To evaluate the release behavior of triptolide in emulsion 2, an in vitro release experiment was conducted. 1 mL of emulsion 2 was placed in a dialysis bag with a molecular weight cutoff of 8-14 kDa, sealed, and immersed in 20 mL of PBS release medium (pH=7.4). Release was carried out at 37℃ and 250 rpm with shaking. Samples were taken at 0.125, 0.25, 0.5, 1, 2, 3, 5, 7, 10, and 14 days, with an equal volume of fresh PBS added after each sampling. The absorbance was measured at 218 nm using UV spectrophotometry, the cumulative release rate of triptolide was calculated, and a release curve was plotted. The results are shown below. Figure 13 As shown.

[0121] Figure 13 The cumulative release rate curves of triptolide from emulsions 2, 8, and oil solution 1 in an environment of 37°C are shown in the embodiments of the present invention.

[0122] according to Figure 13It can be seen that emulsion 2 exhibits an initial burst release followed by a sustained release. On the first day of the experiment, it rapidly releases up to 50% of the triptolide, followed by a sustained, slow release over the next 13 days, ultimately reaching a cumulative release rate of approximately 80%. This indicates that emulsion 2 can achieve a long-term sustained release of triptolide, which is beneficial for the continuous killing of tumor cells. Emulsion 8 only shows a release process in the initial stage of the experiment, reaching a drug release rate of 7% on the first day, and showing no significant drug release behavior in the following 13 days. This indicates that emulsion 8 cannot achieve a long-term sustained release of triptolide, which is detrimental to the continuous killing of tumor cells. Oil solution 1 exhibits a burst release of triptolide in the initial stage of the experiment, reaching a drug release rate of 80% on the first day and reaching a peak release rate (98%) within two days. This indicates that oil solution 1 exhibits a rapid release of triptolide, which can cause severe hepatotoxicity and nephrotoxicity, which is detrimental to the treatment of hepatocellular carcinoma.

[0123] In interventional embolization procedures, real-time visualization of the embolic agent under digital subtraction angiography (DSA) is crucial. CT value tests were performed on air, water, iodized oil, and emulsion 2 of this invention. The results are as follows: Figure 14 As shown.

[0124] Figure 14 This is a comparison (n=3) of the CT values ​​of air, water, iodized oil, and emulsion 2 of the present invention in an embodiment of the present invention.

[0125] according to Figure 14 It can be seen that the CT value of emulsion 2 is similar to that of iodized oil, indicating that it has excellent visibility in vivo.

[0126] Test Example 2: Design an in vitro model to verify the embolization effect

[0127] This invention independently constructed an extracorporeal circulation-liver tumor simulation platform with physiological-grade fluid pressure monitoring function. Figure 15 The vascular embolization performance and clinical applicability of emulsion 2 were systematically evaluated by comparing it with iodized oil embolization agents used in clinical practice. The platform consists of a pulse pump, a constant-temperature reservoir (37℃), a real-time pressure sensing module, and a microfluidic chip. A microfluidic chip with an inner diameter of 100-900 μm was used to simulate the complex capillary network of tumor tissue. Before the experiment, a solution containing rhodamine B (0.05 mg / mL) was used. -1 PBS solution was used as simulated blood for circulatory system prefilling, and the structural integrity and perfusion uniformity of the vascular network were verified by fluorescence imaging. Subsequently, the blood was injected at 1 mL / min using a 2.6 F microcatheter. -1 The injection rate was 2 mL of freshly prepared iodized oil or emulsion 2 (37°C) injected via catheter, and the results were as follows: Figure 16 As shown.

[0128] Figure 16Images and corresponding UV 365 nm fluorescence images of the embolization simulation process of emulsion 2 and iodized oil prepared in Example 1 of this invention in an intravascular simulator. The red liquid (representing blood) is Rhodamine B, and the corresponding fluorescence is red; the yellow liquid (representing contrast agent) is sodium fluorescein, and the corresponding fluorescence is green; the black substance in the microfluidic chip represents emulsion 2.

[0129] according to Figure 16 As can be seen from real-time fluorescence monitoring, emulsion 2 effectively blocked the capillary arterial end simulated by the microfluidic chip, causing the fluorescence signal at the capillary arterial end to completely disappear; while the iodized oil group only showed a brief retention, with the signal intensity significantly attenuating after 5 minutes. To further evaluate embolization durability, fluorescein sodium aqueous solution (0.1 mg / mL) was used after embolization. -1 Simulated angiography and flushing were performed. The results showed that the microfluidic chip in the iodized oil group showed a complete green blood vessel outline, confirming the existence of vascular recanalization; while no obvious fluorescence signal was detected in the emulsion group 2, proving that it could effectively resist the impact of pulsatile perfusion and maintain a stable mechanical embolism state.

[0130] Test Example 3: Constructing a rat liver decellularization model to assess the distribution of emulsion 2 in hepatic blood vessels.

[0131] Fresh rat livers were collected, frozen at -80°C for 24 hours, thawed at room temperature, and then perfused via the portal vein with 0.5% sodium dodecyl sulfate (SDS) solution at a flow rate of 5 mL / min for 48 hours until the liver parenchyma became translucent. Subsequently, emulsion 2 was injected into the decellularized liver via the portal vein, and the spatial distribution and vascular deposition of the embolic agent within the liver were observed using stereomicroscopy and CT imaging, respectively. Results are as follows: Figure 17 and Figure 18 As shown.

[0132] Figure 17 This is a distribution diagram of emulsion 2 in a rat decellularized liver model according to an embodiment of the present invention;

[0133] Figure 18 This is a CT imaging image of emulsion 2 in a rat decellularized liver model according to an embodiment of the present invention.

[0134] according to Figure 17 It can be seen that emulsion 2 deposits well in the arteries after injection and can reach the terminal blood vessels of the liver. According to... Figure 18 As can be seen, CT imaging shows that emulsion 2 is distributed continuously at high density along the vascular tree, and the CT value is significantly higher than the background signal. This further confirms that it can be deeply distributed in the small blood vessels of the liver and is suitable for visualization of transarterial embolization under X-ray guidance.

[0135] Test Example 3: Evaluation of the embolization effect of emulsion 2 in a New Zealand rabbit ear VX2 tumor model

[0136] VX2 tumor tissue suspension was injected near the central artery of the ear of New Zealand rabbits. Once the tumor grew to approximately 100 mm³, emulsion 2 was injected into the blood supply artery of the rabbit ear tumor using a syringe. Iodized oil served as a control group. Subsequently, rabbits in the emulsion 2 group were exposed to AMF for magnetothermal synergistic therapy. During treatment, temperature changes and necrosis status of the New Zealand rabbit ears were monitored using photographs and infrared thermography. After 14 days of treatment, tumor tissue was collected for H&E staining and Prussian blue staining analysis. The results are as follows: Figures 19-22 As shown.

[0137] Figure 19 The images and thermal images of the New Zealand rabbit ear before and after embolization of the ear artery with emulsion 2 and iodized oil in this embodiment of the invention are shown in (A), and the tumor volume change curve over time is shown in (B). Figure 20 Infrared thermal imaging (A) and heating curve (B) of New Zealand rabbit ears embolized with emulsion 2 in an alternating magnetic field according to an embodiment of the present invention; Figure 21 Image of hematoxylin-eosin (H&E) staining of New Zealand rabbit ear tissue 14 days after embolization with emulsion 2 and iodized oil according to an embodiment of the present invention; Figure 22 This is a Prussian blue staining (PB) image of a New Zealand rabbit ear tissue 14 days after embolization with emulsion 2 and iodized oil, according to an embodiment of the present invention.

[0138] according to Figure 19 As shown in (A), pre-embolization thermography revealed abundant blood supply to the tumor area and the aorta. In the initial stage of embolization, both groups achieved good blood flow interruption; however, the iodized oil group showed vascular recanalization one day post-procedure, while the emulsion group maintained a stable embolic state for up to 14 days. According to... Figure 19 As can be seen from (B), the tumor volume in the iodized oil group increased to 5 times its initial volume, while the tumor in the emulsion group 2 significantly shrank and eventually disappeared completely. According to Figure 20 It can be seen that emulsion 2 heated to 45℃ within 10 minutes under an alternating magnetic field of 20kA / m, reaching the tumor ablation temperature. According to... Figure 21 As can be seen from the H&E staining results, the number of tumor cell nuclei was significantly reduced in the emulsion 2 group, while the tumor cells in the iodized oil group showed normal morphology and no obvious abnormalities, indicating that the embolization treatment effect of emulsion 2 was more significant; according to Figure 22 It can be seen that Prussian blue staining confirms that emulsion 2 remained in the blood vessel for a long time, achieving stable embolism.

[0139] Test Example 4: The effect of embolic agents on vascular embolization in vivo.

[0140] Rabbit kidneys, rich in vascular networks, were selected as experimental subjects for embolization treatment to evaluate the in vivo efficacy of emulsion 2 embolization agent on vascular embolization.

[0141] During the experiment, real-time digital subtraction angiography (DSA) was used for monitoring. The specific operation was as follows: a 2.6F microcatheter was precisely guided to the right renal artery through the femoral artery, while the left renal artery remained unprocessed for subsequent comparative analysis.

[0142] Figure 23 Digital subtraction angiography (DSA) images of the renal artery and renal branches of rabbits before and after embolization of emulsion 2 prepared in Example 1 of this invention; Figure 24 The image shows an X-ray fluoroscopic image of emulsion 2 prepared in Example 1 of this invention in an embolized kidney; Figure 25 Cross-sectional images of rabbit kidney CT scans before and 28 days after embolization of emulsion 2 prepared in Example 1 of this invention. Figure 26 These are actual images of the rabbit kidney embolism before and after the emulsion 2 prepared in Example 1 of this invention; Figure 27 Images of hematoxylin and eosin (H&E) staining of tissue sections from rabbit embolized kidneys after applying emulsion 2 prepared in Example 1 of this invention; Figure 28 Prussian blue (PB) staining image of a tissue section of rabbit embolized kidney prepared by emulsion 2 in Example 1 of this invention.

[0143] according to Figure 23 As can be seen, prior to embolization, angiography was performed using iodixanol contrast agent. This step significantly improved the visualization of both kidneys, making the renal vascular structures clearly visible. Subsequently, 200µL of emulsion 2 was injected into the right renal feeding artery via catheter. Post-embolization DSA imaging showed that, compared to the unaffected left kidney, blood flow in the right renal artery completely stopped, specifically manifested as no contrast enhancement in the right kidney, demonstrating that the hydrogel successfully and stably embolized the right renal feeding artery. Figure 24 This further demonstrates the filling effect of emulsion 2 within the renal artery. According to... Figure 25 As can be seen, computed tomography (CT) imaging showed the disappearance of contrast enhancement in the embolized kidney, indicating that the embolism of the right renal artery by emulsion 2 was stable and no recanalization occurred within 28 days. According to Figure 26 It can be seen that, compared with the left kidney, the right kidney showed extensive necrosis and atrophy on day 28 after embolization, while the left kidney showed compensatory hypertrophy. These macroscopic changes are consistent with the aforementioned medical imaging results. According to... Figure 27 It can be seen that on day 28, extensive coagulative necrosis occurred in the renal parenchyma, and the glomeruli and renal tubules were severely damaged (atrophied or even disappeared), resulting in almost complete loss of physiological function. According to... Figure 28 As can be seen from the Prussian blue stained images, the branches of the renal artery with a diameter of 20-300 µm were completely filled with emulsion 2. This demonstrates that emulsion 2 of Example 1 of this invention exhibits stable embolism of the renal artery in vivo.

[0144] The specific embodiments described above further illustrate the purpose, technical solution, and beneficial effects of the present invention. It should be understood that the above descriptions are merely specific embodiments of the present invention and are not intended to limit the present invention. Any modifications, equivalent substitutions, improvements, etc., made within the spirit and principles of the present invention should be included within the protection scope of the present invention.

Claims

1. A temperature-responsive magnetic emulsion embolizer, comprising: Tripterygium wilfordii, a thermosensitive polymer, iodized oil, and magnetic nanoparticles, wherein the thermosensitive polymer can undergo a phase transition and gel at temperatures above 32°C.

2. The emulsion plugging agent according to claim 1, wherein, The emulsion embolizing agent includes water, and the mass ratio of water to iodized oil is (1~3):1, preferably (1.3~2.3):

1.

3. The emulsion plugging agent according to claim 2, wherein, The mass ratio of the magnetic nanoparticles to water is (0.0015~0.003):

1.

4. The emulsion plugging agent according to claim 2 or 3, wherein, The mass ratio of water: thermosensitive polymer: triptolide is 100:(10~20):(0.02~0.06).

5. The emulsion plugging agent according to claim 1, wherein, The thermosensitive polymer includes at least one of poly(N-isopropylacrylamide), poly(N-isopropylmethacrylamide), or poly(N-vinylcaprolactam); The magnetic nanoparticles include Fe3O4.

6. A method for preparing a temperature-responsive magnetic emulsion embolizer, comprising: Tripterygium wilfordii, magnetic nanoparticles, and a thermosensitive polymer were dissolved in a deionized aqueous solution to form a mixed solution. The mixed solution was mixed evenly with iodized oil to obtain the temperature-responsive magnetic emulsion embolizer.

7. The preparation method according to claim 6, wherein, The volume ratio of the mixed solution to the iodized oil is (5~7):(3~5).

8. The preparation method according to claim 6 or 7, wherein, The concentration of the magnetic nanoparticles in the mixed solution is 2 mg / mL to 3 mg / mL; The solid content of the thermosensitive polymer in the mixed solution is 10% (w / v) to 20% (w / v); The concentration of triptolide in the temperature-responsive magnetic emulsion embolizer is 300 ng / mL to 500 ng / mL.

9. The application of a temperature-responsive magnetic emulsion embolization agent in the preparation of anticancer drugs and / or transarterial embolization chemotherapy-magnetic therapy combination drugs.

10. The application according to claim 9, wherein, The anticancer drug mentioned is an anti-liver cancer drug.

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