High-developability and dispersivity liquid embolism agent and application thereof

Abstract

The invention discloses a high-developability and dispersivity liquid embolism agent and application thereof, and belongs to the technical field of medical instruments. The iodinated polymer and PEG-I are compounded, so that the overall iodine content of the liquid embolization agent is increased, and the visibility in an operation is enhanced. Meanwhile, the PEG block polymer and the PEG-I have good compatibility, and the entanglement effect between macromolecular chains can be greatly weakened by adding the liquid PEG-I, so that the overall rheological property of the mixture is enhanced, a macroscopically uniform mixture can be formed, and the dispersion uniformity of the embolization agent in a vascular bed is improved.

Description

Technical Field

[0001] This invention relates to the field of medical device technology, specifically to a highly radioactive and diffusible liquid embolizing agent and its application. Background Technology

[0002] Interventional embolization, guided by imaging equipment (such as X-rays), involves injecting embolic material into the lesion site via arteries or veins using different types of catheters. This blocks or interrupts blood supply, thereby controlling bleeding, treating vascular diseases, treating tumors, and eliminating diseased organs. Currently, most embolic materials used clinically employ temporary external contrast agents, which have several drawbacks: for example, metallic contrast agents such as tantalum powder can cause incomplete embedding, resulting in artifacts and affecting imaging results; iodine-containing non-ionic contrast agents such as iohexol are easily metabolized shortly after the procedure, and follow-up angiography of the embolization site is required, undoubtedly increasing the patient's financial burden and the complexity of the procedure.

[0003] In tumor embolization therapy, contrastability is crucial for operational safety, while diffusion uniformity determines long-term efficacy. During and after embolization, good contrastability allows physicians to monitor the distribution of the embolic agent within the tumor vessels in real time, assessing embolization success and determining whether further adjustments to the embolization strategy are necessary. For example, contrast imaging allows physicians to visually determine whether tumor vessels are completely blocked and whether any residual blood flow channels remain. Uniform diffusion ensures the embolic agent is fully and evenly distributed within the tumor vessels, blocking the tumor's blood supply and thus more effectively inhibiting tumor cell growth and proliferation, achieving better therapeutic results. If the embolic agent does not diffuse uniformly, some tumor tissue may still receive sufficient blood supply, leading to tumor recurrence or progression. Currently used embolization materials, such as solid and liquid embolic agents, often fail to simultaneously meet the dual requirements of contrastability and embolization.

[0004] Patent CN 118755063 B provides a liquid embolization material with self-developing capabilities. It covalently bonds iodine-containing substances to the embolization matrix, resulting in iodine inclusion in the material's structure and enabling real-time imaging. Due to variations in the density and thickness of human tissues and organs, the requirements for contrast agents differ. For scenarios with higher imaging demands, the iodine content grafted into the embolization material in patent CN 118755063 B is limited, making it difficult to meet higher imaging requirements. Furthermore, given that this embolization system is organically compatible, it is difficult to be compatible with water-soluble contrast agents such as iohexol. Therefore, developing a contrast agent compatible with the embolization material in CN118755063 B, and combining it with other agents to simultaneously meet the imaging and dispersibility requirements of this type of medical embolization agent, is crucial. Summary of the Invention

[0005] To address the aforementioned challenges, this invention improves the overall iodine content of the liquid embolizing agent by compounding an iodinated polymer with PEG-I within a specific molecular weight range. The main polymer of the embolizing agent in this invention is the embolizing polymer disclosed in patent CN 118755063 B. The embolizing agent system includes: a PDLLGA embolizing agent system, a PDLLA embolizing agent system, a PLLA embolizing agent system, and a PCL embolizing agent system, preferably the PCL embolizing agent system (PEG-PCL-I). For example, adding PEG-I to the PCL embolizing agent system can increase the iodine content (viscosity) while simultaneously allowing the embolizing agent to form a high-viscosity soft solid without leakage into the blood vessel, and also exhibiting good conformability.

[0006] As a low-molecular-weight liquid, PEG-I, when added to solid / high-viscosity embolic polymers, most significantly acts as a plasticizer. PEG-I can penetrate between the polymer chains of the embolic polymer, increasing chain segment mobility and thus lowering the copolymer's melting temperature (Tm) or glass transition temperature (Tg). This allows the mixture to soften or melt at lower temperatures. Simultaneously, since the embolic polymer is semi-solid and has relatively high viscosity, the introduction of PEG-I can form a homogeneous blend system. Its molecular chains and the segments of the embolic polymer achieve molecular-level mixing through entropy increase, further promoting uniform chain mobility and avoiding performance defects caused by localized phase separation. The addition of liquid PEG-I greatly dilutes the entanglement of polymer chains, resulting in a significant decrease in the overall viscosity of the mixture. PEG blocks and PEG-I exhibit good compatibility (like dissolves like), forming a macroscopically homogeneous mixture. The obtained liquid embolizing agent is a semi-solid that dissolves in an aprotic polar solvent at room temperature, wherein the mass concentration of the liquid embolizing agent is 30-70%, and the aprotic polar solvent is dimethyl sulfoxide or / and dimethyl sulfoxide and ethanol.

[0007] One of the technical solutions of this invention is to provide a liquid embolizing agent with high radioactivity and dispersibility. The liquid embolizing agent includes an iodinated copolymer as the main material and a radioactive material PEG-I, wherein the iodinated copolymer includes a polyester hydrophobic segment and a PEG hydrophilic segment; wherein the polyester hydrophobic segment is one of PDLLGA, PDLLA, PLLA, and PCL; the molecular weight of the PEG hydrophilic segment is 1000-1500; and the molecular weight ratio of the PEG hydrophilic segment to the polyester hydrophobic segment is 0.4-3.9:1.

[0008] The developing material PEG-I is an iodine-substituted PEG derivative.

[0009] Furthermore, the preparation method of the developing material PEG-I is as follows: using triiodobenzoic acid as the iodine source, the iodine group is introduced into the PEG chain through an esterification reaction catalyzed by DCC (dicyclohexylcarbodiimide) and DMAP (4-dimethylaminopyridine).

[0010] The molecular weight of the PEG-I is 200-2000.

[0011] Furthermore, the mass ratio of the iodinated copolymer to the developing material PEG-I is 1~3:1.

[0012] Preferably, the molecular weight ratio of the hydrophilic segment PEG1000 to the hydrophobic segment PDLLGA is 1.3 to 1.8. 1; The molecular weight ratio of hydrophilic segment PEG1500 and hydrophobic segment PDLLGA is 1.9 ~ 3.9:1.

[0013] Preferably, the molecular weight ratio of the hydrophilic segment PEG1000 to the hydrophobic segment PDLLA is 1.0 ~ 1.7. 1; The molecular weight ratio of hydrophilic segment PEG1500 and hydrophobic segment PDLLA is 1.1 ~ 2.8:1.

[0014] Preferably, the molecular weight ratio of the hydrophilic segment PEG1000 to the hydrophobic segment PLLA is 0.8 ~ 1.2. 1; The molecular weight ratio of hydrophilic segment PEG1500 and hydrophobic segment PLLA is 1.2 ~ 1.6:1.

[0015] Preferably, the molecular weight ratio of hydrophilic segment PEG1000 to hydrophobic segment PCL is 0.4 ~ 0.7:1; the molecular weight ratio of hydrophilic segment PEG1500 to hydrophobic segment PCL is 0.7 ~ 1.5:1.

[0016] Preferably, the developer material has a PEG ratio of 200-2000; more preferably, the PEG ratio is 200-600. Preferably, the mass ratio of the iodinated copolymer to the developing material PEG-I is 1~3:1.

[0017] The second technical solution of the present invention provides a method for using a liquid embolizing agent. The liquid embolizing agent is dissolved in a non-proton polar solvent, wherein the mass concentration of the liquid embolizing agent is 30-70%.

[0018] Furthermore, the aprotic polar solvent is dimethyl sulfoxide, or a mixture of dimethyl sulfoxide and ethanol.

[0019] The advantages of this invention are: by compounding iodinated polymers with imaging material PEG-I, this invention increases the overall iodine content (viscosity) of the liquid embolizing agent. The product can achieve distal embolization effect, and after phase change, the liquid embolizing agent can become a soft solid with high viscosity without leaking out of the blood vessel, and has good conformability to adapt to the shape of the blood vessel. Attached Figure Description

[0020] Figure 1 (a) in the figure shows the effect of PECL-7 embolization on rabbit kidneys; Figure 1 (b) is an angiography image 30 minutes after PECL-7 embolization; Figure 2 (a) in the figure shows the effect of PECL1500-PEG200-5 embolization on rabbit kidney embolization; Figure 1 (b) is an angiography image 30 minutes after the PECL1500-PEG200-5 embolization agent was applied. Detailed Implementation

[0021] The following examples are provided to further illustrate the present invention and are intended to explain the invention, not to limit its scope. Unless otherwise specified, all figures are expressed in parts by weight and weight percentages.

[0022] Unless otherwise specified, the raw materials used in this invention are all conventional commercially available products; unless otherwise specified, the methods used in this invention are all conventional methods in the field.

[0023] The embodiments of the present invention will be further described below with reference to several examples.

[0024] It should be understood that the described embodiments are merely some, not all, of the embodiments in this application. All other embodiments obtained by those skilled in the art based on the embodiments in this application without inventive effort are within the scope of protection of this application.

[0025] The terminology used in the embodiments of this application is for the purpose of describing particular embodiments only and is not intended to be limiting of this application. The singular forms “a,” “the,” and “the” used in the embodiments of this application and the appended claims are also intended to include the plural forms unless the context clearly indicates otherwise.

[0026] Example 1: Preparation of PEG-I developing material Preparation method of PEG-I: Weigh 10.0 g of PEG300 and dissolve it in 80 mL of ultra-dry dichloromethane at room temperature with stirring. Weigh 66.4 g of triiodobenzoic acid and dissolve it in 4 mL of N,N-dimethylformamide. Weigh 27.510 g of DCC (dicyclohexylcarbodiimide) and 4.072 g of DMAP (4-dimethylaminopyridine) and dissolve them in 20 mL of ultra-dry dichloromethane. Place the above three solutions in a 250 mL single-necked flask and react for 24 h. After the reaction is completed, the product obtained above is further purified with n-hexane, the precipitate is collected, and then placed in a vacuum oven for 24-72 h to obtain the final product PEG-I.

[0027] The relative molecular weight of the polymer was calculated to be 1104 based on the hydrogen spectrum measured by nuclear magnetic resonance spectroscopy, and the iodine grafting rate was found to be 59% by iodine titration.

[0028] Following the basic operating steps of the examples, PEGs of different molecular weights were reacted with triiodobenzoic acid to obtain different PEG-I copolymers. The specific parameters are shown in the table below: According to the PEG1000-PCL-I block copolymer and PEG1500-PCL-I disclosed in patent CN 118755063 B, the formulation for preventing distal loss of embolic material is shown in the table below: According to the PEG-PDLLGA-I block copolymer, PEG-PDLLA-I block copolymer, and PEG-PLLA-I block copolymer disclosed in patent CN 118755063 B, the formulations that prevent embolic material from leaking from the distal end are shown in the table below: Example 2: PEG1000-PCL-I / PEG200-I composite copolymer Based on the PEG1000-PCL-I block copolymer described above, this invention selects PECL-1 to PECL-5 to combine with developer PEG200-I (iodine content 64%) to obtain composite copolymers with different iodine contents. Specific parameters are shown in the table below: Iodine content is an indicator that directly reflects the imaging properties of embolizing agents. As can be seen from the above experimental examples, PEG-PCL-I is the main material and PEG-I is the imaging material. After being compounded in a certain proportion, the iodine content of the composite polymer can be significantly increased (30~44%).

[0029] Take 0.40g of any of the above composite copolymers, add 0.20g of DMSO and 0.40g of ethanol, and stir to dissolve at room temperature. Seal the completely dissolved liquid embolizing agent in a vial and sterilize it to obtain a long-term autoradiographic in-situ phase change liquid embolizing agent.

[0030] The diffusion effects of several liquid embolic agents were compared through an in vitro simulation experiment. The device consisted of a glass tube (900 mm long, 80 mm outer diameter) and a constant-temperature water tank with a pump, providing a 37°C constant temperature environment for the glass tube. 12 g of 2 mm diameter glass beads were placed in a 10 ml glass column, which was then placed inside the constant-temperature glass tube and connected to a saline bottle via a PVC pipe. The vertical distance between the saline solution and the glass column outlet was 150 cm. A microcatheter was placed inside the glass column via a Y-valve. The flow rate of the saline solution was adjusted to approximately 0.3 ml / s, and a 37°C constant-temperature beaker was placed below the outlet. The embolic agent was injected in portions through the microcatheter using a 1 ml syringe. The precipitation and diffusion of the embolic agent in the glass column were observed, as well as whether any precipitation flowed out through the outlet. The expected result was that precipitate formed inside the glass bead container, effectively filling the gaps between the glass beads, stopping the water flow through the beads, and preventing any precipitation from flowing out of the outlet. The above simulation results show that PEG1000-PCL-I as the main material and PEG200-I as the developing material, when mixed in a certain proportion, can significantly improve the dispersion effect of the embolic agent. When the main material has poor dispersibility, adding a certain amount of PEG200-I can allow PEG200-I to penetrate between the PEG-PCL-I polymer chains, increasing chain segment mobility and greatly diluting the entanglement of polymer chains. This results in a significant decrease in the overall rheological properties of the mixture, leading to uniform dispersion. The addition of a small amount of PEG-I will not significantly improve the dispersibility (e.g., PECL1000-PEG200-1 / 2 / 3, PECL1000-PEG200-7 / 8 / 9, PECL1000-PEG200-10 / 11 / 12). When the main material has uniform dispersibility, excessive PEG200-I will cause the mechanical properties of the mixture to decrease and flow out of the glass column outlet (e.g., PECL1000-PEG200-4 / 5 / 6, PECL1000-PEG200-13 / 14 / 15).

[0031] Example 3: PEG1000-PCL-I / PEG600-I composite copolymer Based on the PEG1000-PCL-I block copolymer described above, this invention selects PECL-1 to PECL-5 to combine with developer PEG600-I (iodine content 48%) to obtain composite copolymers with different iodine contents. Specific parameters are shown in the table below: Take 0.40g of any of the above composite copolymers, add 0.20g of DMSO and 0.40g of ethanol, and stir to dissolve at room temperature. Seal the completely dissolved liquid embolizing agent in a vial and sterilize it to obtain a long-term autoradiographic in-situ phase change liquid embolizing agent.

[0032] The diffusion effects of several liquid embolic agents were compared through an in vitro simulation experiment. The device consisted of a glass tube (900 mm long, 80 mm outer diameter) and a constant-temperature water tank with a pump, providing a 37°C constant temperature environment for the glass tube. 12 g of 2 mm diameter glass beads were placed in a 10 ml glass column, which was then placed inside the constant-temperature glass tube and connected to a saline bottle via a PVC pipe. The vertical distance between the saline solution and the glass column outlet was 150 cm. A microcatheter was placed inside the glass column via a Y-valve. The flow rate of the saline solution was adjusted to approximately 0.3 ml / s, and a 37°C constant-temperature beaker was placed below the outlet. The embolic agent was injected in portions through the microcatheter using a 1 ml syringe. The precipitation and diffusion of the embolic agent in the glass column were observed, as well as whether any precipitation flowed out through the outlet. The expected result was that precipitate formed inside the glass bead container, effectively filling the gaps between the glass beads, stopping the water flow through the beads, and preventing any precipitation from flowing out of the outlet. When PEG1000-PCL-I is used as the main material and PEG600-I is used as the developing material, it exhibits similar effects to PEG200-I. However, PEG600-I is a long-chain molecule with relatively weaker mobility, and its molecular chains are more prone to entanglement. Therefore, it has weaker fluidity than PEG200-I. As a result, when the main material has uniform dispersion, mixing it with PEG600-I at a 1:1 ratio does not cause the mixture to flow out of the glass column outlet (e.g., PECL1000-PEG200-4 / 5 / 6, PECL1000-PEG200-13 / 14 / 15).

[0033] Based on the above experiments, when the molecular weight ratio of hydrophilic PEG1000 to hydrophobic PCL is 0.4~0.5:1, the mass ratio of PEG-PCL-I to PEG200-I should be controlled at 1~2:1, and the mass ratio of PEG-PCL-I to PEG600-I should be controlled at 1~2:1; when the molecular weight ratio of hydrophilic PEG1000 to hydrophobic PCL is 0.6~0.7:1, the mass ratio of PEG-PCL-I to PEG200-I should be controlled at 2~3:1, and the mass ratio of PEG-PCL-I to PEG600-I should be controlled at 1~3:1.

[0034] Example 4: PEG1500-PCL-I / PEG200-I composite copolymer Based on the PEG1500-PCL-I block copolymer described above, this invention selects PECL-6 to PECL-9 to combine with developer PEG200-I (iodine content 64%) to obtain composite copolymers with different iodine contents. Specific parameters are shown in the table below: Take 0.40g of any of the above composite copolymers, add 0.20g of DMSO and 0.40g of ethanol, and stir to dissolve at room temperature. Seal the completely dissolved liquid embolizing agent in a vial and sterilize it to obtain a long-term autoradiographic in-situ phase change liquid embolizing agent.

[0035] The diffusion effects of several liquid embolic agents were compared through an in vitro simulation experiment. The device consisted of a glass tube (900 mm long, 80 mm outer diameter) and a constant-temperature water tank with a pump, providing a 37°C constant temperature environment for the glass tube. 12 g of 2 mm diameter glass beads were placed in a 10 ml glass column, which was then placed inside the constant-temperature glass tube and connected to a saline bottle via a PVC pipe. The vertical distance between the saline solution and the glass column outlet was 150 cm. A microcatheter was placed inside the glass column via a Y-valve. The flow rate of the saline solution was adjusted to approximately 0.3 ml / s, and a 37°C constant-temperature beaker was placed below the outlet. The embolic agent was injected in portions through the microcatheter using a 1 ml syringe. The precipitation and diffusion of the embolic agent in the glass column were observed, as well as whether any precipitation flowed out through the outlet. The expected result was that precipitate formed inside the glass bead container, effectively filling the gaps between the glass beads, stopping the water flow through the beads, and preventing any precipitation from flowing out of the outlet. The above simulation results show that, with PEG1500-PCL-I as the main material, similar experimental phenomena are observed. When the main material has poor dispersibility, adding a certain amount of PEG200-I can lead to a significant decrease in the overall rheological properties of the mixture, resulting in uniform dispersion. The addition of a small amount of PEG-I will not significantly improve the dispersibility, while an excessive amount will cause the mechanical properties of the mixture to decrease and flow out of the glass column outlet (e.g., PECL1500-PEG200-1 / 2 / 3, PECL1500-PEG200-4 / 5 / 6). When the main material has uniform dispersibility, an excessive amount of PEG200-I will cause the mechanical properties of the mixture to decrease and flow out of the glass column outlet (e.g., PECL1000-PEG200-10 / 11 / 12).

[0036] Example 5: PEG1500-PCL-I / PEG600-I composite copolymer Based on the PEG1500-PCL-I block copolymer described above, this invention selects PECL-6 to PECL-9 to combine with developer PEG600-I (iodine content 48%) to obtain composite copolymers with different iodine contents. Specific parameters are shown in the table below: Take 0.30g of any of the above composite copolymers, add 0.30g of DMSO and 0.40g of ethanol, and stir to dissolve at room temperature. Seal the completely dissolved liquid embolizing agent in a vial and sterilize it to obtain a long-term autoradiographic in-situ phase change liquid embolizing agent.

[0037] The diffusion effects of several liquid embolic agents were compared through an in vitro simulation experiment. The device consisted of a glass tube (900 mm long, 80 mm outer diameter) and a constant-temperature water tank with a pump, providing a 37°C constant temperature environment for the glass tube. 12 g of 2 mm diameter glass beads were placed in a 10 ml glass column, which was then placed inside the constant-temperature glass tube and connected to a saline bottle via a PVC pipe. The vertical distance between the saline solution and the glass column outlet was 150 cm. A microcatheter was placed inside the glass column via a Y-valve. The flow rate of the saline solution was adjusted to approximately 0.3 ml / s, and a 37°C constant-temperature beaker was placed below the outlet. The embolic agent was injected in portions through the microcatheter using a 1 ml syringe. The precipitation and diffusion of the embolic agent in the glass column were observed, as well as whether any precipitation flowed out through the outlet. The expected result was that precipitate formed inside the glass bead container, effectively filling the gaps between the glass beads, stopping the water flow through the beads, and preventing any precipitation from flowing out of the outlet. Based on the above experiments, when the molecular weight ratio of hydrophilic segment PEG1500 to hydrophobic segment PCL is 0.7~1.2:1, the mass ratio of PEG-PCL-I and PEG200-I should be controlled at 1~3:1, and the mass ratio of PEG-PCL-I and PEG600-I should be controlled at 3:1; when the molecular weight ratio of hydrophilic segment PEG1500 to hydrophobic segment PCL is 1.2~1.5:1, the mass ratio of PEG-PCL-I and PEG200-I should be controlled at 1~3:1, and the mass ratio of PEG-PCL-I and PEG600-I should be controlled at 2~3:1.

[0038] Example 6: PEG-PDLLA-I / PEG200-I composite copolymer, PEG-PDLLA-I / PEG200-I composite copolymer, PEG-PLLA-I / PEG200-I composite copolymer Based on the PEG-PDLLGA-I / PEG-PDLLA-I / PEG200-I block copolymer described above, and compounded with developer PEG200-I (iodine content 64%), composite copolymers with different iodine contents were obtained. Specific parameters are shown in the table below: Take 0.70g of any of the above composite copolymers, add 0.10g of DMSO and 0.20g of ethanol, and stir to dissolve at room temperature. Seal the completely dissolved liquid embolizing agent in a vial and sterilize it to obtain a long-term autoradiographic in-situ phase change liquid embolizing agent.

[0039] The diffusion effects of several liquid embolic agents were compared through an in vitro simulation experiment. The device consisted of a glass tube (900 mm long, 80 mm outer diameter) and a constant-temperature water tank with a pump, providing a 37°C constant temperature environment for the glass tube. 12 g of 2 mm diameter glass beads were placed in a 10 ml glass column, which was then placed inside the constant-temperature glass tube and connected to a saline bottle via a PVC pipe. The vertical distance between the saline solution and the glass column outlet was 150 cm. A microcatheter was placed inside the glass column via a Y-valve. The flow rate of the saline solution was adjusted to approximately 0.3 ml / s, and a 37°C constant-temperature beaker was placed below the outlet. The embolic agent was injected in portions through the microcatheter using a 1 ml syringe. The precipitation and diffusion of the embolic agent in the glass column were observed, as well as whether any precipitation flowed out through the outlet. The expected result was that precipitate formed inside the glass bead container, effectively filling the gaps between the glass beads, stopping the water flow through the beads, and preventing any precipitation from flowing out of the outlet. The above simulation results show that when the PEG-PDLLGA-I / PEG-PDLLA-I / PEG-PLLA-I block copolymer is compounded with a certain proportion of developer PEG200-I, it not only significantly increases the iodine content, but also greatly reduces the overall rheological properties of the mixture, thus exhibiting diffuse uniformity.

[0040] Example 7: Renal Artery Embolization Experiment Take 0.40g of PECL7 and PECL1500-PEG200-5 copolymers respectively, add 0.20g of DMSO and 0.40g of ethanol, and stir to dissolve at room temperature. Seal the completely dissolved liquid embolizing agent in a vial and sterilize it to obtain an in-situ phase change liquid embolizing agent that can be self-illuminating for a long time.

[0041] Rabbit renal artery embolization experiment: The rabbit was restrained with a fixator. Hair was shaved from the ears, abdomen, and groin. Alcohol was sprayed onto the marginal ear vein to dilate it. 10 mL of prepared urethane solution was injected. The rabbit's leg skin was clamped with hemostatic forceps to confirm complete anesthesia. If there was still a reaction, an appropriate amount of urethane was administered. After the rabbit was fully anesthetized, the next step was performed: The rabbit was fixed in a supine position on an acrylic plate. The limbs were wrapped with masking tape and then fixed to the acrylic plate. The groin was palpated to locate the arterial pulsation point. After confirming the pulsation point, a linear incision was made 2-3 cm to the left of the groin. The femoral bundle, including the femoral vein, femoral artery, and nerve, was dissected using blunt dissection. The femoral artery was completely separated using surgical forceps. The femoral artery was threaded with a puncture needle. After observing arterial blood flowing out of the vessel opening, a guidewire was inserted. After successful insertion, a catheter was inserted. After catheter insertion into the renal artery was observed via DSA (Digital Subtraction Angiography) on the operating table, contrast agent angiography was performed to confirm successful catheter insertion. The catheter was then flushed with normal saline, followed by an injection of 1 mL of embolic solution at a rate of 1 mL / min. PEG300 was then used to advance the remaining embolic agent into the vessel at a rate of 1 mL / min. After injection, a 30-minute wait was observed, and contrast agent was injected again to monitor vascular embolization. Results showed that PECL7 (PEG-PCL-I) and PECL1500-PEG200-5 (PEG-PCL-I / PEG200-I 2:1) were effective embolic agents. Both can achieve distal embolization, but uneven dispersion of the PECL7 embolus is visible. Figure 1 a) PECL1500-PEG200-5 has good diffusion properties, and the embolic material fills the entire blood vessel, making it clearly visible on imaging. Figure 2 b).

[0042] The above embodiments describe in detail the structure, features, and effects of the present invention. The above description is only a preferred embodiment of the present invention. Any changes made in accordance with the concept of the present invention, or equivalent embodiments modified to have equivalent changes, shall still fall within the scope of protection of the present invention if they do not exceed the scope covered by the specification.

Claims

1. A highly radioactive and dispersible liquid embolic agent, characterized in that, The liquid embolizing agent includes an iodinated copolymer as the main material and a developing agent PEG-I. The iodinated copolymer includes a polyester hydrophobic segment and a PEG hydrophilic segment. The polyester hydrophobic segment is one of PDLLGA, PDLLA, PLLA, or PCL. The molecular weight of the PEG hydrophilic segment is 1000-1500. The mass ratio of the iodinated copolymer to the developing agent PEG-I is 1~3:

1.

2. The liquid embolic agent according to claim 1, characterized in that, The developing material PEG-I is an iodine-substituted PEG derivative.

3. The liquid embolic agent according to claim 2, characterized in that, The preparation method of the developing material PEG-I is as follows: using triiodobenzoic acid as the iodine source, the iodine group is introduced into the PEG chain through an esterification reaction catalyzed by DCC (dicyclohexylcarbodiimide) and DMAP (4-dimethylaminopyridine).

4. The liquid embolic agent according to claim 1, characterized in that, The molecular weight of PEG-I is 200-2000.

5. The liquid embolic agent according to claim 1, characterized in that, The molecular weight ratio of PEG hydrophilic segments to polyester hydrophobic segments is 0.4-3.9:

1.

6. A method of using the liquid embolic agent as described in claim 1.

7. The method according to claim 1, characterized in that, The liquid embolizing agent is dissolved in an aprotic polar solvent, wherein the mass concentration of the liquid embolizing agent is 30 to 70%.

8. The method according to claim 7, characterized in that, The aprotic polar solvent is dimethyl sulfoxide, or a mixture of dimethyl sulfoxide and ethanol.

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