Liquid embolism material containing absorbable developer and preparation method thereof

Abstract

The invention belongs to the technical field of medical materials, and particularly relates to a liquid embolism material containing an absorbable developing agent and a preparation method of the liquid embolism material. The liquid embolism material containing the absorbable developer provided by the invention comprises a high polymer material, the absorbable developer and dimethyl sulfoxide, the absorption developer is an iodine-containing oligomer, and is prepared from an iodophenyl compound and an ester cyclic monomer or an ether cyclic monomer through ring opening polymerization under the action of a catalyst. The liquid embolism material provided by the invention can be dissolved in a dimethyl sulfoxide solvent, and can be gradually separated out to form embolism when being in contact with blood; after the absorbable developer material is transferred to tissues in a human body, the iodine-containing oligomer is gradually metabolized and discharged out of the body within 30-90 days.

Description

Technical Field

[0001] This invention belongs to the field of medical materials technology, specifically relating to a liquid embolic material containing an absorbable contrast agent and its preparation method. Background Technology

[0002] Vascular embolization is a surgical procedure that uses a microcatheter inserted through a minimally invasive incision in an artery to inject an embolic material system into the target blood vessel, creating an intravascular embolism and sealing the vessel at the target site. It is commonly used to treat vascular diseases such as aneurysms, arteriovenous malformations or fistulas, hemorrhage, and hypervascular tumors. Currently, commonly used embolic material systems in clinical practice include metal coils, polymeric embolic microspheres, and liquid embolic agents.

[0003] Metal coils and polymeric embolic microspheres are pre-designed to match the size of the target blood vessel before delivery, which can easily lead to mismatches between the embolic material and the vessel size. Liquid embolic material systems are primarily polymeric materials, existing as liquid monomers or solutions dissolved in solvents before injection into the target blood vessel. Upon delivery, they react and solidify or precipitate upon contact with tissue or blood, forming an embolus to block the vessel. Common reactive liquid embolic materials are cyanoacrylates, such as butyl cyanoacrylate and octyl cyanoacrylate. Common solution-based liquid embolic material systems include polyacrylate copolymers, polyacrylamide copolymers, polyethylene glycol copolymers, and biocompatible organic solvents such as dimethyl sulfoxide and hexamethyldisiloxane. In clinical applications, the embolic material system needs to possess radiopaque properties (i.e., non-transmissive linearity) to aid in localization; therefore, a contrast agent needs to be added to the embolic material system. Common contrast agents include metal contrast agents, such as tantalum powder, tantalum oxide, and barium sulfate; common organic contrast agents are iodides, such as iohexol, iopromide, and iomepro. However, common organic contrast agents are too hydrophilic or soluble in blood, and their residence time in blood vessels is too short, which cannot meet the necessary residence time required for surgical procedures when used as liquid embolic agents.

[0004] In the prior art, US patent application number US5667767A discloses a liquid embolizing material comprising a polyethylene-vinyl alcohol copolymer as an embolic agent, tantalum, tantalum oxide, or barium sulfate as a contrast agent, and dimethyl sulfoxide as an organic solvent. After delivery to the target blood vessel, the dimethyl sulfoxide gradually diffuses into the bloodstream, while the insoluble polyethylene-vinyl alcohol copolymer gradually precipitates to form an embolus. Similar to the aforementioned patent, Onyx is a widely used liquid embolizing agent in clinical practice. TM(Manufactured by Medtronic) It is composed of ethylene-vinyl alcohol copolymer, tantalum powder, and dimethyl sulfoxide solvent. Chinese patent application CN119701059A discloses a liquid embolizing agent comprising an ethylene-vinyl alcohol copolymer polymer, carbonyl iron powder, and dimethyl sulfoxide. The carbonyl iron powder acts as a contrast agent, and its suspension performance after mixing with the ethylene-vinyl alcohol copolymer polymer is superior to that of the ethylene-vinyl alcohol copolymer / tantalum system. The main disadvantages of this type of liquid embolizing agent are: 1) The metal contrast agent has poor compatibility with polymeric materials, requiring prolonged stirring and mixing before clinical use to form a homogeneous mixture; 2) The metal contrast agent remains permanently at the target blood vessel site (i.e., it is not absorbed or metabolized in vivo), which can cause severe artifacts in subsequent CT or MRI scans, affecting the visibility of adjacent tissues or impacting secondary surgeries.

[0005] Therefore, developing a liquid embolization material system that contains a contrast agent that can be visualized promptly and gradually absorbed is crucial for clinical needs. Summary of the Invention

[0006] To address the technical problems existing in the prior art, the present invention aims to provide a liquid embolic material containing an absorbable contrast agent and its preparation method. The liquid embolic material containing an absorbable contrast agent provided by the present invention comprises a polymer material, a contrast agent, and a solvent. The polymer material and the contrast agent have good compatibility; the homogeneous solution formed by dissolving in the solvent, when delivered to the target blood vessel site, can precipitate and solidify, forming an embolism and sealing the target blood vessel. The contrast agent is gradually metabolized and excreted from the body within 30-90 days.

[0007] To achieve the above-mentioned objectives, the technical solution of this invention is as follows: A liquid embolic material containing an absorbable developer includes a polymer material, an absorbable developer, and dimethyl sulfoxide; wherein the absorbable developer is an iodine-containing oligomer.

[0008] Furthermore, the iodine-containing oligomer is prepared by ring-opening polymerization of iodophenyl compounds and ester cyclic monomers or ether cyclic monomers under the action of a catalyst.

[0009] Furthermore, the iodophenyl group compound is one of iohexol, iopromide, 2,3,5-triiodobenzoic acid, 2,3,5-triiodophenylmethyl alcohol, iotalalic acid, iodixanol, iopamidol, and 4,4-bis(4-hydroxy-3,5-diiodophenyl)valerate.

[0010] Furthermore, the ester cyclic monomer is one or more of glycolide, lactide, caprolactone, β-propiolactone, and p-dioxanone; the ether cyclic monomer is ethylene oxide.

[0011] Furthermore, the catalyst is tin ethylhexanoate or N,N'-diisopropylcarbodiimide.

[0012] Furthermore, the preparation method of the absorbable developer is as follows: using an iodophenyl group compound as an initiator, mixing it with an ester cyclic monomer or an ether cyclic monomer, degassing under vacuum, adding a catalyst, adjusting to the reaction temperature to carry out the reaction, precipitating in a cold solvent after the reaction is completed, filtering, and obtaining the absorbable developer.

[0013] Furthermore, the preparation method of the absorbable developer also includes carboxylation modification, specifically: dissolving the absorbable developer and succinic anhydride in anhydrous dichloromethane, adding 4-dimethylaminopyridine at 0°C, reacting for 30 min, stirring at room temperature for 8-10 h, adding hydrochloric acid solution, and precipitating in cold methanol to obtain an intermediate; dissolving the intermediate, polyethylene glycol, and dimethylaminobenzoic acid in anhydrous dichloromethane, slowly adding N,N'-diisopropylcarbodiimide at 0°C, stirring at room temperature for 8-10 h, and precipitating in cold methanol to obtain the carboxylated modified absorbable developer.

[0014] Furthermore, the polymer material is one of ethylene-vinyl alcohol copolymer, polylactide, polyglycolic acid, polycaprolactone, polylactide-caprolactone copolymer, polydioxanone, and poly(2-hydroxyethyl methacrylate-siloxane acrylate) copolymer.

[0015] Furthermore, the polymer material has a mass percentage of 10-20%, the absorbable developer has a mass percentage of 10-45%, and the dimethyl sulfoxide has a mass percentage of 35-80%.

[0016] The present invention also provides a method for preparing the liquid embolization material containing absorbable developer, specifically: adding polymer material and absorbable developer to dimethyl sulfoxide, stirring until completely dissolved, to obtain the liquid embolization material containing absorbable developer.

[0017] Compared with the prior art, the liquid embolic material containing absorbable developer and its preparation method provided by the present invention have the following technical advantages: (1) The present invention uses a polymer material, an absorbable contrast agent and a dimethyl sulfoxide solvent to form a liquid embolization material. The polymer material can be dissolved in the dimethyl sulfoxide solvent and gradually precipitates to form an embolism when it comes into contact with blood. The absorbable contrast agent is an iodine-containing polyester or polyether oligomer, which has good compatibility with the polymer material and is easy to mix evenly. After dissolving in the dimethyl sulfoxide solvent, the solution formed is a homogeneous solution. After the liquid embolization material is delivered to the target blood vessel, the dimethyl sulfoxide diffuses into the surrounding blood, and the polymer material / absorbable contrast agent blend precipitates to form an embolism and close the target blood vessel. (2) This invention uses iodophenyl compounds as initiators to prepare iodine-containing oligomers as absorbable imaging agents through ring-opening polymerization with ester cyclic monomers or ether cyclic monomers under the action of a catalyst. The molecular weight is 1000-5000 g / mol. The iodine-containing oligomers and polymer materials are dissolved in dimethyl sulfoxide solvent and mixed evenly. After being delivered to human tissues, the iodine-containing oligomers are gradually metabolized and excreted from the body within 30-90 days. (3) The liquid embolization material containing absorbable contrast agent provided by the present invention has a kinematic viscosity range of 20-40 cSt at 37°C. This indicates that the liquid embolization material containing absorbable contrast agent provided by the present invention can maintain a stable viscosity range at human body temperature and has a certain tolerance to temperature changes. This avoids the problem that the viscosity is too low, causing it to flow rapidly in blood vessels and making it difficult to control its distribution range, and that the viscosity is too high, making it difficult to push. (4) The liquid embolization material containing absorbable contrast agent provided by the present invention precipitates immediately when injected into phosphate buffer solution at 37°C. The precipitate is in the form of clumps with tight internal aggregation. This indicates that the liquid embolization material containing absorbable contrast agent provided by the present invention can quickly solidify to form an embolism in a short time, blocking blood flow in the blood vessels. The formed embolism has high mechanical strength and stability, ensuring the durability of the embolization effect. It can effectively block blood vessels for a long time, achieve the therapeutic purpose, reduce the formation of collateral circulation, and reduce the possibility of lesion recurrence. Attached Figure Description

[0018] Figure 1 This is a schematic diagram of the molecular structure of the absorbable developer prepared in Example 1. Figure 2 This is a schematic diagram of the molecular structure of the absorbable developer prepared in Example 2; Figure 3 This is a schematic diagram of the molecular structure of the absorbable developer prepared in Example 3; Figure 4 This is a schematic diagram of the molecular structure of the absorbable developer prepared in Example 4. Figure 5 The 1H NMR spectrum of the absorbable developer prepared in Example 4-1; Figure 6 Images showing the in vitro degradation test results of the liquid embolization material prepared in Example 4-1; Figure 7 The imaging effect of the liquid embolic material prepared in Example 4-1 after in vitro degradation for different times; Figure 8 The imaging effect of the liquid embolization material prepared in Example 4-1 injected into an animal experiment at 0 days. Figure 9 The imaging effect of the liquid embolic material prepared in Example 4-1 after 10 days of injection in animal experiments; Figure 10 The imaging effect of the liquid embolization material prepared in Example 4-1 after 30 days of injection in animal experiments is shown. Detailed Implementation

[0019] To facilitate understanding of the present invention, a more comprehensive description is provided below, along with preferred embodiments. However, the present invention can be implemented in many different forms and is not limited to the embodiments described herein. Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention pertains. The terminology used herein is for the purpose of describing particular embodiments only and is not intended to limit the invention.

[0020] This specific embodiment provides a liquid embolization material system containing an absorbable developer, which is composed of a polymer material, an absorbable developer, and a dimethyl sulfoxide solvent.

[0021] Absorbable developers are iodine-containing oligomers, formed by the ring-opening polymerization of ester and ether cyclic monomers initiated by the hydroxyl groups in the molecular structure of iodophenyl groups, resulting in iodine-containing oligomer developers with a molecular weight of 1000-5000 g / mol. Absorbable developers are gradually metabolized and excreted from the body within 30-90 days, gradually losing their developing properties.

[0022] Iodophenyl compounds are common iodophenyl compounds, including but not limited to iohexol (CAS: 66108-95-0), iopromide (CAS: 73334-07-3), 2,3,5-triiodobenzoic acid (CAS: 88-82-4), 2,3,5-triiodobenzyl alcohol (CAS: 31075-53-3), iotalalic acid (CAS: 2276-90-6), iodixanol (CAS: 92339-11-2), iopamidol (CAS: 60166-93-0), and 4,4-bis(4-hydroxy-3,5-diiodophenyl)valerate.

[0023] Cyclic ester monomers include, but are not limited to, one or more combinations of glycolide (CAS: 502-97-6), lactide (CAS: 95-96-5), caprolactone (CAS: 502-44-3), β-propiolactone (CAS: 57-57-8), p-dioxanone (CAS: 3041-16-5), and ethylene oxide (CAS: 75-21-8). Cyclic polyester materials can be combined arbitrarily. For example, iohexol (CAS: 66108-95-0) initiates the polymerization of lactide and β-propiolactone (molar ratio: lactide: β-propiolactone = 1:1), and 2,3,5-triiodobenzoic acid (CAS: 88-82-4) initiates the polymerization of caprolactone and ethylene oxide (molar ratio: caprolactone: ethylene oxide = 1:4) after hydroxyl-termined polymerization.

[0024] The polymer material is one of the following: ethylene-vinyl alcohol copolymer, polylactide, polyglycolic acid, polycaprolactone, polylactide-caprolactone copolymer, polydioxanone, and poly(2-hydroxyethyl methacrylate-siloxane acrylate) copolymer.

[0025] The liquid embolization material system consists of the following components: 10-20 wt% polymer material, 10-45 wt% absorbable contrast agent, and 35-80 wt% dimethyl sulfoxide.

[0026] Example 1 Preparation of iodine-containing oligomer developer: Using 2,3,5-triiodobenzyl alcohol (CAS: 31075-53-3) as an initiator, the monomer lactide (CAS: 95-96-5) was mixed with 2,3,5-triiodobenzyl alcohol at a molar ratio of 10-30:1 and added to a round-bottom jar. After vacuum degassing, 0.2% (by weight of monomer) of tin ethylhexanoate catalyst was added, and the mixture was stirred at 130°C for 8 hours. After cooling to room temperature, the solid polymer was dissolved in dichloromethane and then precipitated in cold methanol. This yielded a 2,3,5-triiodobenzyl alcohol-polylactide oligomer (developer structure see [link]). Figure 1 The yield of the synthetic route is 95%-98%. The molecular weight of the iodine-containing oligomer is 1940-4820 g / mol, and the iodine content of the oligomer molecule is 79-198 mg / g. The relationship between the molar ratio of lactide to initiator, the molecular weight of the iodine-containing oligomer, and the iodine content is shown in Table 1.

[0027] Table 1

[0028] Preparation of liquid embolization materials: A liquid embolic material was prepared by dissolving a polymeric material, ethylene-vinyl alcohol copolymer (10 wt%) (Sigma-Aldrich 414093, CAS 25067-34-9, 32% ethylene), and an absorbable developer, 2,3,5-triiodobenzyl alcohol-polylactide oligomer (20 wt%) (1940 g / mol, iodine content 198 mg / g), together in dimethyl sulfoxide.

[0029] Example 2 Preparation of iodine-containing oligomer developer: Using 2,3,5-triiodobenzyl alcohol (CAS: 31075-53-3) as an initiator, the monomer lactide (CAS: 95-96-5) was mixed with 2,3,5-triiodobenzyl alcohol at a molar ratio of 5-10:1 and added to a round-bottom jar. After vacuum degassing, 0.2% (by weight of monomer) of tin ethylhexanoate catalyst was added, and the mixture was stirred at 130°C for 8 hours. After cooling to room temperature, the solid polymer was dissolved in dichloromethane and then precipitated in cold methanol to obtain 2,3,5-triiodobenzyl alcohol-polylactide intermediate 1. The molecular weight of intermediate 1 was 180-4500 g / mol, and the yield was 94-97%.

[0030] Carboxylation modification of intermediate 1: Intermediate 1 and succinic anhydride (molar ratio 1:5) were dissolved in 100 mL of anhydrous dichloromethane. 4-Dimethylaminopyridine (molar ratio of 4-dimethylaminopyridine to intermediate 1 was 2:1) was added at 0 °C, and the reaction was carried out for 0.5 h. Then, the mixture was stirred at room temperature for 8 h. Next, a 2 mol / L HCl solution (molar ratio of HCl to intermediate 1 was 10:1) was added, and the mixture was stirred until homogeneous. After three precipitations in methanol, intermediate 2 was obtained with a yield of 90-95%. Intermediate 2, polyethylene glycol (molar ratio of polyethylene glycol to intermediate 2 is 5:1), and dimethylaminobenzoic acid (molar ratio of dimethylaminobenzoic acid to intermediate 2 is 0.2) were dissolved in anhydrous dichloromethane. N,N'-diisopropylcarbodiimide (molar ratio of N,N'-diisopropylcarbodiimide to intermediate 2 is 5:1) was slowly added at 0°C. After addition, the reaction mixture was stirred at room temperature for 8 hours, and then precipitated three times in cold methanol to obtain 2,3,5-triiodobenzylmethyl alcohol-polylactide-ethylene oxide iodine-containing oligomer (developer structure see...). Figure 2 The yield was 90-95%. The molecular weight of polyethylene glycol (PEG) used in the above reaction route was 300-1000 g / mol, the molecular weight of the iodine-containing oligomer prepared by the route was 1000-5000 g / mol, and the iodine content of the oligomer was 150-264 mg / g. The relationship between the molar ratio of lactide to initiator, the molecular weight of PEG, the molecular weight of the iodine-containing oligomer, and the iodine content is shown in Table 2.

[0031] Table 2

[0032] Preparation of liquid embolization materials: A liquid embolic material was prepared by dissolving a polymeric material, ethylene-vinyl alcohol copolymer (20 wt%) (Sigma-Aldrich 414093, CAS 25067-34-9, 32% ethylene), and an absorbable developer, 2,3,5-triiodobenzyl alcohol-polylactide-ethylene oxide iodine-containing oligomer (40 wt%) (2880 g / mol, iodine content 264 mg / g), in dimethyl sulfoxide.

[0033] Example 3 Preparation of iodine-containing oligomer developer: Iopromide (CAS: 73334-07-3) was used as an initiator. Iopromide monomer (CAS: 502-44-3) was mixed with iopromide at a molar ratio of 10-30:1 and added to a round-bottom jar. After vacuum degassing, 0.2% (by weight) of tin ethylhexanoate catalyst was added. The mixture was stirred at 130°C for 8 hours. After cooling to room temperature, the solid polymer was dissolved in dichloromethane and then precipitated in cold methanol to obtain the iopromide-polycaprolactone oligomer (see developer structure). Figure 3 The yield of the synthetic route is 94%-97%, the molecular weight of the iodine-containing oligomer is 1931-4211 g / mol, and the iodine content of the oligomer molecules is 90-197 mg / g. The relationship between the molar ratio of caprolactone to iopromide, the molecular weight of the iodine-containing oligomer, and the iodine content is shown in Table 3.

[0034] Table 3

[0035] Preparation of liquid embolization materials: A liquid embolic material was prepared by dissolving a polymeric material, ethylene-vinyl alcohol copolymer (15 wt%) (Sigma-Aldrich 414093, CAS 25067-34-9, 32% ethylene), and an absorbable developer, iopromide-polycaprolactone oligomer (30 wt%) (3071 g / mol, iodine content 124 mg / g), together in dimethyl sulfoxide.

[0036] Example 4 Preparation of iodine-containing oligomer developer: Polyethylene glycol (CAS: 25322-68-3), 2,3,5-triiodobenzoic acid (CAS: 88-82-4), and 4-dimethylaminopyridine (CAS: 1122-58-3) with a molecular weight of 1000-4000 were mixed in a molar ratio of 1:3:0.1 and added together with dimethyl sulfoxide into a round-bottom jar (total concentration 0.2-0.3 g / mL). After vacuum degassing, an equimolar amount of catalyst N,N'-diisopropylcarbodiimide was added, and the mixture was stirred at room temperature for 24 hours. The mixture was then precipitated three times in cold isopropanol to obtain 2,3,5-triiodobenzoic acid-polyethylene glycol ester (developer structure see...). Figure 4 The yield was 80-90%, and the molecular weight of the iodine-containing oligomer prepared by the route was 2000-5000 g / mol, with an iodine content of 153-388 mg / g. The relationship between the molecular weight of the developer, PEG, the molecular weight of the iodine-containing oligomer, and the iodine content is shown in Table 4.

[0037] Table 4

[0038] Preparation of liquid embolization materials: The polymeric material ethylene-vinyl alcohol copolymer (15 wt%) (Sigma-Aldrich 414093, CAS 25067-34-9, 32% ethylene) and the absorbable developer 2,3,5-triiodobenzoic acid-polyethylene glycol ester (30 wt%) (4-1, 4-2, 4-3) were dissolved together in dimethyl sulfoxide to prepare the liquid embolization material (4-1, 4-2, 4-3).

[0039] Example 5 The iodine-containing oligomer developer prepared in Example 1 was used, 2,3,5-triiodobenzyl alcohol-polylactide oligomer (3380 g / mol, iodine content 113 mg / g).

[0040] Preparation of liquid embolization materials: A liquid embolic material was prepared by dissolving a polylactide-caprolactone copolymer (15 wt%) (Sigma-Aldrich 457639, 40% lactide, 60% caprolactone) and an absorbable developer 2,3,5-triiodobenzyl alcohol-polylactide oligomer (30 wt%) (3380 g / mol, iodine content 113 mg / g) together in dimethyl sulfoxide.

[0041] Example 6 The iodine-containing oligomer developer prepared in the same way as in Example 1 was used, 2,3,5-triiodobenzyl alcohol-polylactide oligomer (4820 g / mol, iodine content 79 mg / g).

[0042] Preparation of liquid embolization materials: A liquid embolic material was prepared by dissolving poly(2-hydroxyethyl methacrylate-siloxane acrylate) copolymer (2-hydroxyethyl methacrylate to siloxane acrylate molar ratio of 9:1) (10 wt%) and absorbable developer 2,3,5-triiodobenzyl alcohol-polylactide oligomer (40 wt%) (4820 g / mol, iodine content 79 mg / g) together in dimethyl sulfoxide.

[0043] Experimental Example 1 The viscosity, precipitation effect, and non-transmission linearity of the liquid embolizing agents prepared in Examples 1-6 were tested by in vitro simulation experiments.

[0044] Viscosity test: The kinematic viscosity of the obtained liquid embolization material was measured using a rheometer at 37°C; Precipitation effect test: Using a 0.5ml microsyringe, draw 0.5ml of the above embolic agent solution and inject it into phosphate-buffered saline (PBS) at 37 degrees Celsius, and observe the state of the embolic agent after injection into the saline.

[0045] Transmission linearity: The above embolizing agent solution was taken, and the mixed solutions of iodine-containing initiator, ethylene-vinyl alcohol copolymer and DMSO corresponding to the above examples were taken as controls. They were incubated in PBS solution at 37 degrees Celsius for 0 days, 15 days and 30 days. The transmission linearity of the samples was observed at these time points using a conventional X-ray machine.

[0046] The test results are shown in Table 5.

[0047] Table 5 Performance Test Results

[0048] As shown in Table 1, the kinematic viscosity of the liquid embolic material containing absorbable developer provided by the present invention is in the range of 20-40 cSt. When injected into a phosphate buffer solution at 37°C, a precipitate immediately forms, and the precipitate is in clumps with tight internal aggregation. This indicates that the liquid embolic material containing absorbable developer provided by the present invention can rapidly solidify to form an embolus in a short time. Furthermore, the nontransmittance of the absorbable developer provided by the present invention decreases linearly to below 30% after 30 days, indicating that the absorbable developer can effectively develop and gradually degrade and precipitate.

[0049] Experimental Example 2 Molecular structure characterization: The molecular structure was determined by ¹H-NMR using the absorbable developer prepared in Example 4-1, namely 2,3,5-triiodobenzoic acid-polyethylene glycol ester, indicating that the iodine-containing oligomer was successfully prepared. The ¹H NMR spectrum is shown below. Figure 5 .

[0050] Degradability and developability tests: The degradation performance of the liquid embolic material prepared in Example 4-1 was characterized by in vitro simulated degradation tests. The sample solution was extruded into a phosphate buffer solution to precipitate, sealed, and degraded in a shaker at 37°C for 3, 7, 14, and 28 days, respectively. The residual solid was then removed, rinsed with purified water, dried, and dissolved in dimethyl sulfoxide at a concentration of 60 mg / mL. The color intensity was compared by taking photographs. The test results are shown below. Figure 6 .Depend on Figure 6 It can be seen that the longer the degradation time, the lighter the solution color, indicating a lower residual amount of the iodine-containing oligomer. The imaging effects of materials with different degradation times under conventional X-rays are shown in the figure. Figure 7 .Depend on Figure 7 It can be seen that although the color of the solution lightens after 28 days of degradation, the material still has the ability to develop.

[0051] Embolization and Imaging Effects: The vascular embolization and imaging effects of the liquid embolization material prepared in Example 4-1 were determined through in vivo animal experiments. A 0.57 mm vascular microcatheter was advanced into the right auricular artery of a New Zealand rabbit. The catheter was first flushed with contrast agent for positioning, then flushed with dimethyl sulfoxide, and then 1 ml of the above-mentioned embolization material was injected into the right auricular artery. The imaging effect was examined under fluoroscopy at 0, 10, and 30 days after injection. The results are as follows: Figure 8 , Figure 9 and Figure 10 As shown. By Figure 8 As can be seen, after the liquid embolization material is injected, the blood vessels are visible under the fluoroscopy, indicating a significant embolization effect. The arrow points to the catheter visualization point. Figure 9 It was observed that, 10 days after the injection of the liquid embolization material, trace amounts of contrast material were still visible in the right auricular artery of the New Zealand rabbit. Figure 10 It can be seen that on the 30th day after the injection of the liquid embolization material, there was no obvious contrast in the right ear artery of the New Zealand rabbit, which indicates that the iodine-containing oligomer contrast agent material was gradually absorbed in the New Zealand rabbit.

[0052] The above description is only a preferred embodiment of the present invention and is 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 within the protection scope of the present invention.

Claims

1. A liquid embolic material containing an absorbable developer, characterized in that, It includes a polymer material, an absorbable developer, and dimethyl sulfoxide; the absorbable developer is an iodine-containing oligomer.

2. The liquid embolic material containing absorbable developer according to claim 1, characterized in that, The iodine-containing oligomers are prepared by ring-opening polymerization of iodophenyl compounds and ester cyclic monomers or ether cyclic monomers in the presence of a catalyst.

3. The liquid embolization material containing absorbable developer according to claim 2, characterized in that, The iodophenyl group compounds are one of iohexol, iopromide, 2,3,5-triiodobenzoic acid, 2,3,5-triiodophenylmethyl alcohol, iodalalic acid, iodixanol, iopamidol, and 4,4-bis(4-hydroxy-3,5-diiodophenyl)valerate.

4. The liquid embolic material containing absorbable developer according to claim 2, characterized in that, The ester cyclic monomers are one or more of glycolide, lactide, caprolactone, β-propiolactone, and p-dioxanone; the ether cyclic monomers are ethylene oxide.

5. The liquid embolization material containing absorbable developer according to claim 2, characterized in that, The catalyst is tin ethylhexanoate or N,N'-diisopropylcarbodiimide.

6. The liquid embolization material containing absorbable developer according to claim 1, characterized in that, The method for preparing the absorbable developer is as follows: using an iodophenyl group compound as an initiator, mixing it with an ester cyclic monomer or an ether cyclic monomer, degassing under vacuum, adding a catalyst, adjusting to the reaction temperature to carry out the reaction, precipitating in a cold solvent after the reaction is completed, filtering, and obtaining the absorbable developer.

7. The liquid embolic material containing absorbable developer according to claim 6, characterized in that, The preparation method of the absorbable developer also includes carboxylation modification, specifically: dissolving the absorbable developer and succinic anhydride in anhydrous dichloromethane, adding 4-dimethylaminopyridine at 0°C, reacting for 30 min, stirring at room temperature for 8-10 h, adding hydrochloric acid solution, and precipitating in cold methanol to obtain an intermediate; dissolving the intermediate, polyethylene glycol, and dimethylaminobenzoic acid in anhydrous dichloromethane, slowly adding N,N'-diisopropylcarbodiimide at 0°C, stirring at room temperature for 8-10 h, and precipitating in cold methanol to obtain the carboxylated modified absorbable developer.

8. The liquid embolization material containing absorbable developer according to claim 1, characterized in that, The polymer material is one of the following: ethylene-vinyl alcohol copolymer, polylactide, polyglycolic acid, polycaprolactone, polylactide-caprolactone copolymer, polydioxanone, and poly(2-hydroxyethyl methacrylate-siloxane acrylate) copolymer.

9. The liquid embolic material containing absorbable developer according to claim 1, characterized in that, The polymer material comprises 10-20% by mass, the absorbable developer comprises 10-45% by mass, and the dimethyl sulfoxide comprises 35-80% by mass.

10. The method for preparing the liquid embolic material containing absorbable developer according to any one of claims 1-9, characterized in that, Specifically, the polymer material and absorbable developer are added to dimethyl sulfoxide and stirred until completely dissolved to obtain a liquid embolic material containing absorbable developer.

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