Embolism microsphere and preparation method thereof
Through cross-linking and polymerization, embolizing microspheres with network structure are formed, and the polyhydroxy functional groups of polyglycerol and its derivatives form hydrogen bonds with the drug, solving the problems of low drug loading and unstable release rate, and achieving efficient drug loading and sustained release.
Patent Information
- Application Number
- CN202411885424.0
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2024-12-18
- Publication Date
- 2025-03-28
AI Technical Summary
The existing drug-loading embolization microspheres have low drug loading and unstable drug release rate, resulting in insufficient or excessive drug concentration, affecting the efficacy.
Polyglycerol and its derivatives with only polyhydroxy functional groups are cross-linked and polymerized with cross-linking agents with epoxy groups to form a network structure polymer, enhancing interaction with drugs, and achieving good drug-carrying and sustained release properties.
It has achieved high drug-loading performance and stable drug release, overcome the problem of poor drug-loading performance of existing microspheres, improve the efficacy and simplify the process.
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Figure CN119701058A_ABST
Abstract
Description
Technical Field
[0001] The present application relates to the technical field of embolic microspheres, and in particular to an embolic microsphere and a preparation method thereof. Background Art
[0002] Transarterial chemoembolization (TACE) is an interventional medical method specifically used to treat a variety of tumors. Since the late 1970s, TACE has become the standard treatment for patients with liver cancer who cannot be surgically removed. This technology mixes chemotherapy drugs with embolic agents and injects them directly into the blood supply artery of the tumor, which not only blocks the blood and oxygen supply of the tumor, but also forms a high-concentration drug environment in the local tumor, effectively inhibiting the growth and spread of the tumor.
[0003] Drug-Eluting Beads TACE (DEB-TACE) is a carrier for therapeutic embolization and drug delivery, combining the potential synergy between the drug activity mechanism and the local tissue reaction produced by TACE to enhance the therapeutic effect. The ideal situation of drugs delivered by microspheres is to load them into the microspheres at high concentrations, with sustainable or controllable drug release characteristics to improve the therapeutic effect. The drug loading of the microspheres and the controllability of the released drugs have an important influence on improving the therapeutic effect. However, the current drug-loaded embolic microspheres not only face the problem of low drug loading, resulting in too low drug concentration in the tumor microenvironment to achieve the effect of killing tumors. In addition, there is an unstable drug release rate, which causes the local concentration to be too high to produce toxic side effects or cannot act on tumor cells for a long time, thereby affecting the final therapeutic effect. It can be seen that embolic microspheres with good drug loading and release properties are an urgent clinical need.
[0004] The drug loading and release performance of microspheres is closely related to the network structure and groups of the microspheres. Currently, commercially available microspheres mainly rely on the electrostatic attraction between negative ions on the microspheres and some cationic drugs to achieve drug adsorption and release. This method is easily limited by the ionic strength of the microspheres, the type and number of functional groups, the cross-linking degree of the microspheres and the drug structure, and has weak universality for the loading and release control of different drugs. Therefore, it is generally believed that microspheres prepared with monomers with only polyhydroxy functional groups have poor drug loading and release performance or cannot load drugs, and the monomers need to be ionized to improve their drug loading and release performance. However, material modification not only increases the complexity of the process, but also increases the cost. Summary of the invention
[0005] The present application provides an embolic microsphere and a preparation method thereof, so as to overcome the technical prejudice that microspheres prepared from monomers with only polyhydroxyl functional groups have poor drug loading and release performance or are unable to load drugs.
[0006] In a first aspect, an embodiment of the present application provides an embolic microsphere, wherein the embolic microsphere comprises a network structure polymer formed by cross-linking polymerization of a raw material and a cross-linking agent, wherein the raw material comprises polyglycerol and its derivatives, and the cross-linking agent comprises a compound with an epoxy group.
[0007] In the technical scheme of the embodiment of the present application, the embolic microspheres are made of polyglycerol and its derivatives with only polyhydroxyl functional groups as raw materials. Polyglycerol and its derivatives have a high OC ratio, and the OC number ratio is as high as 1:1.5. They have a high density of hydroxyl groups, and adjacent hydroxyl functional groups can work synergistically to form a chain or mesh hydrogen bond network to enhance the interaction with drug molecules. Therefore, there is no need to ionize and modify the monomers to prepare embolic microspheres with good drug loading performance. At the same time, the hydroxyl groups in polyglycerol and its derivatives can form hydrogen bonds with drug molecules, and this interaction helps the adsorption and sustained release of drug molecules in the hydrogel network. In addition, polyglycerol and its derivatives can form a dense network structure after polymerization, which has good loading and release performance potential for drug molecules. It overcomes the technical prejudice that microspheres prepared from monomers with only polyhydroxyl functional groups have poor drug loading and release performance or cannot load drugs.
[0008] In a second aspect, the present invention provides a method for preparing embolic microspheres, the method comprising:
[0009] Mixing raw materials and a cross-linking agent, and pre-cross-linking to obtain an aqueous phase, wherein the raw materials include polyglycerol and its derivatives, and the cross-linking agent includes a compound with an epoxy group;
[0010] The water phase and the oil phase are mixed to form an inverse suspension polymerization system, and a polymerization reaction is carried out to obtain embolic microspheres.
[0011] In the technical solution of the embodiment of the present application, the method uses polyglycerol and its derivatives with only polyhydroxyl functional groups as raw materials. Polyglycerol and its derivatives have a high OC ratio and a high density of hydroxyl groups. Adjacent hydroxyl functional groups can work synergistically to form a chain or mesh hydrogen bond network to enhance the interaction with drug molecules. Therefore, there is no need to ionize the monomers to prepare embolic microspheres with good drug loading performance. At the same time, the hydroxyl groups in the polyhydroxy compounds can form hydrogen bonds with drug molecules. This interaction helps the adsorption and sustained release of drug molecules in the hydrogel network. In addition, polyglycerol and its derivatives can form a dense network structure after polymerization, which has good loading and release performance potential for drug molecules. It overcomes the technical prejudice that microspheres prepared from monomers with only polyhydroxyl functional groups have poor drug loading and release performance or cannot load drugs. BRIEF DESCRIPTION OF THE DRAWINGS
[0012] The accompanying drawings, which are incorporated in and constitute a part of this specification, illustrate embodiments consistent with the present application and, together with the description, serve to explain the principles of the present application.
[0013] In order to more clearly illustrate the embodiments of the present application or the technical solutions in the prior art, the drawings required for use in the embodiments or the description of the prior art will be briefly introduced below. Obviously, for ordinary technicians in this field, other drawings can be obtained based on these drawings without paying any creative labor.
[0014] Figure 1 A flowchart of a method provided in an embodiment of the present application. DETAILED DESCRIPTION
[0015] In order to make the purpose, technical solution and advantages of the embodiments of the present application clearer, the technical solution in the embodiments of the present application will be clearly and completely described below in conjunction with the drawings in the embodiments of the present application. Obviously, the described embodiments are part of the embodiments of the present application, not all of the embodiments. Based on the embodiments in the present application, all other embodiments obtained by ordinary technicians in this field without making creative work are within the scope of protection of this application.
[0016] Unless otherwise specified, various raw materials, reagents, instruments and equipment used in this application can be purchased from the market or prepared by existing methods.
[0017] Various embodiments of the present application may be presented in the form of a range; it should be understood that the description in the form of a range is only for convenience and brevity, and should not be understood as a rigid limitation on the scope of the present application; therefore, it should be considered that the range description has specifically disclosed all possible sub-ranges and single numerical values within the range. In the present application, unless otherwise specified, the directional words used, such as "upper" and "lower", are specifically the directions of the drawings in the accompanying drawings. In addition, in the description of the specification of the present application, the terms "include", "comprise", etc. mean "including but not limited to". In this article, "and / or" describes the association relationship of associated objects, indicating that three relationships may exist. For example, A and / or B can represent: the existence of A alone, the existence of A and B at the same time, and the existence of B alone.
[0018] The inventor intends to provide an embolic microsphere and a preparation method thereof, wherein polyglycerol and its derivatives having only polyhydroxy functional groups are used as raw materials and polymerized with a crosslinking agent having epoxy groups to form the embolic microsphere, and the embolic microsphere has good drug loading and releasing performance and physical properties.
[0019] The embodiment of the present application provides an embolic microsphere, which includes a network structure polymer formed by cross-linking polymerization of a raw material and a cross-linking agent, wherein the raw material includes polyglycerol and its derivatives, and the cross-linking agent includes a compound with an epoxy group.
[0020] The embolic microspheres are made of polyglycerol and its derivatives with only polyhydroxyl functional groups. Polyglycerol and its derivatives have a high OC ratio, and the OC content ratio is 1:1.5. They have a high density of hydroxyl groups. Adjacent hydroxyl functional groups can work synergistically to form a chain or mesh hydrogen bond network to enhance the interaction with drug molecules. Therefore, it is not necessary to ionize and modify the monomers to prepare embolic microspheres with good drug loading performance. At the same time, the hydroxyl groups in polyglycerol and its derivatives can form hydrogen bonds with drug molecules. This interaction helps the adsorption and sustained release of drug molecules in the hydrogel network. In addition, polyglycerol and its derivatives can form a dense network structure after polymerization, which has good loading and release performance potential for drug molecules. It overcomes the technical prejudice that microspheres prepared from monomers with only polyhydroxyl functional groups have poor drug loading and release performance or cannot load drugs.
[0021] In some embodiments, the raw material includes decaglycerol; the compound with an epoxy group is a glycidyl ether compound whose terminal group includes a propylene oxide group; illustratively, the compound with an epoxy group can be selected from at least one of polyethylene glycol diglycidyl ether, glycerol triglycidyl ether or pentaerythritol glycidyl ether.
[0022] In some embodiments, the composition of the embolic microspheres includes the following compounds of Formula I and / or Formula II:
[0023]
[0024]
[0025] Wherein, m and n are independently selected from any positive integer.
[0026] The material of the embolic microspheres has a high density of hydroxyl groups, and adjacent hydroxyl functional groups can work together to form a chain or mesh hydrogen bond network to enhance the interaction with drug molecules. Therefore, it is not necessary to ionize the monomers to prepare embolic microspheres with good drug loading performance. At the same time, the hydroxyl groups in the material of the embolic microspheres can form hydrogen bonds with drug molecules, and this interaction helps the adsorption and sustained release of drug molecules in the hydrogel network. In addition, the material of the embolic microspheres has a dense network structure, which has good loading and release performance potential for drug molecules.
[0027] Figure 1 A flowchart of the method provided in the embodiment of the present application, such as Figure 1As shown, the present application embodiment provides a method for preparing embolic microspheres, characterized in that the method comprises:
[0028] S1. Adding a catalyst to water to prepare an alkaline aqueous solution under stirring conditions, adding a raw material and a cross-linking agent to mix, and pre-cross-linking to obtain an aqueous phase, wherein the raw material includes polyglycerol and its derivatives, and the cross-linking agent includes a compound with an epoxy group;
[0029] In some embodiments, the catalyst may be a strong base, specifically at least one selected from potassium hydroxide and sodium hydroxide.
[0030] In some embodiments, the mass percentage of the catalyst in the aqueous phase is 5% to 20%. Exemplarily, the mass percentage of the catalyst can be 5%, 7%, 9%, 11%, 13%, 15%, 17%, 19%, 20%, etc., and can also be any value within the range of 5% to 20%.
[0031] In some embodiments, the raw material includes decaglycerol. In the aqueous phase, the mass proportion of the raw material is 10% to 40%. Exemplarily, the mass proportion of the raw material can be 10%, 15%, 20%, 25%, 30%, 35%, 40%, etc., and it can also be any value within the range of 10% to 40%.
[0032] In some embodiments, the compound with epoxy group is a glycidyl ether compound whose terminal group includes propylene oxide group; exemplary, the compound with epoxy group can be selected from at least one of polyethylene glycol diglycidyl ether, glycerol triglycidyl ether or pentaerythritol glycidyl ether. Further, the molar percentage of raw material and cross-linking agent is 10% to 50%. Exemplarily, the molar percentage of raw material and cross-linking agent can be 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, etc., which can also be any value within the range of 10% to 50%.
[0033] Specifically, under stirring conditions, the catalyst is first added to water to prepare a catalyst solution, the raw materials are added, and the mixture is fully mixed, and then the cross-linking agent is added dropwise and mixed to obtain a uniform aqueous phase. The stirring time of the aqueous phase is 1 to 240 minutes.
[0034] S2. The aqueous phase and the oil phase are mixed to form an inverse suspension polymerization system, and a polymerization reaction is performed to obtain embolic microspheres.
[0035] In some embodiments, the oil phase includes an oil-soluble dispersant and an oil-phase solvent; illustratively, the oil-soluble dispersant can be selected from at least one of cellulose acetate butyrate, Tween series compounds, Span series compounds, propylene glycol fatty acid esters, polyether alcohols, OP series compounds, or AEO series compounds. The Tween series compounds can be selected from: Tween 20, etc. The Span series compounds can be selected from Span 80, etc. Exemplarily, the oil-phase solvent can be selected from at least one of butyl acetate, petroleum ether, n-hexane, cyclohexane, or paraffin oil.
[0036] In some embodiments, in the oil phase, the mass proportion of the oil-soluble dispersant is 0.5% to 8%. Exemplarily, the mass proportion of the oil-soluble dispersant can be 0.5%, 1%, 1.5%, 2%, 2.5%, 3%, 3.5%, 4%, 4.5%, 5%, 5.5%, 6%, 6.5%, 7%, 7.5%, 8%, etc., and it can also be any value within the range of 0.5% to 8%.
[0037] Exemplarily, the oil phase may be prepared by adding an oil-soluble dispersant to an oily solvent and stirring to dissolve the mixture to form a uniform oil phase.
[0038] In some embodiments, the polymerization temperature is 30-100°C; the polymerization time is 5-36h. Exemplarily, the polymerization temperature can be 30°C, 40°C, 50°C, 60°C, 70°C, 80°C, 90°C, 100°C, etc., and can also be any value within the range of 30-100°C.
[0039] Specifically, the process of forming the reverse suspension polymerization system and the polymerization reaction can be: slowly dropping the aqueous phase solution into the oil phase solution under stirring conditions at room temperature to form an oil-in-water reverse suspension polymerization system. After the dropping is completed, the reverse suspension polymerization system is heated to 40-100°C, and the stirring and heating state is maintained. The reaction time is 5-30 hours, and the stirring rate is 100-700rpm. Then, the stirring and heating are stopped, the layers are allowed to stand, the oil phase is separated, the microspheres are collected, and they are washed and sieved to obtain embolic microspheres.
[0040] The preparation method of the embolic microspheres is simple, and polyglycerol and its derivatives with only polyhydroxyl functional groups are used as raw materials. Polyglycerol and its derivatives have a high OC ratio and a high density of hydroxyl groups. Adjacent hydroxyl functional groups can work synergistically to form a chain or mesh hydrogen bond network to enhance the interaction with drug molecules. Therefore, it is not necessary to ionize and modify the monomers to prepare embolic microspheres with good drug loading performance. At the same time, the hydroxyl groups in the polyhydroxy compounds can form hydrogen bonds with drug molecules, and this interaction helps the adsorption and sustained release of drug molecules in the hydrogel network. In addition, polyglycerol and its derivatives can form a dense network structure after polymerization, which has good loading and release performance potential for drug molecules. It overcomes the technical prejudice that microspheres prepared from monomers with only polyhydroxyl functional groups have poor drug loading and release performance or cannot load drugs.
[0041] The present application will be further described below in conjunction with specific embodiments. It should be understood that these embodiments are intended only to illustrate the present application and are not intended to limit the scope of the present application. The experimental methods for which specific conditions are not specified in the following examples are usually measured according to national standards. If there is no corresponding national standard, then the conditions recommended by the manufacturer are followed.
[0042] Example 1
[0043] This embodiment provides an embolic microsphere, and the preparation process thereof is as follows:
[0044] (1) Preparation of aqueous solution and oil phase solution
[0045] Aqueous phase solution: Under stirring conditions, first prepare NaOH into an alkaline aqueous solution, then add decaglycerol, and then drop ethylene glycol diglycidyl ether and mix well to obtain a uniform aqueous phase solution;
[0046] The mass percentage of decaglycerol in the prepared aqueous phase solution is 16.3wt%, the molar ratio of decaglycerol to ethylene glycol diglycidyl ether is 20%, the mass percentage of NaOH solution is 14.3wt%, and the stirring time of the aqueous phase is 90min.
[0047] Oil phase solution: Cellulose acetate butyrate used as an oil-soluble dispersant is added into butyl acetate at a ratio of 6 wt%.
[0048] (2) Reverse suspension polymerization
[0049] Under stirring conditions at room temperature, the aqueous phase solution was slowly added dropwise to the oil phase solution to form an oil-in-water reverse suspension polymerization system. After the addition was completed, the reverse suspension polymerization system was heated to 85°C and kept stirred and heated at a stirring rate of 300 rpm. After reacting for 17 hours, stirring and heating were stopped.
[0050] (3) Purification and collection of embolic microspheres
[0051] After the reaction is completed, stirring and heating are stopped, the reaction is allowed to stand for stratification, the oil phase is separated, the microspheres are collected, and they are washed and sieved to obtain embolic microspheres.
[0052] The entire synthesis path of this embodiment is as follows:
[0053] Process 1:
[0054]
[0055] Process 2:
[0056]
[0057] Wherein, m and n are independently selected from any positive integer.
[0058] Example 2
[0059] This embodiment provides an embolic microsphere, and the preparation process thereof is as follows:
[0060] (1) Preparation of aqueous solution and oil phase solution
[0061] Aqueous phase solution: Under stirring conditions, first prepare NaOH into an alkaline aqueous solution, then add decaglycerol, and then dropwise add glycerol triglycidyl ether and mix well to obtain a uniform aqueous phase solution;
[0062] The mass percentage of decaglycerol in the prepared aqueous phase solution is 19.2wt%, the molar ratio of decaglycerol to glycerol triglycidyl ether is 20%, the mass percentage of NaOH solution is 16.5wt%, and the stirring time of the aqueous phase is 90min.
[0063] Oil phase solution: Cellulose acetate butyrate used as an oil-soluble dispersant is added into butyl acetate at a ratio of 6 wt%.
[0064] (2) Reverse suspension polymerization
[0065] Under stirring conditions at room temperature, the aqueous phase solution was slowly added dropwise to the oil phase solution to form an oil-in-water reverse suspension polymerization system. After the addition was completed, the reverse suspension polymerization system was heated to 85°C and kept stirred and heated at a stirring rate of 200 rpm. After reacting for 17 hours, stirring and heating were stopped.
[0066] (3) Purification and collection of embolic microspheres
[0067] After the reaction is completed, stirring and heating are stopped, the reaction is allowed to stand for stratification, the oil phase is separated, the microspheres are collected, and they are washed and sieved to obtain embolic microspheres.
[0068] The entire synthesis path of this embodiment is as follows:
[0069] Process 1:
[0070]
[0071] Process 2:
[0072]
[0073] Comparative Example 1
[0074] This comparative example provides an embolic microsphere, and its preparation process is as follows:
[0075] (1) Preparation of aqueous solution and oil phase solution
[0076] Aqueous phase solution: NaOH is added into water and mixed to obtain an alkaline aqueous solution; then, inositol and sodium 2-chloroethylsulfonate are sequentially added into the alkaline aqueous solution and reacted under heating and stirring conditions to obtain a modified solution, wherein the treatment temperature is 60° C. and the reaction time is 90 min; while maintaining the stirring and heating state, pentaerythritol glycidyl ether is added into the modified aqueous solution and mixed to obtain an aqueous phase solution, wherein the stirring and mixing time is 15 min.
[0077] Specifically, in the aqueous phase solution, the amount of inositol added is 10.1% of the mass of the aqueous phase solution, based on the molar amount of inositol added, the molar percentage of sodium 2-chloroethyl sulfonate is 200%, based on the molar amount of inositol added, the molar percentage of pentaerythritol glycidyl ether is 80%, and the amount of catalyst added is 20.2% of the mass of the aqueous phase solution.
[0078] Oil phase solution: Tween 20 and Span 80 used as oil-soluble dispersants are added to liquid paraffin in a mass ratio of 3:10, and stirred and mixed to obtain an oil phase solution, wherein the mass proportion of the oil-soluble dispersant in the oil phase solution is 5%.
[0079] (2) Reverse suspension polymerization
[0080] Under stirring conditions at room temperature, the aqueous phase solution is added dropwise to the oil phase solution to obtain an oil-in-water reverse suspension polymerization system. Then, while maintaining stirring, the oil-in-water reverse suspension polymerization system is sequentially subjected to heating reaction, purification and collection to obtain embolic microspheres. Wherein, while maintaining stirring and sequentially heating reaction of the oil-in-water reverse suspension polymerization system, the stirring speed is 300 rpm, the reaction temperature is 80°C, and the reaction time is 12 h.
[0081] (3) Purification and collection of embolic microspheres
[0082] After the reaction is completed, stirring and heating are stopped, the reaction is allowed to stand for stratification, the oil phase is separated, the microspheres are collected, and they are washed and sieved to obtain embolic microspheres.
[0083] Comparative Example 2
[0084] This comparative example is the same as comparative example 1 except that inositol is not ion-modified.
[0085] The drug loading performance of the embolic microspheres of each embodiment and comparative example was tested. The test process was as follows: 3 groups of 1 ml of the embolic microspheres prepared in each embodiment and comparative example were taken, and the surface moisture of the embolic microspheres was removed by filter paper. The embolic microspheres were transferred into a vial, and 2 mL of 20 mg / mL 5-fluorouracil solution and etoposide solution were added respectively, mixed and shaken, and the concentration of the solution was tested at 5 min, 30 min and 60 min respectively, and the drug loading rate of the embolic microspheres was calculated. The results are shown in the following table:
[0086]
[0087] From the results in the above table, it can be seen that the embolic microspheres prepared in Examples 1-2 all showed good drug loading performance, and Comparative Example 1 also had a certain drug loading capacity, but weaker than Examples 1-2; and Comparative Example 2 had almost no drug loading capacity.
[0088] It can be seen that the embolic microspheres prepared with unmodified decaglycerol in Examples 1 to 2 showed certain drug loading performance, while the embolic microspheres prepared with unmodified inositol in Comparative Example 2 had almost no drug loading performance, indicating that the interaction between the embolic microspheres and the drugs in the present application was relatively strong. The applicant speculates that the embolic microspheres synthesized with decaglycerol as raw material in the present application have higher drug loading performance due to their special network structure and rich polyhydroxyl groups, and the hydroxyl density per unit volume of the network structure of the embolic microspheres is higher, and the resulting interaction force is stronger.
[0089] The drug release performance of the embolic microspheres of each embodiment and comparative example was tested. The test process was as follows: the drug-loaded embolic microspheres were added to a dialysis bag, and then the dialyzed microspheres were placed in a beaker, and physiological saline (20 mL) was added to the beaker and sealed; samples were taken every 5 minutes, 30 minutes, and 60 minutes, and the concentration of the drug in the solution was measured, and the cumulative release amount of the drug-loaded embolic microspheres was calculated. The results are shown in the following table:
[0090]
[0091] From the results in the above table, it can be seen that the embolic microspheres prepared in the examples of the present application show better drug release performance for different drugs than the embolic microspheres prepared in comparative examples 1 to 2. The applicant speculates that the reason is that the embolic microspheres prepared in examples 1 to 2 have a high-density hydroxyl structure and have a strong interaction with the drug, so the drug release is slower. With a good drug release effect, the drug has a longer killing effect, which helps to improve the efficacy.
[0092] The above is only a specific implementation of the present application, so that those skilled in the art can understand or implement the present application. Various modifications to these embodiments will be apparent to those skilled in the art, and the general principles defined herein can be implemented in other embodiments without departing from the spirit or scope of the present application. Therefore, the present application will not be limited to the embodiments shown herein, but will conform to the widest range consistent with the principles and novel features applied for herein.
Claims
1. An embolic microsphere, characterized in that: The embolic microspheres include a network structure polymer formed by cross-linking polymerization of raw materials and a cross-linking agent, wherein the raw materials include polyglycerol and its derivatives, and the cross-linking agent includes a compound with an epoxy group.
2. The embolic microsphere according to claim 1, characterized in that: The raw material includes decaglycerol; and / or, The compound with epoxy group is a glycidyl ether compound whose terminal group includes propylene oxide group; and / or, The compound with epoxy group includes at least one of polyethylene glycol diglycidyl ether, glycerol triglycidyl ether or pentaerythritol glycidyl ether.
3. The embolic microsphere according to claim 1, characterized in that: The components of the embolic microspheres include the following compounds of Formula I and / or Formula II: Wherein, m and n are independently selected from any positive integer.
4. A method for preparing embolic microspheres, characterized in that: The method comprises: Adding a catalyst into water under stirring conditions to prepare an alkaline aqueous solution, adding a raw material and a cross-linking agent to mix, and performing pre-cross-linking to obtain an aqueous phase, wherein the raw material includes polyglycerol and its derivatives, and the cross-linking agent includes a compound with an epoxy group; The water phase and the oil phase are mixed to form an inverse suspension polymerization system, and a polymerization reaction is carried out to obtain embolic microspheres.
5. The method for preparing embolic microspheres according to claim 4, characterized in that: The catalyst comprises at least one of potassium hydroxide and sodium hydroxide; and / or, In the water phase, the mass proportion of the catalyst is 5% to 20%.
6. The method for preparing embolic microspheres according to claim 4, characterized in that: The raw material includes decaglycerol; and / or, In the aqueous phase, the mass proportion of the raw materials is 10% to 40%.
7. The method for preparing embolic microspheres according to claim 4, characterized in that: The compound with epoxy group is a glycidyl ether compound whose terminal group includes propylene oxide group; and / or The compound with epoxy group includes at least one of polyethylene glycol diglycidyl ether, glycerol triglycidyl ether or pentaerythritol glycidyl ether; and / or, The molar percentage of the raw material and the cross-linking agent is 10% to 50%.
8. The method for preparing embolic microspheres according to claim 4, characterized in that: The oil phase includes an oil-soluble dispersant and an oil phase solvent; Optionally, the oil-soluble dispersant includes at least one of cellulose acetate butyrate, Tween series compounds, Span series compounds, propylene glycol fatty acid esters, polyether alcohols, OP series compounds or AEO series compounds; Optionally, the oil phase solvent includes at least one of butyl acetate, petroleum ether, n-hexane, cyclohexane or paraffin oil; Optionally, in the oil phase, the mass proportion of the oil-soluble dispersant is 0.5% to 8%.
9. The method for preparing embolic microspheres according to claim 4, characterized in that: The polymerization temperature is 30-100°C; and / or The polymerization reaction time is 5 to 36 hours.
10. The method for preparing embolic microspheres according to claim 4, characterized in that: The method also includes loading of the drug; Optionally, the drug includes at least one of 5-fluorouracil or etoposide.