CN118831199A - Sodium alginate embolic particles and preparation method and application thereof - Google Patents

Abstract

The application relates to the technical field of biomedicine, and particularly discloses sodium alginate embolic particles, a preparation method and application thereof. The application discloses a preparation method of sodium alginate embolic particles, which comprises the following steps: dissolving, primary freeze-drying, soaking, crosslinking, secondary freeze-drying, crushing, screening and sterilizing; the dissolution is as follows: preparing 1.7-2.3 wt% sodium alginate aqueous solution, adding a freeze-drying protective agent, stirring at 55-65 ℃, and cooling to 0-5 ℃; the infiltration is as follows: soaking the sodium alginate sponge obtained by primary freeze-drying in sodium alginate aqueous solution with the mass concentration of 0.1-0.8wt% to be saturated, so as to obtain a sodium alginate soaked body; the crosslinking is as follows: and soaking the sodium alginate infiltration body in a crosslinking solution for crosslinking reaction. By utilizing the technical scheme provided by the application, the sodium alginate embolic particles with high porosity, uniform particle size, small average pore diameter, proper water absorption, excellent suspension performance and excellent catheter passing performance can be obtained.

Description

Sodium alginate embolic particles and preparation method and application thereof

Technical Field

The present application relates to the technical field of biomedicine, and in particular to a sodium alginate embolic particle and a preparation method and application thereof.

Background Art

At present, hepatocellular carcinoma is one of the more common malignant tumors in stem cells, and cases of this tumor account for about 6% of the world's diagnosed cancer cases. The common treatment for tumors is surgical resection, but for patients with mid-to-late stage tumors, interventional therapy such as transcatheter arterial chemoembolization (TACE) is a more ideal treatment option. In this method, the embolic microspheres injected into the tumor tissue by the catheter not only block the nutrient supply to the tumor tissue but also release anti-tumor drugs. As the concentration of anti-cancer drugs in the tumor tissue increases, it inhibits the lesion site, thereby achieving the effect of treating the tumor.

Modified sodium alginate (SA), also known as algin and alginic acid, is a natural biological macromolecule sodium salt extracted from natural brown algae. It is widely used in food, medicine and other industries because of its non-toxicity, good biocompatibility and wide sources. Especially in the field of biopharmaceutical materials, it has attracted much attention as a drug carrier. There have been some reports on the preparation of embolic agents using sodium alginate as a raw material. Most of them are calcium alginate solids formed by cross-linking sodium alginate with divalent metal ions. The microstructure of this solid is mostly flaky and solid, with low specific surface area, irregular size after water absorption and swelling, and easy to block the tube.

Summary of the invention

In order to solve the above technical problems, the present application provides a sodium alginate embolic particle and a preparation method and application thereof.

In a first aspect, the present application provides a method for preparing sodium alginate embolic particles, which specifically comprises the following steps in sequence:

Dissolving, primary freeze-drying, infiltration, cross-linking, secondary freeze-drying, crushing and screening, and sterilization;

The specific steps of dissolving are: using sodium alginate powder as a raw material, preparing a sodium alginate aqueous solution with a mass concentration of 1.7-2.3wt%, adding tert-butyl alcohol freeze-drying protective agent, stirring at 55-65° C. for 50-70 minutes, and cooling to 0-5° C. while maintaining the stirring state for standby use; the amount of the freeze-drying protective agent used is 8-18 times the weight of the sodium alginate raw material;

The specific steps of the infiltration are: infiltrating the sodium alginate sponge obtained by primary freeze-drying in a sodium alginate aqueous solution with a mass concentration of 0.1 to 0.8 wt % until the sponge reaches a saturated state to obtain a sodium alginate infiltrated body;

The specific steps of cross-linking are: immersing the sodium alginate impregnated body in a cross-linking solution and subjecting the cross-linking reaction to 2 to 6 hours; the cross-linking solution comprises the following components in parts by weight: 40 to 50 parts of anhydrous ethanol, 1 to 3 parts of calcium chloride, and 48 to 58 parts of water.

The present application prepares a sodium alginate aqueous solution of a specific concentration, adds tert-butyl alcohol freeze-drying protective agent and performs primary freeze-drying. The freeze-dried sponge is infiltrated with a sodium alginate aqueous solution of a lower concentration, and then cross-linked, freeze-dried for a second time, crushed and sieved, and sterilized. The obtained sodium alginate embolic particles have a uniform, flat, microcrystalline appearance and morphology, which can effectively prevent the sponge from collapsing, reduce the degree of sponge shrinkage, and keep the sponge in a fluffy microstructure. The embolic particles have high porosity, low average pore size, small swelling degree, and appropriate water absorption. The sodium alginate embolic particles prepared in the present application have excellent suspension performance and catheter passability, which is conducive to the application of the embolic particles.

Aiming at the shortcomings of the prior art embolic agents made of sodium alginate as raw material, which are mostly flaky and solid in microstructure, low in specific surface area, irregular in size after swelling due to water absorption, and easy to block the tube, improvements are made to prepare an embolic agent with high porosity and fluffy structure.

The present application selects tert-butyl alcohol with moderate solubility and volatility as a lyoprotectant to ensure that it can be evenly dispersed in sodium alginate during the preparation process and can be easily removed in subsequent processing to leave the desired pore structure; such a lyoprotectant can form sufficient pores while maintaining a good appearance and morphology.

Preferably, in the specific step of dissolving, the mass concentration of the sodium alginate aqueous solution is 1.9-2.1 wt %.

Preferably, in the specific step of infiltration: the mass concentration of the sodium alginate aqueous solution is 0.2-0.7 wt %

Furthermore, in the specific step of infiltrating: the mass concentration of the sodium alginate aqueous solution is 0.3-0.6wt%.

Through experimental analysis, it can be known that the present application selects the sodium alginate aqueous solution of the above concentration as the infiltration solution to infiltrate the sodium alginate sponge obtained by primary freeze-drying, which can effectively improve the performance of the sodium alginate embolic particles.

Preferably, the cross-linking liquid comprises the following components in parts by weight: 40-50 parts of anhydrous ethanol, 1-3 parts of calcium chloride, and 48-58 parts of water.

Preferably, the cross-linking solution comprises the following components in parts by weight: 40-50 parts of anhydrous ethanol, 1-3 parts of calcium chloride, 2-8 parts of glycerol, 0.3-0.9 parts of lysine, and 48-58 parts of water.

Furthermore, the cross-linking solution comprises the following components in parts by weight: 40-50 parts of anhydrous ethanol, 1-3 parts of calcium chloride, 4-6 parts of glycerol, 0.5-0.7 parts of lysine, and 48-58 parts of water.

Through experimental analysis, it can be known that the present application selects the above components to mix and form a cross-linking liquid, and controls the weight of each component, so that the performance of the sodium alginate embolic particles is further improved.

Preferably, the specific steps of the primary freeze-drying are: cooling from 0 to 5°C to -23 to -28°C at a cooling rate of 0.2 to 1.5°C/min for pre-freezing for 2 to 4 hours, and then freeze-drying at -55 to -65°C for 24 to 60 hours.

Preferably, the specific steps of the secondary freeze-drying are: cooling from 0 to 5°C to -23 to -28°C at a cooling rate of 2-5.5°C/min for pre-freezing for 2 to 4 hours, and then freeze-drying at -55 to -65°C for 24 to 60 hours.

The inventors of the present application discovered that the cooling rate and freeze-drying time in the freezing step have a certain influence on the performance of the sodium alginate embolic particles. Through experimental research, it was found that controlling the cooling rate and freeze-drying time within the above range can avoid the occurrence of adverse problems of the sodium alginate embolic agent and ensure the excellent performance of the sodium alginate embolic particles.

In a second aspect, the present application provides a sodium alginate embolic particle prepared by the above-mentioned method for preparing the sodium alginate embolic particle.

In a third aspect, the present application provides the use of the above-mentioned sodium alginate embolic particles in the preparation of embolic agents.

In summary, the technical solution of this application has the following effects:

The present application improves the porosity and pore size of sodium alginate during molding, forms serial micropores, and increases the specific surface area and fluffiness; the sodium alginate provided by the present application is dissolved, freeze-dried once, cross-linked, freeze-dried twice, crushed, sieved and sterilized to meet clinical needs.

The combination of freeze-drying and infiltration steps in the technical solution provided by the present application can increase the micropores of sodium alginate, so that its structural form is changed from a compact powder to a porous and fluffy state, thereby greatly increasing the specific surface area of sodium alginate and increasing its solubility in water. At the same time, the increase in micropores greatly reduces the hydration of particles and significantly improves the agglomeration phenomenon of sodium alginate during the dissolution process. At the same time, the freezing treatment of the present application converts the water in the solution into ice crystals, and the specific surface area and pores of the obtained sodium alginate ice balls are increased; and the obtained sodium alginate embolic particles have a uniform, flat, microcrystalline appearance and morphology, which can effectively prevent the collapse of the sponge, reduce the degree of sponge shrinkage, and keep the sponge in a fluffy microstructure, with excellent suspension performance and catheter passing performance, which is conducive to the application of embolic particles.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a morphological diagram of the appearance of the sodium alginate sponge obtained by freeze-drying once in Example 1.

FIG. 2 is a morphological diagram of the appearance of the sodium alginate sponge obtained by freeze-drying once in Comparative Example 6.

FIG3 is a morphological diagram of the appearance of the sodium alginate sponge obtained by secondary freeze-drying in Example 1.

FIG. 4 is a morphological diagram of the appearance of the sodium alginate sponge obtained by secondary freeze-drying in Comparative Example 2.

DETAILED DESCRIPTION

The source of sodium alginate was Xi'an Tianzheng Pharmaceutical Excipients Co., Ltd.; the remaining raw materials and reagents were commercially available.

The present application is further described in detail below in conjunction with examples, comparative examples and performance testing experiments. These examples should not be construed as limiting the scope of protection claimed in the present application.

Example

Example 1

Example 1 provides a sodium alginate embolic particle.

The preparation method of sodium alginate embolic particles in this embodiment is specifically as follows:

Dissolution: Dissolve 2g of sodium alginate powder in 98g of purified water using a stirring paddle at 1000r/min, prepare a sodium alginate aqueous solution with a mass concentration of 2wt%, add 20g of tert-butyl alcohol freeze-drying protective agent and keep the temperature at 60℃ and continue stirring for 60min, then cool down to 0-5℃ while keeping stirring for use.

Primary freeze-drying: The above solution was cooled from 0 to 5°C to -23 to -28°C at a cooling rate of 1°C/min for pre-freezing for 3 hours, and then transferred to a freeze dryer and freeze-dried at -60°C for 40 hours to obtain a sodium alginate sponge.

The specific steps of infiltration are: infiltrating the sodium alginate sponge obtained by primary freeze-drying in a sodium alginate aqueous solution with a mass concentration of 0.5wt% until the sponge body reaches a saturated state to obtain a sodium alginate infiltrated body.

Cross-linking: Soak the sodium alginate sponge obtained by freeze-drying once in a cross-linking solution and perform the cross-linking reaction for 4 hours; the preparation method of the cross-linking solution is as follows: take 45g of anhydrous ethanol, 2g of calcium chloride, 5g of glycerol, 0.6g of lysine, and 55g of water and mix them evenly.

Secondary freeze-drying: The cross-linked liquid was cooled to 0-5°C while stirring for standby use, then cooled from 0-5°C to -23-28°C at a cooling rate of 3.5°C/min for pre-freezing for 3h, and then transferred to a freeze dryer and freeze-dried at -60°C for 40h to obtain a sodium alginate sponge.

Crushing and screening; the sponge after secondary freeze-drying is crushed and crushed using a crusher with a screen; the crushed particles are screened using a 50-2000 micron sieve.

Packaging and sterilization: Weigh the sieved powder and pack it into vials (100 mg per vial), seal it and sterilize it by irradiation to obtain sodium alginate embolic particles.

Embodiment 2-7

Examples 2-7 each provide a sodium alginate embolic particle.

The difference between the above embodiment and embodiment 1 is that the mass concentration of the sodium alginate aqueous solution in the dissolving and infiltrating steps is as follows.

In Example 2: In the specific step of dissolving, the mass concentration of the sodium alginate aqueous solution is 1.7 wt %.

In Example 3: In the specific step of dissolving, the mass concentration of the sodium alginate aqueous solution is 2.3 wt %.

In Example 4: In the specific step of infiltration: the mass concentration of the sodium alginate aqueous solution is 0.1wt%.

In Example 5: In the specific step of infiltration: the mass concentration of the sodium alginate aqueous solution is 0.2wt%.

In Example 6: In the specific step of infiltration: the mass concentration of the sodium alginate aqueous solution is 0.7wt%.

In Example 7: In the specific step of infiltration: the mass concentration of the sodium alginate aqueous solution is 0.8wt%

The remaining steps of the preparation method of sodium alginate embolic particles in the above embodiment are the same as those in Example 1.

Embodiment 8-11

Examples 8-11 respectively provide a sodium alginate embolic particle.

The difference between the above embodiment and embodiment 1 is that the preparation method of the cross-linking liquid is specifically as follows.

In Example 8: 45 g of anhydrous ethanol, 2 g of calcium chloride and 55 g of water were uniformly mixed to obtain a cross-linking solution.

In Example 9: 45 g of anhydrous ethanol, 2 g of calcium chloride, 8 g of glycerol, 0.2 g of lysine and 55 g of water were uniformly mixed to obtain a cross-linking solution.

In Example 10: 45 g of anhydrous ethanol, 2 g of calcium chloride, 8 g of glycerol, 0.3 g of lysine and 55 g of water were uniformly mixed to obtain a cross-linking solution.

In Example 11: 45 g of anhydrous ethanol, 3 g of calcium chloride, 2 g of glycerol, 0.9 g of lysine and 55 g of water were uniformly mixed to obtain a cross-linking solution.

The remaining steps of the preparation method of sodium alginate embolic particles in the above embodiment are the same as those in Example 1.

Example 12

Example 12 provides a sodium alginate embolic particle.

The preparation method of sodium alginate embolic particles in this embodiment is specifically as follows:

Dissolution: Dissolve 2g of sodium alginate powder in 98g of purified water using a stirring paddle at 1000r/min, prepare a sodium alginate aqueous solution with a mass concentration of 2wt%, add 20g of tert-butyl alcohol freeze-drying protective agent and keep the temperature at 60℃ and continue stirring for 60min, then cool down to 0-5℃ while keeping stirring for use.

Primary freeze-drying: The above solution was cooled from 0 to 5°C to -23 to -28°C at a cooling rate of 5°C/min for pre-freezing for 3 hours, and then transferred to a freeze dryer and freeze-dried at -60°C for 40 hours to obtain a sodium alginate sponge.

The specific steps of infiltration are: infiltrating the sodium alginate sponge obtained by primary freeze-drying in a sodium alginate aqueous solution with a mass concentration of 0.5wt% until the sponge body reaches a saturated state to obtain a sodium alginate infiltrated body.

Cross-linking: Soak the sodium alginate sponge obtained by freeze-drying once in a cross-linking solution and perform the cross-linking reaction for 4 hours; the preparation method of the cross-linking solution is as follows: take 45g of anhydrous ethanol, 2g of calcium chloride, 5g of glycerol, 0.6g of lysine, and 55g of water and mix them evenly.

Secondary freeze-drying: The cross-linked liquid was cooled to 0-5°C while stirring for standby use, then cooled from 0-5°C to -23-28°C at a cooling rate of 1.5°C/min for pre-freezing for 3h, and then transferred to a freeze dryer and freeze-dried at -60°C for 40h to obtain a sodium alginate sponge.

Crushing and screening: The sponge after secondary freeze-drying is crushed and screened using a crusher with a screen; the crushed particles are screened using a 50-2000 micron sieve.

Packaging and sterilization: Weigh the sieved powder and pack it into vials (100 mg per vial), seal it and sterilize it by irradiation to obtain sodium alginate embolic particles.

Comparative Example

Comparative Example 1

This comparative example provides a sodium alginate embolic particle.

The preparation method of sodium alginate embolic particles in this comparative example is different from that in Example 1 in that there is no infiltration step.

The remaining steps of this comparative example are the same as those of Example 1.

Comparative Examples 2-6

Comparative Examples 2-6 each provide a sodium alginate embolic particle.

The differences between the preparation method of sodium alginate embolic particles in the above comparative example and that in Example 1 are specifically as follows.

In Comparative Example 2: In the specific step of dissolving, the mass concentration of the sodium alginate aqueous solution is 1.5 wt %.

In Comparative Example 3: In the specific step of dissolving, the mass concentration of the sodium alginate aqueous solution is 2.5 wt %.

In Comparative Example 4: In the specific step of infiltration: the mass concentration of the sodium alginate aqueous solution is 0.05wt%.

In Comparative Example 5: In the specific step of infiltration: the mass concentration of the sodium alginate aqueous solution is 1wt%.

In Comparative Example 6: In the specific steps of primary freeze-drying: the freeze-drying protective agent is glycerol.

Comparative Example 7

This comparative example provides a sodium alginate embolic particle.

The preparation method of sodium alginate embolic particles in this comparative example is specifically as follows:

Dissolution: Dissolve 2g of sodium alginate powder in 98g of purified water using a stirring paddle at 1000r/min, prepare a sodium alginate aqueous solution with a mass concentration of 2wt%, add 20g of tert-butyl alcohol freeze-drying protective agent and keep the temperature at 60℃ and continue stirring for 60min, then cool down to 0-5℃ while keeping stirring for use.

Cross-linking: add cross-linking liquid to the above solution and carry out cross-linking reaction for 4 hours; the preparation method of the cross-linking liquid is as follows: take 45g of anhydrous ethanol, 2g of calcium chloride, 5g of glycerol, 0.6g of lysine and 55g of water and mix them evenly.

Freeze-drying: pre-freeze the above solution at a cooling rate of 1°C/min from 0-5°C to -23-28°C for 3 h, and then transfer to a freeze dryer and freeze-dry at -60°C for 40 h to obtain a sodium alginate sponge.

Crushing and screening: The freeze-dried sponge is crushed and screened using a crusher with a screen;

The pulverized particles are sieved using a 50-2000 micron sieve.

Packaging and sterilization: Weigh the sieved powder and pack it into vials (100 mg per vial), seal it and sterilize it by irradiation to obtain sodium alginate embolic particles.

Performance testing

(1) Appearance and performance:

FIG1 is a morphological diagram of the appearance of the sodium alginate sponge obtained by one-time freeze-drying in Example 1; it can be seen from the figure that the sodium alginate sponge has good integrity.

FIG. 2 is a morphological diagram of the appearance of the sodium alginate sponge obtained by freeze-drying once in Comparative Example 6; it can be seen from the figure that the integrity of the sodium alginate sponge is poor.

FIG3 is a morphological diagram of the sodium alginate sponge obtained by secondary freeze-drying in Example 1; it can be seen from the figure that the sodium alginate sponge has good integrity, a uniform, flat, microcrystalline appearance, and can form a sponge with micropores.

FIG4 is a morphological diagram of the appearance of the sodium alginate sponge obtained by secondary freeze-drying in Comparative Example 2; the sodium alginate sponge failed to form micropores and was mostly in the form of flakes after being crushed, which made the catheter passability slightly poor.

(2) Average pore size: The pore size distribution of gelatin particles was determined by mercury intrusion porosimetry according to European Pharmacopoeia 2.9.32.

(3) Porosity detection method: The porosity of sodium alginate embolic particles was detected by mercury intrusion method.

(4) Water absorption ratio: Weigh 100 mg (M1) of sodium alginate embolic particles accurately, immerse them in a beaker filled with 20±2°C water, and stir until the particles are completely soaked and all air is expelled. After absorbing enough water, filter out the excess water in the beaker, weigh the embolic particles again after absorbing water, record it as M2, and calculate the water absorption ratio A, the calculation formula is: A = (M2-M1)/M1×100%. Test results: as shown in Table 1.

Table 1 Performance test results of sodium alginate embolic particles in Examples 1-12 and Comparative Examples 1-7

(5) Suspension: 100 mg of sodium alginate embolic particles were placed in the test solution consisting of water for injection, normal saline, a mixed solution of normal saline and iohexol contrast agent in a volume ratio of 1:5, or a mixed solution of normal saline and iohexol contrast agent in a volume ratio of 1:1. After mixing evenly and reaching a stable state, a 20 mL syringe was used for vertical tube timing to observe the suspension state of the microspheres (good, fair, or poor).

Test results: as shown in Table 2.

(6) Catheter passability: Connect the syringe containing the contrast agent-gelatin particle suspension in performance test method (4) to a 2.7F microcatheter using a 2 ml syringe at a pushing rate of 2 ml/min. Observe and record the state of the microspheres when they enter the microcatheter and when they exit the microcatheter and enter the centrifuge tube (dispersion, adhesion, clumping, wall adhesion, tube blockage).

Test results: as shown in Table 2.

Table 2 Performance test results of sodium alginate embolic particles in Examples 1-12 and Comparative Examples 1-7

Combined with the test results in Table 1-2, the present application uses sodium alginate powder as a raw material, prepares a sodium alginate aqueous solution of a specific concentration, adds a freeze-drying protective agent composed of tert-butyl alcohol, performs a primary freeze-drying, and then infiltrates with a lower concentration of sodium alginate aqueous solution, and then performs cross-linking and secondary freeze-drying. The obtained sodium alginate embolic particles have a uniform, flat, microcrystalline good appearance and morphology, which can effectively prevent the collapse of the sponge, reduce the degree of sponge shrinkage, and keep the sponge fluffy microstructure. The embolic particles have high porosity, low average pore size, small swelling degree, and suitable water absorption; and the sodium alginate embolic particles prepared in the present application have excellent suspension performance and catheter passability, which is conducive to the application of the embolic particles.

Although the present invention has been described in detail above with general descriptions and specific embodiments, it is obvious to those skilled in the art that some modifications or improvements may be made thereto based on the present invention. Therefore, these modifications or improvements made without departing from the spirit of the present invention all fall within the scope of protection claimed by the present invention.

Claims (10)

1. A method for preparing sodium alginate embolic particles, characterized in that it specifically comprises the following steps in sequence: Dissolving, primary freeze-drying, infiltration, cross-linking, secondary freeze-drying, crushing and screening, and sterilization; The specific steps of dissolving are: using sodium alginate powder as a raw material, preparing a sodium alginate aqueous solution with a mass concentration of 1.7-2.3wt%, adding tert-butyl alcohol freeze-drying protective agent, stirring at 55-65° C. for 50-70 minutes, and cooling to 0-5° C. while maintaining the stirring state for standby use; the amount of the freeze-drying protective agent used is 8-18 times the weight of the sodium alginate raw material; The specific step of the infiltration is: infiltrating the sodium alginate sponge obtained by primary freeze-drying in a sodium alginate aqueous solution with a mass concentration of 0.1-0.8wt% until the sponge reaches a saturated state to obtain a sodium alginate infiltrate; The specific steps of cross-linking are: immersing the sodium alginate impregnated body in a cross-linking solution, and performing a cross-linking reaction for 2 to 6 hours; the cross-linking solution comprises the following components in parts by weight: 40 to 50 parts of anhydrous ethanol, 1 to 6 parts of calcium salt, and 48 to 58 parts of water. 2. The method for preparing sodium alginate embolic particles according to claim 1, characterized in that, in the specific step of dissolving, the mass concentration of the sodium alginate aqueous solution is 1.9-2.1wt%. 3. The method for preparing sodium alginate embolic particles according to claim 1, characterized in that in the specific step of infiltrating: the mass concentration of the sodium alginate aqueous solution is 0.2-0.7wt%. 4. The method for preparing sodium alginate embolic particles according to claim 3, characterized in that in the specific step of infiltrating: the mass concentration of the sodium alginate aqueous solution is 0.3-0.6wt%. 5. The method for preparing sodium alginate embolic particles according to claim 1, characterized in that the cross-linking solution comprises the following components in parts by weight: 40-50 parts of anhydrous ethanol, 1-3 parts of calcium salt, and 48-58 parts of water. 6. The method for preparing sodium alginate embolic particles according to claim 5, characterized in that the cross-linking solution comprises the following components in parts by weight: 40-50 parts of anhydrous ethanol, 1-3 parts of calcium chloride, 2-8 parts of glycerol, 0.3-0.9 parts of lysine, and 48-58 parts of water. 7. The method for preparing sodium alginate embolic particles according to claim 1, characterized in that the specific steps of the primary freeze-drying are: cooling from 0~5°C to -23~-28°C at a cooling rate of 0.2-1.5°C/min for pre-freezing for 2~4h, and then freeze-drying at -55~-65°C for 24-60h. 8. The method for preparing sodium alginate embolic particles according to claim 1, characterized in that the specific steps of the secondary freeze-drying are: cooling from 0~5°C to -23~-28°C at a cooling rate of 2-5.5°C/min for pre-freezing for 2~4h, and then freeze-drying at -55~-65°C for 24-60h. 9. A sodium alginate embolic particle, characterized in that it is prepared by the preparation method of the sodium alginate embolic particle according to any one of claims 1 to 8; the sodium alginate embolic particle has an average pore size of 10-200 um, a porosity of 75-95%, and a water absorption rate of 500%-1500%. 10. Use of the sodium alginate embolic particles according to claim 9 in preparing embolic agents.