Gelatin embolization particles, methods of making and using the same

Abstract

The application relates to the technical field of biological medicines, and particularly discloses a gelatin embolization particle and a preparation method and application thereof. The preparation method of the gelatin embolization particle comprises the following steps: taking gelatin as raw material, and performing the following steps of dissolving, foaming, freeze-drying, heat crosslinking, crushing and screening, and sterilization; the foaming step is as follows: nitrogen is introduced into a gelatin aqueous solution with a concentration of 20-100 g / L under a liquid surface, foaming is performed at a rotating speed of 2500-3500 rpm, until no obvious liquid is present at the bottom of a container, and the foaming volume is 1-10 times the original liquid volume; the heat crosslinking step comprises the following steps: the gelatin sponge body is vacuum dried at 60-90 DEG C for 20-30 min, and then vacuum dried at 110-130 DEG C for 10-36 h, and the gelatin embolization particle is obtained. The gelatin embolization particle obtained by the preparation method has high porosity, appropriate water absorption, good in-vitro degradation, excellent suspension performance and catheter passing performance.

Description

TECHNICAL FIELD

[0001] The present application relates to the technical field of biological medicine, in particular to a gelatin embolization particle and a preparation method and application thereof. BACKGROUND

[0002] With the mature preparation of low endotoxin gelatin, medical devices prepared using gelatin have been widely recognized and applied, and iodized oil and gelatin sponge particles are often used in conventional transcatheter arterial chemoembolization (TACE), the gelatin particles are aldehyde cross-linked and freeze-dried, have a long degradation time of 90 days, and the cross-linking agent remains after degradation, which also brings potential harm to patients.

[0003] Therefore, it is urgent to develop a gelatin embolic agent product that can be degraded in a short period of time and completely degraded. SUMMARY

[0004] To solve the above technical problems, the present application provides a gelatin embolization particle and a preparation method and application thereof.

[0005] The present application provides a preparation method of a gelatin embolization particle, which specifically comprises the following steps in sequence:

[0006] Using gelatin as raw material, the gelatin is dissolved, foamed, freeze-dried, crushed, heat-crosslinked, sieved and sterilized.

[0007] The specific steps of foaming are as follows: nitrogen gas is introduced into the surface of a 20-80 g / L gelatin aqueous solution, foaming is carried out at a rotation speed of 2500-3500 rpm until there is no obvious liquid at the bottom of the container, the foaming volume is 1-10 times the original liquid volume, and a gelatin foaming product is obtained.

[0008] The specific steps of heat cross-linking are as follows: the gelatin sponge body prepared by freeze-drying is vacuum dried at 60-90℃ for 20-30 min, and then vacuum dried at 110-130℃ for 10-36 h.

[0009] The present application uses the above technical solution, improves the preparation process, selects low endotoxin and high purity gelatin, and prepares the related product through dissolution, foaming, freeze-drying, heat cross-linking, crushing, sieving and sterilization. The gelatin embolization particle provided in the present application can be completely degraded in a short period of time, thereby meeting the clinical needs; the gelatin embolization particle obtained by the preparation method provided in the present application has high porosity, appropriate water absorption, excellent suspension performance and catheter passing performance, which is helpful for the suspension and transportation of the particles in blood and the better combination with the target blood vessels, and is conducive to the further application of the embolization particles.

[0010] The specific step of heat cross-linking can stabilize the three-dimensional structure of the gelatin mixture, which is not easy to disintegrate and absorb liquid to affect the three-dimensional structure when meeting water; meanwhile, the sterilization effect can be achieved; the endotoxin can be removed; and the use of cross-linking agent is reduced to avoid increasing cytotoxicity.

[0011] In the above technical solution, the quality of raw materials, the parameters of preparation process and the operation conditions should be strictly controlled during preparation to ensure the quality and stability of the product. At the same time, the prepared particles should be strictly detected and verified to ensure their safety and effectiveness.

[0012] Preferably, the specific step of heat cross-linking is that the gelatin sponge body prepared by freeze-drying is vacuum dried at 70-80℃ for 20-30min, and then vacuum dried at 115-125℃ for 110-130min.

[0013] Preferably, the specific step of heat cross-linking is that the gelatin sponge body prepared by freeze-drying is vacuum dried at 60-90℃ for 20-30min, and then vacuum dried at 110-130℃ for 12-18h, and then placed at 40-90℃ for 20-30min after being taken out, and then cooled at room temperature.

[0014] Preferably, the specific step of heat cross-linking is that the gelatin sponge body prepared by freeze-drying is vacuum dried at 60-90℃ for 20-30min, and then vacuum dried at 110-130℃ for 15-16h, and then placed at 60-80℃ for 20-30min after being taken out, and then cooled at room temperature.

[0015] During the experiment, the inventors found that when the temperature of vacuum drying of heat cross-linking is low, the gelatin embolization particles degrade fast, are hydrophilic, but are easy to block the tube and aggregate; when the temperature of vacuum drying of heat cross-linking is high, the gelatin embolization particles degrade slowly, are hydrophobic, the sponge is hard, and the tube is blocked; therefore, the process parameters of heat cross-linking are controlled in the above range.

[0016] Preferably, the specific step of freeze-drying is that the gelatin foam is transferred to a freeze dryer, frozen at -45℃ to -25℃ for 8-16h, and then thawed at 4-25℃ for 8-16h to obtain the gelatin sponge body.

[0017] Preferably, the specific step of freeze-drying is that the gelatin foam is transferred to a freeze dryer, frozen at -45℃ to -25℃ for 8-16h, and then thawed at 4-25℃ for 8-16h to obtain the gelatin sponge body.

[0018] During the experiment, the inventors found that freeze-drying has an impact on the shape and microstructure of the sponge, and when the processing temperature is high, the shrinkage of the gelatin embolization particle sponge is large, the pore size is small, the softness is affected, and the phenomenon of pipe blockage is prone to occur or the liquid absorption speed is too slow; therefore, the process parameters of freeze-drying are controlled in the above range.

[0019] Preferably, the specific step of dissolving is: taking the corresponding weight of gelatin particles according to the concentration of 20-80 g / L, adding them into water, stirring and heating to 55-65℃, and cooling to 25-32℃ after sufficient dissolution to obtain a gelatin aqueous solution.

[0020] Preferably, the specific step of dissolving is: taking the corresponding weight of gelatin particles according to the concentration of 20-80 g / L, adding them into water, stirring and heating to 58-62℃, and cooling to 25-32℃ after sufficient dissolution to obtain a gelatin aqueous solution.

[0021] In the second aspect, the application provides a gelatin embolization particle, which is prepared by the above preparation method.

[0022] In the third aspect, the application provides the use of the above gelatin embolization particle in transcatheter arterial chemoembolization for non-diagnostic purposes.

[0023] In summary, the technical scheme of the application has the following effects:

[0024] The application provides a gelatin embolization particle by improving the preparation process, selecting low-endotoxin and high-purity gelatin, and preparing the related product through dissolution, foaming, freeze-drying, heat crosslinking, crushing, screening and sterilization, which can be completely degraded in a short period of time, thereby meeting the clinical needs; the gelatin embolization particle obtained by the preparation method has high porosity, appropriate water absorption, excellent suspension performance and catheter passing performance, which is helpful for the suspension and transportation of the particles in the blood and the better combination with the target blood vessels, and is conducive to the further application of the embolization particles. BRIEF DESCRIPTION OF DRAWINGS

[0025] Figure 1 The figure is a morphology diagram of the gelatin foams under different foaming volume conditions in Example 1 (from left to right: unfoamed, foamed 3 times, foamed 4 times).

[0026] Figure 2 The figure is a morphology diagram of the gelatin sponge body prepared by freeze-drying in Example 1.

[0027] Figure 3 The figure is a microscope micrograph of the gelatin particles in Example 1. DETAILED DESCRIPTION

[0028] The gelatin raw material (X-Pure 10P HBLV) used in the application is purchased from RoseL.

[0029] The application will be further described in detail in connection with the following examples, comparative examples, and performance test experiments, which are not to be construed as limiting the scope of the application as claimed.

[0030] Example

[0031] Example 1

[0032] Example 1 provides a gelatin embolization particle and a preparation method thereof.

[0033] The specific steps of the preparation method of the gelatin embolization particle in this example are shown as follows.

[0034] Dissolution: 7 g of gelatin particles were dissolved into 100 ml of water for injection, stirred and heated to 60°C, and after complete dissolution, cooled to 30°C to obtain a gelatin aqueous solution with a concentration of 70 g / L, ready for use.

[0035] Foaming: the above gelatin solution was placed in a high-speed stirrer and nitrogen was introduced under the liquid surface, foaming was carried out at 3000 rpm until there was no obvious liquid at the bottom of the container, the foaming volume was 4 times the original liquid volume, and a gelatin foam was obtained. Figure 1 The morphology of the gelatin foam under different foaming volume conditions in Example 1 (from left to right: unfoamed, foamed 3 times, foamed 4 times); therefore, the foaming volume in the subsequent experiments was 4 times the original liquid volume.

[0036] Freeze-drying: the gelatin foam was transferred to a freeze dryer, frozen at -35°C for 12 h, then thawed at 20°C for 4 h, and then thawed at 8°C for 8 h to obtain a gelatin sponge body, the morphology is shown in Figure 1 , which is uniform and complete.

[0037] Thermal crosslinking: the gelatin sponge body prepared by freeze-drying was placed in a vacuum dryer at 75°C for 25 min, then placed in a vacuum dryer at 120°C for 24 h, taken out and placed at 70°C for 25 min, and then cooled at room temperature to obtain

[0038] Crushing and sieving: the sponge was placed in a crusher, the screen was arranged to collect sponge particles of 50-2000 microns, and the morphology was observed under a microscope as shown in Figure 3 , which is uniform and complete, and the particles are average; the above sponge was placed in a sieve with a size of 50-2000 microns and sieved layer by layer to collect.

[0039] Filling and sterilization: 100 mg of particles were weighed into a 7 ml vial, sealed, and sterilized by irradiation at 25 kgy.

[0040] Examples 2-8

[0041] Embodiment 2-8 respectively provides a gelatin embolization particle and a preparation method thereof.

[0042] The above embodiment differs from Embodiment 1 in that the specific step of heat crosslinking is different, and is specifically as shown below.

[0043] In Embodiment 2: the specific step of heat crosslinking is that the gelatin sponge body prepared by freeze-drying is vacuum dried at 60°C for 25 min, then vacuum dried at 120°C for 24 h, taken out and placed at 70°C for 25 min, and then cooled at room temperature.

[0044] In Embodiment 3: the specific step of heat crosslinking is that the gelatin sponge body prepared by freeze-drying is vacuum dried at 90°C for 25 min, then vacuum dried at 120°C for 24 h, taken out and placed at 70°C for 25 min, and then cooled at room temperature.

[0045] In Embodiment 4: the specific step of heat crosslinking is that the gelatin sponge body prepared by freeze-drying is vacuum dried at 75°C for 25 min, then vacuum dried at 110°C for 24 h, taken out and placed at 70°C for 25 min, and then cooled at room temperature.

[0046] In Embodiment 5: the specific step of heat crosslinking is that the gelatin sponge body prepared by freeze-drying is vacuum dried at 75°C for 25 min, then vacuum dried at 130°C for 24 h, taken out and placed at 70°C for 25 min, and then cooled at room temperature.

[0047] In Embodiment 6: the specific step of heat crosslinking is that the gelatin sponge body prepared by freeze-drying is vacuum dried at 75°C for 25 min, then vacuum dried at 120°C for 10 h, taken out and cooled at room temperature.

[0048] In Embodiment 7: the specific step of heat crosslinking is that the gelatin sponge body prepared by freeze-drying is vacuum dried at 75°C for 25 min, then vacuum dried at 120°C for 36 h, taken out and placed at 40°C for 25 min, and then cooled at room temperature.

[0049] In Embodiment 8: the specific step of heat crosslinking is that the gelatin sponge body prepared by freeze-drying is vacuum dried at 75°C for 25 min, then vacuum dried at 120°C for 24 h, taken out and placed at 90°C for 25 min, and then cooled at room temperature.

[0050] The above embodiments are all the same as the remaining steps of the preparation method of the gelatin embolization particle in Embodiment 1.

[0051] Examples 9-11

[0052] Examples 9-11 respectively provide a gelatin embolization particle and a preparation method thereof.

[0053] The above examples differ from Example 1 in that the specific steps of freeze-drying are different, as shown below.

[0054] In Example 9: the specific steps of freeze-drying are: transferring the gelatin foam into a freeze dryer, freezing at -45℃ for 12h, then thawing at 20℃ for 12h, to obtain the gelatin sponge body.

[0055] In Example 10: the specific steps of freeze-drying are: transferring the gelatin foam into a freeze dryer, freezing at -45℃ for 12h, then thawing at 8℃ for 12h, to obtain the gelatin sponge body.

[0056] In Example 11: the specific steps of freeze-drying are: transferring the gelatin foam into a freeze dryer, freezing at -45℃ for 12h, then thawing at 8℃ for 4h, then thawing at 20℃ for 8h, to obtain the gelatin sponge body.

[0057] The above examples are the same as the remaining steps of the preparation method of the gelatin embolization particle in Example 1.

[0058] Examples 12-14

[0059] Examples 12-14 respectively provide a gelatin embolization particle and a preparation method thereof.

[0060] The above examples differ from Example 1 in that the concentration of the gelatin aqueous solution in the dissolving step is different, as shown below.

[0061] In Example 12: dissolving: 2g of gelatin particles are dissolved into 100ml of water for injection, stirred and heated to 60℃, cooled to 30℃ after sufficient dissolution, to obtain a gelatin aqueous solution with a concentration of 20g / L, for use.

[0062] In Example 13: dissolving: 5g of gelatin particles are dissolved into 100ml of water for injection, stirred and heated to 60℃, cooled to 30℃ after sufficient dissolution, to obtain a gelatin aqueous solution with a concentration of 50g / L, for use.

[0063] In Example 14: dissolving: 10g of gelatin particles are dissolved into 100ml of water for injection, stirred and heated to 60℃, cooled to 30℃ after sufficient dissolution, to obtain a gelatin aqueous solution with a concentration of 100g / L, for use.

[0064] The above examples are the same as the remaining steps of the preparation method of the gelatin embolization particle in Example 1.

[0065] Comparative Example

[0066] Comparative Example 1

[0067] The present comparative example provides a gelatin embolization particle and a preparation method thereof.

[0068] The specific steps of the preparation method of the gelatin embolization particle in the present comparative example are shown as follows.

[0069] Dissolution: 7 g of gelatin particles were dissolved into 100 ml of water for injection, stirred and heated to 60°C, and after complete dissolution, cooled to 30°C to obtain a gelatin aqueous solution with a concentration of 70 g / L, which was ready for use.

[0070] Foaming: 20 ml of formaldehyde with a concentration of 1 mg / mL was added to the above gelatin solution, and the solution was placed in a high-speed stirrer and nitrogen was introduced under the liquid surface, foaming was carried out at 3000 rpm until there was no obvious liquid at the bottom of the container, and a gelatin foam was obtained.

[0071] Freeze-drying: the gelatin foam was transferred to a freeze dryer, frozen at -35°C for 12 h, then thawed at 20°C for 4 h, and then thawed at 8°C for 8 h to obtain a gelatin sponge body.

[0072] Thermal crosslinking: the gelatin sponge body prepared by freeze-drying was placed in a 75°C condition for vacuum drying for 25 min, then placed in a 120°C condition for vacuum drying for 24 h, and after taking out, placed in a 70°C condition for 25 min, and then cooled at room temperature to obtain the product.

[0073] Crushing and screening: the sponge was placed in a crusher, and the screen was arranged to collect sponge particles of 50-2000 microns; the above sponge was placed in a sieve with a size of 50-2000 microns, and was collected layer by layer.

[0074] Filling and sterilization: 100 mg of particles were weighed into a 7 ml vial, sealed, and sterilized by irradiation with 25 kgy.

[0075] Comparative Example 2

[0076] The present comparative example provides a gelatin embolization particle and a preparation method thereof.

[0077] The specific steps of the preparation method of the gelatin embolization particle in the present comparative example are shown as follows.

[0078] Dissolution: 7 g of gelatin particles were dissolved into 100 ml of water for injection, stirred and heated to 60°C, and after complete dissolution, cooled to 30°C to obtain a gelatin aqueous solution with a concentration of 70 g / L, which was ready for use.

[0079] Foaming: the above gelatin solution was placed in a high-speed stirrer and nitrogen was introduced under the liquid surface, foaming was carried out at 3000 rpm until there was no obvious liquid at the bottom of the container, and a gelatin foam was obtained.

[0080] Freeze-drying: The gelatin foam was transferred to a freeze-drier, frozen at -35°C for 12 h, then thawed at 20°C for 4 h, and then thawed at 8°C for 8 h to obtain a gelatin sponge body.

[0081] Thermal cross-linking: The gelatin sponge body prepared by freeze-drying was placed in a vacuum dryer at 75°C for 24 h, and then taken out and placed at 70°C for 25 min, and then cooled at room temperature to obtain the product.

[0082] Crushing and screening: The sponge was placed in a crusher, and a screen was arranged to collect sponge particles of 50-2000 microns; the sponge was placed in a sieve with a size of 50-2000 microns, and was collected layer by layer.

[0083] Filling and sterilization: 100 mg of particles were weighed into a 7 ml vial, sealed, and then sterilized by irradiation at 25 kgy.

[0084] Comparative Example 3

[0085] The present comparative example provides a gelatin embolization particle and a preparation method thereof.

[0086] The specific steps of the preparation method of the gelatin embolization particle in the present comparative example are shown as follows.

[0087] Dissolution: 7 g of gelatin particles were dissolved in 100 ml of water for injection, stirred and heated to 60°C, and then cooled to 30°C after complete dissolution to obtain a gelatin aqueous solution with a concentration of 70 g / L.

[0088] Foaming: The gelatin solution was placed in a high-speed stirrer and nitrogen was introduced under the liquid surface, and foaming was carried out at 3000 rpm until there was no obvious liquid at the bottom of the container to obtain a gelatin foam.

[0089] Freeze-drying: The gelatin foam was transferred to a freeze-drier, frozen at -35°C for 12 h, then thawed at 20°C for 4 h, and then thawed at 8°C for 8 h to obtain a gelatin sponge body.

[0090] Thermal cross-linking: The gelatin sponge body prepared by freeze-drying was placed in a vacuum dryer at 75°C for 24 h, and then taken out and placed at 70°C for 25 min, and then cooled at room temperature to obtain the product.

[0091] Crushing and screening: The sponge was placed in a crusher, and a screen was arranged to collect sponge particles of 50-2000 microns; the sponge was placed in a sieve with a size of 50-2000 microns, and was collected layer by layer.

[0092] Filling and sterilization: 100 mg of particles were weighed into a 7 ml vial, sealed, and then sterilized by irradiation at 25 kgy.

[0093] Comparative Examples 4-5

[0094] Comparative Example 4-5 provides a gelatin embolization particle and a preparation method thereof, respectively.

[0095] The above comparative example differs from Example 1 in that the concentration of the gelatin aqueous solution in the dissolving step is different, as shown below.

[0096] In Comparative Example 4: Dissolution: 1 g of gelatin particles was dissolved in 100 ml of water for injection, stirred and heated to 60°C, and after complete dissolution, cooled to 30°C to obtain a gelatin aqueous solution with a concentration of 10 g / L, ready for use.

[0097] In Comparative Example 5: Dissolution: 12 g of gelatin particles was dissolved in 100 ml of water for injection, stirred and heated to 60°C, and after complete dissolution, cooled to 30°C to obtain a gelatin aqueous solution with a concentration of 120 g / L, ready for use.

[0098] The above example is the same as the remaining steps of the preparation method of the gelatin embolization particle in Example 1.

[0099] Performance detection test

[0100] (1) Average pore size: The pore size distribution of the gelatin particles was determined according to the European Pharmacopoeia 2.9.32 mercury intrusion method.

[0101] Test results: as shown in Table 1.

[0102] (2) Water absorption ratio: 100 mg of gelatin particles was accurately weighed, immersed in a beaker containing 20±2°C water, stirred until the microspheres were completely wet and all air was expelled, and after the water was absorbed; the excess water in the beaker was filtered out, and the embolization microspheres after water absorption were weighed again, recorded as M2, and the water absorption ratio A was calculated, the calculation formula was: A = (M2-M1) / M1 x 100%.

[0103] Test results: as shown in Table 1.

[0104] (3) In vitro degradation experiment: 20 mg of gelatin particles was soaked and shaken in a 37°C centrifuge tube containing 30 ml of sterile normal saline, and the change of the gelatin particles was observed every 1 h.

[0105] Test results: as shown in Table 1.

[0106] (4) Suspension: using water for injection, normal saline, a mixed solution of normal saline and iohexol contrast agent with a volume ratio of 1:5, and a mixed solution of normal saline and iohexol contrast agent with a volume ratio of 1:1 as the test solution, 100 mg of gelatin particles was placed in the test solution, mixed uniformly to reach a stable state, and then a 20 mL syringe was used to perform a vertical tube timing, and the suspension state of the microspheres (good, general, poor) was observed.

[0107] The results are shown in Table 1.

[0108] (5) Catheter passability: connect the syringe containing the contrast agent-gelatin particle suspension in the performance detection method (4) to the 2.7F microcatheter, 2ml syringe, push the rate is 2ml / min, observe and record the state of the microspheres entering the microcatheter and the state of the microspheres entering the centrifuge tube from the microcatheter (dispersion, adhesion, clumping, wall sticking, pipe blocking), and record the resistance size.

[0109] The results are shown in Table 2.

[0110] Table 1 Performance detection results of gelatin particles in Examples 1-14 and Comparative Examples 1-5

[0111]

[0112] Table 2 Performance detection results of gelatin particles in Examples 1-14 and Comparative Examples 1-5

[0113]

[0114]

[0115] In combination with the detection results in Tables 1-2, the gelatin embolization particles obtained by using gelatin as raw material, dissolving, foaming, freeze-drying, crushing, heat crosslinking, screening and sterilization have good appearance and morphology, high porosity, low average pore size and suitable water absorption. The suspension performance and catheter passability of the gelatin embolization particles prepared in the application are excellent, which is beneficial to the application of the embolization particles in the non-diagnostic purpose of hepatic arterial chemoembolization.

[0116] In Examples 12-14 and Comparative Examples 4-5, the concentration of the gelatin aqueous solution in the dissolving step directly affects the density of the gelatin sponge. When the concentration of the gelatin aqueous solution is low, the foaming effect is poor, liquid is easily produced at the bottom of the beaker, the strength of the sponge is not enough, the suspension performance is poor, the pipe is not blocked, and the embolization effect is poor. When the concentration of the gelatin aqueous solution is high, the gelatin sponge is hard and brittle, the liquid absorption speed is slow, the pipe is blocked, the suspension is not good, and it is easy to sink to the bottom.

[0117] (5) The embolic agent is applied to animal experiments, and pigs are selected as experimental animals. The experimental animals are placed in the experimental environment 7 days before the operation, so as to adapt to the constant temperature and humidity environment in the animal room, and the animals are illuminated alternately for 12h / 12h per day; the animals are fed with appropriate amount of feed at each time of morning and afternoon; and the animals are free to drink water. Each experimental animal is fasted for 12 hours before the operation, but can drink water freely. The animals are deprived of water in the morning of the day when the operation is to be performed.

[0118] Oral tracheal intubation general anesthesia is assisted by an anesthetic machine; preoperative echocardiography is performed.

[0119] After the animal is transferred into the operating room, the animal is placed on the operating table in right lateral position. The animal's heart rate, pulse, and oxygen saturation are continuously monitored using surface electrodes. The animal's body temperature is monitored using a temperature probe. The surgical field is disinfected with iodophor and covered with sterile drapes. Vascular access is established. Preoperative renal arteriography is performed. The gelatin particles of Example 1 are injected.

[0120] The results of the animal experiments show that the gelatin particles can recanalize the blood vessels within 2-24 hours after embolization, thereby avoiding the necrosis of the entire organ.

[0121] Although the present application has been described in detail with general principles and specific embodiments, modifications or improvements can be made to the present application on the basis of the present application, which is obvious to those skilled in the art. Therefore, these modifications or improvements made on the basis of not deviating from the spirit of the present application, are within the scope of the present application.

Claims

1. A method for preparing a gelatin embolization particle, characterized by, Specifically comprising the following steps in sequence: The gelatin is used as raw material, and the gelatin is dissolved, foamed, freeze-dried, heat-crosslinked, crushed, sieved, and sterilized; The foaming step is specifically as follows: nitrogen gas is introduced into a 70 g / L gelatin aqueous solution under the liquid surface, and foaming is performed at a rotation speed of 3000 rpm until no obvious liquid is present at the bottom of the container, the foaming volume is 4 times the original liquid volume, and a gelatin foam is obtained; The freeze-drying step is specifically as follows: the gelatin foam is transferred to a freeze dryer, frozen at -35℃ for 12 h, then thawed at 20℃ for 4 h, and then thawed at 8℃ for 8 h, and a gelatin sponge body is obtained; The heat-crosslinking step is specifically as follows: the gelatin sponge body prepared by freeze-drying is vacuum-dried at 75℃ for 25 min, then vacuum-dried at 120℃ for 24 h, taken out and placed at 70℃ for 25 min, and then cooled at room temperature, and the gelatin sponge body is obtained; Or the heat-crosslinking step is specifically as follows: the gelatin sponge body prepared by freeze-drying is vacuum-dried at 75℃ for 25 min, then vacuum-dried at 120℃ for 36 h, taken out and placed at 40℃ for 25 min, and then cooled at room temperature, and the gelatin sponge body is obtained; Or the heat-crosslinking step is specifically as follows: the gelatin sponge body prepared by freeze-drying is vacuum-dried at 75℃ for 25 min, then vacuum-dried at 120℃ for 24 h, taken out and placed at 90℃ for 25 min, and then cooled at room temperature, and the gelatin sponge body is obtained.

2. The method of claim 1, wherein the gelatin particles are prepared by the steps of: The dissolving step is specifically as follows: a corresponding weight of gelatin particles is added to water at a concentration of 70 g / L, stirred and heated to 55-65℃, and then cooled to 25-32℃ after complete dissolution, and a gelatin aqueous solution is obtained.

3. A gelatin embolization particle, characterized by, The gelatin plug particles are prepared by the preparation method of any one of claims 1-2.

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