Leaching method for preparing targeted therapeutic drug

Abstract

The invention discloses a leaching method for preparing a targeted therapeutic drug, which comprises the following steps: S1, adjusting CO2 to a critical temperature of 31.1 DEG C and a critical pressure of 7.38 MPa or above to a supercritical state, pre-leaching iodine-131 labeled carbon microspheres, then adding a surface modifier, and treating iodine-131 labeled carbon microsphere suspension with high-frequency ultrasonic waves; s2, transferring an iodine-131 labeled carbon microsphere suspension subjected to supercritical CO2 pre-leaching and surface treatment to a lead shielding centrifugal tube, adding 8-12mL of a leaching buffer solution into 1mL of carbon microspheres, performing vortex mixing, discarding supernate, and repeating twice; s3, enabling the carbon microsphere suspension to pass through an anion exchange column, flushing a resin column by using a leaching buffer solution, and collecting carbon microspheres in effluent; and S4, carrying out vortex mixing by using sterile injection water suspended carbon microspheres, discarding the supernate, repeating for three times, and enabling the suspension to pass through a sterile filter membrane. According to the method, the free iodine-131 in the iodine-131 carbon microspheres can be effectively removed, the medicine safety is guaranteed, and the potential harm to the thyroid gland of a patient is reduced.

Description

Technical Field

[0001] This invention relates to the field of targeted therapy drug technology, and in particular to a rinsing method for preparing targeted therapy drugs. Background Technology

[0002] Iodine-131 carbon microspheres are important radioactive targeted therapies widely used in medical fields such as tumor treatment. Their preparation process is quite complex. First, the carbon microspheres are soaked in nitric acid solution to adjust the pH. Then, they are soaked in silver nitrate solution to adsorb silver ions into the microspheres. Next, they are soaked again in nitric acid solution to remove unadsorbed silver ions. Then, an iodine-131 solution is added, and the iodine-131 ions react with the silver ions to form silver iodide precipitate, thus immobilizing iodine-131 within the carbon microspheres. However, free iodine-131 inevitably remains after this process, so it must be treated using a rinsing process.

[0003] The rinsing process for iodine-131 carbon microspheres is crucial because once free iodine-131 enters the body, it is actively taken up by the thyroid gland through blood circulation. Clinical studies have shown that even a trace amount of free iodine-131, accounting for only 1% of the total activity, can lead to serious consequences such as hypothyroidism or radiation thyroiditis, significantly impacting patients' health and quality of life.

[0004] However, current traditional rinsing processes have limitations. Firstly, they have limited effectiveness in removing free iodine-131. Common physical or chemical rinsing methods struggle to reach free iodine-131 deep within the porous structure of carbon microspheres, resulting in residual free iodine-131 in the final product, posing health risks to patients. Secondly, some traditional rinsing methods, while removing free iodine-131, may damage the structure and properties of the iodine-131 carbon microspheres. For example, the use of strong chemical reagents may alter the surface properties of the carbon microspheres, affecting their targeting and biocompatibility in vivo, and reducing the therapeutic effect of the drug.

[0005] Therefore, it is necessary to provide a rinsing method for preparing targeted therapeutic drugs to solve the above-mentioned technical problems. Summary of the Invention

[0006] This invention overcomes the shortcomings of the prior art and provides a rinsing method for preparing targeted therapeutic drugs.

[0007] To achieve the above objectives, the technical solution adopted by the present invention is: a rinsing method for preparing targeted therapeutic drugs, comprising the following steps:

[0008] S1. Adjust CO2 to a critical temperature of 31.1℃ and a critical pressure of 7.38MPa or higher to bring CO2 into a supercritical state. Use supercritical CO2 to pre-wash iodine-131 labeled carbon microspheres. After pre-washing, add a surface modifier and use high-frequency ultrasound to sonicate the iodine-131 labeled carbon microsphere suspension.

[0009] S2. Transfer the iodine-131 labeled carbon microsphere suspension that has undergone supercritical CO2 pre-rinsing and surface treatment to a lead-shielded centrifuge tube. Add buffer solution at a ratio of 8-12 mL rinsing buffer solution per 1 mL carbon microsphere and vortex mix. Then discard the supernatant and repeat this step twice.

[0010] S3. Pass the carbon microsphere suspension through an anion exchange column, then rinse the resin column with elution buffer and collect the carbon microspheres in the effluent.

[0011] S4. After vortexing the carbon microspheres suspended in sterile water for injection, discard the supernatant and repeat this step 3 times. Then, pass the carbon microsphere suspension through a sterile filter membrane.

[0012] In a preferred embodiment of the present invention, in S1, the temperature range for pre-rinsing the iodine-131 labeled carbon microspheres with supercritical CO2 is 35-45°C, and the pressure range is 15-25 MPa.

[0013] In a preferred embodiment of the present invention, in S1, the surface modifier is polyethylene glycol, and the mass percentage of the surface modifier relative to the mass of the iodine-131 labeled carbon microspheres ranges from 1 to 10%.

[0014] In a preferred embodiment of the present invention, in S1, the ultrasonic frequency range is 20-40kHz, the power range is 150-250W, and the processing time ranges from 1 to 3 minutes.

[0015] In a preferred embodiment of the present invention, in step S2, the vortex mixing time ranges from 4 to 6 minutes, the centrifugation speed of the lead-shielded centrifuge tube ranges from 2500 to 3500 rpm, the centrifugation temperature ranges from 2 to 6°C, and the centrifugation time ranges from 6 to 8 minutes.

[0016] In a preferred embodiment of the present invention, in step S3, the flow rate of the carbon microsphere suspension through the anion exchange column is in the range of 0.8-1.2 mL / min.

[0017] In a preferred embodiment of the present invention, in step S4, the centrifugal speed of the vortex mixing is in the range of 2500-3500 rpm, and the centrifugation time is in the range of 8-12 min.

[0018] In a preferred embodiment of the present invention, in step S4, after the carbon microsphere suspension passes through a sterile filter membrane, the surface of the carbon microspheres is rinsed with 70% ethanol, and then rinsed twice with sterile water for injection.

[0019] In a preferred embodiment of the present invention, the pore size of the sterile filter membrane is 0.22 μm.

[0020] In a preferred embodiment of the present invention, in step S4, the volume of sterile injection water used to suspend the carbon microspheres is 15-25 times the volume of the carbon microspheres.

[0021] This invention addresses the shortcomings of the prior art and has the following beneficial effects:

[0022] (1) This invention provides a rinsing method for preparing targeted therapeutic drugs. This rinsing method can effectively remove free iodine-131 from iodine-131 carbon microspheres. Supercritical CO2 has the characteristics of both gas and liquid, with high diffusivity and strong dissolving ability. It can penetrate into the nanoscale pores of carbon microspheres and has excellent solubility for nonpolar / weakly polar free iodine molecules, removing free iodine-131 to below the safe limit. Free iodine-131 can be actively taken up by the thyroid gland, and even trace amounts can lead to hypothyroidism or radiation thyroiditis. This method ensures the safety of drug use and reduces potential harm to the patient's thyroid gland.

[0023] (2) This invention provides a rinsing method for preparing targeted therapeutic drugs. By adding a surface modifier (polyethylene glycol) in S1, polyethylene glycol can effectively restore the dispersibility of carbon microspheres, ensuring that the carbon microspheres can be uniformly dispersed in the solution in the subsequent vortex mixing step, avoiding the problem of low dispersion efficiency caused by agglomeration. This not only ensures the smooth progress of each step in the rinsing process, allowing the carbon microspheres to fully contact the rinsing buffer and remove free iodine-131 more efficiently, but also maintains the stability and uniformity of the carbon microspheres, providing a strong guarantee for the preparation of high-quality targeted therapeutic drugs. Attached Figure Description

[0024] To more clearly illustrate the technical solutions in the embodiments of the present invention or the prior art, the drawings used in the description of the embodiments or the prior art will be briefly introduced below. Obviously, the drawings described below are only some embodiments recorded in the present invention. For those skilled in the art, other drawings can be obtained based on these drawings without creative effort.

[0025] Figure 1 This is a flowchart illustrating a preferred embodiment of the present invention. Detailed Implementation

[0026] The technical solutions of the embodiments of the present invention will be clearly and completely described below with reference to the accompanying drawings. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention.

[0027] Many specific details are set forth in the following description in order to provide a full understanding of the invention. However, the invention may also be practiced in other ways different from those described herein. Therefore, the scope of protection of the invention is not limited to the specific embodiments disclosed below.

[0028] like Figure 1 As shown, the present invention provides a rinsing method for preparing targeted therapeutic drugs, comprising the following steps:

[0029] S1. Adjust CO2 to a critical temperature of 31.1℃ and a critical pressure of 7.38MPa or higher to bring CO2 into a supercritical state. Under the conditions of a temperature range of 35-45℃ and a pressure range of 15-25MPa, use supercritical CO2 to pre-wash iodine-131 labeled carbon microspheres. After pre-washing, add polyethylene glycol at a mass of 1-10% of the mass of iodine-131 labeled carbon microspheres as a surface modifier. Use high-frequency ultrasound with a frequency range of 20-40kHz and a power range of 150-250W to sonicate the iodine-131 labeled carbon microsphere suspension for 1-3 minutes.

[0030] It should be noted that: CO2 was adjusted to a critical temperature of 31.1℃ and a critical pressure of 7.38 MPa or higher to induce a supercritical state, and the iodine-131-labeled carbon microspheres were pre-washed at 35-45℃ and 15-25 MPa. Supercritical CO2, with its high diffusivity and strong dissolving ability, can penetrate into the nanoscale pores of the carbon microspheres, effectively dissolving and removing free iodine-131 to below safe limits, ensuring drug safety and reducing potential harm to the patient's thyroid. Simultaneously, appropriate temperature and pressure conditions maintain the structural stability of the carbon microspheres. After pre-washing, an amount equal to 1% of the mass of the iodine-131-labeled carbon microspheres was added. -10% polyethylene glycol is used as a surface modifier, which can restore the dispersibility of carbon microspheres, prevent agglomeration, and ensure that the carbon microspheres are in full contact with the rinsing buffer in subsequent steps, thereby improving the efficiency of removing free iodine-131. It can also enhance the stability and uniformity of carbon microspheres. Subsequently, the carbon microsphere suspension is ultrasonically treated with high-frequency ultrasound in the frequency range of 20-40kHz and the power range of 150-250W for 1-3 minutes. This can accelerate the binding of polyethylene glycol and carbon microspheres, making the surface modification more uniform. At the same time, the cavitation effect of ultrasound can enhance the contact between carbon microspheres and supercritical CO2, further improving the removal effect of free iodine-131.

[0031] S2. Transfer the iodine-131 labeled carbon microsphere suspension that has undergone supercritical CO2 pre-washing and surface treatment to a lead-shielded centrifuge tube. Add buffer at a ratio of 8-12 mL of rinsing buffer to 1 mL of carbon microspheres. Vortex mix for 4-6 min, then centrifuge at 2500-3500 rpm at 2-6℃ for 6-8 min. Discard the supernatant and repeat this step twice.

[0032] It should be noted that: the iodine-131 labeled carbon microsphere suspension, after supercritical CO2 pre-rinsing and surface treatment, was transferred to lead-shielded centrifuge tubes. This effectively shielded the carbon microspheres from radiation, ensuring the safety of the operators. Adding elution buffer at a ratio of 8-12 mL of elution buffer per 1 mL of carbon microspheres not only dissolves residual supercritical CO2, unreacted surface modifiers, and other impurities on the surface of the carbon microspheres, but also maintains the stability of the physicochemical properties of the carbon microsphere suspension, preventing aggregation or denaturation of the carbon microspheres. Next, vortexing for 4-6 minutes ensures sufficient contact between the carbon microspheres and the elution buffer, accelerating the dissolution of impurities. Then, centrifugation at 2500-3500 rpm and 2-6°C for 6-8 minutes reduces the activity of the carbon microspheres, minimizing interactions and preventing aggregation. Simultaneously, centrifugation causes the carbon microspheres to precipitate, while impurities remain in the supernatant, achieving effective separation. Repeating this step twice further improves the impurity removal rate, making the carbon microspheres purer and enhancing the quality and safety of targeted therapy drugs.

[0033] S3. Pass the carbon microsphere suspension through the anion exchange column at a flow rate of 0.8-1.2 mL / min, then rinse the resin column with elution buffer and collect the carbon microspheres in the effluent.

[0034] It should be noted that the carbon microsphere suspension is passed through the anion exchange column at a flow rate of 0.8-1.2 mL / min. This flow rate allows the negatively charged impurity ions to fully exchange with the resin and be adsorbed, achieving effective separation from the carbon microspheres and achieving purification. At the same time, it reduces the impact on the carbon microspheres, protecting their structural integrity and dispersibility. The resin column is then washed with elution buffer, which further elutes the impurities adsorbed on the resin, thoroughly removing them and carrying away all the carbon microspheres retained in the column, improving the carbon microsphere recovery rate and avoiding raw material waste. Finally, the carbon microspheres in the effluent are collected, resulting in carbon microspheres with most of the negatively charged impurities removed and significantly improved purity.

[0035] S4. Suspend the carbon microspheres in 15-25 times the volume of sterile water for injection and vortex mix. Then centrifuge at 2500-3500 rpm for 8-12 min, discard the supernatant, and repeat this step 3 times. Then pass the carbon microsphere suspension through a sterile filter membrane with a pore size of 0.22 μm, rinse the surface of the carbon microspheres with 70% ethanol, and then rinse twice with sterile water for injection.

[0036] It should be noted that suspending the carbon microspheres in 15-25 times their volume of sterile water for injection and vortexing them not only dilutes and disperses impurities on and around the carbon microspheres but also maintains their stability. Next, centrifuging at 2500-3500 rpm for 8-12 minutes and discarding the supernatant allows for the separation of impurities from the carbon microspheres. This process is repeated three times to gradually improve the purity and concentration of the carbon microspheres. The carbon microsphere suspension is then passed through a sterile filter membrane with a pore size of 0.22 μm, which traps microorganisms and particles larger than 0.22 μm, further enhancing sterility and purity and ensuring drug quality. Finally, the carbon microspheres are rinsed with 70% ethanol for disinfection and sterilization, followed by two rinses with sterile water for injection to remove any residual ethanol and prevent any impact on the performance of the carbon microspheres.

[0037] Example 1:

[0038] S1. CO2 was adjusted to a temperature of 40℃ and a pressure of 20MPa to induce a supercritical state. Under these conditions, iodine-131-labeled carbon microspheres were pre-washed using supercritical CO2. After pre-washing, polyethylene glycol (PEG) at 5% by mass of the iodine-131-labeled carbon microspheres was added as a surface modifier. The iodine-131-labeled carbon microsphere suspension was then sonicated for 2 minutes using high-frequency ultrasound at 30kHz and 200W.

[0039] S2. Transfer the iodine-131 labeled carbon microsphere suspension that has undergone supercritical CO2 pre-rinsing and surface treatment to a lead-shielded centrifuge tube. Add buffer at a ratio of 1 mL carbon microspheres to 10 mL rinsing buffer and vortex for 5 min. Then centrifuge at 3000 rpm and 4°C for 7 min, discard the supernatant, and repeat this step twice.

[0040] S3. Pass the carbon microsphere suspension through the anion exchange column at a flow rate of 1 mL / min, then rinse the resin column with elution buffer and collect the carbon microspheres in the effluent.

[0041] S4. Suspend the carbon microspheres in 20 times their volume of sterile water for injection and vortex mix. Then centrifuge at 3000 rpm for 10 min, discard the supernatant, and repeat this step 3 times. Then pass the carbon microsphere suspension through a sterile filter membrane with a pore size of 0.22 μm, rinse the surface of the carbon microspheres with 70% ethanol, and then rinse twice with sterile water for injection.

[0042] Example 2:

[0043] This embodiment is basically the same as Embodiment 1, except that: in step S1, CO2 is adjusted to a temperature of 35°C and a pressure of 20MPa to bring CO2 into a supercritical state. Under this condition, supercritical CO2 is used to pre-wash the iodine-131 labeled carbon microspheres. After pre-washing, polyethylene glycol is added as a surface modifier at a mass of 5% of the iodine-131 labeled carbon microspheres. The iodine-131 labeled carbon microsphere suspension is ultrasonically treated for 2 minutes using high-frequency ultrasound at a frequency of 30kHz and a power of 200W.

[0044] Example 3:

[0045] This embodiment is basically the same as Embodiment 1, except that in step S1, CO2 is adjusted to a temperature of 45°C and a pressure of 20MPa to bring it into a supercritical state. Under these conditions, supercritical CO2 is used to pre-wash the iodine-131 labeled carbon microspheres. After pre-washing, polyethylene glycol is added as a surface modifier at a mass of 5% of the iodine-131 labeled carbon microspheres. The iodine-131 labeled carbon microsphere suspension is ultrasonically treated for 2 minutes using a high-frequency ultrasonic wave with a frequency of 30kHz and a power of 200W.

[0046] Example 3:

[0047] This embodiment is basically the same as Embodiment 1, except that in step S2, the iodine-131 labeled carbon microsphere suspension that has undergone supercritical CO2 pre-washing and surface treatment is transferred to a lead-shielded centrifuge tube, and buffer is added at a ratio of 1 mL carbon microspheres to 8 mL rinsing buffer. The mixture is vortexed for 5 min. Then, it is centrifuged at 3000 rpm and 4°C for 7 min, the supernatant is discarded, and this step is repeated twice.

[0048] Example 4:

[0049] This embodiment is basically the same as Embodiment 1, except that in step S2, the iodine-131 labeled carbon microsphere suspension that has undergone supercritical CO2 pre-washing and surface treatment is transferred to a lead-shielded centrifuge tube, and buffer is added at a ratio of 1 mL carbon microspheres to 12 mL rinsing buffer. The mixture is vortexed for 5 min. Then, it is centrifuged at 3000 rpm and 4°C for 7 min, the supernatant is discarded, and this step is repeated twice.

[0050] Example 5:

[0051] This embodiment is basically the same as Embodiment 1, except that in step S3, the carbon microsphere suspension is passed through the anion exchange column at a flow rate of 0.8 mL / min, and then the resin column is rinsed with elution buffer to collect the carbon microspheres in the effluent.

[0052] Example 6:

[0053] This embodiment is basically the same as Embodiment 1, except that in step S3, the carbon microsphere suspension is passed through the anion exchange column at a flow rate of 1.2 mL / min, and then the resin column is rinsed with elution buffer to collect the carbon microspheres in the effluent.

[0054] Comparative Example 1:

[0055] This comparative example is basically the same as Example 1, except that: in step S1, supercritical CO2 pre-washing is not performed, and the rest is the same as S1 in Example 1.

[0056] Comparative Example 2;

[0057] This comparative example is basically the same as Example 1, except that in step S1, the CO2 is adjusted to a temperature of 40°C and a pressure of 20 MPa to bring it into a supercritical state. Under these conditions, the iodine-131-labeled carbon microspheres are pre-washed using supercritical CO2. After pre-washing, polyethylene glycol is not added as a surface modifier, and high-frequency ultrasonic treatment is not performed.

[0058] Experimental plan:

[0059] Sample preparation: Iodine-131 labeled carbon microspheres were prepared according to the methods of Examples 1-6 and Comparative Examples 1 and 2.

[0060] Parallel experiments: At least three parallel samples were set up for each example and comparative example to ensure the reliability and accuracy of the experimental data.

[0061] Data to be measured:

[0062] Removal rate of free iodine-131: The radioactivity of free iodine-131 in the samples before and after treatment was determined by radioactive counting method and radioactive detector.

[0063] The formula for calculating the removal rate of free iodine-131 is:

[0064]

[0065] Method for determining the dispersibility of carbon microspheres: Take a small amount of sample and observe the dispersion state of carbon microspheres under a microscope. Analyze the proportion of aggregated carbon microspheres using image analysis software.

[0066] Particle size analysis: The particle size distribution of carbon microspheres was determined using a laser particle size analyzer, and the average particle size and polydispersity index (PDI) were calculated. The closer the PDI is to 0, the more uniform the carbon microspheres are dispersed.

[0067] Carbon microsphere recovery rate: The carbon microsphere recovery rate is calculated by weighing the carbon microspheres before and after treatment. The calculation formula is:

[0068]

[0069] Surface properties of carbon microspheres: The surface morphology of carbon microspheres was observed using scanning electron microscopy (SEM), and the elemental composition and chemical state of the carbon microsphere surface were analyzed using X-ray photoelectron spectroscopy (XPS).

[0070] Drug targeting: Select appropriate cell lines or animal models, add carbon microsphere samples labeled with fluorescent or radioactive tracers to the cell culture system or inject them into the animal body, observe the distribution of carbon microspheres in cells or in vivo using techniques such as fluorescence microscopy and radioactive imaging, and calculate the uptake rate of carbon microspheres by the targeted tissue or cells.

[0071] Table 1:

[0072]

[0073] As shown in Table 1, Example 1 demonstrates significant advantages in both experimental data and preparation steps, fully proving that it has the best effect.

[0074] Experimental data show that Example 1 performed exceptionally well; its free iodine-131 removal rate reached 98.25%, far exceeding that of the comparative example and other examples, maximizing drug safety and reducing potential harm to the patient's thyroid; the carbon microsphere aggregation rate was only 3.12%, and the polydispersity index (PDI) was 0.11, demonstrating good dispersibility, which helps to fully contact with the rinsing buffer to improve impurity removal efficiency and ensure uniform drug distribution and targeting in vivo; the carbon microsphere recovery rate reached 95.36%, effectively reducing raw material waste, lowering costs, and improving production efficiency; the targeted tissue uptake rate was 85.21%, significantly higher than other groups, indicating strong drug targeting and potentially better therapeutic effects.

[0075] In the preparation steps, the supercritical CO2 pre-rinsing conditions in Example 1 were suitable; the CO2 was adjusted to a supercritical state of 40℃ and 20MPa, so that the supercritical CO2 had a suitable density and diffusivity, which could better penetrate the pores of carbon microspheres, enhance the solubility of free iodine-131, and improve the removal rate. In contrast, the temperature of 35℃ in Example 2 may have resulted in slightly lower supercritical CO2 activity, and the temperature of 45℃ in Example 3 may have affected the structure of carbon microspheres.

[0076] Example 1: The surface modification and ultrasonic treatment were appropriate; 5% by mass of polyethylene glycol was added as a surface modifier, and high-frequency ultrasonic treatment at 30kHz and 200W was performed for 2 minutes; polyethylene glycol improved the surface properties of carbon microspheres, reduced the interaction force between carbon microspheres, and reduced agglomeration; ultrasonic treatment promoted the uniform distribution of polyethylene glycol and enhanced the modification effect; Comparative Example 2 did not perform this operation, resulting in a significant increase in the agglomeration rate of carbon microspheres and poor dispersibility.

[0077] In the subsequent elution and anion exchange column operation, the parameters in Example 1 were reasonable; adding 1 mL of carbon microspheres to 10 mL of elution buffer, vortexing for 5 min, and centrifuging at 3000 rpm and 4°C for 7 min could fully dissolve and separate impurities; while adding 8 mL of buffer in Example 3 may not have fully dissolved impurities, and adding 12 mL of buffer in Example 4 may have reduced the centrifugation efficiency; in addition, passing the carbon microsphere suspension through the anion exchange column at a flow rate of 1 mL / min can ensure sufficient contact to remove impurities and avoid problems caused by improper flow rate; the flow rate of 0.8 mL / min in Example 5 resulted in a long processing time, and the flow rate of 1.2 mL / min in Example 6 resulted in incomplete impurity removal.

[0078] In summary, Example 1 demonstrates superior performance in experimental data indicators such as free iodine-131 removal rate, carbon microsphere dispersibility, carbon microsphere recovery rate, and targeted tissue uptake rate. Furthermore, its preparation steps, including supercritical CO2 pre-rinsing conditions, surface modification and ultrasonic treatment, rinsing, and anion exchange column operating parameters, are more rationally optimized.

[0079] Based on the preferred embodiments of the present invention described above, those skilled in the art can make various changes and modifications without departing from the inventive concept. The technical scope of this invention is not limited to the contents of the specification, but must be determined according to the scope of the claims.

Claims

1. A method for preparing targeted therapeutic drugs by rinsing, characterized in that, Includes the following steps: S1. Adjust CO2 to a critical temperature of 31.1℃ and a critical pressure of 7.38MPa or higher to bring CO2 into a supercritical state. Use supercritical CO2 to pre-wash iodine-131 labeled carbon microspheres. After pre-washing, add a surface modifier and use high-frequency ultrasound to sonicate the iodine-131 labeled carbon microsphere suspension. S2. Transfer the iodine-131 labeled carbon microsphere suspension that has undergone supercritical CO2 pre-rinsing and surface treatment to a lead-shielded centrifuge tube. Add buffer solution at a ratio of 8-12 mL rinsing buffer solution per 1 mL carbon microsphere and vortex mix. Then discard the supernatant and repeat this step twice. S3. Pass the carbon microsphere suspension through an anion exchange column, then rinse the resin column with elution buffer and collect the carbon microspheres in the effluent. S4. After vortexing the carbon microspheres suspended in sterile water for injection, discard the supernatant and repeat this step 3 times. Then, pass the carbon microsphere suspension through a sterile filter membrane.

2. The rinsing method for preparing targeted therapeutic drugs according to claim 1, characterized in that: In S1, the temperature range for pre-rinsing the iodine-131 labeled carbon microspheres with supercritical CO2 is 35-45°C, and the pressure range is 15-25 MPa.

3. The rinsing method for preparing targeted therapeutic drugs according to claim 1, characterized in that: In S1, the surface modifier is polyethylene glycol, and the mass percentage of the surface modifier relative to the mass of the iodine-131 labeled carbon microspheres ranges from 1% to 10%.

4. The rinsing method for preparing targeted therapeutic drugs according to claim 1, characterized in that: In S1, the ultrasonic frequency range is 20-40kHz, the power range is 150-250W, and the processing time ranges from 1 to 3 minutes.

5. The rinsing method for preparing targeted therapeutic drugs according to claim 1, characterized in that: In S2, the vortex mixing time ranges from 4 to 6 minutes, the centrifugation speed of the lead-shielded centrifuge tubes ranges from 2500 to 3500 rpm, the centrifugation temperature ranges from 2 to 6 degrees Celsius, and the centrifugation time ranges from 6 to 8 minutes.

6. The rinsing method for preparing targeted therapeutic drugs according to claim 1, characterized in that: In S3, the flow rate of the carbon microsphere suspension through the anion exchange column ranges from 0.8 to 1.2 mL / min.

7. The rinsing method for preparing targeted therapeutic drugs according to claim 1, characterized in that: In S4, the centrifugal speed range for vortex mixing is 2500-3500 rpm, and the centrifugation time ranges from 8 to 12 min.

8. The rinsing method for preparing targeted therapeutic drugs according to claim 1, characterized in that: In step S4, after the carbon microsphere suspension passes through a sterile filter membrane, the surface of the carbon microspheres is rinsed with 70% ethanol, and then rinsed twice with sterile water for injection.

9. The rinsing method for preparing targeted therapeutic drugs according to claim 8, characterized in that: The sterile filter membrane has a pore size of 0.22 μm.

10. The rinsing method for preparing targeted therapeutic drugs according to claim 1, characterized in that: In step S4, the volume of sterile injectable water used to suspend the carbon microspheres is 15-25 times the volume of the carbon microspheres.

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