Embolism radiotherapy composition as well as preparation method and application thereof

Abstract

The invention relates to the technical field of medical materials, and discloses an embolism radiotherapy composition as well as a preparation method and application thereof. The composition comprises a water phase and an oil phase, and the volume ratio of the water phase to the oil phase is (5: 5)-(9: 1); the water phase comprises temperature-sensitive nanogel, a water phase developing agent and ultrapure water; the temperature-sensitive nanogel accounts for 0.1-10.0% of the total mass of the embolism radiotherapy composition, and the water-phase developing agent accounts for 1-50% of the total mass of the embolism radiotherapy composition; the oil phase is radioactive iodine oil. The temperature-sensitive nanogel has an emulsifying effect on radioactive iodized oil, the temperature-sensitive nanogel and the radioactive iodized oil are blended through a medical three-way cock to form a temperature-sensitive iodized oil Pickering emulsion, the temperature-sensitive iodized oil Pickering emulsion is still kept stable under blood flow flushing, and the capability of achieving'conformal embolism + internal irradiation 'synergistic treatment is achieved. After the radioactive iodinated oil disclosed by the invention is gelatinized by the temperature-sensitive nanogel, the embolism is improved, and the problem that the radioactive iodinated oil enters non-targeted tissues to cause radioactive injury is solved.

Description

Technical Field

[0001] The present invention relates to the technical field of medical materials, in particular to an embolization radiotherapy composition, a preparation method and application thereof. Background Art

[0002] Liver cancer is the sixth most common cancer in the world and the fourth leading cause of cancer death. Since early liver cancer is highly hidden, with no obvious symptoms and difficult to diagnose, a large number of patients are not diagnosed until the middle and late stages. This means that only 25% of early cases can be treated through surgical resection, liver transplantation and other means. In addition, liver cancer has a strong tolerance to conventional chemotherapy and radiotherapy. Therefore, developing comprehensive liver cancer treatments, improving patient survival rates and improving patient quality of life have become major issues that urgently need to be addressed in my country's population and health fields.

[0003] Radiotherapy plays a central role in curing cancer. According to statistics, about 50% of cancer patients have received radiotherapy. Intratumoral irradiation therapy is to introduce a radiation therapy source into the human body, so that the radiation source enters the tumor or is close to the surface of the tumor for irradiation. Its characteristic is that the radiation source can be irradiated as close to the tumor tissue as possible, so that the tumor tissue can receive an effective killing dose while reducing damage to normal tissue. The methods of intratumoral irradiation include intracavitary irradiation, radioactive particle implantation, and transarterial radioembolization (TARE). TARE achieves the dual killing effects of blocking tumor blood supply and internal irradiation by delivering radioactive microspheres to the artery. Clinical studies have also proven the safety and effectiveness of TARE in the treatment of liver cancer. And because the killing effect of radiotherapy on tumor cells is delayed, TARE has a longer progression time, better tumor suppression effect, and less post-embolism syndrome.

[0004] Yttrium 90( 90 Y) Microspheres are the most widely used embolic agents for TARE, with a particle size of 20-30 μm and a half-life of 2.67 days. They can emit beta rays and penetrate 2.5-11 mm tissue depth to perform local radiotherapy on diseased tissues. 90 Due to its small particle size, Y can only embolize small blood supply arteries, and has a poor overall embolization effect on tumors, mainly relying on its radioactivity to kill tumors. At the same time, the high price is also a limitation. 90 One of the reasons why Y embolic microspheres are widely used in clinical practice.

[0005] Early listing 131 I-Lipiodol radioactive iodized oil also has poor embolic properties and easily enters non-targeted tissues through blood circulation after injection, causing radioactive damage to normal tissues, which also affects its clinical use. Therefore, it is necessary to solve the safety issues caused by its insufficient embolic properties. Summary of the invention

[0006] In view of the deficiencies of the prior art, the present invention provides an embolic radiotherapy composition, a preparation method and application thereof. The thermosensitive nanogel in the embolic radiotherapy composition of the present invention can realize a "sol-gel" phase transition by temperature induction, has good fluidity at room temperature, can penetrate deep into tumor capillaries, and after being injected into blood vessels, changes from liquid to solid at body temperature, thereby realizing "long-term conformal embolization" of the tumor vascular network, which can significantly improve the defect of poor embolization in the existing TARE treatment. In addition, the thermosensitive nanogel of the present invention has an emulsifying effect on radioactive iodized oil. The two can be blended through a medical three-way stopcock to form a thermosensitive iodized oil Pickering emulsion, which remains stable under blood flow flushing, thereby realizing the synergistic treatment of "conformal embolization + internal irradiation". After the radioactive iodized oil of the present invention is emulsified by the thermosensitive nanogel, the embolic property is improved, thereby solving the problem of radioactive damage caused by its entry into non-targeted tissues.

[0007] In order to achieve the above object, the present invention adopts the following technical solutions:

[0008] An embolization radiotherapy composition comprises an aqueous phase and an oil phase, wherein the volume ratio of the aqueous phase to the oil phase is 5:5 to 9:1;

[0009] The aqueous phase includes a thermosensitive nanogel, an aqueous developer and ultrapure water; the thermosensitive nanogel accounts for 0.1 to 10.0% of the total mass of the embolization radiotherapy composition, and the aqueous developer accounts for 1% to 50% of the total mass of the embolization radiotherapy composition;

[0010] The oil phase is radioiodized oil.

[0011] In a specific embodiment, the oil phase is obtained by reacting Na 131 I 131 Prepared by exchanging halogen between I and I atom in iodized oil 131 I-labeled radioactive iodized oil. In practical applications, an oil-soluble modification scheme can also be used. 177 Lu, 188 Ho et al. used an oil-soluble chelating agent for modification and dissolved it in iodized oil.

[0012] In a specific embodiment, the thermosensitive nanogel is one or a combination of poly (N-isopropylacrylamide) polymers having a three-dimensional network structure.

[0013] In a specific embodiment, the polymerization monomer of the thermosensitive nanogel is N-isopropyl acrylamide, and the comonomer is one or a combination of N-n-propyl acrylamide, methacrylate, acrylate, acrylic acid, and acrylamide.

[0014] In a specific embodiment, the thermosensitive nanogel is prepared by the following steps:

[0015] The polymerization monomer, comonomer, sodium dodecyl sulfate and cross-linking agent are added to a three-necked flask equipped with a reflux condenser and a gas guide device, and dissolved with ultrapure water under magnetic stirring. High-purity nitrogen is then introduced into the reaction system for 20 min to 40 min, and the reaction system is heated to 65° C. to 75° C., an initiator is added, and the reaction is carried out at 65° C. to 75° C. in a nitrogen atmosphere for 4 to 6 hours to obtain a white turbid suspension. The suspension is dialyzed and purified in ultrapure water and then freeze-dried, and the freeze-dried powder is collected to obtain;

[0016] Among them, the molar ratio of the polymerized monomer to the comonomer is (80-99):(1-20), the total molar concentration of the monomer is 0.1-0.2 mol / L; the molar concentration of the sodium dodecyl sulfate is 0.5-5 mmol / L; the cross-linking agent accounts for 0.2-10% of the total molar number of the monomer; and the molar concentration of the initiator is 1-5 mmol / L.

[0017] In a specific embodiment, the cross-linking agent is N,N'-methylenebisacrylamide; and the initiator is potassium persulfate.

[0018] In a specific embodiment, the aqueous developer is one or a combination of iohexol, iopamidol, iofluanidole, and iodixanol.

[0019] In a specific embodiment, the surfactant is polyoxyethylene hydrogenated castor oil or Span-80.

[0020] The present invention also specifically protects a method for preparing an embolization radiotherapy composition, comprising the following steps:

[0021] (1) Preparation of thermosensitive nanogels

[0022] The polymerization monomer, comonomer, sodium dodecyl sulfate and cross-linking agent are added to a three-necked flask equipped with a reflux condenser and a gas guide device, and dissolved with ultrapure water under magnetic stirring. High-purity nitrogen is then introduced into the reaction system for 20 min to 40 min, and the reaction system is heated to 65° C. to 75° C., an initiator is added, and the reaction is carried out at 65° C. to 75° C. in a nitrogen atmosphere for 4 to 6 hours to obtain a white turbid suspension. The suspension is dialyzed and purified in ultrapure water and then freeze-dried, and the freeze-dried powder is collected to obtain;

[0023] The molar ratio of the polymerizable monomer to the comonomer is (80-99):(1-20), the total molar concentration of the monomer is 0.1-0.2 mol / L; the molar concentration of the sodium dodecyl sulfate is 0.5-5 mmol / L; the crosslinking agent accounts for 0.2-10% of the total molar number of the monomer; the molar concentration of the initiator is 1-5 mmol / L;

[0024] (2) Preparation of aqueous phase

[0025] The thermosensitive nanogel, aqueous developer and ultrapure water are mixed according to the formula and stirred evenly to obtain the product;

[0026] (3) Preparation of oil phase

[0027] By reacting Na 131 I 131 I was prepared by exchanging halogen with I atom in iodized oil. 131 I-labeled radioiodized oil;

[0028] (4) Preparation of radioembolic composition

[0029] Use a three-way stopcock to mix the water phase and the oil phase according to the oil-water ratio of the formula.

[0030] The present invention also specifically protects the use of an embolization radiotherapy composition in the preparation of embolization radiotherapy drugs.

[0031] Compared with the prior art, the present invention has the following beneficial effects:

[0032] (1) The vascular embolization effect of the embolization radiotherapy composition of the present invention is stronger.

[0033] The thermosensitive nanogel in the composition of the present invention can utilize temperature induction to achieve a "sol-gel" phase transition, has good fluidity at room temperature, and can penetrate deep into tumor capillaries. After being injected into the blood vessels, it changes from liquid to solid at body temperature, thereby achieving "long-term conformal embolization" of the tumor vascular network, which can significantly improve the defect of poor embolization effect in existing TARE treatment.

[0034] (2) The present invention can realize intraoperative self-radiography.

[0035] The composition of the present invention contains an aqueous contrast agent and iodized oil, and can be used for real-time development through DSA during surgery without the need for additional injection of a developer, thereby being easy to operate.

[0036] (3) The present invention improves the problem of off-target radiation emission and has high safety.

[0037] The existing TARE treatment, taking yttrium-90 microspheres as an example, has poor embolic effect and is prone to off-target dispersion during and after surgery, damaging normal tissues and organs. 131 I-Lipiodol radioactive iodized oil also has poor embolic properties and easily enters non-targeted tissues through blood circulation after injection, causing radioactive damage to normal tissues, which also affects its clinical use. The composition of the present invention can be stably present for a long time after being cast in tumor blood vessels, and the risk of radiation leakage is greatly reduced.

[0038] (4) The radioactive iodized oil of the present invention has high radioactivity stability after being emulsified by the thermosensitive nanogel. DETAILED DESCRIPTION

[0039] The present invention is further described below in conjunction with specific embodiments, but the embodiments do not limit the present invention in any form. Unless otherwise specified, the raw materials and reagents used in the embodiments of the present invention are conventionally purchased raw materials and reagents.

[0040] Example 1

[0041] An embolization radiotherapy composition is prepared by the following steps:

[0042] (1) N-isopropylacrylamide (0.18 mol / L), butyl methacrylate (4 mmol / L), sodium dodecyl sulfate (0.75 mmol / L), and N,N'-methylenebisacrylamide (4 mmol / L) were added to a three-necked flask equipped with a reflux condenser and a gas guide device, and dissolved with ultrapure water (the amount of ultrapure water was determined by the concentration of other components and the actual amount of feed) under magnetic stirring. High-purity nitrogen was then introduced into the reaction system for 30 min. The reaction system was heated to 65°C, and an initiator potassium persulfate (1.5 mmol / L) was added. The reaction was carried out at 65°C in a nitrogen atmosphere for 4 h to obtain a white turbid suspension. The suspension was dialyzed and purified in ultrapure water and then freeze-dried. The freeze-dried powder was collected to obtain poly(N-isopropylacrylamide-co-butyl methacrylate) thermosensitive nanogel.

[0043] (2) The thermosensitive nanogel, ultrapure water, and aqueous developer (iohexol) are mixed in a mass ratio of 5:55:40 and stirred evenly to obtain an aqueous phase.

[0044] (3) In a glass bottle, add Na 131 I solution (0.1ml, 20mg / ml), evaporate to dryness, add 200ml acetone after cooling to room temperature, shake gently, slowly add the prepared iodized oil / acetone solution (0.6ml iodized oil, 3ml acetone, mutual solution) into the glass bottle, then place a stirrer, stir and react in a 40℃ water bath for 1.5h. After the reaction is completed, increase the water bath temperature (60-70℃), evaporate most of the acetone solvent, and then use a water pump to reduce pressure and evaporate the small amount of acetone remaining in the iodized oil to obtain radioactive iodine labeled iodized oil (oil phase).

[0045] (4) Use a medical three-way stopcock to mix the water phase and the oil phase in a ratio of 1:1.

[0046] Example 2

[0047] An embolization radiotherapy composition is prepared by the following steps:

[0048] (1) N-isopropylacrylamide (0.1 mol / L), N-n-propylacrylamide (10 mmol / L), sodium dodecyl sulfate (0.2 mmol / L), and N,N'-methylenebisacrylamide (8 mmol / L) were added to a three-necked flask equipped with a reflux condenser and a gas guide device, and dissolved with ultrapure water (the amount of ultrapure water is determined by the concentration of other components and the actual amount of feed) under magnetic stirring. High-purity nitrogen was then introduced into the reaction system for 40 min. The reaction system was heated to 75°C, and an initiator potassium persulfate (1.5 mmol / L) was added. The reaction was carried out at 75°C in a nitrogen atmosphere for 6 h to obtain a white turbid suspension. The suspension was dialyzed and purified in ultrapure water and then freeze-dried. The freeze-dried powder was collected to obtain poly(N-isopropylacrylamide-co-N-n-propylacrylamide) thermosensitive nanogel.

[0049] (2) The above-mentioned thermosensitive nanogel, ultrapure water, and aqueous phase developer (iopamidol) are mixed in a mass ratio of 4:36:60 and stirred evenly to obtain an aqueous phase.

[0050] (3) In a glass bottle, add Na 131 I solution (0.1ml, 20mg / ml), evaporate to dryness, add 200ml acetone after cooling to room temperature, shake gently, slowly add the prepared iodized oil / acetone solution (0.6ml iodized oil, 3ml acetone, mutual solution) into the glass bottle, then place a stirrer, stir and react in a 40℃ water bath for 1.5h. After the reaction is completed, increase the water bath temperature (60-70℃), evaporate most of the acetone solvent, and then use a water pump to reduce pressure and evaporate the small amount of acetone remaining in the iodized oil to obtain radioactive iodine labeled iodized oil (oil phase).

[0051] (4) Use a medical three-way stopcock to mix the water phase and the oil phase in a ratio of 7:3.

[0052] Example 3

[0053] An embolization radiotherapy composition is prepared by the following steps:

[0054] (1) N-isopropylacrylamide (0.15 mol / L), acrylic acid (4 mmol / L), sodium dodecyl sulfate (1 mmol / L), and N,N'-methylenebisacrylamide (4 mmol / L) were added to a three-necked flask equipped with a reflux condenser and a gas guide device, and dissolved with ultrapure water (the amount of ultrapure water was determined by the concentration of other components and the actual amount of feed) under magnetic stirring. High-purity nitrogen was then introduced into the reaction system for 30 min. The reaction system was heated to 70°C, and an initiator potassium persulfate (1.5 mmol / L) was added. The reaction was carried out at 70°C in a nitrogen atmosphere for 6 h to obtain a white turbid suspension. The suspension was dialyzed and purified in ultrapure water and then freeze-dried. The freeze-dried powder was collected to obtain poly(N-isopropylacrylamide-co-acrylic acid) thermosensitive nanogel.

[0055] (2) The above-mentioned thermosensitive nanogel, ultrapure water, and aqueous phase developer (iodixanol) are mixed in a mass ratio of 6:39:55 and stirred evenly to obtain an aqueous phase.

[0056] (3) In a glass bottle, add Na 131 I solution (0.1ml, 20mg / ml), evaporate to dryness, add 200ml acetone after cooling to room temperature, shake gently, slowly add the prepared iodized oil / acetone solution (0.6ml iodized oil, 3ml acetone, mutual solution) into the glass bottle, then place a stirrer, stir and react in a 40℃ water bath for 1.5h. After the reaction is completed, increase the water bath temperature (60-70℃), evaporate most of the acetone solvent, and then use a water pump to reduce pressure and evaporate the small amount of acetone remaining in the iodized oil to obtain radioactive iodine labeled iodized oil (oil phase).

[0057] (4) Use a medical three-way stopcock to mix the water phase and the oil phase in a ratio of 6:4.

[0058] Example 4

[0059] An embolization radiotherapy composition is prepared by the following steps:

[0060] (1) N-isopropylacrylamide (0.15 mol / L), acrylamide (4 mmol / L), sodium dodecyl sulfate (2 mmol / L), and N,N'-methylenebisacrylamide (8 mmol / L) were added to a three-necked flask equipped with a reflux condenser and a gas guide device, and dissolved with ultrapure water (the amount of ultrapure water was determined by the concentration of other components and the actual amount of feed) under magnetic stirring. High-purity nitrogen was then introduced into the reaction system for 30 min. The reaction system was heated to 68°C, and an initiator potassium persulfate (2 mmol / L) was added. The reaction was carried out in a nitrogen atmosphere at 68°C for 4.5 h to obtain a white turbid suspension. The suspension was dialyzed and purified in ultrapure water and then freeze-dried. The freeze-dried powder was collected to obtain poly(N-isopropylacrylamide-co-acrylamide) thermosensitive nanogel.

[0061] (2) The above-mentioned thermosensitive nanogel, ultrapure water, and aqueous phase developer (iohexol) are mixed in a mass ratio of 5:55:40 and stirred evenly to obtain an aqueous phase.

[0062] (3) In a glass bottle, add Na 131 I solution (0.1ml, 20mg / ml), evaporate to dryness, add 200ml acetone after cooling to room temperature, shake gently, slowly add the prepared iodized oil / acetone solution (0.6ml iodized oil, 3ml acetone, mutual solution) into the glass bottle, then place a stirrer, stir and react in a 40℃ water bath for 1.5h. After the reaction is completed, increase the water bath temperature (60-70℃), evaporate most of the acetone solvent, and then use a water pump to reduce pressure and evaporate the small amount of acetone remaining in the iodized oil to obtain radioactive iodine labeled iodized oil (oil phase).

[0063] (4) Use a medical three-way stopcock to mix the water phase and the oil phase in a ratio of 6:4.

[0064] Comparative Example 1:

[0065] Based on Example 1, the radioactive iodized oil is not emulsified by the thermosensitive nanogel.

[0066] An embolization radiotherapy composition is prepared by the following steps:

[0067] (1) N-isopropylacrylamide (0.18 mol / L), butyl methacrylate (4 mmol / L), sodium dodecyl sulfate (0.75 mmol / L), and N,N'-methylenebisacrylamide (4 mmol / L) were added to a three-necked flask equipped with a reflux condenser and a gas guide device, and dissolved with ultrapure water (the amount of ultrapure water was determined by the concentration of other components and the actual amount of feed) under magnetic stirring. High-purity nitrogen was then introduced into the reaction system for 30 min. The reaction system was heated to 65°C, and an initiator potassium persulfate (1.5 mmol / L) was added. The reaction was carried out at 65°C in a nitrogen atmosphere for 4 h to obtain a white turbid suspension. The suspension was dialyzed and purified in ultrapure water and then freeze-dried. The freeze-dried powder was collected to obtain poly(N-isopropylacrylamide-co-butyl methacrylate) thermosensitive nanogel.

[0068] (2) The above-mentioned thermosensitive nanogel, ultrapure water, and aqueous developer (iohexol) were mixed in a mass ratio of 5:55:40, stirred evenly, and then Na 131 I solution (0.1ml, 20mg / ml) can be used to obtain the aqueous phase.

[0069] (3) Use a medical three-way stopcock to mix the aqueous phase and iodized oil in a ratio of 1:1.

[0070] Radiostability test method:

[0071] Take 1 ml of the sample to be tested and put it into a 2 ml glass bottle. Solidify it in a constant temperature water bath at 50°C for 1 hour. The sample is separated into a solid phase and a liquid phase. The solid phase is the embolic composition after gelation, and the liquid phase is the precipitated water phase. The radioactivity values ​​of the solid phase and the liquid phase after solidification are detected respectively. The higher the proportion of the radioactivity value of the solid phase after solidification, the higher the radioactivity stability.

[0072] Test results:

[0073]

[0074] Compared with the comparative example, the radioactive iodized oil in the example has high radioactivity stability after being emulsified by the thermosensitive nanogel.

[0075] The above embodiments have provided a detailed introduction to the technical solutions provided by the present invention. Specific examples are used herein to illustrate the principles and implementation methods of the embodiments of the present invention. The description of the above embodiments is only applicable to help understand the principles of the embodiments of the present invention. At the same time, for those skilled in the art, according to the embodiments of the present invention, there may be changes in the specific implementation methods and application scopes. In summary, the content of this specification should not be understood as limiting the present invention.

Claims

1. An embolization radiotherapy composition, characterized in that: It comprises a water phase and an oil phase, wherein the volume ratio of the water phase to the oil phase is 5:5 to 9:1; The aqueous phase includes a thermosensitive nanogel, an aqueous developer and ultrapure water; the thermosensitive nanogel accounts for 0.1 to 10.0% of the total mass of the embolization radiotherapy composition, and the aqueous developer accounts for 1% to 50% of the total mass of the embolization radiotherapy composition; The oil phase is radioiodized oil.

2. The embolization radiotherapy composition according to claim 1, characterized in that: The oil phase reacts with Na 131 I 131 Prepared by exchanging halogen between I and I atom in iodized oil 131 I-labeled radioiodized oil.

3. The embolization radiotherapy composition according to claim 1, characterized in that: The thermosensitive nanogel is one or a combination of poly N-isopropylacrylamide polymers having a three-dimensional network structure.

4. The embolization radiotherapy composition according to claim 1, characterized in that: The polymerization monomer of the thermosensitive nanogel is N-isopropyl acrylamide, and the comonomer is one or a combination of N-n-propyl acrylamide, methacrylate, acrylate, acrylic acid, and acrylamide.

5. The embolization radiotherapy composition according to claim 4, characterized in that: The thermosensitive nanogel is prepared by the following steps: The polymerization monomer, comonomer, sodium dodecyl sulfate and cross-linking agent are added to a three-necked flask equipped with a reflux condenser and a gas guide device, and dissolved with ultrapure water under magnetic stirring. High-purity nitrogen is then introduced into the reaction system for 20 min to 40 min, and the reaction system is heated to 65° C. to 75° C., an initiator is added, and the reaction is carried out at 65° C. to 75° C. in a nitrogen atmosphere for 4 to 6 hours to obtain a white turbid suspension. The suspension is dialyzed and purified in ultrapure water and then freeze-dried, and the freeze-dried powder is collected to obtain; The molar ratio of the polymerizable monomer to the comonomer is (80-99):(1-20), the total molar concentration of the monomer is 0.1-0.2 mol / L; the molar concentration of the sodium dodecyl sulfate is 0.5-5 mmol / L; the crosslinking agent accounts for 0.2-10% of the total molar number of the monomer; and the molar concentration of the initiator is 1-5 mmol / L.

6. The embolization radiotherapy composition according to claim 5, characterized in that: The cross-linking agent is N,N'-methylenebisacrylamide.

7. The embolization radiotherapy composition according to claim 5, characterized in that: The initiator is potassium persulfate.

8. The embolization radiotherapy composition according to claim 1, characterized in that: The aqueous developer is one or a combination of iohexol, iopamidol, iofluaniol and iodixanol.

9. The method for preparing the embolization radiotherapy composition according to any one of claims 1 to 8, characterized in that: The following steps are involved: (1) Preparation of thermosensitive nanogels The polymerization monomer, comonomer, sodium dodecyl sulfate and cross-linking agent are added to a three-necked flask equipped with a reflux condenser and a gas guide device, and dissolved with ultrapure water under magnetic stirring. High-purity nitrogen is then introduced into the reaction system for 20 min to 40 min, and the reaction system is heated to 65° C. to 75° C., an initiator is added, and the reaction is carried out at 65° C. to 75° C. in a nitrogen atmosphere for 4 to 6 hours to obtain a white turbid suspension. The suspension is dialyzed and purified in ultrapure water and then freeze-dried, and the freeze-dried powder is collected to obtain; The molar ratio of the polymerizable monomer to the comonomer is (80-99):(1-20), the total molar concentration of the monomer is 0.1-0.2 mol / L; the molar concentration of the sodium dodecyl sulfate is 0.5-5 mmol / L; the crosslinking agent accounts for 0.2-10% of the total molar number of the monomer; the molar concentration of the initiator is 1-5 mmol / L; (2) Preparation of aqueous phase The thermosensitive nanogel, aqueous developer and ultrapure water are mixed according to the formula and stirred evenly to obtain the product; (3) Preparation of oil phase By reacting Na 131 I 131 I was prepared by halogen exchange with I atom in iodized oil. 131 I-labeled radioiodized oil; (4) Preparation of radioembolic composition Use a three-way stopcock to mix the water phase and the oil phase according to the oil-water ratio of the formula.

10. Use of the embolization radiotherapy composition according to any one of claims 1 to 8 in the preparation of embolization radiotherapy drugs.

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