CN115944753A - Organic-inorganic composite radiotherapy microspheres and preparation method thereof - Google Patents

Abstract

The invention relates to the field of C03C17/23, in particular, the invention relates to an organic-inorganic composite radiotherapy microsphere and a preparation method thereof. The organic-inorganic composite radiotherapy microspheres are hydrogel microspheres inlaid with ⁹⁰ Y inorganic particles, wherein the particle diameter of the ⁹⁰ Y inorganic particles is 5-50 microns, and the hydrogel microspheres have a particle diameter of 30-300 microns. This type of composite microsphere has a high ⁹⁰ Y loading capacity, and the ⁹⁰ Y element will not fall off. At the same time, the hydrogel network shell can load chemotherapy drugs, realizing the combination of d-TACE and TARE treatment methods. In addition, we designed large-sized microspheres of more than 100um through the design of shell hydrogel microspheres, which cleverly solved the risk of small microspheres penetrating hepatic sinusoids, and did not require pre-operation before surgery. Nuclide microspheres for TARE therapy of liver cancer.

Description

A kind of organic-inorganic composite radiotherapy microsphere and preparation method thereof

technical field

The invention relates to the field of C03C17/23, in particular, the invention relates to an organic-inorganic composite radiotherapy microsphere and a preparation method thereof.

Background technique

Since liver cancer is a silent disease, it is asymptomatic in the early stage, and the course of the disease develops rapidly, so the vast majority of patients are in the middle and late stages when they are discovered. For patients with advanced liver cancer, transarterial chemoembolization (TACE ¹ ) is basically performed according to clinical guidelines. Early c-TACE uses lipiodol or PVA particles, gelatin sponge particles or blank microspheres to embolize the blood supply artery of the tumor target, and blocks the blood supply of the tumor through "starvation" treatment to achieve the purpose of killing the tumor. In recent years, with the introduction of foreign drug-loaded embolic microspheres, more and more patients and doctors have begun to accept these products. Different from traditional c-TACE, this type of TACE surgery using drug-loaded microspheres to achieve drug sustained release is defined as d-TACE surgery. American Poco and Mairuitong drug-loaded embolic microspheres have been launched in China successively. At present, only Hengrui Jialisheng's drug-loaded embolic microspheres have been approved by the Food and Drug Administration in China.

Transarterial embolization radiotherapy (TARE) surgery developed on the basis of d-TACE surgery has gradually entered the field of vision of Chinese doctors. Different from d-TACE microspheres, the drugs contained in TARE microspheres are radioactive nuclide drugs. Currently, only two TARE radiotherapy microspheres are on the market in the world, namely SIR-Spheres and TheraSphere. Both are Y90 radiotherapy microspheres, the former is resin Y90 microspheres, and the latter is glass Y90 microspheres. SIR-Spheres was acquired by China's Grand Pharmaceutical in 2018, and TheraSphere was acquired by Boston Scientific. Compared with resin microspheres, glass microspheres themselves contain Y-89 components, which have stable performance, good spheroidization, chemical inertness, non-toxicity, and their physical and chemical properties remain unchanged after high-flux neutron bombardment. Microspheres have a large specific gravity and are easy to deposit, but the radioactive activity per unit of microspheres is high, and the number of microspheres required is small, so the embolization effect of tumor blood vessels is small, and at the same time, it can reduce the occurrence of ectopic embolism caused by reflux Rate. The disadvantage is that the glass microspheres themselves cannot be degraded in the body and will remain permanently in the liver. The advantages of resin microspheres are low density and good floatability. The disadvantage is that there is a risk of falling off the Y90 element, and the Y90 load is low.

Therefore, it is necessary to provide a resin microsphere with a Y90 element that is not easy to fall off and has a high Y90 loading.

Contents of the invention

Aiming at some problems existing in the prior art, the first aspect of the present invention provides an organic-inorganic composite radiotherapy microsphere, which is a hydrogel microsphere inlaid with ⁹⁰ Y inorganic particles, wherein the particle size of the ⁹⁰ Y inorganic particles is 5-50 microns, the particle size of hydrogel microspheres is 30-300 microns, and the loading of ⁹⁰ Y inorganic particles is 10-50 vol%.

^{The 90} Y inorganic particles are obtained from ^{the 89} Y inorganic particles, and ^{the 89} Y inorganic particles can be Y ₂ O ₃ , Y ₂ (CO ₃ ) ₂ , YPO ₄ or other inorganic Y-containing precipitation compounds.

In one embodiment, the material of the hydrogel microspheres is an organic polymer compound containing a hydroxyl group, preferably selected from one of PVA, PAA, hyaluronic acid, and polysaccharide polymer compounds (such as chitosan). one or more species.

In one embodiment, the hydrogel microspheres are compounds grafted with anionic groups, preferably, the anionic groups are selected from any one of sulfonate, phosphate, carbonate, sulfate, and acetate , the compound grafted with anionic groups is used to load cationic chemotherapeutic drugs.

In one embodiment, the hydrogel microsphere is a compound grafted with cationic groups, preferably, the cationic group is NH ⁴⁺ , and the compound grafted with cationic groups is used to load anionic drugs.

The second aspect of the present invention provides a method for preparing the organic-inorganic composite radiotherapy microspheres, comprising the following steps:

(1) Synthesize hydrogel microspheres by reverse-phase suspension polymerization, and wash, dehydrate, and dry;

(2) The hydrogel microspheres obtained in step (1) absorb water and swell in the ⁸⁹ Y ³⁺ ion solution, and after removing the excess ⁸⁹ Y ³⁺ ion solution, soak the obtained microspheres in an alkaline solution, so that the microspheres The ⁸⁹ Y ³⁺ ions in the spherical hydrogel network are precipitated from the solution to form inorganic particles containing ⁸⁹ Y. After cleaning, the particle size is sieved, and then dehydrated;

(3) The microspheres obtained in step (2) are put into a reactor for irradiation treatment.

In one embodiment, the step (1) includes: after grafting a polymerizable functional group to an organic polymer compound containing a hydroxyl group, and then copolymerizing it with an ionic acrylic monomer in a reverse-phase suspension polymerization manner to form a polymer hydrogel glue microspheres.

In the present application, the polymerizable functional group can include acrylate group, acrylamide group and the like.

In the present application, the ionic acrylic acid monomer can include 2-acrylamide-2-methylpropanesulfonate sodium monomer and the like.

In a preferred embodiment, the step (1) includes:

1) Synthesis of a functionalized macromolecular hydrogel intermediate: Add 1 mass part of an organic polymer compound containing a hydroxyl group with a weight average molecular weight of 2×10 ⁴ -2×10 ⁵ into a flask filled with a specified amount of pure water, Stir for 10 minutes to make it evenly dispersed; heat up to 90-100°C, after the organic polymer compound containing hydroxyl is completely dissolved, cool down to below 25°C, add N-(2,2-dimethoxy 1-5% mass parts of ethyl ethyl)-2-acrylamide, after stirring for 10 minutes, 50% mass parts of concentrated hydrochloric acid was added dropwise to the solution, and the reaction continued to stir for 6-7 hours after the dropwise addition, and then the crude product was collected. After washing, removing water, concentrating and drying, a functionalized macromolecular hydrogel intermediate is obtained;

2) Synthesis of hydrogel microspheres: Dissolve ionic acrylic acid monomer and persulfate in water, stir and mix at 25°C until the persulfate is completely dissolved, then add the functionalized macromolecular hydrogel intermediate and stir Uniformly, the polymer monomer solution is obtained and stirred evenly; another butyl acetate is added, cellulose acetate is added, and _N2 gas is introduced at the same time, stirred, heated to a constant temperature of 50-75°C, and then the above polymer monomer solution and Tetramethylethylenediamine forms an oil-water mixed reaction system. In the oil-water mixed reaction system, the total concentration of polymer monomers is 50-100g/L, wherein functionalized macromolecular hydrogel intermediates account for the total concentration of polymer monomers 70-90% of the total mass, ionic acrylic acid monomer accounts for 4-8% of the total mass of the polymer monomer, the concentration of persulfate is 3-6g/L, and the concentration of tetramethylethylenediamine is 1-5g/L , the concentration of cellulose acetate is 2-4g/L; the oil-water mixed reaction system continues to stir and react at 50-75°C for 2-4 hours. After the reaction is completed, filter the reaction mixture to collect microspheres, and then use butyl acetate, Washed with ethyl acetate and acetone, and then dried in vacuum to obtain hydrogel microspheres.

In one embodiment, step (2) includes: fully mixing the hydrogel microspheres obtained in step (1) with 1 mg/mL-100 mg/mL ⁸⁹ Y ³⁺ ion solution, Vibrate for 20-60 minutes, remove the reaction solution by filtration, and then wash repeatedly with purified water to obtain hydrogel microspheres containing ⁸⁹ Y ³⁺ ions. Soak the hydrogel microspheres that have absorbed ⁸⁹ Y ³⁺ ions in NaOH solution, and shake at a constant temperature of 20°C-50°C for 20-60 minutes to form ⁸⁹ Y ₂ O ₃ precipitates, remove the reaction solution by filtration, and use purified water Repeated cleaning, sieving through a sieve, repeated washing with acetone, and drying the microspheres in an oven to obtain organic-inorganic composite microspheres containing ⁸⁹ Y.

In one embodiment, step (3) includes: sealing the microspheres obtained in step (2) in a quartz glass tube and placing them in a nuclear reactor radiation with a thermal neutron flux higher than 5×10 ¹³ n/cm ² .s According to the method, ⁹⁰ Y ₂ O ₃ is generated by ⁸⁹ Y(n,r) ⁹⁰ Y reaction, the specific activity is greater than 370GBq(10Ci)/gY, and ⁹⁰ Y organic-inorganic composite microspheres are obtained.

The organic-inorganic composite radiotherapy microspheres of this application are given by means of interventional catheters and syringes.

In this application, firstly, polymers such as hydroxyl-modified polyvinyl alcohol and sodium 2-acrylamide-2-methylpropanesulfonate are used as the main raw materials to conduct two-step cross-linked hydrogel microspheres through reverse-phase suspension polymerization, and then pass through acetone Dehydration and water absorption of ⁸⁹ Y3+ ion solution to obtain hydrogel microspheres containing ⁸⁹ Y3 ⁺ ions. After removing the excess ⁸⁹ Y3+ ions by filtration, the obtained hydrogel microspheres containing ⁸⁹ Y ³⁺ ions are then precipitated into ⁸⁹ Y2O3 particles in an alkaline solution to form an organic-inorganic composite hydrogel containing ⁸⁹ Y2O3 particles Microspheres. The above composite microspheres were washed and filtered several times, followed by particle size sieving and acetone dehydration to obtain ⁸⁹ Y2O3@PVA organic-inorganic composite microspheres with satisfactory dispersion. Finally, the microspheres were placed in the reactor for irradiation to obtain composite microspheres containing ⁹⁰ Y. This type of composite microsphere has a high ⁹⁰ Y loading capacity, and the ⁹⁰ Y element will not fall off. At the same time, the hydrogel network shell can load chemotherapy drugs, realizing the combination of d-TACE and TARE treatment methods. In addition, we designed large-sized microspheres of more than 100um through the design of shell hydrogel microspheres, which cleverly solved the risk of small microspheres penetrating hepatic sinusoids, and did not require pre-operation before surgery. Nuclide microspheres for TARE therapy of liver cancer.

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

The structure of the ⁹⁰ Y organic-inorganic composite radiotherapy microspheres of this application is shown in Figure 1. The blue part is organic cross-linked polyvinyl alcohol hydrogel microspheres (30-300 microns), and the yellow part is _{Y2O3 inorganic} particle microspheres. Balls (5-50 microns), the inorganic-organic composite radiotherapy microspheres have the following advantages: Y ₂ O ₃ loading capacity is high; Y ⁹⁰ elements will not fall off; the blue part can also carry chemotherapy drugs, so d-TACE can be Combined with TARE; through the large particle size of organic cross-linked polyvinyl alcohol hydrogel microspheres, the risk of small microspheres penetrating the liver sinusoids is solved, no pre-operation is required, and the shunt number is measured; through the hydrogel microspheres Content adjustment, microsphere density is low, and floatability is good; for the source of the nuclide, whether it is the microsphere first and then the nuclide (into the reactor irradiation method), or the nuclide first and then the microsphere (Sr-Y generator method) ) are tried.

In addition, this type of composite microsphere has a high ⁹⁰ Y loading capacity, and the ⁹⁰ Y element will not fall off. At the same time, the hydrogel network shell can load chemotherapy drugs, realizing the combination of d-TACE and TARE treatment methods. In addition, we can obtain large-sized microspheres of more than 100um through the design of shell hydrogel microspheres, which cleverly solves the risk of small microspheres penetrating the liver sinusoids, and does not require pre-operation before surgery, which is an ideal application. Nuclide microspheres for TARE treatment of liver cancer.

Description of drawings

Fig. 1 is a structural schematic diagram of ⁹⁰ Y organic-inorganic composite radiotherapy microspheres in the present application;

Fig. 2 is the structural representation of polymer hydrogel microsphere in the embodiment 1 of the present application;

Fig. 3 is a schematic diagram of the structure of ⁸⁹ Y organic-inorganic composite radiotherapy microspheres in Example 1 of the present application.

Detailed ways

The present invention is described below through specific embodiments, but not limited to the specific examples given below.

Example 1

Organic-inorganic composite radiotherapy microspheres are prepared as follows:

(1) Synthesis of macromolecule hydrogel microspheres: ① Synthesis of functional macromolecular hydrogel intermediates: add pure water to a flask filled with a specified amount of pure water (the amount of water is 90 times the mass of polyvinyl alcohol) 1 mass part of polyvinyl alcohol with a weight-average molecular weight of 2×10 ⁴ , stirred for 10 minutes to disperse it evenly; heated up to 95°C, and after the reaction system was completely dissolved, cooled to below 25°C, added N- (2,2-dimethoxyethyl)-2-acrylamide (Shanghai Xuntang Chemical Technology Co., Ltd., brand: NAAADA210805) 1% by mass, after stirring for 10 minutes, add 50% by mass of concentrated hydrochloric acid dropwise to the solution After the dropwise addition, the reaction continued to stir for 6.5 hours, then the crude product was collected, washed, dehydrated, concentrated, and dried to obtain a functionalized macromolecular hydrogel intermediate; ②Synthesis of hydrogel microspheres: take 2- Sodium acrylamide-2-methylpropanesulfonate monomer and persulfate are dissolved in water, stirred and mixed at 25°C until the persulfate is completely dissolved, then the above-mentioned functionalized macromolecular hydrogel intermediate is added and stirred evenly to obtain Polymer monomer solution and stir evenly; take another butyl acetate, add cellulose acetate, and feed _N2 gas at the same time, stir, heat to a constant temperature of 50°C, and then add the above polymer monomer solution and tetramethylethylene diethylene glycol in sequence Amines form an oil-water mixed reaction system, and the oil-water mixed reaction system continues to stir and react at 50°C for 3 hours. After the reaction is completed, the reaction mixture is filtered to collect microspheres, and then repeatedly washed with butyl acetate, ethyl acetate and acetone to obtain The hydrogel microspheres are then placed in an oven to dry the microspheres. see picture 1.

Wherein, in the oil-water mixed reaction system, the total concentration of the polymer monomer is 80g/L, wherein the functionalized macromolecular hydrogel intermediate accounts for 80% of the total mass of the polymer monomer, and 2-acrylamide-2- Sodium methylpropanesulfonate monomer accounts for 5% of the total mass of polymer monomers, the concentration of persulfate is 5g/L, the concentration of tetramethylethylenediamine is 3g/L, and the concentration of cellulose acetate is 34g/L.

(2) Preparation of ⁸⁹ Y organic-inorganic composite radiotherapy microspheres: fully mix the hydrogel microspheres obtained above with 50 mg/mL ⁸⁹ YCl ₃ solution, shake at a constant temperature of 30°C for 30 minutes, remove the reaction solution by filtration, Subsequently, it was repeatedly washed with purified water to obtain hydrogel microspheres containing ⁸⁹ Y ³⁺ ions. Soak the hydrogel microspheres that have adsorbed ⁸⁹ Y ³⁺ ions in NaOH solution, and shake at a constant temperature of 30°C for 30 minutes to form ⁸⁹ Y ₂ O ₃ precipitates, remove the reaction solution by filtration, wash repeatedly with purified water, and sieve After mesh sieving, the microspheres were repeatedly washed with acetone, and placed in an oven to dry the microspheres to obtain ⁸⁹ Y-containing organic-inorganic composite radiotherapy microspheres. See Figure 2.

(3) Preparation of ⁹⁰ Y organic-inorganic composite radiotherapy microspheres: the above-mentioned ⁸⁹ Y ₂ O ₃ composite radiotherapy microspheres were sealed in a quartz glass tube and placed in a thermal neutron flux higher than 5×10 ¹³ n/cm ² .s ⁹⁰ Y 90 Y ₂ O ₃ is generated by ⁸⁹ Y(n,r) ⁹⁰ Y reaction, the specific activity is greater than 370GBq(10Ci)/gY, and ⁹⁰ Y organic-inorganic composite radiotherapy microspheres are obtained.

In this embodiment, the particle size of ⁹⁰ Y ₂ O ₃ is 5-30 microns, and the particle size of the microspheres is 50-300 microns.

Example 2

(1) The synthesis of polymer hydrogel microspheres is the same as described in Example 1. The difference is that the weight average molecular weight of polyvinyl alcohol is 2×10 ⁵ , and N-(2,2-dimethoxyethyl)-2-acrylamide is 3% by mass.

(2) The preparation of ⁸⁹ Y organic-inorganic composite radiotherapy microspheres is the same as that described in Example 1.

(3) The preparation of ⁹⁰ Y organic-inorganic composite radiotherapy microspheres is the same as that described in Example 1.

In this embodiment, the particle size of ⁹⁰ Y ₂ O ₃ is 5-30 microns, and the particle size of the microspheres is 100-300 microns.

Example 3

(1) The synthesis of polymer hydrogel microspheres is the same as described in Example 1. The difference is that the molecular weight of polyvinyl alcohol is 2×10 ⁵ , N-(2,2-dimethoxyethyl)-2-acrylamide is 5% by mass, and the heating temperature of the synthesis system of hydrogel microspheres is is 75°C.

(2) The preparation of ⁸⁹ Y organic-inorganic composite radiotherapy microspheres is the same as that described in Example 1.

(3) The preparation of ⁹⁰ Y organic-inorganic composite radiotherapy microspheres is the same as that described in Example 1.

In this example, the particle size of ⁹⁰ Y ₂ O ₃ is 20-50 microns, and the particle size of the microspheres is 100-300 microns.

Example 4

(1) The synthesis of polymer hydrogel microspheres is the same as described in Example 1. The difference is that the reactant polyvinyl alcohol is changed to polyethylene glycol.

(2) The preparation of ⁸⁹ Y organic-inorganic composite radiotherapy microspheres is the same as that described in Example 1.

(3) The preparation of ⁹⁰ Y organic-inorganic composite radiotherapy microspheres is the same as that described in Example 1.

In this embodiment, the particle size of ⁹⁰ Y ₂ O ₃ is 5-30 microns, and the particle size of the microspheres is 50-300 microns.

Example 5

(1) The synthesis of polymer hydrogel microspheres is the same as described in Example 1. The difference is that the reactant polyvinyl alcohol is changed into chitosan.

(2) The preparation of ⁸⁹ Y organic-inorganic composite radiotherapy microspheres is the same as that described in Example 1.

(3) The preparation of ⁹⁰ Y organic-inorganic composite radiotherapy microspheres is the same as that described in Example 1.

In this embodiment, the particle size of ⁹⁰ Y ₂ O ₃ is 5-30 microns, and the particle size of the microspheres is 50-300 microns.

Example 6

(1) The synthesis of polymer hydrogel microspheres is the same as described in Example 1.

(2) The preparation of ⁸⁹ Y organic-inorganic composite radiotherapy microspheres is the same as that described in Example 1. The difference is that the concentration of ⁸⁹ YCl ₃ solution is 100mg/mL.

(3) The preparation of ⁹⁰ Y organic-inorganic composite radiotherapy microspheres is the same as that described in Example 1.

In this embodiment, the particle size of ⁹⁰ Y ₂ O ₃ is 20-50 microns, and the particle size of the microspheres is 50-300 microns.

Example 7

(1) The synthesis of polymer hydrogel microspheres is the same as described in Example 1.

(2) The preparation of ⁸⁹ Y organic-inorganic composite radiotherapy microspheres is the same as that described in Example 1. The difference is that the alkaline solution is changed from NaOH to Na ₂ CO ₃ , and the generation of ⁸⁹ Y inorganic particles is changed from ⁸⁹ Y ₂ O ₃ to ⁸⁹ Y ₂ (CO ₃ ) ₃ .

(3) The preparation of ⁹⁰ Y organic-inorganic composite radiotherapy microspheres is the same as that described in Example 1.

In Example ⁸⁹ , the particle size of Y ₂ (CO ₃ ) ₃ is 15-30 microns, and the particle size of microspheres is 50-300 microns.

Example 8

(1) The synthesis of polymer hydrogel microspheres is the same as described in Example 1.

(2) The preparation of ⁸⁹ Y organic-inorganic composite radiotherapy microspheres is the same as that described in Example 1. The difference is that the alkaline solution is changed from NaOH to NaHCO ₃ , and the ⁸⁹ Y inorganic particles are changed from ⁸⁹ Y ₂ O ₃ to ⁸⁹ Y ₂ (CO ₃ ) ₃ .

(3) The preparation of ⁹⁰ Y organic-inorganic composite radiotherapy microspheres is the same as that described in Example 1.

In Example ⁸⁹ , the particle size of Y ₂ (CO ₃ ) ₃ is 15-30 microns, and the particle size of microspheres is 50-300 microns.

Example 9

(1) The synthesis of polymer hydrogel microspheres is the same as described in Example 1.

(2) The preparation of ⁸⁹ Y organic-inorganic composite radiotherapy microspheres is the same as that described in Example 1. The difference is that the alkaline solution is changed from NaOH to NH ₄ HCO ₃ , and the ⁸⁹ Y inorganic particles are changed from ⁸⁹ Y ₂ O ₃ to ⁸⁹ Y ₂ (CO ₃ ) ₃ .

(3) The preparation of ⁹⁰ Y organic-inorganic composite radiotherapy microspheres is the same as that described in Example 1.

In Example ⁸⁹ , the particle size of Y ₂ (CO ₃ ) ₃ is 15-30 microns, and the particle size of microspheres is 50-300 microns.

Claims (10)

1. An organic-inorganic composite radiotherapy microsphere is characterized in that it is a hydrogel microsphere inlaid with ⁹⁰ Y inorganic particles, wherein the particle diameter of the ⁹⁰ Y inorganic particles is 5-50 microns, and the particle diameter of the hydrogel microspheres is 5-50 microns. The diameter is 30-300 microns, and the loading amount of ⁹⁰ Y inorganic particles is 10-50 vol%. 2. The organic-inorganic composite radiotherapy microsphere according to claim 1, wherein the material of the hydrogel microsphere is an organic polymer compound containing a hydroxyl group, preferably selected from PVA, PAA, hyaluronic acid, polysaccharide One or more of polymer-like compounds. 3. The organic-inorganic composite radiotherapy microsphere according to claim 2, wherein ⁹⁰ Y inorganic particles are obtained from ⁸⁹ Y inorganic particles, and ⁸⁹ Y inorganic particles are selected from Y ₂ O ₃ , Y ₂ (CO ₃ ) ₂ , YPO One or more of ₄ . 4. The organic-inorganic composite radiotherapy microsphere according to any one of claims 1-3, characterized in that the hydrogel microsphere is a compound grafted with anionic or cationic groups. 5. The organic-inorganic composite radiotherapy microsphere according to claim 4, wherein the anionic group is selected from any one of sulfonate, phosphate, carbonate, sulfate and acetate. 6 . The organic-inorganic composite radiotherapy microsphere according to claim 4 , wherein the cationic group is NH ₄ ⁺ . 7. A method for preparing organic-inorganic composite radiotherapy microspheres according to any one of claims 1-6, characterized in that it comprises the following steps: (1) Synthesize hydrogel microspheres by reverse-phase suspension polymerization, and wash, dehydrate, and dry; (2) The hydrogel microspheres obtained in step (1) absorb water and swell in the ⁸⁹ Y ³⁺ ion solution, and after removing the excess ⁸⁹ Y ³⁺ ion solution, soak the obtained microspheres in an alkaline solution, so that the microspheres The ⁸⁹ Y ³⁺ ions in the spherical hydrogel network are precipitated from the solution to form inorganic particles containing ⁸⁹ Y. After cleaning, the particle size is sieved, and then dehydrated; (3) The microspheres obtained in step (2) are put into a reactor for irradiation treatment. 8. according to the preparation method of the described organic-inorganic composite radiotherapy microsphere of claim 7, it is characterized in that, described step (1) comprises: After grafting polymerizable functional group to the organic polymer compound containing hydroxyl, then with ionic acrylic acid The monomers are copolymerized in the way of reverse phase suspension polymerization to form polymer hydrogel microspheres. 9. The method for preparing organic-inorganic composite radiotherapy microspheres according to claim 7, wherein step (2) comprises: mixing the hydrogel microspheres obtained in step (1) with 1 mg/mL-100 mg/mL ⁸⁹ Y Mix the ³⁺ ion solution thoroughly, shake at a constant temperature of 20°C-50°C for 20-60 minutes, remove the reaction solution by filtration, and then wash repeatedly with purified water to obtain hydrogel microspheres containing ⁸⁹ Y ³⁺ ions; use NaOH Soak the hydrogel microspheres that have adsorbed ⁸⁹ Y ³⁺ ions in the solution, and shake at a constant temperature of 20°C-50°C for 20-60 minutes to form ⁸⁹ Y ₂ O ₃ precipitates, remove the reaction solution by filtration, and wash repeatedly with purified water , after being sieved through a sieve, washed repeatedly with acetone, and placed in an oven to dry the microspheres to obtain organic-inorganic composite microspheres containing ⁸⁹ Y. 10. according to the preparation method of the described organic-inorganic composite radiotherapy microsphere of claim 8 or 9, it is characterized in that, step (3) comprises: the microsphere that step (2) obtains is sealed in quartz glass tube and placed in thermal neutron Irradiated by a nuclear reactor with a flux higher than 5×10 ¹³ n/cm ² .s, the ⁸⁹ Y(n,r) ⁹⁰ Y reacts to generate ⁹⁰ Y ₂ O ₃ , and the specific activity is greater than 370GBq(10Ci)/gY, resulting in ⁹⁰ Y organic-inorganic composite microspheres.

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