Engineered radioactive polymeric microsphere, and preparation and application thereof

Patent metadata

Field	Value
Publication number	US-11865196-B2
Application number	US-202318339195-A
Country	US
Kind code	B2
Filing date	Jun 21, 2023
Priority date	Jun 27, 2022
Publication date	Jan 9, 2024
Grant date	Jan 9, 2024

Abstract

An engineered radioactive polymeric microsphere, and a preparation and application thereof. The preparation method includes: adding a styrene monomer and a disperser and/or a crosslinker into a medium, followed by feeding of nitrogen or helium and stirring to obtain a first reaction mixture; heating the first reaction mixture, and adding an initiator, followed by reaction under stirring at a constant temperature to obtain a second reaction mixture; subjecting the second reaction mixture to washing with ethanol and water, and vacuum drying to obtain a crude polymeric microsphere; subjecting the crude polymeric microsphere to radiation-induced graft polymerization with a functional monomer to obtain the functionalized polymeric microsphere; and exposing the functionalized polymeric microsphere to a radionuclide to prepare the engineered radioactive polymeric microsphere.

First claim

What is claimed is:

1. A method for preparing an engineered radioactive polymeric microsphere, comprising:
adding 10 g of a styrene monomer and 1 g of sodium dodecyl sulfate (SDS) to 20 mL of deionized water, followed by stirring at room temperature in a nitrogen atmosphere for 2 h to obtain a first reaction mixture;
heating the first reaction mixture to 50° C. and adding 2 g of dibenzoyl peroxide to the first reaction mixture, followed by reaction under stirring at a constant temperature for 6 h to obtain a second reaction mixture; and
subjecting the second reaction mixture to washing with ethanol and 60° C. water, and vacuum drying to obtain a crude polymeric microsphere;
weighing 3 g of the crude polymeric microsphere followed by irradiation in the exposure to a cobalt source at room temperature under an air atmosphere to obtain an irradiated polymeric microsphere, wherein a radiation absorbed dose is 100 kGy; adding 60 mL of deionized water and 10 mL of vinylphosphonic acid to a conical flask followed by stirring for 1 h to obtain a vinylphosphonic acid solution; adding 3 g of the irradiated polymeric microsphere to the vinylphosphonic acid solution followed by nitrogen feeding for 20 min to remove oxygen and sealing to obtain a third reaction mixture; subjecting the third reaction mixture to reaction in a 55° C. water bath for 3 h and vacuum filtration to obtain a grafted polymeric microsphere; and subjecting the grafted polymeric microsphere to washing with deionized water and drying in a vacuum oven for 24 h to obtain a phosphate-based polymeric microsphere; and
mixing 0.5 g of the phosphate-based polymeric microsphere with 1 mL of a 0.5 mCi/μL 177 LuCl 3 solution at room temperature under ultrasonic oscillation for 30 min to obtain an engineered phosphate-based 177 Lu polymeric microsphere with a diameter of 40 μm.

2. A method for preparing an engineered radioactive polymeric microsphere, comprising:
adding 20 g of a styrene monomer and 3 g of sodium dodecyl sulfate (SDS) to 50 mL of ethanol, followed by stirring at room temperature in a helium atmosphere for 1 h to obtain a first reaction mixture;
heating the first reaction mixture to 60° C. and adding 0.5 g of azobisisobutyronitrile to the first reaction mixture, followed by reaction under stirring at a constant temperature for 4 h to obtain a second reaction mixture; and
subjecting the second reaction mixture to washing with ethanol and 60° C. water, and vacuum drying to obtain a crude polymeric microsphere;
weighing 5 g of the crude polymeric microsphere followed by irradiation in the exposure to an electron beam at room temperature under an air atmosphere to obtain an irradiated polymeric microsphere, wherein a radiation absorbed dose is 300 kGy; adding 50 mL of deionized water, 10 mL of vinyl pyrrolidone and 15 mL of 4-vinylaniline to a conical flask followed by stirring for 2 h to obtain a mixed solution; adding 4 g of the irradiated polymeric microsphere to the mixed solution followed by nitrogen feeding for 40 min to remove oxygen and sealing to obtain a third reaction mixture; subjecting the third reaction mixture to reaction in a 65° C. water bath for 6 h and vacuum filtration to obtain a grafted polymeric microsphere; and subjecting the grafted polymeric microsphere to washing with deionized water and drying in a vacuum oven for 24 h to obtain an amino-based polymeric microsphere; and
mixing 2.0 g of the amino-based polymeric microsphere with 1 mL of a 0.5 mCi/μL 177 LuCl 3 solution at room temperature under ultrasonic oscillation for 30 min to obtain an engineered amino-based 177 Lu polymeric microsphere with a diameter of 80 μm.

3. A method for preparing an engineered radioactive polymeric microsphere, comprising:
adding 12 g of a styrene monomer and 4 g of sodium dodecyl sulfate (SDS) to 80 mL of deionized water, followed by stirring at room temperature in a nitrogen atmosphere for 1 h to obtain a first reaction mixture;
heating the first reaction mixture to 50° C. and adding 1.2 g of azobisisobutyronitrile to the first reaction mixture, followed by reaction under stirring at a constant temperature for 3 h to obtain a second reaction mixture; and
subjecting the second reaction mixture to washing with ethanol and 60° C. water, and vacuum drying to obtain a crude polymeric microsphere;
weighing 4 g of the crude polymeric microsphere followed by irradiation in the exposure to an electron beam at room temperature under an air atmosphere to obtain an irradiated polymeric microsphere, wherein a radiation absorbed dose is 200 kGy; adding 50 mL of deionized water, 10 mL of acrylic acid and 10 g of 2-methacryloyloxyethyl phosphorylcholine to a conical flask followed by stirring for 2 h to obtain a mixed solution; adding 2 g of the irradiated polymeric microsphere to the mixed solution followed by nitrogen feeding for 30 min to remove oxygen and sealing to obtain a third reaction mixture; subjecting the third reaction mixture to reaction in a water bath for 5 h and vacuum filtration to obtain a grafted polymeric microsphere; and subjecting the grafted polymeric microsphere to washing with deionized water and drying in a vacuum oven for 24 h to obtain a carboxyl-phosphorylcholine-based polymeric microsphere; and
mixing 1.2 g of the carboxyl-phosphorylcholine-based polymeric microsphere with 2 mL of a 0.5 mCi/μL 177 LuCl 3 solution at room temperature under ultrasonic oscillation for 30 min to obtain an engineered carboxyl-phosphorylcholine-based 177 Lu polymeric microsphere with a diameter of 60 μm.

Assignees

• Univ Xiamen
• Univ Shanghai

Inventors

• Liu Gang
• Xu Xiao
• Ma Hongjuan
• Zhao Zhenwen
• Chen Hu
• He Pan
• Liu Chao
• Chu Chengchao
• Li Dong

Classifications

• A61K51/1251 Primary

  micro- or nanospheres, micro- or nanobeads, micro- or nanocapsules · CPC title

• A61N5/1002

  Intraluminal radiation therapy · CPC title

• A61P35/00 Primary

  Antineoplastic agents · CPC title

• C08F257/02 Primary

  on to polymers of styrene or alkyl-substituted styrenes · CPC title

• C08K3/06

  Sulfur · CPC title