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EP-4740968-A1 - SUSPENSION CONTAINING RADIOACTIVE MICROSPHERES, AND PREPARATION METHOD THEREFOR AND USE THEREOF

EP4740968A1EP 4740968 A1EP4740968 A1EP 4740968A1EP-4740968-A1

Abstract

A suspension containing radioactive microspheres. The radioactive microsphere comprises a resin microsphere and a radionuclide loaded on the resin microsphere, wherein the average particle size of the radioactive microsphere is 25 µm to 40 µm. By means of controlling the proportion of non-spherical microspheres in the radioactive microspheres to be within 5%, the distribution density of the microspheres at a tumor part is increased, the effect of killing tumors is improved, and the treatment safety is improved.

Inventors

  • WU, XIAOYAN
  • HUANG, XIAOKE
  • TANG, Weikun
  • SHU, Chong
  • ZHANG, SHIMIN
  • WANG, Shuqun
  • HU, Xixi
  • CHEN, JIANXIA
  • LIANG, Jin
  • ZHOU, DAN

Assignees

  • Chengdu Shetai Medical Technology Co., Ltd

Dates

Publication Date
20260513
Application Date
20240705

Claims (20)

  1. A suspension, wherein the suspension comprises radioactive microspheres, and the radioactive microspheres comprise resin microspheres and radionuclides loaded on the resin microspheres, the radioactive microspheres have an average particle size of 25 µm to 40 µm, and the radioactive microspheres have a non-spherical ratio of 5% or less.
  2. The suspension according to claim 1, wherein the non-spherical ratio means the ratio of the number of non-spherical radioactive microspheres to the total number of radioactive microspheres in the suspension, and a non-spherical radioactive microsphere is a radioactive microsphere with a minimum radius of less than 75% of the radius of an initial microsphere; and/or, in the suspension, the radioactive microspheres have a non-spherical ratio or less; and/or, in the suspension, the percentage of radioactive microspheres having a particle size of 20 µm to 60 µm is greater than 85% in terms of the number of the radioactive microspheres; and/or, the material of the resin microspheres is selected from at least one of crosslinked polystyrene resin, crosslinked polyethylene resin and crosslinked polydivinylbenzene resin, preferably, the material of the resin microspheres is selected from a polystyrene resin carrying sulfonic acid groups and crosslinked with divinylbenzene; and/or, the resin microspheres are any one of resin microspheres carrying sulfonic acid groups, resin microspheres carrying nitro groups, and carbonized resin microspheres; and/or, the radionuclides are selected from an isotope of at least one of yttrium, lutetium, indium, holmium, samarium, iodine, phosphorus, iridium, or rhenium, preferably the radionuclides are selected from yttrium [ 90 Y]; and/or, the suspension further comprises water for injection.
  3. The suspension according to claim 1 or 2, wherein each mL of the suspension comprises yttrium [ 90 Y] with an activity of 300-700 MBq.
  4. A suspension comprising radioactive microspheres, wherein the radioactive microspheres comprise resin microspheres and radionuclides loaded on the resin microspheres, the material of the resin microspheres comprises at least one of polystyrene, polyethylene, or polydivinylbenzene, or a crosslinked polymer thereof, and the radioactive microspheres have an average particle size of 25 µm to 40 µm, and have a non-spherical ratio of 5% or less.
  5. The suspension according to claim 4, wherein the non-spherical ratio means the ratio of the number of non-spherical radioactive microspheres to the total number of radioactive microspheres in the suspension, and a non-spherical radioactive microsphere is a radioactive microsphere with a minimum radius of less than 75% of the radius of an initial microsphere.
  6. The suspension according to claim 4 or 5, wherein in the suspension, the percentage of radioactive microspheres having a particle size of 20 µm to 60 µm is greater than 85% in terms of the number of the radioactive microspheres; and/or the radioactive microspheres have a non-spherical ratio or less; and/or, the material of the resin microspheres is selected from crosslinked polystyrene microspheres with a crosslinking degree to 10%.
  7. The suspension comprising radioactive microspheres according to at least one of claims 4-6, characterized in that the resin microspheres are sulfonated, nitrated or carbonized resin microspheres.
  8. The suspension comprising radioactive microspheres according to at least one of claims 4-7, characterized in that , the radionuclides are selected from an isotope of at least one of yttrium, lutetium, indium, holmium, samarium, iodine, phosphorus, iridium, or rhenium.
  9. The suspension comprising radioactive microspheres according to at least one of claims 4-8, wherein the material of the resin microspheres is selected from a polystyrene resin carrying sulfonic acid groups and crosslinked with divinylbenzene.
  10. The suspension comprising radioactive microspheres according to at least one of claims 4-9, characterized in that the suspension further comprises water for injection.
  11. The suspension comprising radioactive microspheres according to at least one of claims 4-10, wherein the radionuclides are selected from yttrium [ 90 Y], and each mL of the suspension comprises yttrium [ 90 Y] with an activity of 300-700 MBq.
  12. The suspension comprising radioactive microspheres according to at least one of claims 4-11, characterized in that the radionuclides are selected from yttrium [ 90 Y], the material of the resin microspheres is selected from sulfonated polystyrene partially crosslinked with divinylbenzene, the suspension further comprises water for injection, and each mL of the suspension comprises yttrium [ 90 Y] with an activity of 300-700 MBq.
  13. A preparation method for a suspension comprising radioactive microspheres, characterized in that , the method comprises: mixing resin microspheres with a radionuclide compound in a solution to react, thereby obtaining the suspension comprising radioactive microspheres; wherein the material of the resin microspheres comprises at least one of polystyrene, polyethylene, or polydivinylbenzene, or a crosslinked polymer thereof, and the radioactive microspheres have an average particle size of from 25 µm to 40 µm, and a non-spherical ratio of 5% or less.
  14. The preparation method according to claim 13, characterized in that the resin microspheres are subjected to sulfonation, nitration or carbonization treatment prior to being mixed with the radionuclide compound.
  15. A preparation method for a suspension, comprising: mixing the resin microspheres and a radionuclide compound in a solution for reacting to obtain the suspension comprising radioactive microspheres; wherein in the suspension, the radioactive microspheres have an average particle size of 25 µm to 40 µm and a non-spherical ratio of 5% less.
  16. The preparation method according to claim 15, wherein the resin microspheres are subjected to sulfonation, nitration or carbonization treatment prior to being mixed with the radionuclide compound.
  17. Use of The suspension according to any one of claims 1 to 12, or the suspension prepared by the method according to any one of claims 13-16 in the preparation of a medicament for treating a tumor, wherein the tumor is preferably a primary or secondary liver cancer.
  18. A method of treating a tumor, comprising: administering to a tumor patient a suspension, wherein the suspension comprises radioactive microspheres, and the radioactive microspheres comprise resin microspheres and radionuclides loaded on the resin microspheres, the radioactive microspheres have an average particle size of 25 µm to 40 µm, and the radioactive microspheres have a non-spherical ratio of 5% or less.
  19. The method according to claim 18, wherein the tumor is primary or secondary liver cancer.
  20. The method according to claim 18 or 19, wherein the non-spherical ratio means the ratio of the number of non-spherical radioactive microspheres to the total number of radioactive microspheres in the suspension, and a non-spherical radioactive microsphere is a radioactive microsphere with a minimum radius of less than 75% of the radius of an initial microsphere; and/or, the material of the resin microspheres is selected from at least one of crosslinked polystyrene resin, crosslinked polyethylene resin and crosslinked polydivinylbenzene resin, preferably the material of the resin microspheres is selected from a polystyrene resin carrying sulfonic acid groups and crosslinked with divinylbenzene; and/or, the resin microspheres are any one of resin microspheres carrying sulfonic acid groups, resin microspheres carrying nitro groups, and carbonized resin microspheres; and/or, the radionuclides are selected from an isotope of at least one of yttrium, lutetium, indium, holmium, samarium, iodine, phosphorus, iridium, or rhenium, preferably the radionuclides are selected from yttrium [ 90 Y], and each mL of the suspension comprises yttrium [ 90 Y] with an activity of 300-700 MBq.

Description

This application claims the priority of Chinese Patent Application No. 2023108208986 filed on July 6, 2023, the disclosure of which applications are incorporated herein by reference in their entirety. Technical Field The present application relates to the medical field, and specifically to a suspension comprising radioactive microspheres, and preparation methods and uses thereof. Background There are currently many treatments for malignant tumors, including chemotherapy, radiation therapy, interventional therapy, and bio-immunotherapy. Radiation therapy has become a key treatment for certain cancers as most patients have been diagnosed with cancer at an intermediate to advanced stage, losing the opportunity for surgical treatment, and are no longer sensitive to chemotherapeutic drugs after multiple chemotherapy treatments. Radioactive microsphere therapy involves preparing radioactive materials into microspheres of regular size, and the microspheres are injected into the arterial blood supply of the target organ and emit large doses of high-energy rays to kill tumor tissue. Due to the limited tissue penetration depth of the rays, nearby healthy tissues are spared. Radioactive microspheres mainly comprise a carrier and a nuclide loaded on the carrier, and the nuclides currently being used in radioactive microspheres include yttrium[90Y], phosphorus[32P], iodine[131I], iodine[125I], technetium[99mTc], rhenium[99mTc], and holmium[166Ho]. Resin microspheres, which have a density closer to that of blood and are thus less likely to settle, have been used as carriers clinically, especially in the treatment of liver cancer (HCC). Although radioactive microsphere therapy is less harmful to patients' normal tissues, some patients still experience adverse reactions after being subjected to the radioactive microsphere therapy, and the existing radioactive microspheres are more effective against small tumors with a volume of <10 cc, and the distribution of radioactive microspheres within the boundaries of large tumors with a volume of>10 cc, especially in deeper parts of the tumors, needs to be improved. Summary In view of this, the present application provides a suspension comprising radioactive microspheres and preparation methods and uses thereof, aiming to reduce the adverse reactions that the existing radioactive microspheres bring about and improve therapeutic effects. In a first aspect, the present application provides a suspension comprising radioactive microspheres, wherein the suspension comprises radioactive microspheres; the radioactive microspheres comprise resin microspheres and radionuclides loaded on the resin microspheres; the radioactive microspheres have an average particle size of 25 µm to 40 µm; and the radioactive microspheres have a non-spherical ratio of 5% or less. Alternatively, the non-spherical ratio means the ratio of the number of non-spherical radioactive microspheres to the total number of radioactive microspheres in the suspension, and a non-spherical radioactive microsphere is a radioactive microsphere with a minimum radius of less than 75% of the radius of an initial microsphere. Alternatively, the percentage of radioactive microspheres of 20 µm to 60 µm in the suspension is greater than 85% in terms of the number of the radioactive microspheres. Alternatively, the material of the resin microspheres is at least one material selected from the group consisting of crosslinked polystyrene resin, crosslinked polyethylene resin, and crosslinked polydivinylbenzene resin. Alternatively, the resin microspheres are any one of resin microspheres with sulfonic acid groups, resin microspheres with nitro groups, and carbonized resin microspheres. Alternatively, the radionuclides are selected from an isotope of at least one of yttrium, lutetium, indium, holmium, samarium, iodine, phosphorus, iridium, or rhenium. Alternatively, the radioactive microspheres of the suspension have a non-spherical ratio of 2% or less. Alternatively, the material of the resin microspheres is selected from the group consisting of a polystyrene resin with sulfonic acid groups and crosslinked with divinylbenzene. Alternatively, the radionuclides are selected from yttrium [90Y]. Alternatively, the suspension comprises yttrium [90Y] with an activity of 300-700 MBq per milliliter (1 mL). Alternatively, the suspension further comprises water for injections. In a second aspect, the present application provides a suspension comprising radioactive microspheres, wherein the radioactive microspheres comprise resin microspheres and radionuclides loaded on the resin microspheres, the material of the resin microspheres comprises at least one of polystyrene, polyethylene, or polydivinylbenzene, or a crosslinked polymer thereof, and the radioactive microspheres have an average particle size of 25 µm to 40 µm, and a non-spherical ratio of 5% or less. Alternatively, the non-spherical ratio means the ratio of the number of non-spherical radi