CN114699542B - Radioactive glass microsphere - Google Patents
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- CN114699542B CN114699542B CN202210297070.2A CN202210297070A CN114699542B CN 114699542 B CN114699542 B CN 114699542B CN 202210297070 A CN202210297070 A CN 202210297070A CN 114699542 B CN114699542 B CN 114699542B
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- 239000011521 glass Substances 0.000 title claims abstract description 110
- 230000002285 radioactive effect Effects 0.000 title claims abstract description 105
- 239000004005 microsphere Substances 0.000 title claims abstract description 102
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims abstract description 15
- BDAGIHXWWSANSR-NJFSPNSNSA-N hydroxyformaldehyde Chemical compound O[14CH]=O BDAGIHXWWSANSR-NJFSPNSNSA-N 0.000 claims abstract description 13
- SIWVEOZUMHYXCS-UHFFFAOYSA-N oxo(oxoyttriooxy)yttrium Chemical compound O=[Y]O[Y]=O SIWVEOZUMHYXCS-UHFFFAOYSA-N 0.000 claims abstract description 13
- 229910000018 strontium carbonate Inorganic materials 0.000 claims abstract description 13
- MMKQUGHLEMYQSG-UHFFFAOYSA-N oxygen(2-);praseodymium(3+) Chemical compound [O-2].[O-2].[O-2].[Pr+3].[Pr+3] MMKQUGHLEMYQSG-UHFFFAOYSA-N 0.000 claims abstract description 9
- 229910003447 praseodymium oxide Inorganic materials 0.000 claims abstract description 9
- 229910052814 silicon oxide Inorganic materials 0.000 claims abstract description 9
- 239000002245 particle Substances 0.000 claims description 7
- 235000012239 silicon dioxide Nutrition 0.000 claims description 3
- 239000000377 silicon dioxide Substances 0.000 claims description 3
- VWQVUPCCIRVNHF-OUBTZVSYSA-N Yttrium-90 Chemical compound [90Y] VWQVUPCCIRVNHF-OUBTZVSYSA-N 0.000 abstract description 21
- 206010028980 Neoplasm Diseases 0.000 abstract description 17
- 230000009286 beneficial effect Effects 0.000 abstract description 16
- 238000000034 method Methods 0.000 abstract description 14
- 238000002591 computed tomography Methods 0.000 abstract description 13
- AMWRITDGCCNYAT-UHFFFAOYSA-L hydroxy(oxo)manganese;manganese Chemical compound [Mn].O[Mn]=O.O[Mn]=O AMWRITDGCCNYAT-UHFFFAOYSA-L 0.000 abstract description 12
- 238000001727 in vivo Methods 0.000 abstract description 10
- 238000003384 imaging method Methods 0.000 abstract description 7
- RVTZCBVAJQQJTK-UHFFFAOYSA-N oxygen(2-);zirconium(4+) Chemical compound [O-2].[O-2].[Zr+4] RVTZCBVAJQQJTK-UHFFFAOYSA-N 0.000 abstract description 7
- CHWRSCGUEQEHOH-UHFFFAOYSA-N potassium oxide Chemical compound [O-2].[K+].[K+] CHWRSCGUEQEHOH-UHFFFAOYSA-N 0.000 abstract description 7
- 229910001950 potassium oxide Inorganic materials 0.000 abstract description 7
- KOPBYBDAPCDYFK-UHFFFAOYSA-N caesium oxide Chemical compound [O-2].[Cs+].[Cs+] KOPBYBDAPCDYFK-UHFFFAOYSA-N 0.000 abstract description 6
- 229910001942 caesium oxide Inorganic materials 0.000 abstract description 6
- BPUBBGLMJRNUCC-UHFFFAOYSA-N oxygen(2-);tantalum(5+) Chemical compound [O-2].[O-2].[O-2].[O-2].[O-2].[Ta+5].[Ta+5] BPUBBGLMJRNUCC-UHFFFAOYSA-N 0.000 abstract description 6
- 229910001936 tantalum oxide Inorganic materials 0.000 abstract description 6
- 229910001928 zirconium oxide Inorganic materials 0.000 abstract description 5
- 230000008569 process Effects 0.000 abstract description 4
- 239000002331 radioactive microsphere Substances 0.000 abstract description 3
- 238000002834 transmittance Methods 0.000 abstract description 3
- 230000005855 radiation Effects 0.000 description 17
- 239000000203 mixture Substances 0.000 description 11
- NUJOXMJBOLGQSY-UHFFFAOYSA-N manganese dioxide Chemical group O=[Mn]=O NUJOXMJBOLGQSY-UHFFFAOYSA-N 0.000 description 10
- CIOAGBVUUVVLOB-OUBTZVSYSA-N strontium-89 Chemical compound [89Sr] CIOAGBVUUVVLOB-OUBTZVSYSA-N 0.000 description 10
- 229940006509 strontium-89 Drugs 0.000 description 9
- CIOAGBVUUVVLOB-BJUDXGSMSA-N strontium-87 Chemical compound [87Sr] CIOAGBVUUVVLOB-BJUDXGSMSA-N 0.000 description 7
- 230000000694 effects Effects 0.000 description 6
- PUDIUYLPXJFUGB-OUBTZVSYSA-N praseodymium-142 Chemical compound [142Pr] PUDIUYLPXJFUGB-OUBTZVSYSA-N 0.000 description 6
- 238000010968 computed tomography angiography Methods 0.000 description 5
- 230000009477 glass transition Effects 0.000 description 5
- 238000012360 testing method Methods 0.000 description 5
- 230000004071 biological effect Effects 0.000 description 4
- NQKXFODBPINZFK-UHFFFAOYSA-N dioxotantalum Chemical group O=[Ta]=O NQKXFODBPINZFK-UHFFFAOYSA-N 0.000 description 4
- 239000002994 raw material Substances 0.000 description 4
- 229910052777 Praseodymium Inorganic materials 0.000 description 3
- 229910045601 alloy Inorganic materials 0.000 description 3
- 239000000956 alloy Substances 0.000 description 3
- 230000008859 change Effects 0.000 description 3
- 230000002349 favourable effect Effects 0.000 description 3
- 238000002594 fluoroscopy Methods 0.000 description 3
- 239000007789 gas Substances 0.000 description 3
- 239000000843 powder Substances 0.000 description 3
- 238000000634 powder X-ray diffraction Methods 0.000 description 3
- 239000007787 solid Substances 0.000 description 3
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 2
- 229910000722 Didymium Inorganic materials 0.000 description 2
- 241000224487 Didymium Species 0.000 description 2
- 229910004298 SiO 2 Inorganic materials 0.000 description 2
- 238000002441 X-ray diffraction Methods 0.000 description 2
- MCMNRKCIXSYSNV-UHFFFAOYSA-N ZrO2 Inorganic materials O=[Zr]=O MCMNRKCIXSYSNV-UHFFFAOYSA-N 0.000 description 2
- HNZHVTZRIBKSIO-UHFFFAOYSA-N [Cs+].[Cs+].[O-][O-] Chemical group [Cs+].[Cs+].[O-][O-] HNZHVTZRIBKSIO-UHFFFAOYSA-N 0.000 description 2
- 238000010521 absorption reaction Methods 0.000 description 2
- 230000000903 blocking effect Effects 0.000 description 2
- 239000000470 constituent Substances 0.000 description 2
- 230000001276 controlling effect Effects 0.000 description 2
- 230000007423 decrease Effects 0.000 description 2
- 230000004907 flux Effects 0.000 description 2
- 239000000155 melt Substances 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 230000001575 pathological effect Effects 0.000 description 2
- PUDIUYLPXJFUGB-UHFFFAOYSA-N praseodymium atom Chemical compound [Pr] PUDIUYLPXJFUGB-UHFFFAOYSA-N 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- 230000002035 prolonged effect Effects 0.000 description 2
- 230000001105 regulatory effect Effects 0.000 description 2
- LIVNPJMFVYWSIS-UHFFFAOYSA-N silicon monoxide Chemical compound [Si-]#[O+] LIVNPJMFVYWSIS-UHFFFAOYSA-N 0.000 description 2
- 229910052712 strontium Inorganic materials 0.000 description 2
- CIOAGBVUUVVLOB-UHFFFAOYSA-N strontium atom Chemical compound [Sr] CIOAGBVUUVVLOB-UHFFFAOYSA-N 0.000 description 2
- 230000009885 systemic effect Effects 0.000 description 2
- 238000009827 uniform distribution Methods 0.000 description 2
- 238000001291 vacuum drying Methods 0.000 description 2
- 229910052727 yttrium Inorganic materials 0.000 description 2
- VWQVUPCCIRVNHF-UHFFFAOYSA-N yttrium atom Chemical compound [Y] VWQVUPCCIRVNHF-UHFFFAOYSA-N 0.000 description 2
- 230000004913 activation Effects 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 229910052786 argon Inorganic materials 0.000 description 1
- 210000001367 artery Anatomy 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 238000000889 atomisation Methods 0.000 description 1
- 239000003519 biomedical and dental material Substances 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 238000013170 computed tomography imaging Methods 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 230000008878 coupling Effects 0.000 description 1
- 238000010168 coupling process Methods 0.000 description 1
- 238000005859 coupling reaction Methods 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 231100000263 cytotoxicity test Toxicity 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 238000000113 differential scanning calorimetry Methods 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 230000002708 enhancing effect Effects 0.000 description 1
- 239000001307 helium Substances 0.000 description 1
- 229910052734 helium Inorganic materials 0.000 description 1
- SWQJXJOGLNCZEY-UHFFFAOYSA-N helium atom Chemical compound [He] SWQJXJOGLNCZEY-UHFFFAOYSA-N 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 238000002386 leaching Methods 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 229910052754 neon Inorganic materials 0.000 description 1
- GKAOGPIIYCISHV-UHFFFAOYSA-N neon atom Chemical compound [Ne] GKAOGPIIYCISHV-UHFFFAOYSA-N 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 238000010791 quenching Methods 0.000 description 1
- 230000000171 quenching effect Effects 0.000 description 1
- 230000000191 radiation effect Effects 0.000 description 1
- 239000012217 radiopharmaceutical Substances 0.000 description 1
- 229940121896 radiopharmaceutical Drugs 0.000 description 1
- 230000002799 radiopharmaceutical effect Effects 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- 238000007086 side reaction Methods 0.000 description 1
- CIOAGBVUUVVLOB-AHCXROLUSA-N strontium-84 Chemical compound [84Sr] CIOAGBVUUVVLOB-AHCXROLUSA-N 0.000 description 1
- CIOAGBVUUVVLOB-YPZZEJLDSA-N strontium-86 Chemical compound [86Sr] CIOAGBVUUVVLOB-YPZZEJLDSA-N 0.000 description 1
- CIOAGBVUUVVLOB-IGMARMGPSA-N strontium-88 atom Chemical compound [88Sr] CIOAGBVUUVVLOB-IGMARMGPSA-N 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 238000003325 tomography Methods 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
Classifications
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K51/00—Preparations containing radioactive substances for use in therapy or testing in vivo
- A61K51/12—Preparations containing radioactive substances for use in therapy or testing in vivo characterised by a special physical form, e.g. emulsion, microcapsules, liposomes, characterized by a special physical form, e.g. emulsions, dispersions, microcapsules
- A61K51/1241—Preparations containing radioactive substances for use in therapy or testing in vivo characterised by a special physical form, e.g. emulsion, microcapsules, liposomes, characterized by a special physical form, e.g. emulsions, dispersions, microcapsules particles, powders, lyophilizates, adsorbates, e.g. polymers or resins for adsorption or ion-exchange resins
- A61K51/1244—Preparations containing radioactive substances for use in therapy or testing in vivo characterised by a special physical form, e.g. emulsion, microcapsules, liposomes, characterized by a special physical form, e.g. emulsions, dispersions, microcapsules particles, powders, lyophilizates, adsorbates, e.g. polymers or resins for adsorption or ion-exchange resins microparticles or nanoparticles, e.g. polymeric nanoparticles
- A61K51/1251—Preparations containing radioactive substances for use in therapy or testing in vivo characterised by a special physical form, e.g. emulsion, microcapsules, liposomes, characterized by a special physical form, e.g. emulsions, dispersions, microcapsules particles, powders, lyophilizates, adsorbates, e.g. polymers or resins for adsorption or ion-exchange resins microparticles or nanoparticles, e.g. polymeric nanoparticles micro- or nanospheres, micro- or nanobeads, micro- or nanocapsules
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K49/00—Preparations for testing in vivo
- A61K49/04—X-ray contrast preparations
- A61K49/0433—X-ray contrast preparations containing an organic halogenated X-ray contrast-enhancing agent
- A61K49/0447—Physical forms of mixtures of two different X-ray contrast-enhancing agents, containing at least one X-ray contrast-enhancing agent which is a halogenated organic compound
- A61K49/0476—Particles, beads, capsules, spheres
- A61K49/048—Microparticles, microbeads, microcapsules, microspheres, i.e. having a size or diameter higher or equal to 1 micrometer
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
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- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Nanotechnology (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Engineering & Computer Science (AREA)
- Optics & Photonics (AREA)
- Dispersion Chemistry (AREA)
- Physics & Mathematics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Glass Compositions (AREA)
Abstract
The invention provides a radioactive glass microsphere, which consists of 10-30% of yttrium oxide, 35-70% of silicon oxide, 0-25% of strontium carbonate, 0-40% of any one of manganese oxide and potassium oxide, 0-25% of praseodymium oxide, 0-25% of cesium oxide, 0-25% of zirconium oxide and 0-25% of tantalum oxide. 10-30% of yttrium oxide contained in the radioactive glass microspheres can release a certain dose of radioactive element yttrium-90 after being activated in vivo to provide higher radiant energy, and the radioactive microspheres have lower density of 2-3.7 g/cc, are composed of inorganic matters, have non-contractibility and non-transmittance, are beneficial to being smoothly conveyed to tumor sites in vivo and uniformly distributed at the tumor sites, and are beneficial to being visually guided in the conveying process by using CT scanning, perspective and X-ray imaging.
Description
Technical Field
The invention relates to the technical field of biomedical materials, in particular to radioactive glass microspheres.
Background
The treatment method of external irradiation is utilized to treat malignant tumors, and the irradiation dose is greatly limited in consideration of avoiding damage to normal tissues near an irradiation part or causing systemic side effects, so that the dose of external irradiation cannot reach the radical treatment dose of tumors.
The radioactive microsphere is infused into a human body through a local artery, so that the radioactive nuclide is concentrated in the tissue of a tumor area, and compared with external irradiation, the treatment method for generating radical irradiation effect on the tumor area has the advantages of small radiation damage to local normal tissue, no systemic side reaction and good application prospect.
The key to internal irradiation therapy is to enable the radiopharmaceutical to be distributed evenly within the tumor to cover the entire tumor tissue and to provide sufficient radiant energy to reach the radical dose of the tumor, and to require full range fluoroscopic guidance.
Therefore, there is a need to develop a novel radioactive glass microsphere with high radiant activity energy so as to be smoothly delivered in vivo under perspective guidance and achieve uniform distribution at tumor sites.
Disclosure of Invention
The invention aims to provide a novel radioactive glass microsphere with high radiation active energy, so that the radioactive glass microsphere can be smoothly conveyed in a human body under the guidance of fluoroscopy and is beneficial to achieving uniform distribution at a tumor part.
To achieve the above object, the radioactive glass microspheres of the present invention have a density of 2 to 3.7 g/cc and consist of the following components:
10-30% by mole of yttrium oxide, 35-70% by mole of silicon oxide, 0-25% by mole of strontium carbonate, 0-40% by mole of any one of manganese oxide and potassium oxide, 0-25% by mole of praseodymium oxide, 0-25% by mole of cesium oxide, 0-25% by mole of zirconium oxide, and 0-25% by mole of tantalum oxide.
The radioactive glass microsphere has the beneficial effects that: 10-30% of yttrium oxide contained in the radioactive glass microspheres can release a certain dose of radioactive element yttrium-90 after being activated in vivo so as to provide higher radiant energy, and the radioactive microspheres have lower density of 2-3.7 g/cc, are composed of inorganic matters, have non-contractibility and non-transmittance, are beneficial to smoothly conveying to tumor sites in vivo and uniformly distributing to the tumor sites, and are beneficial to visually guiding in the conveying process by using CT scanning, perspective and X-ray imaging.
In some embodiments, the radioactive glass microspheres have an average particle size of 15 to 200 microns and a glass transition temperature of 620 to 670 degrees celsius. The beneficial effects are that: facilitating the smooth transportation of the radioactive glass microspheres in the body and being non-contractible.
In some embodiments, the mole percent of yttrium oxide is 15-20%. The beneficial effects are that: is beneficial to regulating and controlling the density and radiation dosage of the radioactive glass microsphere and is beneficial to the smooth transportation of the radioactive glass microsphere in the body.
In some embodiments, the mole percent of the silicon oxide is 50-65%.
In some embodiments, the mole percent of strontium carbonate is 10-25%.
In some embodiments, the mole percent of praseodymium oxide is from 5 to 15%.
In some embodiments, the molar percentage of cesium oxide is 5-15%.
In some embodiments, the mole percent of the silicon oxide is 40-60%. The beneficial effects are that: is beneficial to regulating and controlling the density of the radioactive glass microspheres and is beneficial to the smooth transportation of the radioactive glass microspheres in the body.
In some embodiments, the mole percent of manganese oxide is 10-30%.
In some embodiments, the mole percent of tantalum oxide is 5-15%.
In some aspects, the yttrium oxide is yttrium oxide, the silicon oxide is silicon dioxide, the strontium carbonate is strontium carbonate, the manganese oxide is manganese dioxide, the potassium oxide is potassium oxide, the praseodymium oxide is didymium oxide, the cesium oxide is cesium dioxide, the zirconium oxide is zirconium dioxide, and the tantalum oxide is tantalum dioxide.
Drawings
FIG. 1 is an XRD pattern of radioactive glass microspheres of the invention, having sample numbers DS101, DS102, DS103, DS105, DS106, DS107, DS109, DS110, DS111, DS112 and DS114, respectively;
FIG. 2 is a microscopic morphology of radioactive glass microspheres of sample number DS101 of the present invention;
FIG. 3a is a graph showing the CT angiography of radioactive glass microspheres of sample number DS104 placed in a glass vial after CT scanning at a peak voltage of 120 kV;
FIG. 3b is a graph showing the CT angiography of the radioactive glass microspheres of sample number DS107 placed in a glass vial after CT scanning at a peak voltage of 120 kV;
FIG. 3c is a graph showing the sample DS112 radioactive glass microspheres in a glass vial of the present invention after CT scanning at a peak voltage of 120 kV, and CT angiography;
FIG. 3d is a graph showing the sample DS115 radioactive glass microspheres in a glass vial of the present invention after CT scanning at a peak voltage of 120 kV, and CT angiography;
FIG. 4a is a graph showing the variation of yttrium-90 radiation dose over 168 hours after irradiation of 100 mg of radioactive glass microspheres according to the present invention, wherein the sample numbers are DS103, DS107, DS108, DS109, DS113, DS114 and DS115, respectively;
FIG. 4b is a graph showing the variation trend of the radiation dose of praseodymium-142 within 168 hours after the irradiation of the radioactive glass microspheres with sample numbers of DS103, DS107, DS108, DS109, DS113, DS114 and DS115 and mass of 100 mg respectively;
FIG. 4c is a graph showing the variation trend of the irradiation dose of strontium-89 within 168 hours after the irradiation of the radioactive glass microspheres with sample numbers DS103, DS107, DS108, DS109, DS113, DS114 and DS115, respectively, and the mass of 100 mg according to the present invention;
FIG. 4d is a graph showing the variation trend of the irradiation dose of strontium-87 in 168 hours after the irradiation of the radioactive glass microspheres with sample numbers DS103, DS107, DS108, DS109, DS113, DS114 and DS115, respectively, and the mass of 100 mg according to the present invention;
FIG. 4e is a graph showing the variation of the purity of yttrium-90 nuclides over time after irradiation for 168 hours after irradiation of 100 mg of radioactive glass microspheres according to the present invention, wherein the sample numbers are DS103, DS107, DS108, DS109, DS113, DS114 and DS115, respectively.
Detailed Description
For the purpose of making the objects, technical solutions and advantages of the embodiments of the present invention more apparent, the technical solutions in the embodiments of the present invention will be clearly and completely described below, and it is apparent that the described embodiments are some embodiments of the present invention, but not all embodiments. All other embodiments, which can be made by those skilled in the art based on the embodiments of the invention without making any inventive effort, are intended to be within the scope of the invention. Unless otherwise defined, technical or scientific terms used herein should be given the ordinary meaning as understood by one of ordinary skill in the art to which this invention belongs. As used herein, the word "comprising" and the like means that elements or items preceding the word are included in the element or item listed after the word and equivalents thereof without precluding other elements or items.
Aiming at the problems existing in the prior art, the embodiment of the invention provides a radioactive glass microsphere with the density of 2-3.7 g/cc, which consists of the following components:
10-30% by mole of yttrium oxide, 35-70% by mole of silicon oxide, 0-25% by mole of strontium carbonate, 0-40% by mole of any one of manganese oxide and potassium oxide, 0-25% by mole of praseodymium oxide, 0-25% by mole of cesium oxide, 0-25% by mole of zirconium oxide, and 0-25% by mole of tantalum oxide.
Specifically, the mole percentages are mole percentages of each constituent component in the radioactive glass microsphere.
In some embodiments of the invention, the yttrium oxide is yttrium oxide (Y) 2 O 3 ) The silicon oxide is silicon dioxide (SiO 2 ) The strontium carbonate is strontium carbonate (SrCO) 3 ) The manganese oxide is manganese dioxide (MnO), and the potassium oxide is potassium oxide (K) 2 O), the praseodymium oxide is didymium trioxide (Pr) 2 O 3 ) The cesium oxide is cesium dioxide (CsO) 2 ) The zirconium oxide is zirconium dioxide (ZrO 2 ) The tantalum oxide is tantalum dioxide (TaO) 2 )。
In some embodiments of the invention, the radioactive glass microspheres are solid powder, and the average particle size of the radioactive glass microspheres is not more than 15-200 microns, which is beneficial to smooth transportation in vivo.
In some embodiments of the invention, the radioactive glass microspheres have a glass transition temperature of 620-670 ℃.
The technical scheme of the invention is explained in detail by examples 1-3.
Example 1
The present embodiments provide a first set of radioactive glass microspheres and a method of preparing each radioactive glass microsphere in the first set of radioactive glass microspheres. The preparation method of each radioactive glass microsphere in the first radioactive glass microsphere group specifically comprises the following steps:
s11: providing a uniformly mixed first inorganic mixture as a raw material, placing the raw material at 100 ℃ for vacuum drying for 1-3 hours, and preheating the raw material to 1350-1600 ℃ in a high-temperature box-type furnace to obtain a melt.
S12: quenching the melt in water to obtain a frit, and then vacuum drying the frit at 100 ℃ for 24 hours to obtain a dried frit.
S13: the dried frit was ground into a solid powder using a planetary ball mill.
S14: and (3) putting the solid powder into a gas flame to remelt so as to obtain spheroidized melt.
S15: and (3) cooling and screening the spheroidized melt in sequence to obtain the radioactive glass microspheres with the average particle size of 15-200 microns.
In the step S14 of some embodiments of the present invention, the gas flame is an oxygen flame.
In other embodiments of the invention, the remelting is performed using a radio frequency induction coupling or direct current plasma arc torch discharge method. The plasma gas is any one of argon, helium or neon to improve the purity of the obtained radioactive glass microspheres.
In the step S15 of some embodiments of the present invention, the spheroidization is performed by an atomization method or a rotating electrode method, which are conventional technical means used by those skilled in the art, and are not described herein.
Each radioactive glass microsphere in the first inorganic mixture and the first set of radioactive glass microspheres comprises 15-20% by mole of Y 2 O 3 50-65 mol% of SiO 2 10-25 mol% SrCO 3 And 5-15 mol% Pr 2 O 3 Composition is prepared.
Specifically, table 1 provides the mole percentages of each constituent component of the radioactive glass microspheres having sample numbers DS101 to DS115, respectively.
TABLE 1
In some embodiments of the invention, the following are set forth in Table 1Pr of (2) 2 O 3 Replaced by CsO 2 15 new radioactive glass microspheres were formed.
In example 1 of the present invention, the XRD patterns shown in FIG. 1 were obtained by examining the crystallization properties of radioactive glass microspheres having sample numbers DS101, DS102, DS103, DS105, DS106, DS107, DS109, DS110, DS111, DS112 and DS114 by X-Ray powder Diffraction (XRD). The specific implementation of the X-ray powder diffraction method is a means known to those skilled in the art, and will not be described herein.
Referring to fig. 1, 14 radioactive glass microspheres, sample nos. DS101 to DS114, each exhibited significant amorphous characteristics. As is known in the art, amorphous alloys have long-range disorder and short-range order characteristics, and have no defects such as grain boundaries and stacking faults in structure, so that the amorphous alloys are superior to crystalline alloys with the same composition in terms of strength, toughness, stability and the like.
In example 1 of the present invention, the structure of the radioactive glass microspheres with sample number DS101 was observed by using a Hitachi S-4700 scanning electron microscope at a magnification of 300 times, and a microstructure chart shown in FIG. 2 was obtained. Referring to FIG. 2, the radioactive glass microspheres with sample number DS101 were excellent in sphericity.
In example 1 of the present invention, 15 kinds of radioactive glass microspheres described in table 1 were tested for glass transition temperature Tg by a differential scanning calorimeter (Differential Scanning Calorimetry, DSC) method according to ASTM E-1356 test standard, and 15 kinds of radioactive glass microspheres described in table 1 were examined for density ρ according to ASTM B923 test standard, and the test results obtained are summarized in table 2.
TABLE 2
Referring to table 2, the density of 15 radioactive glass microspheres is distributed in the range of 3.0 g/cc-3.6 g/cc, the glass transition temperature is distributed in the range of 627-666 ℃, the higher glass transition temperature is favorable for enhancing the stability of the radioactive glass microspheres, the lower density is favorable for smooth in-vivo transportation, the average particle size of 15-200 microns and the composition components of the radioactive glass microspheres are inorganic matters, and the radioactive glass microspheres can be uniformly distributed at the tumor part and are not contractible after being smoothly transported to the tumor part in vivo, so that the radionuclide concentration in the tumor tissue is favorable, and a good operation basis is provided for realizing radical treatment of tumors.
Example 1 of the present invention uses an axial siemens 128 somatim flash definition scan (Computerized Tomography) to axially CT scan radioactive glass microspheres of different sample numbers loosely placed in different vials at different voltage peaks to obtain different Hounsfield Units (HU) under CT scan as shown in table 3. The specific implementation of the axial siemens 128 somom flash definition scan is a well-known means for those skilled in the art, and will not be described herein.
Wherein the first HU value is obtained at a voltage peak of 70 kv and the second HU value is obtained at a voltage peak of 120 kv. The thickness of the radioactive glass microspheres in each vial was 1mm and the scanning pitch was 0.5.
TABLE 3 Table 3
As a common knowledge, the working principle of CT in medical development is to measure the human body according to the difference of the absorption and transmittance of X-rays by different tissues of the human body. In particular, imaging is performed with the degree of blocking of X-rays, the greater the density and thickness of the substance, the greater the degree of blocking, the better the imaging effect, i.e., the higher the value of HU. While the HU suitable for medical CT scan has a value of about 6000-13000, and the 15 radioactive glass microspheres with sample numbers DS101 to DS115 shown in Table 3 have a value in the range of 6000-7200, so that the HU is suitable for medical CT, i.e. after the radioactive glass microspheres are introduced into human body, the medical CT can be used for scanning, perspective and X-ray imaging for accurate guiding and positioning.
Fig. 3a to 3d are images of radioactive glass microspheres with sample numbers DS104, DS107, DS112 and DS115 respectively placed in different glass bottles, after CT scanning at a peak voltage of 120 kv, the radioactive glass microspheres in the corresponding glass bottles were placed on a layer of white paper for CT angiography. Further referring to fig. 3a to 3d, it can be seen that the radioactive glass microspheres with sample numbers DS104, DS107, DS112 and DS115 have good CT imaging performance.
In-vitro cytotoxicity test was performed according to the ISO10993 standard in example 1 of the present invention, and the percentage of biological activity of the radioactive glass microsphere leaching solutions of different mass concentrations after 24 hours was examined to obtain the experimental results shown in table 4.
TABLE 4 Table 4
Referring to Table 4, when the concentration of the impregnating solution was 100%, the percentages of the biological activities of the radioactive glass microspheres of the sample numbers DS103, DS107 and DS110 were 70% or more, except that the percentages of the biological activities of the radioactive glass microspheres of the sample numbers were relatively low. When the concentration of the impregnating solution is 75%, 50% and 25%, respectively, the biological activity percentage corresponding to the radioactive glass microspheres of all sample numbers is above 70%. It can be seen that each radioactive glass microsphere of the first set of radioactive glass microspheres substantially meets the requirements for biocompatibility in the biomedical material field.
Each radioactive glass microsphere of the first set of radioactive glass microspheres of embodiment 1 of the present invention contains yttrium element, strontium element and praseodymium element.
Wherein the method comprises the steps ofThe high-energy beta rays of the yttrium-90 of yttrium element after thermal neutron activation can continuously act on the tumor. The half-life period of Pr-142 is longer and the absorption sectional area is large in the decay products of praseodymium. The strontium element Sr-89 exists as stable strontium-84, strontium-86, strontium-87 and strontium-88 isotopes, and the mass percentages of the three isotopes are respectively 0.56%, 9.86%, 7.0% and 82.58%. The half lives of the strontium-89 and the strontium-89 are longer than those of the yttrium-90, so that the radioactive glass microspheres with sample numbers of DS103, DS107, DS108, DS109, DS113, DS114 and DS115 and mass of 100 mg are irradiated in the embodiment 1, and the irradiation doses of yttrium-90, strontium-87, strontium-89 and praseodymium-142 and the change conditions of the nuclide purity of yttrium-90 with the time after the irradiation within 0-168 hours after the end of the irradiation are examined respectively, so as to obtain the comparison graphs of the change trend of the irradiation doses of yttrium-90, strontium-87, strontium-89 and praseodymium-142 and the change trend of the nuclide purity of yttrium-90 with the time after the irradiation, respectively shown in fig. 4a to 4 e. Neutron flux of 2X 10 for irradiation -14 Neutrons/cm.s. The specific implementation of the irradiation is a routine technical means for a person skilled in the art, and will not be described here in detail.
Referring to fig. 4a, as the time after the irradiation is completed is prolonged, the radiation dose of yttrium-90 steadily decreases from 10000-17000MBq to 2000-6000MBq within 168 hours after the irradiation is completed, namely, after the radioactive glass microspheres with sample numbers of DS103, DS107, DS108, DS109, DS113, DS114 and DS115 are activated by neutrons, yttrium-90 can continuously and stably release high-energy beta radiation, and the attenuation trend of the high-energy beta radiation is more gentle, which is beneficial to the subsequent practical application process, according to the size and specific pathological conditions of the target part, the radiation dose can be maintained within a reasonable range within the effective treatment time by adjusting the mass and average particle size of the radioactive glass microspheres introduced into the human body, and can continuously act on the target part.
Referring to fig. 4a and 4b, as the time after the end of irradiation was prolonged, the dose of praseodymium-142 of all samples was decreased from 1500-4500MBq to less than 10 within 168 hours from the end of irradiation, and the decrease trend was significantly faster than that of yttrium-90, so that the effect of yttrium-90 irradiation was not affected.
Referring to fig. 4c and 4d, the radiation dose of strontium-89 remains substantially between 0.5 and 2MBq for 168 hours from the end of irradiation, the radiation dose of strontium-87 drops rapidly from 600 to 1800MBq to less than 10MBq for 24 hours from the end of irradiation, and the radiation dose is 0 for 24 to 168 hours. It can be seen that the presence of strontium-89 and strontium-87 has little effect on the radiation effect of yttrium-90, and therefore, referring to fig. 4e, the purity of the nuclide of yttrium-90 has a significant tendency to increase within 24-72 hours after the end of irradiation, and reaches more than 99% within 72-168 hours.
The irradiation is performed on radioactive glass microspheres with sample numbers of DS101, DS102, DS104, DS105, DS106, DS110, DS111 and DS112, respectively, and the mass of the radioactive glass microspheres is 100 milligrams, the radiation doses of yttrium-90, strontium-87, strontium-89 and praseodymium-142 within 0 to 168 hours after the irradiation is finished, and the variation of the nuclide purity of yttrium-90 along with the time after the irradiation is similar to the variation trend shown in fig. 4a to 4e, and the description is omitted herein.
From the above analysis, since yttrium-90 can continuously and stably release high-energy beta radiation, and the attenuation trend of the high-energy beta radiation is gentle, the method is beneficial to the subsequent actual application process, and according to the size of a target part and specific pathological conditions, the irradiation dose can be maintained within a reasonable range in the effective treatment time and can continuously act on the target part by adjusting the mass and the average particle size of the radioactive glass microspheres introduced into the human body. Therefore, example 1 of the present invention also examined 15 samples described in Table 1 for neutron flux of 2X 10 -14 The mass of each sample of yttrium-90 producing a radiation dose of 4GBq, the corresponding post-irradiation time, the radiation doses of strontium-89 and praseodymium-142, and the nuclide purity of yttrium-90 after irradiation in neutron/square centimeter.sec conditions are counted as shown in Table 5.
TABLE 5
Example 2
Example 2 of the present invention provides a second set of radioactive glass microspheres, each of which is different from the first set of radioactive glass microspheres of example 1 in the preparation method of each of the radioactive glass microspheres, in that: the raw material for preparing the radioactive glass microspheres is a second inorganic mixture.
Each radioactive glass microsphere in the second inorganic mixture and the second set of radioactive glass microspheres comprises 13-30% by mole of Y 2 O 3 SiO 40-60 mol% 2 10-30 mol% MnO and 5-15 mol% ZrO 2 Composition is prepared.
Table 6 of inventive example 2 provides the mole percent content of each component of 15 radioactive glass microspheres having glass sample numbers S201 through S215.
TABLE 6
Example 2 of the present invention examined the density ρ of the 15 radioactive glass microspheres described in table 6 according to ASTM B923 test standard and the 15 radioactive glass microspheres described in table 6 loosely placed in different vials were scanned by axial CT scan at a voltage peak of 120 kv using an axial siemens 128 somom flash definition to obtain different HU values. See table 7 for density and HU values. The specific implementation of the axial siemens 128 somom flash definition scan is a well-known means for those skilled in the art, and will not be described herein. The thickness of the radioactive glass microspheres in each vial was 1mm and the scanning pitch was 0.5.
TABLE 7
Referring to Table 7, all samples had densities of 2.2-2.9 g/cc, with lower densities, facilitating smooth delivery of radioactive glass microspheres in vivo. The HU values for the samples at the voltage peaks of 120 kilovolts are 2140-10828, so that the remaining samples, except DS204 and DS205 and DS210, are suitable for medical CT scanning, fluoroscopy, and X-ray imaging.
Example 3
Embodiment 3 of the present invention provides a third set of radioactive glass microspheres, each of which is different from the method of preparing each of the radioactive glass microspheres of the first set of radioactive glass microspheres of embodiment 1 in that: the radioactive glass microspheres are prepared from a third inorganic mixture.
Each radioactive glass microsphere in the third inorganic mixture and the third set of radioactive glass microspheres comprises 13-30% by mole of Y 2 O 3 SiO 40-60 mol% 2 10-30 mol% MnO and 5-15 mol% TaO 2 Composition is prepared.
Table 8 of inventive example 3 provides the mole percentages of each component of the 15 radioactive glass microspheres with glass sample numbers S301 through S315.
TABLE 8
Example 3 of the present invention the density ρ of the 15 radioactive glass microspheres described in table 8 was examined according to ASTM B923 test standard and the 15 radioactive glass microspheres described in table 8 loosely placed in different vials were scanned axially CT at a voltage peak of 120 kv using an axial siemens 128 somom flash definition to obtain different HU values, see table 9 for density and HU values. The specific implementation of the axial siemens 128 somom flash definition scan is a well-known means for those skilled in the art, and will not be described herein. The thickness of the radioactive glass microspheres in each vial was 1mm and the scanning pitch was 0.5.
TABLE 9
Referring to Table 9, all samples had densities of 2.5-3.6 g/cc, with lower densities, facilitating smooth delivery of radioactive glass microspheres in vivo. The HU value of the sample at the voltage peak of 120 kv is 4926-18047, so that the rest of the samples except DS305, DS309 and DS313 are suitable for medical CT scan, fluoroscopy and X-ray imaging.
While embodiments of the present invention have been described in detail hereinabove, it will be apparent to those skilled in the art that various modifications and variations can be made to these embodiments. It is to be understood that such modifications and variations are within the scope and spirit of the present invention as set forth in the following claims. Moreover, the invention described herein is capable of other embodiments and of being practiced or of being carried out in various ways.
Claims (3)
1. A radioactive glass microsphere having a density of 2-3.7 g/cc, said radioactive glass microsphere comprising the following components:
15-20% by mole of yttrium oxide, 50-65% by mole of silicon oxide, 10-25% by mole of strontium carbonate, and 5-15% by mole of praseodymium oxide.
2. The radioactive glass microspheres according to claim 1, wherein the average particle size of the radioactive glass microspheres is 15-200 microns.
3. The radioactive glass microsphere according to claim 1, wherein the yttrium oxide is yttrium oxide, the silicon oxide is silicon dioxide, the strontium carbonate is strontium carbonate, and the praseodymium oxide is praseodymium oxide.
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