CN111920966A - Radioactive particle, and preparation method and application thereof - Google Patents
Radioactive particle, and preparation method and application thereof Download PDFInfo
- Publication number
- CN111920966A CN111920966A CN201910394215.9A CN201910394215A CN111920966A CN 111920966 A CN111920966 A CN 111920966A CN 201910394215 A CN201910394215 A CN 201910394215A CN 111920966 A CN111920966 A CN 111920966A
- Authority
- CN
- China
- Prior art keywords
- solution
- radionuclide
- porous
- radioactive
- porous solid
- Prior art date
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- 239000002245 particle Substances 0.000 title claims abstract description 211
- 230000002285 radioactive effect Effects 0.000 title claims abstract description 166
- 238000002360 preparation method Methods 0.000 title claims abstract description 51
- 239000007787 solid Substances 0.000 claims abstract description 108
- 150000001450 anions Chemical class 0.000 claims abstract description 82
- 150000001768 cations Chemical class 0.000 claims abstract description 78
- 239000002244 precipitate Substances 0.000 claims abstract description 70
- 229910052751 metal Inorganic materials 0.000 claims abstract description 36
- 239000002184 metal Substances 0.000 claims abstract description 36
- 206010028980 Neoplasm Diseases 0.000 claims abstract description 22
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims abstract description 19
- GWEVSGVZZGPLCZ-UHFFFAOYSA-N Titan oxide Chemical compound O=[Ti]=O GWEVSGVZZGPLCZ-UHFFFAOYSA-N 0.000 claims abstract description 16
- 239000012621 metal-organic framework Substances 0.000 claims abstract description 14
- 239000000463 material Substances 0.000 claims abstract description 12
- 239000005909 Kieselgur Substances 0.000 claims abstract description 11
- 229910021536 Zeolite Inorganic materials 0.000 claims abstract description 9
- 229960000892 attapulgite Drugs 0.000 claims abstract description 9
- 239000013310 covalent-organic framework Substances 0.000 claims abstract description 9
- HNPSIPDUKPIQMN-UHFFFAOYSA-N dioxosilane;oxo(oxoalumanyloxy)alumane Chemical compound O=[Si]=O.O=[Al]O[Al]=O HNPSIPDUKPIQMN-UHFFFAOYSA-N 0.000 claims abstract description 9
- 229910052625 palygorskite Inorganic materials 0.000 claims abstract description 9
- 229920000642 polymer Polymers 0.000 claims abstract description 9
- 239000010457 zeolite Substances 0.000 claims abstract description 9
- PNEYBMLMFCGWSK-UHFFFAOYSA-N aluminium oxide Inorganic materials [O-2].[O-2].[O-2].[Al+3].[Al+3] PNEYBMLMFCGWSK-UHFFFAOYSA-N 0.000 claims abstract description 8
- 239000003575 carbonaceous material Substances 0.000 claims abstract description 8
- 239000003814 drug Substances 0.000 claims abstract description 8
- 239000004408 titanium dioxide Substances 0.000 claims abstract description 6
- 238000003756 stirring Methods 0.000 claims description 41
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 41
- 235000002639 sodium chloride Nutrition 0.000 claims description 39
- -1 strontium-90 ions Chemical class 0.000 claims description 39
- VWQVUPCCIRVNHF-OUBTZVSYSA-N Yttrium-90 Chemical compound [90Y] VWQVUPCCIRVNHF-OUBTZVSYSA-N 0.000 claims description 32
- 150000003839 salts Chemical class 0.000 claims description 31
- 239000011148 porous material Substances 0.000 claims description 26
- 229910052727 yttrium Inorganic materials 0.000 claims description 21
- 238000000034 method Methods 0.000 claims description 20
- 239000001488 sodium phosphate Substances 0.000 claims description 20
- 229910000162 sodium phosphate Inorganic materials 0.000 claims description 20
- RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 claims description 20
- 229910019142 PO4 Inorganic materials 0.000 claims description 17
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims description 16
- PXHVJJICTQNCMI-UHFFFAOYSA-N Nickel Chemical compound [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 claims description 13
- CIOAGBVUUVVLOB-NJFSPNSNSA-N Strontium-90 Chemical compound [90Sr] CIOAGBVUUVVLOB-NJFSPNSNSA-N 0.000 claims description 13
- 229940044173 iodine-125 Drugs 0.000 claims description 13
- ZCYVEMRRCGMTRW-YPZZEJLDSA-N iodine-125 Chemical compound [125I] ZCYVEMRRCGMTRW-YPZZEJLDSA-N 0.000 claims description 12
- 238000004519 manufacturing process Methods 0.000 claims description 11
- VWQVUPCCIRVNHF-UHFFFAOYSA-N yttrium atom Chemical compound [Y] VWQVUPCCIRVNHF-UHFFFAOYSA-N 0.000 claims description 11
- WCUXLLCKKVVCTQ-UHFFFAOYSA-M Potassium chloride Chemical compound [Cl-].[K+] WCUXLLCKKVVCTQ-UHFFFAOYSA-M 0.000 claims description 10
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 claims description 10
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 claims description 10
- OAICVXFJPJFONN-OUBTZVSYSA-N Phosphorus-32 Chemical compound [32P] OAICVXFJPJFONN-OUBTZVSYSA-N 0.000 claims description 9
- 239000011575 calcium Substances 0.000 claims description 9
- 229940097886 phosphorus 32 Drugs 0.000 claims description 9
- 239000004332 silver Substances 0.000 claims description 9
- 229910052709 silver Inorganic materials 0.000 claims description 9
- 229910052712 strontium Inorganic materials 0.000 claims description 9
- CIOAGBVUUVVLOB-UHFFFAOYSA-N strontium atom Chemical compound [Sr] CIOAGBVUUVVLOB-UHFFFAOYSA-N 0.000 claims description 9
- LWIHDJKSTIGBAC-UHFFFAOYSA-K tripotassium phosphate Chemical compound [K+].[K+].[K+].[O-]P([O-])([O-])=O LWIHDJKSTIGBAC-UHFFFAOYSA-K 0.000 claims description 9
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 claims description 8
- 229910001424 calcium ion Inorganic materials 0.000 claims description 8
- 239000010452 phosphate Substances 0.000 claims description 8
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 claims description 8
- 239000011780 sodium chloride Substances 0.000 claims description 8
- JLVVSXFLKOJNIY-UHFFFAOYSA-N Magnesium ion Chemical compound [Mg+2] JLVVSXFLKOJNIY-UHFFFAOYSA-N 0.000 claims description 7
- BPQQTUXANYXVAA-UHFFFAOYSA-N Orthosilicate Chemical compound [O-][Si]([O-])([O-])[O-] BPQQTUXANYXVAA-UHFFFAOYSA-N 0.000 claims description 7
- BQCADISMDOOEFD-UHFFFAOYSA-N Silver Chemical compound [Ag] BQCADISMDOOEFD-UHFFFAOYSA-N 0.000 claims description 7
- 235000010443 alginic acid Nutrition 0.000 claims description 7
- 229920000615 alginic acid Polymers 0.000 claims description 7
- 238000006243 chemical reaction Methods 0.000 claims description 7
- 229910001425 magnesium ion Inorganic materials 0.000 claims description 7
- PXHVJJICTQNCMI-RNFDNDRNSA-N nickel-63 Chemical compound [63Ni] PXHVJJICTQNCMI-RNFDNDRNSA-N 0.000 claims description 7
- NBIIXXVUZAFLBC-HOSYLAQJSA-K trioxido(oxo)-$l^{5}-phosphane Chemical compound [O-][32P]([O-])([O-])=O NBIIXXVUZAFLBC-HOSYLAQJSA-K 0.000 claims description 7
- PNDPGZBMCMUPRI-HVTJNCQCSA-N 10043-66-0 Chemical compound [131I][131I] PNDPGZBMCMUPRI-HVTJNCQCSA-N 0.000 claims description 6
- FHVDTGUDJYJELY-UHFFFAOYSA-N 6-{[2-carboxy-4,5-dihydroxy-6-(phosphanyloxy)oxan-3-yl]oxy}-4,5-dihydroxy-3-phosphanyloxane-2-carboxylic acid Chemical compound O1C(C(O)=O)C(P)C(O)C(O)C1OC1C(C(O)=O)OC(OP)C(O)C1O FHVDTGUDJYJELY-UHFFFAOYSA-N 0.000 claims description 6
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 claims description 6
- BHPQYMZQTOCNFJ-UHFFFAOYSA-N Calcium cation Chemical compound [Ca+2] BHPQYMZQTOCNFJ-UHFFFAOYSA-N 0.000 claims description 6
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 claims description 6
- 229940072056 alginate Drugs 0.000 claims description 6
- XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 claims description 6
- NINIDFKCEFEMDL-AKLPVKDBSA-N Sulfur-35 Chemical compound [35S] NINIDFKCEFEMDL-AKLPVKDBSA-N 0.000 claims description 5
- 239000001103 potassium chloride Substances 0.000 claims description 5
- 235000011164 potassium chloride Nutrition 0.000 claims description 5
- 229910000160 potassium phosphate Inorganic materials 0.000 claims description 5
- 235000011009 potassium phosphates Nutrition 0.000 claims description 5
- 229910000029 sodium carbonate Inorganic materials 0.000 claims description 5
- IXPNQXFRVYWDDI-UHFFFAOYSA-N 1-methyl-2,4-dioxo-1,3-diazinane-5-carboximidamide Chemical compound CN1CC(C(N)=N)C(=O)NC1=O IXPNQXFRVYWDDI-UHFFFAOYSA-N 0.000 claims description 4
- FOIXSVOLVBLSDH-UHFFFAOYSA-N Silver ion Chemical compound [Ag+] FOIXSVOLVBLSDH-UHFFFAOYSA-N 0.000 claims description 4
- 239000004115 Sodium Silicate Substances 0.000 claims description 4
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 claims description 4
- 229910052791 calcium Inorganic materials 0.000 claims description 4
- 229910052759 nickel Inorganic materials 0.000 claims description 4
- 229910001453 nickel ion Inorganic materials 0.000 claims description 4
- 229910000027 potassium carbonate Inorganic materials 0.000 claims description 4
- 235000011181 potassium carbonates Nutrition 0.000 claims description 4
- OTYBMLCTZGSZBG-UHFFFAOYSA-L potassium sulfate Chemical compound [K+].[K+].[O-]S([O-])(=O)=O OTYBMLCTZGSZBG-UHFFFAOYSA-L 0.000 claims description 4
- 229910052939 potassium sulfate Inorganic materials 0.000 claims description 4
- 235000011151 potassium sulphates Nutrition 0.000 claims description 4
- 239000000661 sodium alginate Substances 0.000 claims description 4
- 235000010413 sodium alginate Nutrition 0.000 claims description 4
- 229940005550 sodium alginate Drugs 0.000 claims description 4
- 235000017550 sodium carbonate Nutrition 0.000 claims description 4
- 235000011008 sodium phosphates Nutrition 0.000 claims description 4
- NTHWMYGWWRZVTN-UHFFFAOYSA-N sodium silicate Chemical compound [Na+].[Na+].[O-][Si]([O-])=O NTHWMYGWWRZVTN-UHFFFAOYSA-N 0.000 claims description 4
- 229910052911 sodium silicate Inorganic materials 0.000 claims description 4
- 229910052938 sodium sulfate Inorganic materials 0.000 claims description 4
- 235000011152 sodium sulphate Nutrition 0.000 claims description 4
- 229910001427 strontium ion Inorganic materials 0.000 claims description 4
- 239000004111 Potassium silicate Substances 0.000 claims description 3
- XMBWDFGMSWQBCA-RNFDNDRNSA-M iodine-131(1-) Chemical compound [131I-] XMBWDFGMSWQBCA-RNFDNDRNSA-M 0.000 claims description 3
- 239000000737 potassium alginate Substances 0.000 claims description 3
- 235000010408 potassium alginate Nutrition 0.000 claims description 3
- MZYRDLHIWXQJCQ-YZOKENDUSA-L potassium alginate Chemical compound [K+].[K+].O1[C@@H](C([O-])=O)[C@@H](OC)[C@H](O)[C@H](O)[C@@H]1O[C@@H]1[C@@H](C([O-])=O)O[C@@H](O)[C@@H](O)[C@H]1O MZYRDLHIWXQJCQ-YZOKENDUSA-L 0.000 claims description 3
- NNHHDJVEYQHLHG-UHFFFAOYSA-N potassium silicate Chemical compound [K+].[K+].[O-][Si]([O-])=O NNHHDJVEYQHLHG-UHFFFAOYSA-N 0.000 claims description 3
- 235000019353 potassium silicate Nutrition 0.000 claims description 3
- 229910052913 potassium silicate Inorganic materials 0.000 claims description 3
- 235000019794 sodium silicate Nutrition 0.000 claims description 3
- VEQPNABPJHWNSG-UHFFFAOYSA-N Nickel(2+) Chemical compound [Ni+2] VEQPNABPJHWNSG-UHFFFAOYSA-N 0.000 claims 1
- 229940079593 drug Drugs 0.000 abstract description 4
- 239000000243 solution Substances 0.000 description 185
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 48
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- 238000001959 radiotherapy Methods 0.000 description 14
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- UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 12
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- 238000009616 inductively coupled plasma Methods 0.000 description 5
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- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 3
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- OBOSXEWFRARQPU-UHFFFAOYSA-N 2-n,2-n-dimethylpyridine-2,5-diamine Chemical compound CN(C)C1=CC=C(N)C=N1 OBOSXEWFRARQPU-UHFFFAOYSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 2
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- UXBZSSBXGPYSIL-UHFFFAOYSA-K yttrium(iii) phosphate Chemical compound [Y+3].[O-]P([O-])([O-])=O UXBZSSBXGPYSIL-UHFFFAOYSA-K 0.000 description 2
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Images
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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/02—Inorganic compounds
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Abstract
The invention provides a preparation method of radioactive particles, which comprises the steps of preparing a first solution and a second solution, wherein the first solution contains at least one kind of cation; the second solution contains at least one anion, the cation and/or the anion comprising a radionuclide; taking a certain amount of hydrophilic porous solid carrier, slowly and dropwise adding the first solution and the second solution into the porous solid carrier, reacting anions in the second solution with metal cations in the first solution in the porous holes to generate radionuclide precipitates, and collecting the radionuclide precipitates to obtain radioactive particles; the porous solid support comprises at least one of a carbon-based material, alumina particles, titanium dioxide, diatomaceous earth, attapulgite, zeolite, a metal organic framework material, and a covalent organic framework polymer. The preparation method is simple and easy to operate, short in time consumption and low in cost. The invention also provides the radioactive particles and the application thereof in the medicines for treating tumors.
Description
Technical Field
The invention belongs to the technical field of preparation of radiopharmaceuticals, and particularly relates to a radioactive particle and a preparation method and application thereof.
Background
The malignant tumor has the characteristics of high morbidity, high mortality rate and the like, and is one of the major diseases which seriously threaten the life safety of people at present. Tumor radiotherapy (radiotherapy) is a local treatment method for treating tumors by utilizing radioactive rays, and the role and the position of the tumor radiotherapy in tumor treatment are increasingly highlighted; however, radiotherapy generally belongs to 'all-line killing', and kills tumors and normal tissues at the same time. Tumor radiotherapy comprises external irradiation and internal irradiation modes; for some tumors which are far away from skin tissues and grow in vivo, the radiation directly reaches the tumor tissues through in vivo irradiation, and the irradiation amount of normal tissues around the tumor is small, so that a better treatment effect can be obtained. For example, the Selective Internal Radiation Therapy (SIRT) technique developed recently is to inject a drug containing a radioactive isotope into the body or insert an apparatus into close proximity or into a target tissue for radiation Therapy, wherein the radioactive substance is selectively delivered to the tumor tissue, the dose of the radiation to the tumor tissue is high, and the amount of the radioactive substance entering the surrounding normal tissue is low, so that the damage to the normal tissue is small.
However, most of the existing medicines containing radioactive isotopes are radioactive microspheres loaded with radionuclides such as yttrium (Y) -90, phosphorus (P) -32 and the like by using glass or resin as a matrix, and the radioactive glass microspheres or resin microspheres have some defects. For example, the high density of glass in radioactive glass microspheres (2.0cm/g-2.7cm/g) requires glycerol to be introduced into tumor sites, which affects the therapeutic effect; meanwhile, the radioactive glass microspheres must be irradiated by a reactor, but impurities in the glass raw materials can generate nuclides which release gamma rays after neutron irradiation, so that a patient suffers from unnecessary radioactive damage; and the preparation process of the radioactive glass microspheres is complex and the reaction conditions are harsh. For the radioactive resin microspheres, the acting force between most of radioactive nuclides loaded on the surfaces of the radioactive resin microspheres and the resin microspheres is small, and the radioactive resin microspheres are easy to fall off from the surfaces of the resin microspheres and enter human blood, so that the radioactive resin microspheres are harmful to human bodies. The radionuclide is exchanged into the resin and is fixed in the resin by a coating method, so that the radionuclide release rate is high and cannot meet the requirement of treatment. In addition, the radioactive resin microspheres also have the problems of limited exchange capacity of the resin and long time consumption in the preparation process.
Therefore, the development of the radioactive particles which are safe, stable, convenient and practical in structure, simple and efficient in preparation process has important significance for tumor radiotherapy.
Disclosure of Invention
In order to solve the problems, the invention provides radioactive particles, and a preparation method and application thereof, wherein the preparation method of the radioactive particles is simple and easy to operate, and has the advantages of short time consumption, high utilization rate of radioactive nuclides, environmental friendliness, low cost and the like.
In a first aspect, the present invention also provides a method for preparing radioactive particles, comprising:
preparing a first solution, wherein the first solution contains at least one kind of cation;
preparing a second solution containing at least one anion, said cation and/or said anion comprising a radionuclide, said anion being capable of reacting with said cation to form a radionuclide precipitate;
taking a certain amount of hydrophilic porous solid carrier, slowly dropwise adding the first solution into the porous solid carrier, and fully stirring to make the first solution enter porous holes of the porous solid carrier; slowly dripping the second solution into the porous solid carrier, stirring to enable the second solution to enter the porous holes, enabling anions in the second solution to react with metal cations in the first solution in the porous holes to generate radionuclide precipitates, containing the radionuclide precipitates in the porous holes, and collecting to obtain radioactive particles; wherein the porous solid support comprises at least one of a carbon-based material, alumina, titania, diatomaceous earth, attapulgite, zeolite, a metal organic framework material, and a covalent organic framework polymer.
The radionuclide of the present invention refers to an unstable nucleus which spontaneously emits radiation (e.g., alpha-ray, beta-ray, etc.) and forms a stable nuclide by decay. The radionuclide may be a metallic radionuclide and/or a non-metallic radionuclide. The radionuclide may be an artificial radionuclide or a natural radionuclide.
In the invention, the porous solid carriers are all porous materials which have stable structures, hydrophilicity and water insolubility. Wherein the carbon-based material may include, but is not limited to, at least one of activated carbon, carbon nanotubes, and carbon microspheres.
The alumina and the titanium dioxide have stable porous metal oxide particles. The diatomaceous earth is a siliceous rock containing small amounts and many kinds of metal oxides (e.g., Al)2O3、Fe2O3CaO, MgO) and organic matter. The attapulgite is a crystalline hydrated magnesium aluminum silicate mineral. The zeolite is an ore having a framework structure, which may be, for example, a moleculeAnd (5) screening the particles.
The metal organic framework Materials (MOFs) refer to metal organic framework crystal materials with periodic network structures formed by organic ligands and metal ions through a self-assembly process. In the invention, the metal organic framework material comprises MOFs constructed by nitrogen-containing heterocyclic ligands, MOFs constructed by organic carboxylic acid ligands and MOFs constructed by nitrogen-oxygen containing mixed ligands according to the category of the organic ligands. The covalent organic framework polymers (COFs) are crystalline microporous polymers.
Optionally, the porous solid support further comprises at least two of the carbon-based material, alumina, titania, diatomaceous earth, attapulgite, zeolite, metal organic framework material, and covalent organic framework polymer.
Further optionally, the porous solid support comprises at least one of diatomaceous earth, attapulgite, and zeolite.
In the present invention, the shape of the porous solid support includes one or more of a spherical shape and a non-spherical shape. Further, the shape of the porous solid support includes one or more of a spherical shape, a spheroidal shape, a square shape, a rod shape, a sheet shape, and a random shape. For example, in one embodiment of the present invention, the porous solid support is spherical in shape. In another embodiment of the present invention, the porous solid support is spheroidal in shape.
In the present invention, the cation and/or the anion comprises a radionuclide, including the following three embodiments:
in a first embodiment of the invention, both said cations in said first solution and said anions in said second solution comprise radionuclides.
In a second embodiment of the invention, said cations in said first solution comprise radionuclides and said anions in said second solution do not comprise radionuclides.
In a third embodiment of the invention, the anion in the second solution comprises a radionuclide and the cation in the first solution is free of a radionuclide.
Optionally, the cations in the first solution comprise at least one metal radionuclide.
Alternatively, the cations in the first solution may include, but are not limited to, at least one of strontium (Sr-90), yttrium-90 (Y-90), and nickel-63 (Ni-63). For example, the cation is strontium-90 ion (C:)90Sr2+) Yttrium-90 ion(s) (iii)90Y3 +) And nickel-63 ions: (63Ni2+) At least one of (1).
Optionally, the radionuclide contained in the anion in the second solution may include, but is not limited to, at least one of phosphorus-32, sulfur-35 and iodine-125, iodine-131. For example, the anion includes phosphate-32 acid group(s) ((R))32PO4 3-) Thio-35 acid radical (35SO4 2-) Iodine-131 ion (a)131I-) And iodine-125 ion (125I-) At least one of (1).
In the present invention, the radionuclide-containing cation in the first solution and the radionuclide-containing anion in the second solution may both be derived from corresponding commercially available medical-grade radionuclide-containing solutions.
Further, when the anion does not comprise a radionuclide, the anion comprises Phosphate (PO)4 3-) Carbonate (CO)3 2-) Sulfate radical (SO)4 2-) Alginic acid radical, hydroxyl radical (OH)-) And Silicate (SiO)3 2-) At least one of (1).
In particular, the radionuclide precipitates may be selected from, but are not limited to, yttrium phosphate-90 (I), (II), (III), (IV90YPO4) Strontium phosphate-90: (90Sr3(PO4)2) Nickel carbonate-63 (63NiCO3) Iodine-125 silver (Ag)125I) Iodine-131 silver (Ag)131I) And calcium phosphate-32 (Ca)3(32PO4)2) At least one of (1).
For example, the radionuclide precipitate can also be yttrium-90 (P-32) phosphate90Y32PO4) Or strontium-90 (P-32)90Sr3(32PO4)2)。
Optionally, the first solution further comprises a non-radioactive metal cation capable of reacting with the anion in the second solution to form a second precipitate; the non-radioactive metal cation comprises strontium ion (Sr)2+) Yttrium ion (Y)3+) Nickel ion (Ni)2+) Calcium ion (Ca)2+) Silver ion (Ag)+) And magnesium ion (Mg)2+) One or more of (a).
Optionally, the anion that reacts to form the second precipitate may or may not include a radionuclide.
The second precipitate of the present invention may in one aspect be involved in modulating the size of radioactivity of the radionuclide in a unit mass of the radioactive particles. The second precipitate, on the other hand, may also improve the formation of the radionuclide precipitate to some extent by adjusting the concentration of the non-radioactive metal cations and anions that form themselves. The second precipitate is also stably accommodated in the porous pores of the porous solid carrier, and the second precipitate and the radionuclide precipitate can mutually enhance the stability of each other in the porous pores.
Further optionally, the nonradioactive metal cations in the first solution and the cations in the first solution may be isotopic to each other. For example, in one embodiment of the present invention, when the cation in the first solution is yttrium-90 ion, the nonradioactive metal cation is yttrium 89 ion. In another embodiment of the present invention, when the cations in the first solution are nickel-63 ions, the nonradioactive metal cations are nickel 58 ions.
Alternatively, when the radionuclide-containing cation does not have a corresponding stable isotope, the metal cation may be selected from at least one of calcium ion, magnesium ion, and silver ion.
In the invention, the first solution and the second solution are both solutions without sediment and suspended particles. For example, in one embodiment of the invention, the first solution comprises a first soluble salt that includes a radionuclide-containing cation. The anion of the first soluble salt can be, but is not limited to, a halide ion, such as chloride.
In one embodiment of the present invention, the second solution includes a second soluble salt, and the cation in the second soluble salt can be, but is not limited to, sodium ion and/or potassium ion. When the anion of the second soluble salt is free of a radionuclide, the anion of the second soluble salt comprises at least one of phosphate, carbonate, sulfate, alginate, hydroxide, and silicate. For example, the second soluble salt includes sodium phosphate, potassium phosphate, sodium carbonate, potassium carbonate, sodium sulfate, potassium sulfate, sodium hydroxide, sodium alginate ((C)6H7O6Na)n) And sodium silicate.
Further, the first solution further comprises a third soluble salt comprising a non-radioactive metal cation; the anion in the third soluble salt can be, but is not limited to, a halide ion; such as chloride ions.
Further, optionally, the anion of the third soluble salt may be the same as or different from the anion of the first soluble salt. For example, in one embodiment of the present invention, the anion of the third soluble salt is the same as the anion of the first soluble salt. The anion in the first solution is derived from the anions of the first and third soluble salts.
In the preparation method of the present invention, when the anion in the second solution comprises a radionuclide, the cation in the first solution is in excess relative to the anion in the second solution; the cation in the first solution may completely precipitate the anion in the second solution.
Further, when the anion in the second solution comprises a radionuclide, the second solution also contains a radionuclideA non-radioactive anion may be included and the cation in the first solution may also completely precipitate the non-radioactive anion in the second solution. For example, the anion in the second solution is32PO4 3-The second solution may further contain PO4 3-The first solution may contain a large amount of Ca2+Ca in the first solution2+Can completely precipitate out the second solution32PO4 3-And PO4 3-。
For example, the non-radioactive anion in the second solution can be an anion dissolved in a fourth soluble salt in the second solution, and the non-radioactive anion can be at least one of phosphate, carbonate, sulfate, alginate, hydroxide, and silicate.
Optionally, the porous solid carrier further contains water and a soluble metal salt in the porous pores, wherein the soluble metal salt includes one or more of sodium chloride, potassium chloride, sodium phosphate, potassium phosphate, sodium sulfate, potassium sulfate, sodium carbonate, potassium carbonate, sodium alginate, potassium alginate, sodium silicate, and potassium silicate.
In the invention, the soluble metal salt comprises the second soluble salt which is not reacted completely and a soluble secondary salt generated by the reaction of the second solution and the first solution. The soluble secondary salt formed by the reaction of the second solution with the first solution is a salt formed by an anion in the first solution and a cation in the second solution. Alternatively, the salt formed by the anion in the first solution and the cation in the second solution may include, but is not limited to, at least one of sodium chloride and potassium chloride.
Alternatively, in the preparation method, the collecting of the radioactive particles may be directly collecting the radioactive particles. The process of collecting the resulting radioactive particles may also be an indirect collection of the resulting radioactive particles. For example, the radioactive particles are collected after steps of deionization washing, filtration and drying.
In the invention, water and soluble metal salt in the porous holes in the radioactive particles collected after the steps of washing with deionized water, filtering, drying and the like can be removed.
For example, the radioactive particles are collected after the steps of washing with deionized water, filtering and drying, and only the radionuclide precipitate and the second precipitate are contained in the porous pores of the radioactive particles.
In the present invention, when the soluble metal salt in the porous pores of the radioactive particles has no additional harmful side effects on the human body, the radioactive particles can be obtained by direct collection. For example, the soluble metal salt may be, but is not limited to, sodium chloride, potassium chloride or phosphate, or the amount of the soluble metal salt is too small to cause harm to the human body.
Optionally, the pH of the first solution ranges from 6.0 to 8.0. Further, the pH of the first solution ranges from 6.5 to 7.5.
Optionally, the pH of the second solution ranges from 6.0 to 12.0. Further, the pH of the second solution ranges from 6.5 to 10.
In the preparation method of the present invention, the total volume of the first solution and the second solution is less than or equal to the total water absorption capacity of the porous solid support.
Further, the total volume of the first solution and the second solution is less than the total water uptake of the porous solid support.
In the invention, the porous solid carrier is a hydrophilic material with porous holes and is insoluble in water. The porous solid support also has a certain amount of water uptake (water adsorption). I.e. the porous solid support may adsorb a certain amount of an aqueous solution. The porous solid supports of different materials may have different water absorption capacities.
The total water absorption capacity of the porous solid carrier refers to the volume of the porous solid carrier which can absorb water maximally when the porous solid carrier maintains a powdery state (or a monodisperse state) at normal temperature and normal pressure. The unit of water uptake of the porous solid support can be expressed in volume units, such as mL.
In addition, the total water absorption of the porous solid support can also be obtained by converting the mass of the porous solid support and the water absorption of the porous solid support. The water absorption of the porous solid carrier according to the present invention refers to the ratio (%) of the mass of the maximum aqueous solution that the porous solid carrier maintains in powder form absorption to the dry weight of the porous solid carrier.
In the present invention, since the total volume of the first solution and the second solution is less than or equal to the total water absorption of the certain amount of porous solid support, in the preparation process of the radioactive particles, the first solution and the second solution all enter the porous pores of the porous solid support, and the prepared radioactive particles are in a dispersed powdery form.
In the invention, the volume of the first solution or the second solution can be adjusted according to the concentration of the solute in the respective solution; to achieve that the anion of the second solution can completely precipitate the radionuclide-containing cation in the first solution, or to achieve that the cation of the first solution can completely precipitate the radionuclide-containing anion in the second solution.
Optionally, the volume ratio of the first solution to the second solution is 1: (0.1-10).
Further optionally, the volume ratio of the first solution to the second solution is 1: (0.5-2). For example, in one embodiment of the present invention, the volume ratio of the first solution to the second solution is 1: 1.
optionally, the porous solid support is stirred thoroughly after the first solution is slowly added dropwise and before the second solution is slowly added dropwise. Wherein, the stirring speed in the full stirring process can be 60-100 r/min, and the stirring time is 1-10 min. By stirring the porous solid support, the first solution can be dispersed more uniformly and enter the porous holes of the porous solid support more completely.
Further, optionally, after stirring to allow the second solution to enter the porous pores, the porous solid support to which the first solution and the second solution have been added dropwise is sufficiently stirred. Wherein, the stirring speed in the full stirring process can be 60-100 r/min, and the stirring time is 1-10 min.
The second solution can be dispersed more uniformly by fully stirring the porous solid carrier to which the first solution and the second solution are dripped, so that the second solution enters into porous holes of the porous solid carrier more completely; more importantly, the anions in the second solution can be encouraged to more fully form radionuclide precipitates with the cations comprising the metal radionuclide.
In the preparation method, the particle size of the porous solid carrier is 0.05-600 μm.
Further, optionally, the porous solid support has a particle size of 0.05 μm to 600 μm.
Further, optionally, the porous solid support has a particle size of 10 μm to 500 μm.
Further, optionally, the porous solid support has a particle size of 10 μm to 300 μm.
Further, optionally, the porous solid support has a particle size of 10 μm to 100 μm.
Further, optionally, the porous solid support has a particle size of 30 μm to 80 μm.
Optionally, the porous solid support has a porous pore size of 0.1nm to 600 nm.
Further, optionally, the porous solid support has a porous pore size of 0.1nm to 50 nm.
Further, optionally, the porous solid support has a porous pore size of 0.1nm to 20 nm.
In the invention, the porous aperture of the porous solid carrier is nano-scale and very small, and the radionuclide precipitate can be embedded in the porous holes of the porous solid carrier, so that the structure is stable. The radioactive particles of the present invention have very low radionuclide release rates, and the radionuclide does not substantially separate from the porous solid support.
In the present invention, the porous solid support may be subjected to a particle size screening process prior to use in the preparation of the radioactive particles. The particle size screening process may be carried out by conventional screening means, such as classifying means by a screen mesh or the like having a certain pore size.
The traditional preparation method of the radioactive particles is complicated, long in time consumption, high in cost and even has environmental pollution. Therefore, compared with the traditional preparation method, the preparation method of the radioactive particles developed by the invention is simpler and easier to operate; and the whole preparation process is extremely short in time consumption, and is particularly suitable for preparing the radioactive particles of the metal radionuclide with short half life. In addition, the preparation method is green and environment-friendly and has low cost.
In a second aspect, the present invention provides a radioactive particle comprising a porous solid support and at least one radionuclide precipitate contained within porous pores of the porous solid support; the porous solid support is hydrophilic, the radionuclide precipitates are generated by the reaction of cations and anions, and the cations and/or the anions comprise radionuclides; the porous solid support comprises at least one of a carbon-based material, alumina particles, titanium dioxide, diatomaceous earth, attapulgite, zeolite, a metal organic framework material, and a covalent organic framework polymer.
In the present invention, the cation and/or the anion comprises a radionuclide, including the following three embodiments:
in a first embodiment of the invention, the radionuclide precipitate is generated by reacting a cation comprising the radionuclide and an anion, the anion being free of the radionuclide.
In a second embodiment of the invention, the radionuclide precipitate is generated by reacting a cation with an anion, the anion comprising the radionuclide, the cation being free of the radionuclide.
In a third embodiment of the invention, the radionuclide precipitate is generated by reacting a cation and an anion, both of which comprise a radionuclide.
Optionally, the cation comprises at least one of a metal radionuclide.
Further, optionally, the cation may comprise the radionuclide including but not limited to at least one of strontium, yttrium-90, and nickel-63. For example, the cation is at least one of strontium-90 ion, yttrium-90 ion, and nickel-63 ion.
Optionally, the anion comprises at least one of a non-metallic radionuclide.
Further, optionally, the anion comprises the radionuclide may include, but is not limited to, at least one of phosphorus-32, sulfur-35, iodine-131, and iodine-125. For example, the anion includes at least one of phosphate-32, sulfate-35, iodide-131, and iodide-125 ions.
Optionally, when the anion does not comprise the radionuclide, the anion comprises at least one of phosphate, carbonate, sulfate, alginate, hydroxide, and silicate.
Specifically, the radionuclide precipitates may be, but not limited to, at least one selected from the group consisting of yttrium phosphate-90, strontium phosphate-90, nickel carbonate-63, silver iodide-125, silver iodide-131, and calcium phosphate-32. The radionuclide precipitate can also be yttrium-90 phospho-32 or strontium-90 phospho-32.
In the present invention, the radionuclide precipitates are solid substances that are hardly soluble in water, and almost no cations or anions containing the radionuclide are released in an aqueous solution. The radionuclide precipitate is stably accommodated in the porous holes of the porous solid carrier, has wide application range to temperature and pH, and is very stable in the temperature and pH range of a human body.
In the present invention, the radionuclide precipitates contained in the porous pores may be one kind, or two or more kinds of radionuclide precipitates. Each of the radionuclide precipitates may contain one kind of radionuclide, or two or more kinds of radionuclides.
For example, in one embodiment of the present invention, the radionuclide precipitate is a Sr-90-containing radionuclide precipitate, a Y-90-containing radionuclide precipitate, or a Ni-63-containing radionuclide precipitate; in another embodiment of the present invention, the porous pores contain two radionuclide precipitates, wherein one of the radionuclide precipitates contains Y-90; the other radionuclide precipitate contains Sr-90; in other embodiments, the radionuclide precipitate may contain both radionuclides, e.g., the radionuclide precipitate contains both Sr-90 and Y-90.
Specifically, the radionuclide precipitates may be, but not limited to, at least one selected from the group consisting of yttrium phosphate-90, strontium phosphate-90, and nickel carbonate-63.
In the present invention, the shape of the radioactive particles includes one or more of a spherical shape and a non-spherical shape. Further, the shape of the radioactive particles includes one or more of a spherical shape, a spheroidal shape, a square shape, a rod shape, a flake shape, and a random shape. For example, in one embodiment of the present invention, the radioactive particles are spherical in shape.
Optionally, the porous solid support further comprises a second precipitate within the porous pores, the second precipitate resulting from the reaction of a non-radioactive metal cation and the anion, the non-radioactive metal cation comprising one or more of strontium ion, yttrium ion, nickel ion, calcium ion, silver ion, and magnesium ion.
Alternatively, the anion that reacts with the non-radioactive metal cation to form the second precipitate may or may not include a radionuclide. In an embodiment of the invention, when the anion does not comprise the radionuclide, the anion comprises at least one of phosphate, carbonate, sulfate, alginate, hydroxide and silicate. When the anion comprises a radionuclide, the radionuclide that the anion comprises may include, but is not limited to, at least one of phosphorus-32, sulfur-35 and iodine-125, iodine-131.
Further, optionally, the non-radioactive metal cation and the cation that reacts to generate the radioactive precipitate may be isotopic to each other. For example, in one embodiment of the present invention, when the cation reacted to form the radionuclide precipitate is yttrium-90 ion, the nonradioactive metal cation is yttrium 89 ion. In another embodiment of the present invention, when the cation reacted to form the radionuclide precipitate is nickel-63 ion, the nonradioactive metal cation is nickel 58 ion.
Alternatively, the non-radioactive metal cation may be selected from at least one of calcium, magnesium and silver ions when the cation reacted to form the radionuclide precipitate is free of the corresponding stable isotope.
Optionally, the porous solid carrier further comprises water and a soluble metal salt in the porous pores, wherein the soluble metal salt comprises one or more of sodium chloride, potassium chloride, sodium phosphate, potassium phosphate, sodium sulfate, potassium sulfate, sodium carbonate, potassium carbonate, sodium alginate, potassium alginate, sodium silicate and potassium silicate.
Optionally, the porous solid support has a porous pore size of 0.1nm to 600 nm.
Further, optionally, the porous solid support has a porous pore size of 0.1nm to 50 nm.
Further, optionally, the porous solid support has a porous pore size of 0.1nm to 20 nm.
In the invention, the porous aperture of the porous solid carrier is nano-scale and very small, and the radionuclide precipitate can be embedded in the porous holes of the porous solid carrier, so that the structure is stable. The radioactive particles of the present invention have very low radionuclide release rates, and the radionuclide does not substantially separate from the porous solid support.
Optionally, the porous solid support has a particle size of 0.05 μm to 600 μm.
Further, optionally, the porous solid support has a particle size of 10 μm to 500 μm.
Further, optionally, the porous solid support has a particle size of 10 μm to 300 μm.
Further, optionally, the porous solid support has a particle size of 10 μm to 100 μm.
Further, optionally, the porous solid support has a particle size of 30 μm to 80 μm.
Further, optionally, the porous solid support has a particle size of 30 μm to 60 μm. For example, the particle size of the porous solid support particles may be, but is not limited to, 30 μm, or 35 μm, or 40 μm, or 45 μm, or 50 μm, or 55 μm, or 60 μm.
In the radioactive particles of the present invention, the mass of the radionuclide precipitates in the porous pores of the porous solid carrier per unit mass can be adjusted according to actual requirements. Accordingly, the radioactivity of the radionuclide in the radioactive particles can be adjusted according to actual needs.
Optionally, the radionuclide has a radioactivity of 0.1-50 GBq per gram of the radioactive particles. Further optionally, the radionuclide has a radioactivity of 0.1-30 GBq per gram of the radioactive particles.
The radioactive particles of the second aspect of the present invention are produced by the production method of the first aspect of the present invention.
In a third aspect, the present invention also provides a use of the radioactive particles prepared by the preparation method according to the first aspect of the present invention in the preparation of a medicament for treating tumors.
The radioactive particles have the characteristics of stable structure, low release rate of radioactive nuclide, high safety and low cost, so the radioactive particles have wide application prospect in the field of preparing medicaments for treating tumors.
For example, the invention also provides a formulation for radiotherapy comprising the radioactive particles and a pharmaceutically acceptable excipient.
The pharmaceutically acceptable excipient of the present invention refers to an adjuvant which does not cause side effects. Alternatively, the excipients may include, but are not limited to, diluents, binders, fillers, film coating polymers, plasticizers, glidants, disintegrants, lubricants and release rate modifiers.
In one embodiment of the present invention, the excipient may be physiological saline. Since the radioactive particles of the present invention have hydrophilicity; thus, the radioactive particles can be uniformly distributed in the physiological saline.
The radioactive particles of the present invention may contain at least one radionuclide, and the radioactivity of the radioactive particles can be controlled by adjusting the precipitation content of the radionuclide; the radioactive particles have stable structures and low release rate of the radioactive nuclide, and the particle size range is 0.05-600 mu m; can be used for preparing most of medical radiotherapeutic preparations; the preparation can be widely used as a radiotherapy medicament for treating various diseases such as tumors and the like.
In one embodiment of the invention, the preparation can reach the tumor site by perfusion, and the radionuclide precipitates in the porous pores of the radioactive particles contained in the preparation can emit beta rays to kill the tumor so as to achieve the purpose of treatment; the preparation for radiotherapy can also effectively control tumor invasion and metastasis, has a strong killing effect on tumor cells, and has very low damage on normal cells around the tumor.
The preparation can be applied to arterial perfusion embolism radiotherapy of liver cancer, and can also be applied to radiotherapy of other malignant tumors, such as breast cancer, lung cancer, kidney cancer, tongue cancer and the like.
The beneficial effects of the invention include:
(1) the preparation method of the radioactive particles is simple and easy to operate, the time consumption of the whole preparation process is extremely short, and the preparation method can be used for preparing the radioactive particles containing the radioactive nuclide with short half-life; the radionuclide in the preparation method has high utilization rate, is green and environment-friendly, has low cost, and can be suitable for industrial large-scale production.
(2) The radioactive particles comprise a porous solid carrier and at least one radionuclide precipitate contained in porous holes of the porous solid carrier; the radioactive particles have stable structures, low release rate of radioactive nuclides, adjustable particle size, adjustable species and adjustable radioactivity of the radioactive nuclides in the radionuclide precipitates, high safety and wide application prospect.
(3) The radioactive particles have wide application prospect in the field of preparing medicines for treating tumors, have the characteristics of high safety, low cost and the like, can regulate and control the activity and the particle size of the radioactive particles according to actual requirements, and can be used for radiotherapy preparations of various malignant tumors.
Drawings
FIG. 1 is a schematic flow chart of a method for preparing radioactive particles according to an embodiment of the present invention.
Detailed Description
While the following is a description of the preferred embodiments of the present invention, it will be understood by those skilled in the art that various changes and modifications may be made without departing from the spirit and scope of the invention.
Unless otherwise specified, all chemical reagents used in the preparation method are commercially available reagents.
Referring to fig. 1, fig. 1 is a schematic flow chart of a method for preparing radioactive particles according to an embodiment of the present invention, including the following steps:
s10, preparing a first solution, wherein the first solution contains at least one kind of cation;
s20, preparing a second solution, wherein the second solution contains at least one anion, the cation and/or the anion comprises a radionuclide, and the anion can react with the cation to generate radionuclide precipitation;
s30, taking a certain amount of hydrophilic porous solid carrier, slowly dropwise adding the first solution into the porous solid carrier, and fully stirring to make the first solution enter porous holes of the porous solid carrier; slowly dripping the second solution into the porous solid carrier, stirring to enable the second solution to enter the porous holes, enabling anions in the second solution to react with metal cations in the first solution in the porous holes to generate radionuclide precipitates, containing the radionuclide precipitates in the porous holes, and collecting to obtain radioactive particles; wherein the porous solid support comprises at least one of a carbon-based material, alumina particles, titanium dioxide, diatomaceous earth, attapulgite, zeolite, a metal organic framework material, and a covalent organic framework polymer.
Alternatively, in the preparation method of the radioactive particles, the first solution and/or the second solution may be prepared before the preparation. When the half-life of the radionuclide is short, temporary configuration during preparation may be selected.
The following examples are intended to illustrate the invention in more detail.
Control group 1 (Cold experiment)
The control group 1 in this embodiment is carried out strictly according to the steps of the method for preparing radioactive particles according to the present invention, with the difference that: the purpose of changing the radioactive nuclide Y-90 solution into the stable isotope Y-89 solution without radioactivity is to facilitate the ion concentration detection and reduce the damage of the radioactive nuclide to detection personnel and equipment.
A method of making non-radioactive yttrium phosphate (Y-89) -containing particles, comprising:
weighing calcium chloride and yttrium chloride hexahydrate, dissolving in deionized water, mixing well, preparing 1L calcium chloride containing 1mol/L and 10L-6A first solution of yttrium chloride in mol/L (about 89 ppm);
weighing sodium phosphate, dissolving the sodium phosphate with deionized water, fully and uniformly mixing, and preparing 1L of a second solution containing 0.7mol/L of sodium phosphate;
weighing 20g of monodisperse porous solid carrier, placing the porous solid carrier in a wide-mouth container, wherein the particle size of the porous solid carrier is about 50 mu m, the total water absorption capacity of the porous solid carrier is about 20mL, slowly dropwise adding 10mL of the first solution into the container, and stirring the porous solid carrier while dropwise adding; after the addition was complete, the porous solid support was stirred for another 10 minutes to fully disperse the porous solid support. Then slowly dripping 10mL of second solution into the container while stirring, and stirring for 10 minutes after dripping; the resulting yttrium phosphate-containing nonradioactive particles were then collected.
Example 1
A method of making a yttrium-90-containing radioactive particle, comprising:
weighing 10mL of medical radioactive yttrium chloride-90 solution, and measuring the radioactivity of the solution to be 10GBq by using a radioactivity meter; about 1.11g of anhydrous calcium chloride was added to the solution, and after thoroughly mixing, a first solution containing 0.01mol of calcium chloride and 10GBq of yttrium chloride-90 was prepared.
Weighing sodium phosphate, dissolving with deionized water, and preparing 1L of a second solution containing 0.7mol/L of sodium phosphate;
weighing 20g of monodisperse porous active carbon particles, placing the monodisperse porous active carbon particles in a wide-mouth container, wherein the particle size of the porous active carbon particles is about 50 microns, the total water absorption capacity of the porous active carbon particles is about 20mL, slowly dropwise adding all the first solution into the container, and stirring the porous active carbon particles while dropwise adding; after the dropwise addition, the mixture is stirred for 10 minutes to fully disperse the porous active carbon particles. Then slowly dripping 10mL of second solution into the container while stirring, and stirring for 10 minutes after dripping; then collecting the radioactive particles containing yttrium-90.
In the preparation process of example 1, the second solution is prepared in advance, and it takes about 35 minutes for the first solution to be prepared and the radioactive particles containing yttrium-90 to be received. 1g of the prepared yttrium-90-containing radioactive particles were weighed and tested by a radioactivity meter, and the radioactivity of 1g of the radioactive particles was measured to be 0.25 GBq. And the surface appearances of the radioactive particles and the porous active carbon particles are not obviously different by characterizing the prepared radioactive particles and the used porous active carbon particles.
Example 2
A method of making a yttrium-90-containing radioactive particle, comprising:
weighing 20mL of medical radioactive yttrium chloride-90 solution, and measuring the radioactivity of the solution to be 40GBq by using a radioactivity meter; about 2.78g of anhydrous calcium chloride was added to the solution and mixed well to prepare a first solution containing 0.025mol of calcium chloride and 50GBq of yttrium chloride-90.
Weighing sodium phosphate, dissolving with deionized water, and preparing 1L of a second solution containing 0.7mol/L of sodium phosphate;
weighing 50g of monodisperse porous diatomite particles and placing the particles into a wide-mouth container, wherein the particle size of the porous diatomite particles is about 60 mu m, the total water absorption capacity of the porous diatomite particles is about 40mL, slowly dropwise adding all the first solution into the container, and stirring the porous diatomite particles while dropwise adding; after the dropwise addition was completed, the mixture was stirred for another 10 minutes to sufficiently disperse the porous diatomaceous earth particles. Then slowly dripping 20mL of second solution into the container while stirring, and stirring for 10 minutes after dripping; then collecting the radioactive particles containing yttrium-90.
In the preparation process of example 2, the second solution is prepared in advance, and it takes about 40 minutes to prepare the first solution and finally receive the yttrium-90-containing radioactive particles. 1g of the prepared yttrium-90-containing radioactive particles were weighed and tested by a radioactivity meter, and the radioactivity of 1g of the radioactive particles was measured to be 0.44 GBq.
Example 3
A method of making a yttrium-90-containing radioactive particle, comprising:
weighing 25mL of medical radioactive yttrium chloride-90 solution, and measuring the radioactivity of the solution to be 50GBq by using a radioactivity meter; about 7.6g of solid yttrium chloride hexahydrate is added to the solution and mixed well to prepare a first solution containing 0.025mol yttrium chloride and 50GBq yttrium chloride-90.
Weighing sodium phosphate, dissolving with deionized water, and preparing 1L of a second solution containing 1.1mol/L of sodium phosphate;
weighing 50g of monodisperse porous activated carbon particles and placing the particles into a wide-mouth container, wherein the particle size of the porous activated carbon particles is about 30 microns, the total water absorption capacity of the porous activated carbon particles is about 50mL, slowly dripping about all the first solution into the container, and stirring the porous activated carbon particles while dripping; after the dropwise addition, the mixture is stirred for 10 minutes to fully disperse the porous active carbon particles. Then slowly dripping 25mL of second solution into the container while stirring, and stirring for 10 minutes after dripping; then collecting the radioactive particles containing yttrium-90.
In the preparation process of this example 3, the second solution is prepared in advance, and it takes about 44 minutes for the first solution to be prepared and finally the radioactive particles containing yttrium-90 are received. 1g of the prepared yttrium-90-containing radioactive particles were weighed and tested by a radioactivity meter, and the radioactivity of 1g of the radioactive particles was measured to be 0.50 GBq.
Example 4
A method of making a yttrium-90-containing radioactive particle, comprising:
weighing 25mL of medical radioactive yttrium chloride-90 solution, and measuring the radioactivity of the solution to be 50GBq by using a radioactivity meter; about 2.38g of magnesium chloride was added to the solution and mixed well to prepare a first solution containing 0.025mol of magnesium chloride and 50GBq of yttrium chloride-90.
Weighing sodium phosphate, dissolving with deionized water, and preparing 1L of a second solution containing 1.0mol/L of sodium phosphate;
weighing 50g of monodisperse porous active carbon particles, placing the monodisperse porous active carbon particles in a wide-mouth container, wherein the particle size of the porous active carbon particles is about 30 mu m, the total water absorption capacity of the porous active carbon particles is about 50mL, slowly dropwise adding all the first solution into the container, and stirring the porous active carbon particles while dropwise adding; after the dropwise addition, the porous activated carbon particles were transferred to a dispersion machine and dispersed for 5 minutes at 100 rpm. Then slowly dripping 25mL of second solution into the container while stirring, transferring the porous activated carbon particles into a dispersion machine after dripping, and dispersing for 5 minutes under the condition of 100 revolutions per minute; then collecting the radioactive particles containing yttrium-90.
In the preparation process of this example 4, the second solution is prepared in advance, and it takes about 40 minutes to prepare the first solution and finally receive the yttrium-90-containing radioactive particles. 1g of the prepared yttrium-90-containing radioactive particles were weighed and tested by a radioactivity meter, and the radioactivity of 1g of the radioactive particles was measured to be 0.50 GBq.
Example 5
A method of making strontium-90-containing radioactive particles, comprising:
weighing 10mL of medical radioactive strontium chloride-90 solution, and measuring the radioactivity of the solution to be 16GBq by using a radioactivity meter; about 1.11g of anhydrous calcium chloride was added to the solution, and after thoroughly mixing, a first solution containing 0.01mol of calcium chloride and 16GBq of strontium chloride-90 was prepared.
Weighing sodium phosphate, dissolving with deionized water, and preparing 1L of a second solution containing 0.7mol/L of sodium phosphate;
weighing 20g of monodisperse porous active carbon particles, placing the monodisperse porous active carbon particles in a wide-mouth container, wherein the particle size of the porous active carbon particles is about 50 microns, the total water absorption capacity of the porous active carbon particles is about 20mL, slowly dropwise adding all the first solution into the container, and stirring the porous active carbon particles while dropwise adding; after the dropwise addition, the mixture is stirred for 10 minutes to fully disperse the porous active carbon particles. Then slowly dripping 10mL of second solution into the container while stirring, and stirring for 10 minutes after dripping; then collecting the radioactive particles containing strontium-90.
In the preparation process of example 1, the second solution is prepared in advance, and it takes about 35 minutes for the first solution to be prepared and the radioactive particles containing strontium-90 to be received. 1g of the prepared strontium-90-containing radioactive particles were weighed and tested by a radioactivity meter, and the radioactivity of 1g of the radioactive particles was measured to be 0.40 GBq.
Example 6
A method of making a radioactive nickel-63 containing particle, comprising:
weighing 10mL of medical radioactive nickel-63 ion solution, and measuring the radioactivity of the medical radioactive nickel-63 ion solution to be 16GBq by using a radioactivity meter; about 1.11g of anhydrous calcium chloride was added to the solution, and after thoroughly mixing, a first solution containing 0.01mol of calcium chloride and 16GBq of nickel-63 ions was prepared.
Weighing sodium phosphate, dissolving with deionized water, and preparing 1L of a second solution containing 1.1mol/L of sodium carbonate;
weighing 20g of monodisperse porous diatomite particles and placing the particles into a wide-mouth container, wherein the particle size of the porous diatomite particles is about 50 microns, the total water absorption capacity of the porous diatomite particles is about 20mL, slowly dropwise adding all the first solution into the container, and stirring the porous diatomite particles while dropwise adding; after the dropwise addition was completed, the mixture was stirred for another 10 minutes to sufficiently disperse the porous diatomaceous earth particles. Then slowly dripping 10mL of second solution into the container while stirring, and stirring for 10 minutes after dripping; the resulting nickel-63 containing radioactive particles are then collected.
In the preparation process of example 1, the second solution is prepared in advance, and it takes about 35 minutes for the first solution to be prepared and finally the radioactive particles containing nickel-63 to be received. 1g of the prepared nickel-63-containing radioactive particles were weighed and tested by a radioactivity meter, and the radioactivity of 1g of the radioactive particles was measured to be 0.40 GBq.
Example 7
A method of making a phosphorus-32 containing radioactive particle, comprising:
weighing anhydrous calcium chloride, adding deionized water, fully and uniformly mixing, and then fixing the volume to 10mL to prepare a first solution containing 0.015mol of calcium chloride.
Weighing 10mL of medical radioactive sodium phosphate-32 solution, and measuring the radioactivity of the solution to be 10GBq by using a radioactivity meter; about ordinary sodium phosphate solid was added to the solution and mixed well to make a second solution containing about 0.007mol sodium phosphate and 10GBq sodium phosphate-32.
Weighing 20g of monodisperse porous active carbon particles, placing the monodisperse porous active carbon particles in a wide-mouth container, wherein the particle size of the porous active carbon particles is about 50 microns, the total water absorption capacity of the porous active carbon particles is about 20mL, slowly dropwise adding all the first solution into the container, and stirring the porous active carbon particles while dropwise adding; after the dropwise addition, the mixture is stirred for 10 minutes to fully disperse the porous active carbon particles. Then slowly dripping all the second solution into the container while stirring, and stirring for 10 minutes after dripping; the radioactive particles containing phosphorus-32 are then collected.
In the preparation process of example 1, the second solution is prepared in advance, and it takes about 35 minutes for the first solution to be prepared and the radioactive particles containing phosphorus-32 to be received. 1g of the prepared phosphorus-32-containing radioactive particles were weighed and tested by a radioactivity meter, and the radioactivity of 1g of the radioactive particles was measured to be 0.25 GBq.
Example 8
A method of making iodine-125 containing radioactive particles comprising:
weighing silver nitrate, adding deionized water, fully and uniformly mixing, and fixing the volume to 10mL to prepare a first solution containing 0.012mol of silver nitrate.
Weighing 10mL of medical radioactive iodine-125 sodium solution, and measuring the radioactivity of the solution to be 10GBq by using a radioactivity meter; adding solid sodium chloride into the solution, and fully and uniformly mixing to prepare a second solution containing about 0.01mol of sodium chloride and 10GBq of iodine-125 sodium chloride.
Weighing 20g of monodisperse porous active carbon particles, placing the monodisperse porous active carbon particles in a wide-mouth container, wherein the particle size of the porous active carbon particles is about 50 microns, the total water absorption capacity of the porous active carbon particles is about 20mL, slowly dropwise adding all the first solution into the container, and stirring the porous active carbon particles while dropwise adding; after the dropwise addition, the mixture is stirred for 10 minutes to fully disperse the porous active carbon particles. Then slowly dripping all the second solution into the container while stirring, and stirring for 10 minutes after dripping; then collecting the radioactive particles containing iodine-125.
In the preparation process of this example 1, the second solution is prepared in advance, and it takes about 35 minutes for the first solution to be prepared and the iodine-125-containing radioactive particles to be received. 1g of the prepared iodine-125-containing radioactive particles are weighed and tested by a radioactivity meter, and the radioactivity of 1g of the radioactive particles is 0.25 GBq.
Effects of the embodiment
Radioactivity detection
Each 1g of the radioactive particles prepared in examples 1 to 8 was weighed and named as Experimental group 1 to Experimental group 8, respectively. To each group of radioactive particles, 20mL of 10% physiological saline was added and sealed. Then, the mixture was placed in a thermostat at 50 ℃ for 24 hours, and after centrifugation, the filtrate was collected and tested by a radioactivity meter, respectively, and the results are shown in Table 1.
TABLE 1 test data sheet for radioactivity in the test groups
As can be seen from the test data, the radioactive particles prepared in examples 1 to 8 of the present invention all showed good structural stability, and radioactivity was detected after long-term immersion, and the release rate of the radionuclide was close to 0%, indicating that there was no risk of leakage of the radionuclide in the radioactive particles prepared by the preparation method of the present invention.
Effect of embodiment two
Ion concentration detection
3g of non-radioactive particles containing yttrium 89 prepared by the preparation method described in the control group 1 was added with 20mL of 10% physiological saline and sealed. Then placing in a thermostat at 50 deg.C, taking out every day, shaking for 5min, and standing for 14 days. After 14 days, the filtrate was collected by centrifugation, and the yttrium ion concentration in the filtrate was measured by ICP (inductively coupled plasma spectrometer).
Wherein, the ICP test result shows that the concentration of the yttrium ions in the filtrate is less than 0.02mg/L (lower than the detection limit, namely, the yttrium ions are not detected).
Then, 0.3g of nonradioactive particles was weighed, 20mL of 10% nitric acid solution was added, the mixture was immersed for 4 hours, the volume was adjusted to 50mL, and the filtrate was collected by centrifugation and tested for the yttrium ion concentration in the filtrate by ICP.
Wherein, the ICP test result shows that the concentration of yttrium ions in the filtrate is 40 ppm.
According to the analysis of the test data, in the non-radioactive particles containing yttrium 89 prepared by the preparation method of comparative group 1, yttrium is accommodated in the porous holes of the porous solid carrier in a precipitation form, the structure is stable, and almost no yttrium ions are released in the soaking process for 14 days. The release of yttrium ions from the non-radioactive particles can only be detected after dissolution of the yttrium phosphate precipitate in the porous pores with nitric acid.
While the foregoing is directed to the preferred embodiment of the present invention, it will be understood by those skilled in the art that various changes and modifications may be made without departing from the spirit and scope of the invention.
Claims (17)
1. A method of preparing radioactive particles, comprising:
preparing a first solution, wherein the first solution contains at least one kind of cation;
preparing a second solution containing at least one anion, said cation and/or said anion comprising a radionuclide, said anion being capable of reacting with said cation to form a radionuclide precipitate;
taking a certain amount of hydrophilic porous solid carrier, slowly dropwise adding the first solution into the porous solid carrier, and fully stirring to make the first solution enter porous holes of the porous solid carrier; slowly dripping the second solution into the porous solid carrier, stirring to enable the second solution to enter the porous holes, enabling anions in the second solution to react with metal cations in the first solution in the porous holes to generate radionuclide precipitates, containing the radionuclide precipitates in the porous holes, and collecting to obtain radioactive particles; wherein the porous solid support comprises at least one of a carbon-based material, alumina particles, titanium dioxide, diatomaceous earth, attapulgite, zeolite, a metal organic framework material, and a covalent organic framework polymer.
2. The method of claim 1, wherein the cations in the first solution comprise at least one of strontium-90 ions, yttrium-90 ions, and nickel-63 ions; the radionuclide contained in the anion in the second solution includes at least one of phosphorus-32, sulfur-35, iodine-131, and iodine-125.
3. The method of claim 1, wherein when the anion does not comprise the radionuclide, the anion comprises at least one of phosphate, carbonate, sulfate, hydroxide, alginate, and silicate.
4. The method of claim 1, wherein when said cation does not contain said radionuclide, said cation comprises at least one of silver ion, calcium ion, and magnesium ion.
5. The method of any one of claims 1 to 4, wherein the first solution further comprises a non-radioactive metal cation capable of reacting with the anion in the second solution to form a second precipitate; the non-radioactive metal cations include one or more of strontium ions, yttrium ions, nickel ions, calcium ions, silver ions, and magnesium ions.
6. The method of claim 1, wherein the total volume of the first solution and the second solution is less than or equal to the total water uptake of the porous solid support.
7. The production method according to any one of claims 1 to 4, wherein the porous solid support has a particle size of 0.05 μm to 600 μm; the porous aperture of the porous solid carrier is 0.1nm-600 nm.
8. A radioactive particle comprising a porous solid support and at least one radionuclide precipitate contained within porous pores of the porous solid support; the porous solid support is hydrophilic, the radionuclide precipitates are generated by the reaction of cations and anions, and the cations and/or the anions comprise radionuclides; the porous solid support comprises at least one of a carbon-based material, alumina particles, titanium dioxide, diatomaceous earth, attapulgite, zeolite, a metal organic framework material, and a covalent organic framework polymer.
9. The radioactive particle of claim 8, wherein said cation comprises said radionuclide including at least one of strontium-90, yttrium-90, and nickel-63.
10. The radioactive particle of claim 8, wherein said anion comprises said radionuclide including at least one of phosphorus-32, sulfur-35, iodine-131 and iodine-125.
11. The radioactive particle of claim 8, wherein when said anion does not contain said radionuclide, said anion comprises at least one of phosphate, carbonate, sulfate, hydroxide, alginate, and silicate.
12. The radioactive particle of claim 8, wherein when said cation does not include said radionuclide, said cation comprises at least one of silver, calcium and magnesium ions.
13. The radioactive particle of claim 8, wherein said radionuclide precipitates comprise at least one of yttrium phosphate-90, strontium phosphate-90, nickel carbonate-63, silver iodide-125, silver iodide-131, and calcium phosphate-32.
14. The radioactive particle according to any one of claims 8 to 13, further comprising a second precipitate within said porous pores of said porous solid support, said second precipitate resulting from the reaction of a non-radioactive metal cation comprising one or more of strontium, yttrium, nickel, calcium and magnesium ions with said anion.
15. The radioactive particle according to any one of claims 8 to 13, wherein the radionuclide has a radioactivity of 0.1GBq to 50GBq per gram weight of the radioactive particle.
16. The radioactive particulate of any one of claims 8 to 13, further comprising water and a soluble metal salt within said porous pores of said porous solid support, said soluble metal salt comprising one or more of sodium chloride, potassium chloride, sodium phosphate, potassium phosphate, sodium sulfate, potassium sulfate, sodium carbonate, potassium carbonate, sodium alginate, potassium alginate, sodium silicate and potassium silicate.
17. Use of radioactive particles prepared by the process according to any one of claims 1 to 7 for the preparation of a medicament for the treatment of tumors.
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| CN106178006A (en) * | 2016-08-11 | 2016-12-07 | 李淑惠 | Medical iodine 131 carbosphere and preparation method thereof |
| CN107715122A (en) * | 2016-08-11 | 2018-02-23 | 李茂良 | Medical yttrium phosphate [90Y32PO4] carbosphere and preparation method thereof |
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