CN107715122B - Medical yttrium phosphate [ alpha ], [ alpha90Y32PO4]Carbon microsphere and preparation method thereof - Google Patents

Medical yttrium phosphate [ alpha ], [ alpha90Y32PO4]Carbon microsphere and preparation method thereof Download PDF

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CN107715122B
CN107715122B CN201610655102.6A CN201610655102A CN107715122B CN 107715122 B CN107715122 B CN 107715122B CN 201610655102 A CN201610655102 A CN 201610655102A CN 107715122 B CN107715122 B CN 107715122B
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yttrium phosphate
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李茂良
蔡继鸣
胡学正
葛强
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Chengdu New Medical Technology Co., Ltd.
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Chengdu Nurit Medical Technology Co Ltd
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Abstract

The invention discloses a medical yttrium phosphate used for treating tumor90Y32PO4]Carbon microspheres and a preparation method thereof. Medical yttrium phosphate [ alpha ], [ alpha90Y32PO4]The carbon microspheres are adsorbed by carbon microspheres90YCl3Yttrium tartrate-90 (produced by reaction with tartaric acid solution)90Y-tartaric acid) complex, then Na3 32PO4Solution treatment generation90Y32PO4The sediment is solidified and purified. The medical yttrium phosphate of the invention90Y32PO4) Yttrium of carbo-microsphere pair (90The adsorption and solidification efficiency of Y) nuclide is greater than 95%, and the adsorption and solidification efficiency of Y) nuclide is higher than that of P-32 (P-32)32The adsorption and solidification efficiency of P) nuclide is higher than 99%, and the medical yttrium phosphate (P) nuclide is further purified and treated90Y32PO4) Yttrium-90 of carbosphere (90Y) and phosphorus-32: (32P) is less than 0.01 percent, has good biocompatibility and can be used for in-vivo tumor radiotherapy.

Description

Medical yttrium phosphate [ alpha ], [ alpha90Y32PO4]Carbon microsphere and preparation method thereof
Technical Field
The invention relates to a tumor radiotherapy medicament and a preparation method thereof, in particular to medical yttrium phosphate90Y32PO4]Carbon microspheres and a preparation method thereof.
Background
Malignant tumors are diseases that seriously endanger human health, and surgical therapy, chemotherapy and radiotherapy are the main methods for treating malignant tumors at present. Because most patients enter the middle and late stages when cancer is diagnosed, the chance of surgical treatment is lost, and the patients are not sensitive to chemotherapeutic drugs after multiple times of chemotherapy, and radiotherapy becomes a key treatment means for some cancers. For example, there are 46.61 ten thousand cases estimated from 2015 years of liver cancer cases in ChinaThe estimated value of death cases was 42.21 ten thousand, and the number of cases of liver CANCER and death cases were ranked in the third place among all CANCERs [ Wanqing Chen, Jie He, et al]. About 70% of liver cancer patients in China are found to be in a late stage [ Wumengtao, the current situation and prospect of the development of hepatectomy technology in China, J.Zhonghua surgical, 2010.48 (3): 161-162]And is influenced by various factors, only about 20% of the patients can be surgically excised [ Chilobrachys jingzhao 29495, Yangzhiliao, research and development of primary liver cancer, Shanghai medical university Press, 1990,1-19]. Thus, non-surgical intervention (Interventional Treatment) has become an important tool in liver cancer Treatment [ Lencioni R, Croceti L, Dessimone P, et al, Loco-regional Interventional Treatment of hepatocellularcacinoma: technologies, outmeters, and future therapies. Transpl Int,2010,23(7):698 703-]. However, after the liver arterial embolization chemotherapy, the residual live cancer cells are generated beside the cancer and become the source of recurrence or metastasis [ Dayimin, enlaung, Chenhan, etc.. the pathological morphology of the liver arterial perfused with chemotherapeutic embolization agent, the journal of Chinese medicine, 1991,71:366]Studies have shown [ Lewandowski RJ, Kulik LM, Riaz A, et al. A comparative analysis of metabolic downscaling for a acellular cardio. chemoembolisation conversion radiology).American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons2009; 9(8): 1920-8]Compared with the treatment of liver cancer by the transcatheter arterial embolism radiotherapy and the transcatheter arterial embolism chemotherapy, the tumor response rate is obviously improved (61% vs. 37%), and the survival rate without events is improved (17.7 months vs. 7.1 months). Therefore, the treatment of malignant tumor by radioactive embolism microsphere through artery is a very effective method.
Yttrium-90 (90Y) and phosphorus-32: (32P) are two most commonly used therapeutic nuclides in nuclear medicine, both of which can be prepared into radioactive glass microspheres for tumor treatment, Yttrium-90: (B)90Y) glass microspheres have high specific radioactivity, but yttrium-90: (90Y) short half-life (64 h), and phosphorus-32: (32P) glass microspheres have a low specific radioactivity, but phosphorus-32: (32P) longer half-life (about 14 d), each with advantages and disadvantages for the treatment of tumors.
Disclosure of Invention
The invention aims to provide a new type of yttrium-90 (II) with simple process, high nuclide adsorption rate and low release rate90Y) and phosphorus-32: (32P) of yttrium phosphate for medical use90Y32PO4]Carbon microspheres and a preparation method thereof.
In order to achieve the purpose, the invention adopts the following technical scheme:
the invention uses carbon microsphere as a carrier to absorb radioactivity90YCl3Radioactive complexes of solutions and tartaric acids: (90Y-tartaric acid), and radioactive sodium phosphate (Na)3 32PO4) Solution reaction to produce radioactive yttrium phosphate (Y) in carbon microsphere32PO4) Precipitating, thereby dissolving yttrium-90: (90Y) and phosphorus-32: (32P) solidifying the two nuclides, and further purifying to prepare the medical yttrium phosphate (B)90Y32PO4) Carbon microspheres. The medical yttrium phosphate (I) prepared by the invention90Y32PO4) Carbon microsphere Yttrium-90 (III)90The adsorption rate of Y nuclide is higher than 95 percent, and the adsorption rate to phosphorus-32: (32The adsorption efficiency of P species is higher than 99%, and yttrium-90: (B)90Y) and phosphorus-32: (32P) the release rate of both nuclides is lower than 0.01 percent, and the total specific radioactivity is higher, so that the effective treatment time on the tumor is longer, and the radionuclide is more suitable for tumor radiotherapy.
The carbon microsphere adsorption of the invention is physical adsorption, because of phosphorus-32 (C)32P) nuclide is Na3 32PO4The compound exists in the form of compound and can not be directly adsorbed by the carbon microsphere, but32PO4 3-Ions (including nonradioactive PO)4 3-Ions) and radioactivity90Y3+Ions (including nonradioactive Y)3+Ion) reaction to produce insoluble yttrium phosphate [ Yttrium ], [ solution ]90Y32PO4](including non-radioactive YPO)4) Precipitate, and therefore should be put in advanceNature of fire90Y3+Ions (including nonradioactive Y)3+Ion) is adsorbed in the carbon microsphere, and then yttrium phosphate is generated in the carbon microsphere90Y32PO4]Precipitation, simultaneous solidification of both yttrium-90 and phosphorus-32 species within the carbon microspheres, but due to yttrium-90: (b)90Y) nuclide is90YCl3In the form of a compound, yttrium-90: (90Y) is a cation in the positive trivalent state (90Y3+) When the acidity of the solution is high, the amount of the carbon microspheres directly adsorbed by physical adsorption is small (<30mgY/g microsphere), when the pH value of the solution is more than 1,90Y3+the ions are easy to hydrolyze to generate precipitates, so the adsorption of the carbon microspheres to yttrium-90 (C:)90Y) nuclide amount to generate more yttrium phosphate [ Yttrium ], [ beta ]90Y32PO4]Precipitation, which must be prevented by appropriate measures90Y3+Ion hydrolysis and improved adsorption of yttrium-90 by carbon microspheres90Y) adsorption capacity of the nuclide. The specific method is to select a complexing agent and90Y3+ion generation of a stable complex to prevent90Y3+Hydrolyzing the ion and making the complex be firmly adsorbed by carbon microsphere, then using Na3 32PO4Solution and adsorbed by carbon micro-sphere90Y3+Ion reaction to produce insoluble yttrium phosphate90Y32PO4]The two nuclides of yttrium-90 and phosphorus-32 are simultaneously solidified in the carbon microsphere by precipitation, and then further purified to prepare the medical yttrium phosphate [ 2 ]90Y32PO4]Carbon microspheres. The release rate of the carbon microsphere to yttrium-90 nuclide and phosphorus-32 nuclide is lower than 0.01 percent, and the requirement of treating tumors is met. Through screening tests, the invention finds that the complexing agent tartaric acid can be mixed with90Y3+Formation of complexation90Y3+The tartaric acid complex is adsorbed by the carbon microspheres, and32PO4 3+can be combined with90Y3+Reacting to produce yttrium phosphate [ 2 ]90Y32PO4]Precipitating and simultaneously solidifying two radionuclides of yttrium-90 and phosphorus-32 in the carbon microsphere, thereby preparing the yttrium phosphate [ yttrium ], [ phosphorus ], [ 32 ]90Y32PO4]Carbon microspheres. The preparation method comprisesThe method comprises the following steps:
medical yttrium phosphate [ alpha ]90Y32PO4]The carbon microsphere consists of mainly carbon microsphere and deposited and solidified radionuclides yttrium-90 and phosphorus-32 in the carbon microsphere.
Further, the medical yttrium phosphate carbon microsphere is prepared by the following method: adsorption by carbon microspheres90YCl3Solution and tartaric acid solution90Y-tartaric acid complex, with radioactive sodium phosphate Na3 32PO4Reacting the solution to produce yttrium phosphate [ 2 ]90Y32PO4]The precipitate is solidified and then is further purified to prepare the product.
Medical yttrium phosphate [ alpha ]90Y32PO4]The preparation method of the carbon microsphere comprises the following steps:
(1) adsorption90Preparation of carbon microspheres of Y-tartaric acid complex: mixing carbon microspheres with90Mixing the Y-tartaric acid complex solution, shaking at 40-50 deg.C for 40-60 min, separating solid and liquid, removing reaction solution, washing with purified water repeatedly, and washing off unadsorbed substances90Y-tartaric acid complex, namely adsorbs90Carbon microspheres of a Y-tartaric acid complex;
(2) medical yttrium phosphate [ alpha ], [ alpha90Y32PO4]Preparing carbon microspheres: by containing32Radioactive Na with P greater than 7.4GBq (200mCi)3 32PO4Soaking in the solution to adsorb90Carbon microspheres of Y-tartaric acid complex, and shaking the mixture at constant temperature of 40-50 ℃ for 20-30 minutes to generate90Y32PO4Precipitating, solidifying yttrium-90 nuclide and phosphorus-32 nuclide, removing reaction liquid by solid-liquid separation, and repeatedly cleaning with purified water to obtain medical yttrium phosphate [ 2 ]90Y32PO4]Carbon microspheres.
The radioactive Na3 32PO4The preparation method of the solution comprises the following steps: sealing magnesium hydrogen phosphate or aluminum phosphate in quartz glass tube and placing in the quartz glass tube under the condition that the flux of thermal neutrons is higher than 5 x 1013n/cm2S nuclear reactor irradiation, via31P(n,r)32P production of radioactive MgH32PO4Or radioactive Al32PO4，32P has a nuclear purity of not less than 99.9% and a specific radioactivity of greater than 148G Bq (4Ci)/gP, is dissolved in hydrochloric acid and Mg is precipitated with NaOH solution2+Ions and Al3+Ion, MgH32PO4Or Al32PO4Conversion to radioactive Na3 32PO4，Na3 32PO4The radiochemical purity of the solution is not less than 95% per ml Na3 32PO4The radioactivity concentration of the solution is not less than 14.8GBq (400mCi)/mL, and the solution is diluted to the required concentration according to the use requirement when in use.
The above-mentioned90The preparation method of the Y-tartaric acid complex comprises the following steps: will be provided with90YCl3The solution and tartaric acid solution are mixed according to the molar ratio of 1:2-2.5 to generate90Y-tartaric acid complex, wherein the pH value of the solution is 1.0-2.0.
The above-mentioned90YCl3The solution is prepared by mixing Y2O3Sealed in a quartz glass tube and arranged in a position where the flux of thermal neutrons is higher than 5 multiplied by 1013n/cm2S nuclear reactor irradiation, via89Y(n,r)90Formation of Y by reaction90Y2O3Specific radioactivity greater than 370G Bq (10Ci)/gY, dissolved with hydrochloric acid, which90YCl3Y of solution3+The ion concentration is 40 mg/mL-60mg/mL, the pH value of the solution is lower than 1.0,90YCl3nuclear purity of the solution90Y is not less than 99.9%, radiochemical purity is not less than 95%, the radioactivity concentration per milliliter is not less than 18.5GBq (500mCi)/mL, and the radioactive concentration is diluted to the required radioactivity concentration according to the use requirement when in use.
The tartaric acid solution is prepared by dissolving tartaric acid with purified water, and the concentration of the tartaric acid solution is 0.1 g/mL.
The medical yttrium phosphate [ Yttrium ], [90Y32PO4]The preparation method of the carbon microsphere also comprises purification treatment of the carbon microsphere, which specifically comprises the following steps: soaking carbon microsphere in ethyl acetate, acetone or ethanol to remove lipid, soaking in sodium hydroxide solution to remove alkali-soluble impurities, and repeatedly cleaning with purified waterAnd (3) soaking the mixture in nitric acid to remove acid-soluble impurities when the mixture is alkalescent, and cleaning the mixture with purified water until the pH value is 1-2 for later use.
The carbon microsphere is prepared by carbonizing a microsphere prepared from organic materials rich in carbon at high temperature, and removing various impurities through degreasing, alkali washing, acid washing and the like to prepare the spherical particle which is harmless to human bodies and has good biocompatibility.
The diameter of the carbon microsphere is 20-30 μm.
The diameter of the carbon microsphere is 30-100 μm.
The diameter of the carbon microsphere is more than 100 μm.
The diameter of the carbon microsphere is 10-100 nm.
The diameter of the carbon microsphere is 100-150 nm.
The medical yttrium phosphate carbon microsphere medium-carbon microsphere pair32The adsorption rate of P nuclide is higher than 99 percent, and the P nuclide is adsorbed90The adsorption rate of the Y nuclide is higher than 95 percent.
The medical yttrium phosphate [ Yttrium ], [90Y32PO4]In the carbon microsphere90Y nuclide and32the P nuclide release rates are all lower than 0.01 percent.
A preparation for in vivo tumor radiotherapy is prepared from the medical yttrium phosphate carbon microspheres. Yttrium-90 (C) in formulations for in vivo tumor radiotherapy90Y) has a radioactivity of 1.85GBq-14.8GBq (50mCi-400mCi), phosphorus-32: (32P) has a radioactivity of 1.85GBq-7.4 GBq (50mCi-200mCi), and the particle size of the carbon microsphere is determined according to the application: medical yttrium phosphate [ 2 ] with particle size of 20-30 μm90Y32PO4]The carbon microsphere is mainly used for arterial perfusion embolism radiotherapy liver cancer, and the carbon microsphere with the particle size of 30-100 mu m can be used for tumors rich in blood vessels, such as lung cancer, kidney cancer, tongue cancer, breast cancer, cervical cancer and the like, and can also be directly dispersed and injected into other tumors; the particle size is more than 100 μm, and the preparation can be used for radioactive implantation treatment of tumors; medical yttrium phosphate with particle size of 100 and 150nm90Y32PO4]The carbon microsphere is mainly used for treating lymph cancer and its metastatic cancer, and has a particle size of 10-100nm90Y32PO4]The carbon microsphere has tumor-oriented property, and can be usedCan be used for tumor targeted therapy.
The medical yttrium phosphate [ 2 ]90Y32PO4]Use of a carbon microsphere in the manufacture of a medicament for treating a mammal having a medical condition, wherein said medical yttrium phosphate90Y32PO4]The carbon microspheres are administered using an interventional catheter, syringe or in vivo implant.
The invention has the beneficial effects that:
1. the yttrium phosphate of the present invention90Y32PO4]The carbon microspheres are obtained by adsorbing with carbon microspheres90Y-tartaric acid complex, and Na3 32PO4Solution treatment generation90Y32PO4Precipitating, solidifying and purifying to obtain the medical carbon microsphere yttrium-90: (90The adsorption rate of Y) is higher than 95 percent, and the adsorption rate to phosphorus-32 (C)32The adsorption efficiency of P) species is higher than 99%, while for yttrium-90: (B)90Y) and phosphorus-32: (32P) two nuclides release rate is lower than 0.01 percent, and the biocompatibility is good, the medical yttrium phosphate [ yttrium ], [ P ] developed by the invention90Y32PO4]The total specific radioactivity of the carbon microspheres is higher, so that the effective treatment of tumors is prolonged, and the carbon microspheres are more beneficial to treating various tumors. The medical yttrium phosphate of different particle sizes of the present invention90Y32PO4]The carbon microsphere can be used for embolizing and radiotherapy of tumors containing abundant blood vessels, such as liver cancer, or other tumors by scattered injection radiotherapy, or can be used for treating lymph cancer and lymph metastasis cancer, and contains some tumor-oriented functional groups90Y32PO4]The carbon microsphere can also be used for treating other tumors.
2. The method is simple, and has less introduced impurities and high product purity.
3. Yttrium-90 (90Y) and phosphorus-32: (32P) has high utilization rate, generates less radioactive wastes and is beneficial to environmental protection.
4. Yttrium-90 (90Y) and phosphorus-32: (32P) has low release rate and good safety.
5.[90Y32PO4]Carbon microThe radioactivity of the ball can be adjusted in time according to individual needs, and the individualized accurate treatment requirements can be met at any time.
6. Yttrium-90 (90Y) and phosphorus-32: (32P) is easily obtained from a variety of channels, and yttrium phosphate [ Yttrium ], [90Y32PO4]The normal production of the carbon microspheres is not influenced by the supply of raw materials, and the perennial production supply requirements can be met.
7. Yttrium phosphate [ alpha ]90Y32PO4]The carbon microsphere has higher specific radioactivity, has longer effective duration of treatment time on the tumor, and is more beneficial to the effective treatment on the tumor.
8. Medical yttrium phosphate [ alpha ], [ alpha90Y32PO4]The carbon microsphere has low production cost and is convenient to popularize and apply.
Detailed Description
Examples
(1) And (3) carbon microsphere purification treatment: soaking in organic solvent such as ethyl acetate, acetone or ethanol to remove fat; soaking in dilute sodium hydroxide solution (0.1-0.5 mol/L) to remove alkali-soluble impurities, and repeatedly washing to alkalescence (pH of 8-10); then dilute nitric acid (0.1 mol/L-0.5 mol/L) is used for soaking and removing acid-soluble impurities, and the pH value is cleaned to be 1-2.
(2) 30g of commercially available guaranteed magnesium hydrogen phosphate (MgHPO)4) Or aluminum phosphate (AlPO)4) Sealed in a quartz glass tube and arranged in a position where the flux of thermal neutrons is higher than 5 multiplied by 1013n/cm2S nuclear reactor irradiation, via31P(n,r)32P produces radioactive magnesium hydrogen phosphate (MgH)32PO4) Or radioactive aluminum phosphate (Al)32PO4），32The nuclear purity of P is not less than 99.9%, the specific radioactivity is more than 148GBq (4Ci)/gP, and the P is prepared by diluting HCl solution [ the HCl solution is diluted by 36-38% HCl solution and water according to the proportion of 1:1 (mL/mL)]Dissolving and precipitating Mg with NaOH solution2+Ions and Al3+Ion, MgH32PO4And Al32PO4Conversion to radioactive Na3 32PO4，Na3 32PO4The radiochemical purity of the solution is not less than 95%. Every milli of Chinese characterRaise Na3 32PO4The radioactivity concentration of the solution is not less than 14.8GBq (400mCi)/mL, and the solution is diluted to the required concentration according to the use requirement when in use.
(3) Mixing commercially available guaranteed reagent 25g Y2O3Sealed in a quartz glass tube and arranged in a position where the flux of thermal neutrons is higher than 5 multiplied by 1013n/cm2S nuclear reactor irradiation, via89Y(n,r)90Formation of Y by reaction90Y2O3A specific activity greater than 370G Bq (10Ci)/gY,90the nuclear purity of Y is not less than 99.9%, and then 300mL of HCl solution is used (the HCl solution is diluted by 36-38% HCl solution and water according to the ratio of 1:1 (mL/mL)]Dissolving with mild heating, cooling to room temperature, transferring to 500mL volumetric flask, diluting with distilled water to desired volume90YCl3The solution is prepared by mixing a solvent and a solvent,90YCl3the radiochemical purity of the solution is not less than 95%.90YCl3The solution has a radioactivity concentration of at least 18.5GBq (500mCi)/mL (Y)3+The ion concentration is 40 mg/mL-60 mg/mL), and when in use, the solution is diluted to the required radioactive concentration according to the use requirement.
(4) Analytically pure tartaric acid is dissolved by purified water to prepare tartaric acid solution, the concentration of the tartaric acid solution is 0.1g/mL, and the tartaric acid solution is used for preparing Y-tartaric acid complex.
(5) Prepared as described in the step (3) above90YCl3Mixing the solution and the tartaric acid solution prepared in the step (4) according to a molar ratio of 1:2-2.5 to generate90Y-tartaric acid complex, wherein the pH of the solution is 1.0-2.0.
(6) Mixing 1-3g of carbon microspheres with 5-10mL90Mixing the Y-tartaric acid complex solution (Y content greater than 100 mg), shaking at 40-50 deg.C for 40-60 min, removing reaction solution by solid-liquid separation (centrifugation or filtration), washing with purified water 5mL repeatedly, and washing off unadsorbed substances90Y-tartaric acid complex, namely adsorbs90The carbon microsphere of the Y-tartaric acid complex, the content of the yttrium (Y) adsorbed by the carbon microsphere is more than 95mg, can be used for preparing the yttrium phosphate [ Yttrium ], [ 2 ]90Y32PO4]Carbon microspheres.
(7) 5-10mL of a solution prepared by step (2) containingIs provided with32Na with P greater than 7.4GBq (200mCi) (containing 50-60mg of total phosphorus)3 32PO4Soaking 1-3g of the adsorbed substance prepared in step (6) in the solution90The carbon microsphere after the Y-tartaric acid complex is shaken for 20 to 30 minutes at the constant temperature of between 40 and 50 ℃ to generate90Y32PO4Precipitation, simultaneous solidification with-90: (90Y) and phosphorus-32: (32P) two nuclides, and is repeatedly washed by 5mL of purified water after reaction liquid is removed by solid-liquid separation (centrifugation or filtration) to obtain the medical yttrium phosphate [ 2 ]90Y32PO4]Carbon microspheres.
The yttrium phosphate [ Yttrium ], [ 2 ] prepared in this example90Y32PO4]Carbon microsphere Yttrium-90 (III)90Y) adsorption rate higher than 95% for P-32: (32P) adsorption rate higher than 99%, and yttrium-90: (B)90Y) and phosphorus-32: (32P) the release rate of both nuclides is lower than 0.01 percent, has good biocompatibility and can be used for tumor radiotherapy.

Claims (18)

1. Medical yttrium phosphate [ alpha ]90Y32PO4]The carbon microsphere is characterized in that: the medical yttrium phosphate carbon microsphere mainly comprises a carbon microsphere and radionuclides yttrium-90 and phosphorus-32 which are precipitated and solidified in the carbon microsphere, and specifically comprises the following components: mixing carbon microspheres with90Mixing the Y-tartaric acid complex solution, shaking at 40-50 deg.C for 40-60 min, separating solid and liquid, removing reaction solution, washing with purified water repeatedly, and washing off unadsorbed substances90Y-tartaric acid complex, namely adsorbs90Carbon microspheres of a Y-tartaric acid complex; by containing32Radioactive Na with P greater than 7.4GBq (200mCi)3 32PO4Soaking in the solution to adsorb90Carbon microspheres of Y-tartaric acid complex, and shaking the mixture at constant temperature of 40-50 ℃ for 20-30 minutes to generate90Y32PO4Precipitating, solidifying yttrium-90 nuclide and phosphorus-32 nuclide, removing reaction liquid by solid-liquid separation, and repeatedly cleaning with purified water to obtain medical yttrium phosphate [ 2 ]90Y32PO4]Carbon microspheres.
2. The medical yttrium phosphate [ 2 ] according to claim 190Y32PO4]The carbon microsphere is characterized in that: the radioactive Na3 32PO4The preparation method of the solution comprises the following steps:
sealing magnesium hydrogen phosphate or aluminum phosphate in quartz glass tube and placing in the quartz glass tube under the condition that the flux of thermal neutrons is higher than 5 x 1013n/cm2S nuclear reactor irradiation, via31P(n,r)32P production of radioactive MgH32PO4Or radioactive Al32PO4，32P has a nuclear purity of not less than 99.9% and a specific radioactivity of greater than 148G Bq (4Ci)/gP, is dissolved in hydrochloric acid and Mg is precipitated with NaOH solution2+Ions and Al3 +Ion, MgH32PO4Or Al32PO4Conversion to radioactive Na3 32PO4，Na3 32PO4The radiochemical purity of the solution is not less than 95% per ml Na3 32PO4The radioactivity concentration of the solution is not less than 14.8GBq (400mCi)/mL, and the solution is diluted to the required concentration according to the use requirement when in use.
3. The medical yttrium phosphate [ 2 ] according to claim 190Y32PO4]The carbon microsphere is characterized in that: the above-mentioned90The preparation method of the Y-tartaric acid complex comprises the following steps: will be provided with90YCl3The solution and tartaric acid solution are mixed according to the molar ratio of 1:2-2.5 to generate90Y-tartaric acid complex, wherein the pH value of the solution is 1.0-2.0.
4. The medical yttrium phosphate [ 2 ] according to claim 390Y32PO4]The carbon microsphere is characterized in that: the above-mentioned90YCl3The solution is prepared by mixing Y2O3Sealed in a quartz glass tube and arranged in a position where the flux of thermal neutrons is higher than 5 multiplied by 1013n/cm2S nuclear reactor irradiation, via89Y(n,r)90Formation of Y by reaction90Y2O3Specific radioactivity greater than 370G Bq (10Ci)/gY, using hydrochloric acidDissolution of which90YCl3Y of solution3+The ion concentration is 40 mg/mL-60mg/mL, the pH value of the solution is lower than 1.0,90YCl3nuclear purity of the solution90Y is not less than 99.9%, radiochemical purity is not less than 95%, the radioactivity concentration per milliliter is not less than 18.5GBq (500mCi)/mL, and the radioactive concentration is diluted to the required radioactivity concentration according to the use requirement when in use.
5. The medical yttrium phosphate [ 2 ] according to claim 390Y32PO4]The carbon microsphere is characterized in that: the tartaric acid solution is prepared by dissolving tartaric acid with purified water, and the concentration of the tartaric acid solution is 0.1 g/mL.
6. The medical yttrium phosphate [ 2 ] according to any one of claims 1 to 590Y32PO4]The carbon microsphere is characterized in that: the medical yttrium phosphate [ Yttrium ], [90Y32PO4]The preparation method of the carbon microsphere also comprises purification treatment of the carbon microsphere, which specifically comprises the following steps: soaking carbon microsphere in ethyl acetate, acetone or ethanol to remove fat, soaking in sodium hydroxide solution to remove alkali-soluble impurities, repeatedly cleaning with purified water to weak alkalinity, soaking in nitric acid to remove acid-soluble impurities, and cleaning with purified water to pH of 1-2.
7. The medical yttrium phosphate [ 2 ] according to any one of claims 1 to 590Y32PO4]The carbon microsphere is characterized in that: the carbon microsphere is prepared by carbonizing a microsphere prepared from organic materials rich in carbon at high temperature, and removing various impurities through degreasing, alkali washing and acid washing.
8. The medical yttrium phosphate [ 2 ] according to any one of claims 1 to 590Y32PO4]The carbon microsphere is characterized in that: the method is characterized in that: the diameter of the carbon microsphere is 20-30 μm.
9. The medical yttrium phosphate [ 2 ] according to any one of claims 1 to 590Y32PO4]The carbon microsphere is characterized in that: the method is characterized in that: the diameter of the carbon microsphere is 30-100 μm.
10. The medical yttrium phosphate [ 2 ] according to any one of claims 1 to 590Y32PO4]The carbon microsphere is characterized in that: the method is characterized in that: the diameter of the carbon microsphere is larger than 100 μm.
11. The medical yttrium phosphate [ 2 ] according to any one of claims 1 to 590Y32PO4]The carbon microsphere is characterized in that: the diameter of the carbon microsphere is 10-100 nm.
12. The medical yttrium phosphate [ 2 ] according to any one of claims 1 to 590Y32PO4]The carbon microsphere is characterized in that: the diameter of the carbon microsphere is 100-150 nm.
13. The medical yttrium phosphate [ 2 ] according to any one of claims 1 to 590Y32PO4]The carbon microsphere is characterized in that: the medical yttrium phosphate carbon microsphere medium-carbon microsphere pair32The adsorption rate of P nuclide is higher than 99 percent, and the P nuclide is adsorbed90The adsorption rate of the Y nuclide is higher than 95 percent.
14. The medical yttrium phosphate [ 2 ] according to any one of claims 1 to 590Y32PO4]The carbon microsphere is characterized in that: in the medical yttrium phosphate carbon microsphere90Y nuclide and32the P nuclide release rates are all lower than 0.01 percent.
15. A preparation for in vivo tumor radiotherapy, which is prepared from the medical yttrium phosphate carbon microsphere of any one of claims 1 to 5.
16. The formulation for use as in vivo tumor radiotherapy according to claim 15, characterized in that: the radioactivity of yttrium-90 in the preparation for in vivo tumor radiotherapy is 1.85GBq-14.8GBq (50mCi-400mCi), and the radioactivity of phosphorus-32 is 1.85GBq-7.4 GBq (50mCi-200 mCi).
17. The medical yttrium phosphate [ 2 ] of any one of claims 1 to 590Y32PO4]Use of carbon microspheres in the manufacture of a medicament for the treatment of a mammal suffering from a medical condition.
18. The use of claim 17, wherein the medical yttrium phosphate [ Yttrium ], [90Y32PO4]The carbon microspheres are administered using an interventional catheter, syringe or in vivo implant.
CN201610655102.6A 2016-08-11 2016-08-11 Medical yttrium phosphate [ alpha ], [ alpha90Y32PO4]Carbon microsphere and preparation method thereof Active CN107715122B (en)

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