CN1141146C - Pure beta ray corrying safe microball and its preparation - Google Patents

Abstract

The present invention discloses a safe microsphere carried with pure beta rays and a preparation process thereof, which relates to a safe microsphere carried with pure beta rays capable of curing cancer after being activated and a preparation process thereof. The safe microball is made by compounding a glass microsphere carried with pure beta rays and an anticorrosive coating layer applied to the external surface of the glass microsphere by a sol-gel method. The present invention has the largest advantage that radioisotope in not easy to penetrate and move into blood, in-vitro physiological simulation liquid immersion tests show that the dissolution rate of the corresponding nuclide of the safe microsphere is reduced by 1 to 2 orders of magnitude as compared with the dissolution rate of the nuclide of a microsphere without the anticorrosive coating layer. The safe microsphere has no radioactive pollution, high chemical stability, simple preparation process, and safe and reliable operation. The safe microsphere carried with pure beta rays is extensively used for internal radiotherapy to cure cancer.

Description

Safe microspheres loaded with pure beta rays and preparation method thereof

technical field

The invention relates to a glass microsphere with high chemical stability loaded with pure beta ray for cancer treatment after activation by neutrons and its technology.

Background technique

Surgery, chemotherapy and radiotherapy are traditional cancer treatment methods. As we all know, radiotherapy is more targeted and flexible than chemotherapy. Cancer patients are more willing to use radiotherapy for direct treatment, so that the tumor can be shrunk to obtain a chance of surgery, or the tumor cells can be completely killed and necrotic. Although cancer cells absorb radiation more easily than normal cells, normal cells are still damaged by radiation after all. Therefore, the radiation dose of external radiotherapy is generally not large enough to kill all cancer cells, thus affecting the curative effect. In the early 1980s, interventional internal radiation therapy was started abroad, in which isotopes capable of emitting radiation were complexed with polymer resins, and then inserted into the tumor site in the body. However, in actual use, it was found that the combination of radionuclides and macromolecules is not strong, and it is easy to fall off into an ion state, which flows to various parts of the body, causing greater harm.

Japanese Patent Laid-Open No. 5-208918 discloses a method for ion sputtering to infiltrate radioactive isotope phosphorus into SiO ₂ glass microsphere outer surface layer to form phosphorus-infiltrated glass microspheres for radiotherapy cancer. The phosphorus in the surface layer of the glass microspheres of the invention is easily dissolved in the blood, and flows to various parts of the whole body, causing harm. For this reason, Chinese invention patent CN 1080266 A on January 5, 1994 discloses a kind of phosphorus 32 series glass microspheres. It is smelted from salts such as phosphate, magnesium silicate, and aluminum silicate. In 1991, U.S. Patent No. 5,011,677 disclosed yttrium-aluminum-silicate glass microspheres smelted at high temperature. Compared with polymer resin microspheres , although the radioactive isotopes of the above two patents are more firmly bound to the vitreous body, the common disadvantage is that there is still a phenomenon that some radionuclides are leached out from the glass microspheres. In the blood, it brings harm to the health of patients, and the glass microspheres of the previous patent also contain impurity rays of considerable intensity in addition to beta rays.

Contents of the invention

The purpose of the present invention is to design a kind of glass microsphere that radionuclides are not easy to fall off, simple in structure, safe to use, and become only loaded with pure beta rays after being activated by neutrons. Another object of the present invention is to provide a method for manufacturing the safe microspheres.

In order to achieve the above object, the present invention is carried out like this, the safety microsphere is composed of a glass microsphere loaded with pure beta rays after neutron activation, and a corrosion-resistant coating coated on its outer surface . The anti-corrosion coating is SiO ₂ , or/and Al ₂ O ₃ , or/and TiO ₂ , or/and ZrO ₂ . The glass microspheres loaded with pure β rays are Y-89 glass microspheres containing Y ₂ O ₃ , SiO ₂ , Al ₂ O ₃ , or P-31 glass containing P ₂ O ₅ , Al ₂ O ₃ , MgO Microspheres.

The step of preparing microspheres of the present invention is; first add surfactant and stir in glass microspheres, surfactant can adopt polyethylene glycol or silane coupling agent, the amount of adding is to add 0.3 in every 100 grams of glass microspheres -0.5 g of surfactant. Then soak the above-mentioned glass microspheres in an anti-corrosion coating material containing 50-100% ethyl orthosilicate, 0-30% aluminum nitrate, 0-20% butyl titanate, and 0-30% zirconium nitrate. Stir in the sol solution of the above-mentioned glass microspheres to gel the surface layer of the above-mentioned treated glass microspheres, then remove the organic solvent by cyclone drying after solid-liquid separation, and then age at room temperature for 20-30 days, and finally in the muffle furnace for 300- Heating, evaporating and heat treatment at 600°C to make it vitrified, the safety microspheres coated with anti-corrosion coating on the surface of the present invention are obtained. After being activated by neutrons, the safe microspheres of the present invention can be loaded with nuclide Y-90 or P-32 emitting pure beta rays, and have a strong ability to kill and injure all cancer cells in the human body.

Invention Features and Advancement

The biggest advantage of the safe microsphere of the present invention is that it is safe and reliable. Because the outer surface of the glass microsphere containing radioisotope is firmly coated with a layer of corrosion-resistant coating film, it has extremely stable chemical properties, so radioisotope is not easy to pass through. The leaching process migrates into the blood, and there is no radioactive pollution from impurity rays, which is very reliable and safe.

Another advantage of the safety microspheres of the present invention is that under neutron irradiation, they can be activated into nuclide Y-90 or P-32 containing a single pure beta ray, and they can be smoothly inserted into designated parts of the body. Animal experiments and clinical use in hospitals have confirmed that such microspheres have a strong ability to kill all cancer cells in the human body, especially effective against liver cancer, colon cancer, and pancreatic cancer.

Another advantage of the present invention is that the preparation method is simple and easy to control, and the corrosion-resistant coating of the safety microsphere prepared by the method of the present invention can firmly adhere to the surface of the glass microsphere without the coating falling off. The composition of the corrosion-resistant coating will not emit any other long-lived harmful impurity rays under the activation of neutron rays. The glass microspheres and the corrosion-resistant coating will not chemically react to change their respective characteristics. The dissolution rate of the radionuclide is 1-2 orders of magnitude lower than that of the original glass microspheres without the anti-corrosion coating.

Implementation of the invention

The specific structure and manufacturing method of the present invention are given by the following examples and accompanying drawings.

Fig. 1 is a structural schematic diagram of the present invention.

Fig. 2 is a process flow diagram of the present invention. Below in conjunction with accompanying drawing, the present invention will be further described;

Please refer to accompanying drawing 1 at first, safety microsphere of the present invention is made up of glass microsphere 1 and corrosion-resistant coating 2 that are loaded with pure beta ray after neutron activation. Glass microspheres 1 loaded with pure β rays after neutron activation are Y-89 glass microspheres containing Y ₂ O ₃ , SiO ₂ , Al ₂ O ₃ , or containing P ₂ O ₅ , Al ₂ O ₃ , MgO P-31 glass microspheres.

Then please refer to accompanying drawing 2, the method for preparing safety microsphere of the present invention is as follows: first put glass microsphere 1 into the container, spray into 0.3～0.5 gram surfactant polyethylene glycol or silane coupling agent, stir, Make it moist to complete pretreatment 3. Then soak the above-mentioned glass microspheres 1 in a container of a sol solution composed of 50-100% tetraethyl orthosilicate, 0-30% aluminum nitrate, 0-20% butyl titanate, and 0-30% zirconium nitrate, Stir on a magnetic stirrer, and perform gel coating treatment on the surface of glass microspheres 4. Then carry out solid-liquid separation 5. Then, the glass microspheres 1 and the hot air at 40-60°C enter the cyclone drier in the same direction for drying 6, after removing part of the organic solvent, the wet gel becomes a dry gel. Aging at room temperature for 20-30 days stabilizes the gel 7. Finally, heating and evaporating heat treatment 8 at 300-600°C in a muffle furnace to make it vitrified to form SiO ₂ , or/and Al ₂ O ₃ , or/and TiO ₂ , or/and ZrO ₂ corrosion-resistant coating 2 of the present invention safety microspheres.

Example 1:

Put 100 grams of Y-89 glass microspheres 1 containing Y ₂ O ₃ , SiO ₂ , and Al ₂ O ₃ in a container, add 0.4 grams of silane coupling agent surfactant, stir to complete pretreatment 3, and then soak in Containing 100% tetraethyl orthosilicate solution sol, put it on a magnetic stirring table, stir for gelation and coating treatment 4, then separate solid and liquid 5, take out the coated glass microspheres, and place them in the cyclone dryer inlet Carry out cyclone drying together with the dry hot air entering in the same direction 6, after removing part of the organic solvent, age at room temperature for 25 days to make the polymerization stable 7, and finally heat and evaporate heat treatment 8 in a muffle furnace at 500-600 °C to make it Vitrification, that is to make the surface of the present invention has SiO ₂ coated yttrium-containing safety microspheres. The diameter of the safety glass microspheres is in the range of 20-60 μm. The dissolution rate of this kind of glass microspheres coated with _SiO2 was 9×10 ^-7 g/g in physiological simulated liquid for 30 days, while the dissolution rate of the original glass microspheres was 3.6×10 ^-5 g/g , which is reduced by 2 orders of magnitude. After being activated by neutrons, the safe microspheres of the present invention can be loaded with pure beta-ray nuclide Y-90, and have a strong ability to kill all cancer cells in the human body.

Example 2:

100 grams of P-31 glass microspheres 1 containing P ₂ O ₅ , Al ₂ O ₃ , and MgO were mixed with 0.5 grams of polyethylene glycol, stirred to make it wet, and pretreatment 3 was completed. Then soak the above-mentioned glass microspheres 1 in a sol solution composed of 80-90% tetraethyl orthosilicate and 10-20% aluminum nitrate capable of forming a corrosion-resistant coating 2, and stir to perform gel coating treatment 4 , the above-mentioned treated glass microsphere gel substance is subjected to solid-liquid separation 5, the glass microsphere 1 coated with sol is taken out, and the cyclone is carried out at the entrance of the cyclone dryer together with the dry hot air at 40-60°C entering in the same direction Drying 6, removing part of the organic solvent, aging at room temperature for 30 days to stabilize the polymerization 7, and finally heating and evaporating heat treatment 8 in a muffle furnace at 400-500 ° C to make it vitrified, and obtain SiO ₂ and Al ₂ O on the surface _3- coated phosphorus-containing safety microspheres. The diameter of the safety microsphere is in the range of 15-55 μm. The glass microspheres coated with SiO ₂ and Al ₂ O ₃ had a phosphorus dissolution rate of 2.2×10 ^-5 g/g in a physiological simulated solution for 30 days, and the dissolution rate of the original glass microspheres was 7.9×10 ^{- 3} g/g, reduced by 1 to 2 orders of magnitude. Example 3:

100 grams of P-31 glass microspheres 1 containing P ₂ O ₅ , Al ₂ O ₃ , and MgO were mixed with 0.5 grams of polyethylene glycol, stirred to make it wet, and pretreatment 3 was completed. Then soak the above-mentioned glass microspheres 1 in a sol solution composed of 80-95% tetraethyl orthosilicate and 5-20% butyl titanate that can form a corrosion-resistant coating 2 and stir to carry out gel coating Treatment 4, the glass microsphere gel material treated above is subjected to solid-liquid separation 5, the glass microsphere 1 coated with sol is taken out, and the dry hot air at 40-60°C entering in the same direction is placed at the entrance of the cyclone dryer Carry out cyclone drying 6, remove part of the organic solvent, and age at room temperature for 30 days to stabilize the polymerization 7, and finally heat and evaporate heat treatment 8 in a muffle furnace at 400-500 ° C to make it vitrified, and obtain SiO ₂ and TiO on the surface _2- coated phosphorus-containing safety microspheres. The diameter of the safety microsphere is in the range of 15-55 μm. The dissolution rate of phosphorus in the glass microspheres coated with SiO ₂ and TiO ₂ in the physiological simulation solution for 30 days is 5.3×10 ^-5 g/g, and the dissolution rate of the original glass microspheres is 7.9×10 ^-3 g /g, decreased by 1 to 2 orders of magnitude.

Example 4:

100 grams of P-31 glass microspheres 1 containing P ₂ O ₅ , Al ₂ O ₃ , and MgO were mixed with 0.5 grams of polyethylene glycol, stirred to make it wet, and pretreatment 3 was completed. Then soak the above-mentioned glass microspheres 1 in a sol solution composed of 80-95% tetraethyl orthosilicate and 5-20% zirconium nitrate capable of forming a corrosion-resistant coating 2, and stir to perform gel coating treatment 4 , the above-mentioned treated glass microsphere gel substance is subjected to solid-liquid separation 5, the glass microsphere 1 coated with sol is taken out, and the cyclone is carried out at the entrance of the cyclone dryer together with the dry hot air at 40-60°C entering in the same direction Drying 6, removing part of the organic solvent, aging at room temperature for 30 days to stabilize the polymerization 7, and finally heating and evaporating heat treatment 8 in a muffle furnace at 400-500 ° C to make it vitrified, and obtain SiO ₂ and ZrO on the surface _2- coated phosphorus-containing safety microspheres. The diameter of the safety microsphere is in the range of 15-55 μm. The dissolution rate of phosphorus in the glass microspheres coated with SiO ₂ and ZrO ₂ is 6.4×10 ^-6 g/g in the physiological simulated liquid for 30 days, and the dissolution rate of the original glass microspheres is 7.9×10 ^-3 g /g, reduced by 3 orders of magnitude.

Claims (4)

1, a kind of after neutron activation the safe microball of pure beta ray corrying, it is characterized in that: be composited by glass microsphere that is loaded with pure beta ray (1) and the anti-corrosion coating (2) that is coated on its outer surface thereof through producing after the neutron activation.

2, safe microball according to claim 1 is characterized in that: described anti-corrosion coating (2) is SiO ₂, or/and Al ₂O ₃, or/and TiO ₂, or/and ZrO ₂

3, safe microball according to claim 1 is characterized in that: described after neutron activation the glass microsphere (1) of pure beta ray corrying be to contain Y ₂O ₃, SiO ₂, Al ₂O ₃The Y-89 glass microsphere, or contain P ₂O ₅, Al ₂O ₃, MgO the P-31 glass microsphere.

4, a kind of after neutron activation the preparation method of the safe microball of pure beta ray corrying, it is characterized in that: at first glass microsphere (1) adding is filled in the container of surfactant, carry out pretreatment (3), then it is immersed in can form anti-corrosion coating (2) by ethyl orthosilicate 50-100%, aluminum nitrate 0-30%, butyl titanate 0-20%, stir in the sol solution that zirconium nitrate 0-30% forms, after finishing the coated processing of gelation (4), filter (5), subsequent again carrying out after cyclone drying (6) removes organic solvent, under the room temperature ageing 20-30 days (7), 300-600 ℃ of following heating evaporation heat treatment (8) in muffle furnace at last, make its vitrification, promptly make the safe microball of surface-coated anti-corrosion coating of the present invention (2).