Method for cleaning and separating radioactive yttrium-90 glass microspheres

Abstract

The invention provides a method for cleaning and separating radioactive yttrium-90 glass microspheres. The method comprises the following steps: cleaning yttrium-90 glass microspheres with a cesium acetate aqueous solution; filtering and separating the cleaned yttrium-90 glass microspheres; and drying the yttrium-90 glass microspheres subjected to filtering separation. By means of the method, the yttria-90 glass microspheres can be effectively cleaned, and the purity and safety of the yttria-90 glass microspheres are improved.

Description

Technical Field

[0001] The invention relates to the technical field of radioactive glass microspheres, in particular to a method for cleaning and separating radioactive yttrium-90 glass microspheres. Background Art

[0002] Microsphere radioembolization therapy is a targeted tumor radiotherapy technology. This technology is widely used in selective internal radiotherapy (SIRT) for malignant tumors such as liver tumors. It kills cancer cells through targeted high-dose high-energy β radiation at the lesion, while protecting healthy tissues and organs. The microsphere products currently available in the world include 90 Y resin microspheres and glass microspheres have been included in multiple authoritative liver cancer diagnosis and treatment standards and guidelines.

[0003] In order to ensure the safety of the use of yttrium-90 glass microspheres, the glass microspheres and yttrium-90 should be firmly combined, that is, the free yttrium-90 (i.e., the leaching rate) cannot exceed the medical requirements. Therefore, for yttrium-90 glass microspheres, it is necessary to conduct a leaching rate test, which requires cleaning and separation operations. The existing cleaning and separation methods for radioactive yttrium-90 glass microspheres have poor cleaning effects and are prone to nuclear contamination. Therefore, it is urgent to propose a new cleaning and separation method for yttrium-90 glass microspheres to solve the above problems. Summary of the invention

[0004] In view of this, the main purpose of the present invention is to provide a method for cleaning and separating radioactive yttrium-90 glass microspheres, which can effectively clean the yttrium-90 glass microspheres, reduce nuclear contamination during operation and improve the safety of operation.

[0005] To achieve the above object, the present invention provides a method for cleaning and separating radioactive yttrium-90 glass microspheres. The method comprises the following operations:

[0006] Wash the yttrium-90 glass microspheres with cesium acetate aqueous solution;

[0007] filtering and separating the washed yttrium-90 glass microspheres; and

[0008] The yttrium-90 glass microspheres separated by filtration are dried.

[0009] In some embodiments, the method further comprises: preparing an aqueous solution of cesium acetate. In some embodiments, the method further comprises: preparing an aqueous solution of cesium acetate with a density of 1.5 g / mL to 3 g / mL. In a specific embodiment, an aqueous solution of cesium acetate with a density of 2 g / mL is prepared.

[0010] In some embodiments, the mass ratio of the cesium acetate aqueous solution to the yttrium-90 glass microspheres is 2: 1 to 40: 1. In a specific embodiment, the mass ratio of the cesium acetate aqueous solution to the yttrium-90 glass microspheres is 20:1.

[0011] In some embodiments, when cleaning is performed, an aqueous cesium acetate solution is placed in a container, the opening of the container is subsequently sealed, and then yttrium-90 glass microspheres are introduced.

[0012] In some embodiments, when cleaning is performed, vibration cleaning is performed first, and then ultrasonic cleaning is performed, wherein the vibration cleaning is repeated 2 to 4 times.

[0013] In some embodiments, after each vibration cleaning, the floating and suspended yttrium-90 glass microspheres are removed. Further, the interval between vibration cleaning is 0.5 hour to 1 hour.

[0014] In some embodiments, ultrasonic cleaning is performed at a power of 20 Hz to 45 Hz and a temperature of 30° C. to 40° C. for 10 to 15 minutes. Further, ultrasonic cleaning is repeated 2 to 3 times, and between ultrasonic cleanings, the yttrium-90 glass microspheres are soaked in 37° C. physiological saline, and then ultrasonic cleaning is continued with deionized water.

[0015] In some embodiments, the filtration is performed through glass fiber filter paper. Further, the filtration operation is repeated 3 to 6 times.

[0016] In some embodiments, the drying is performed at a temperature of 60° C. to 80° C. for 240 minutes to 300 minutes.

[0017] In some embodiments, the method of the present application further comprises an operation of cleaning the equipment, wherein the equipment comprises containers and instruments used in the method.

[0018] Furthermore, the present invention also relates to the use of the radioactive yttrium-90 glass microspheres provided by the method of the present invention in the preparation of drugs for treating tumors. BRIEF DESCRIPTION OF THE DRAWINGS

[0019] Figure 1 The flowchart of an embodiment of the cleaning and separation method of the present application is shown in FIG.

[0020] Figure 2 This is a flow chart of another embodiment of the cleaning and separation method of the present application.

[0021] Figure 3 The vibration washing operation of the present application is shown.

[0022] Figure 4 The filtering operation of the present application is shown.

[0023] Figure 5 Shown is a microscopic image of Yttrium-90 glass microspheres before cleaning.

[0024] Figure 6 A microscopic image of Yttrium-90 glass microspheres after cleaning and separation according to the method of the present application is shown. DETAILED DESCRIPTION

[0025] The following specific embodiments are discussed in conjunction with the accompanying drawings to illustrate the exemplary embodiments. The specific embodiments included herein should not be construed as limiting the present invention. Further, although specific language may be used to describe the embodiments herein, the features, actions and / or structures, the claims are not limited to the described features, actions and / or structures. It will be appreciated by those skilled in the art that other embodiments, including improvements, are within the spirit and scope of the present invention.

[0026] Throughout the specification, unless otherwise specifically stated, the terms used herein should be understood as the meanings commonly used in the art. Therefore, unless otherwise defined, all technical and scientific terms used herein have the same meanings as those generally understood by those skilled in the art to which the invention belongs.

[0027] Yttrium-90 glass microspheres refer to glass microspheres loaded with yttrium-90, which are currently mainly used in the treatment of liver cancer. Therefore, their binding firmness, cleanliness and density affect their therapeutic effect and safety.

[0028] Reference Figure 1 , the method of the present application comprises:

[0029] S1: Washing yttrium-90 glass microspheres with cesium acetate aqueous solution;

[0030] S2: filtering and separating the washed yttrium-90 glass microspheres; and

[0031] S3: Drying the yttrium-90 glass microspheres separated by filtration.

[0032] In the present application, yttrium-90 glass microspheres are cleaned with cesium acetate aqueous solution. Wherein, cesium acetate is stable at room temperature and pressure, and when cesium acetate absorbs enough water, the carboxyl group in the acetate ion undergoes hydrolysis reaction to generate acetic acid and cesium ions, thereby causing the deliquescence of cesium acetate. The solubility of cesium acetate in 100mL water is 945g at room temperature, and at 89°C, its solubility in 100mL water can reach 1346g. Further, its molecular structure contains acetate ions, has certain nucleophilic properties, can effectively clean the surface of radioactive yttrium-90 glass microspheres, remove the floating objects attached to its surface, and ensure the purity of yttrium-90 glass microspheres.

[0033] In the present application, a cesium acetate aqueous solution with a density of 1.5 g / mL to 3 g / mL is prepared. By preparing a cesium acetate aqueous solution in this density range, it is possible to select a yttrium-90 glass microsphere with a density greater than 1.5 g / mL, thereby making it easy to prepare a uniform yttrium-90 glass microsphere suspension, which will not precipitate in advance or be washed away by the blood flow in the body. Further, the density of the cesium acetate aqueous solution is 2 g / mL, thereby obtaining yttrium-90 glass microspheres with a density greater than 2 g / mL.

[0034] In the present application, the mass ratio of the cesium acetate aqueous solution to the yttrium-90 glass microspheres is 2:1 to 40:1. By using such a mass ratio of the cleaning solution and the object to be cleaned, on the one hand, the yttrium-90 glass microspheres can be effectively cleaned, and on the other hand, excessive waste will not be caused. Further, the mass ratio of the cesium acetate aqueous solution to the yttrium-90 glass microspheres is 20:1.

[0035] In this application, in order to reduce nuclear contamination during operation and improve the safety of the operation, the cleaning operation is carried out under sealed conditions. And the staff needs to wear protective equipment during microscopic observation.

[0036] Specifically, a prepared cesium acetate aqueous solution with a density of 2 g / mL is placed in a cleaning container (eg, a beaker), the opening of the cleaning container (eg, a beaker) is sealed, and yttrium-90 glass microspheres are introduced.

[0037] In the above operation, there is no particular limitation on the container as long as it can contain the cesium acetate aqueous solution.

[0038] There is no particular limitation on the material used to seal the opening, as long as it can prevent leakage of radioactive substances or radiation contamination, such as tin foil or aluminum foil.

[0039] There is no specific limitation on the method of introducing yttrium-90 glass microspheres, as long as it can prevent leakage of radioactive materials or radiation pollution, for example, yttrium-90 glass microspheres can be introduced through pipelines. It should be understood that there is no specific limitation on pipelines, as long as they have excellent radiation resistance and chemical resistance, such as EPDM, which can resist 100-200KGY radiation, has excellent chemical resistance, acid, alkali, detergent, animal and vegetable oils, alcohol, ketone, etc.; outstanding water resistance, superheated water resistance, water vapor resistance; polar oil resistance.

[0040] Specifically, the cleaning operation S1 can be performed in the following manner: the cleaning beaker is sealed with tin foil, and a feed port is opened at the center of the tin foil, an EPDM rubber pipe is inserted into the feed port, and yttrium-90 glass microspheres are fed into the cleaning beaker through the EPDM rubber pipe.

[0041] In the present application, the cleaning operation S1 includes two sub-operations: vibration cleaning S1a and ultrasonic cleaning S1b (eg Figure 2 shown).

[0042] "Vibration cleaning" refers to cleaning by "vibration". In the present application, it is necessary to repeat 2 to 4 times. After each vibration cleaning, the glass microspheres are left to stand for 0.5 to 1 hour to remove the floating and suspended glass microspheres, thereby obtaining the desired density, for example, yttrium-90 glass microspheres greater than 2 g / mL.

[0043] Specifically, vibration cleaning includes introducing yttrium-90 glass microsphere powder from a pipeline into a cleaning container (such as a cesium acetate aqueous solution (eg, a density of 2 g / mL)) containing Figure 3 As shown), seal the container, put the container into a vibration cleaning machine, and stir it thoroughly by vibration, and the vibration time is set to 10 minutes to 20 minutes.

[0044] "Ultrasonic cleaning" refers to cleaning by "ultrasonic waves". In ultrasonic cleaning, ultrasonic cleaning machines are usually used. Here, it should be explained that the principle of ultrasonic cleaning machines is that the high-frequency oscillation signal emitted by the ultrasonic generator is converted into high-frequency mechanical oscillation by the transducer and propagated to the medium-cleaning solvent. The ultrasonic wave radiates forward in the cleaning liquid in a sparse and dense manner, causing the liquid to flow and produce tens of thousands of tiny bubbles with a diameter of 50μm to 500μm. The tiny bubbles in the liquid vibrate under the action of the sound field. These bubbles are formed and grown in the negative pressure area of ​​the longitudinal propagation of ultrasonic waves, and in the positive pressure area, when the sound pressure reaches a certain value, the bubbles rapidly increase and then suddenly close. When the bubbles close, shock waves are generated, and thousands of atmospheres of pressure are generated around them, destroying insoluble dirt and dispersing them in the cleaning liquid. When the group particles are wrapped in oil and adhere to the surface of the cleaning parts, the oil is emulsified and the solid particles are detached, thereby achieving the purpose of purifying the cleaning parts.

[0045] In the present application, the cleaning container is sent into an ultrasonic cleaning machine for fixation. During this process, the cleaning container is sealed, and the container should remain stable during transfer to avoid leakage, fully ensuring the sealing and stability of the container during the cleaning process, which can effectively avoid leakage caused by tilting, thereby ensuring safety during the cleaning and separation process.

[0046] In the present application, after ultrasonic cleaning is completed, observe whether there are floating objects (such as yttrium oxide) on the surface of the container. If there are floating objects, clean them in time, and then continue ultrasonic cleaning. After the floating objects are salvaged, replace the solution with 37°C physiological saline to soak and wash the sediment to fully remove the yttrium oxide attached to the surface of the glass microspheres, and then replace it with deionized water. This process can be repeated 2 to 4 times.

[0047] In the present application, the filtering and impurity removal S2 can be carried out by filter paper. Filter paper is a scientific tool, which can effectively filter impurities and has been widely used in various fields. According to the different types of fibers constituting the filter paper, the performance and use of the filter paper are also different. There are ordinary filter papers for general occasions, glass fiber filter papers for high temperatures, and polypropylene filter papers for super clean use. Glass fiber filter paper is made by wet forming process, has the characteristics of uniform fiber distribution, large dust holding capacity, low resistance, high strength, etc., and is an ideal air filter material.

[0048] In this application, if Figure 4 As shown, filtering and impurity removal S2 includes: rolling the filter paper into a funnel shape, placing the filter paper in a receiving container (such as a beaker), pouring the yttrium-90 glass microspheres after ultrasonic cleaning onto the filter paper for filtering and impurity removal. This process can be repeated 3 to 6 times, such as 3, 4, 5, and 6 times. In addition, the filtering and impurity removal operation also includes: neutralizing the filtered water with soapy water, for example, the volume ratio of the filtered water to the soapy water is 1:4 to 1:6, such as selecting to use a 1:5 soapy water solution, that is, a soapy water solution of 5 times the volume of the solution to be treated.

[0049] In the present application, drying S3 includes: drying the yttrium-90 glass microspheres at 60°C to 80°C for 240 minutes to 300 minutes. Specifically, the yttrium-90 glass microspheres are placed in a drying box together with the filter paper used in filtering and removing impurities S2 for drying; after drying, the filter paper is separated from the yttrium-90 glass microspheres (for example, the yttrium-90 glass microspheres are scraped off from the filter paper by a scraper), and the filter paper is washed with soapy water after removal, and the filter paper is uniformly treated (for example, destroyed) after washing; the obtained yttrium-90 glass microspheres are placed in a constant temperature oscillating device for leaching rate test.

[0050] Finally, cleaning equipment S4: Use soapy water to clean the utensils (e.g., beakers, funnels, and receiving beakers) and instruments (e.g., vibration cleaning machines, ultrasonic cleaning machines) used in the method, as well as destroy filter paper. It should be understood that soapy water can be used not only to clean the surface of objects, but also to clean the body to remove radiation particles and radioactive substances on the surface, thereby reducing damage to the body. When using soapy water for cleaning, use running water and follow the doctor's advice to minimize radiation hazards.

[0051] In this application, it is desirable to use a variety of radiation-resistant materials for sealing during the operation to avoid leakage during the cleaning and separation process and contaminate the laboratory, and to thoroughly clean the utensils and instruments used in the cleaning process to ensure that there will be no leakage and contamination incidents, and to further improve the safety of cleaning and separation of yttrium-90 glass microspheres. Moreover, it is desirable that the staff wear protective clothing when contacting non-sealed containers containing yttrium-90 glass microspheres, for example, during the vibration cleaning operation, when cleaning the floating objects on the surface of the container, open the beaker seal, put the leaked net into the beaker for salvage, and the staff need to wear protective clothing during the observation process with a microscope.

[0052] The present invention is described in more detail below by examples. It should be understood that the examples described below are exemplary and are only used to explain the present application, and should not be construed as limiting the present application. Where specific techniques or conditions are not indicated in the examples, the techniques or conditions described in the literature in this area or the product specifications are used. Where the reagents or instruments used are not indicated by the manufacturer, they are all conventional products that can be obtained commercially.

[0053] Example

[0054] Preparation of Yttrium-90 Glass Microspheres

[0055] Yttrium-90 glass microspheres were prepared according to the method described in CN117326785. Subsequently, an optical microscope (MSD105 monocular, Maishidi Technology Co., Ltd.) was used to observe the yttrium-90 glass microspheres at a magnification of 50 times. The resulting image is shown in Figure 5 middle.

[0056] Preparation of cleaning agent

[0057] Using an electronic balance and a measuring cylinder, prepare an aqueous solution of cesium acetate with a density of 2 g / mL.

[0058] Vibration cleaning

[0059] 30 mL of the prepared cesium acetate aqueous solution was placed in a clean beaker, the opening of the beaker was sealed, and an yttrium-90 glass microsphere introduction pipe was connected.

[0060] 3 g of the prepared yttrium-90 glass microspheres were introduced from the pipeline into a cleaning beaker containing cesium acetate aqueous solution, and the beaker was sealed. The beaker was placed in a vibration cleaning machine (Guohua, SHA-C), and fully stirred by vibration for 15 minutes. After uniform stirring, it was allowed to stand for 0.5 hours to remove floating and suspended glass microspheres.

[0061] The above steps were repeated three times to obtain yttrium-90 glass microspheres with a density greater than 2 g / mL.

[0062] Ultrasonic cleaning

[0063] The beaker containing yttrium-90 glass microspheres after the previous operation was sealed and sent into an ultrasonic cleaning machine (Ningbo Xinzhi Biology, SB-120DT), fixed, and set the cleaning time to 15 minutes, the cleaning power to 30 Hz, and the cleaning temperature to 37°C. The beaker should be kept stable during transfer to avoid leakage, and the sealing and stability of the beaker during the cleaning process should be fully guaranteed.

[0064] Filtering and removing impurities

[0065] like Figure 4 As shown, the filter paper is rolled into a funnel shape and placed in a receiving beaker, and the yttrium-90 glass microspheres cleaned by ultrasonic wave are poured onto the filter paper for filtering and removing impurities.

[0066] Repeat the above steps 3 times.

[0067] drying

[0068] The yttrium-90 glass microspheres and the filter paper are sent to a drying box for drying. The drying time is 300 minutes and the drying temperature is 70°C. After drying, the yttrium-90 glass microspheres are scraped off the filter paper with a scraper and collected in a container.

[0069] Equipment cleaning

[0070] Clean the beaker, vibration cleaning machine, and ultrasonic cleaning machine used in the above process with soapy water, and destroy the filter paper.

[0071] Using an optical microscope (MSD105 monocular, Maxidi Technology Co., Ltd.), the cleaned yttrium-90 glass microspheres were observed at 50 times magnification. The image is shown in Figure 6 middle.

[0072] Comparing the microscope images before and after cleaning, it can be seen Figure 5 There are obviously many impurities in the microscope image. Figure 6 Only yttrium-90 glass microspheres were seen under the microscope, which shows that the method of the present application is effective and meaningful for treating yttrium-90 glass microspheres.

[0073] Although embodiments of the present invention have been shown and described, it will be appreciated by those skilled in the art that various changes, modifications, substitutions and variations may be made to the embodiments without departing from the principles and spirit of the present invention, and that the scope of the present invention is defined by the appended claims and their equivalents.

Claims

1. A method for cleaning and separating radioactive yttrium-90 glass microspheres, comprising the following operations: Wash the yttrium-90 glass microspheres with cesium acetate aqueous solution; filtering and separating the washed yttrium-90 glass microspheres; and The yttrium-90 glass microspheres separated by filtration are dried.

2. The cleaning and separation method according to claim 1, wherein: The method further comprises: preparing the cesium acetate aqueous solution; wherein preferably the density of the cesium acetate aqueous solution is 1.5 g / mL to 3 g / mL, preferably 2 g / mL.

3. The cleaning and separation method according to claim 1 or 2, wherein: The mass ratio of the cesium acetate aqueous solution to the yttrium-90 glass microspheres is 2:1 to 40:1, preferably 20:

1.

4. The cleaning and separation method according to any one of claims 1 to 3, wherein: In the cleaning, the cesium acetate aqueous solution is placed in a container, the opening of the container is then sealed, and then yttrium-90 glass microspheres are introduced.

5. The cleaning and separation method according to any one of claims 1 to 4, wherein: The cleaning includes first performing vibration cleaning and then performing ultrasonic cleaning, wherein the vibration cleaning is repeated 2 to 4 times.

6. The cleaning and separation method according to claim 5, wherein: The cleaning further comprises: removing floating and suspended yttrium-90 glass microspheres after each vibration cleaning; preferably, the interval between the vibration cleanings is 0.5 hour to 1 hour.

7. The cleaning and separation method according to claim 5, wherein: The ultrasonic cleaning is performed at a power of 20 Hz to 45 Hz and a temperature of 30° C. to 40° C. for 10 to 15 minutes; optionally, the ultrasonic cleaning is repeated 2 to 3 times, wherein the yttrium-90 glass microspheres are soaked in 37° C. physiological saline between ultrasonic cleanings, and then ultrasonic cleaning is continued with deionized water.

8. The cleaning and separation method according to any one of claims 1 to 7, wherein: The filtration is performed through glass fiber filter paper, and preferably, the filtration is repeated 3 to 6 times.

9. The cleaning and separation method according to any one of claims 1 to 8, wherein: The drying is performed at a temperature of 60° C. to 80° C. for 240 minutes to 300 minutes.

10. The cleaning and separation method according to any one of claims 1 to 9, wherein: The cleaning and separation method also includes the operation of cleaning equipment, wherein the equipment includes containers and instruments used in the method.

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