RADIOACTIVE GLASS MICROSPHERES FOR EMBOLIZATION, PREPARATION METHOD AND APPLICATION THEREOF

Abstract

The present invention provides radioactive glass microspheres for embolization and a preparation method and an application thereof. A nuclide oxide and a foaming agent are added into a glass matrix, blended and uniformly mixed for making the foaming agent decomposed and vaporized at a high temperature to generate bubbles, so as to prepare the radioactive glass microspheres for embolization with cavities. The radioactive glass microspheres for embolization have a density of 1.4-2.3 g/cm.sup.3, a nuclide loading rate of 15-40 wt % and a higher and more stable radiation dose, can achieve better distribution and deposition effects in liver blood vessels after injection, and can achieve a better therapeutic effect for hepatocellular carcinoma (HCC).

Claims

1. Radioactive glass microspheres for embolization, wherein the glass microspheres comprise glass microsphere bodies and cavities formed in the glass microsphere bodies, and the glass microsphere bodies contain a nuclide oxide; and the glass microspheres have a density of not higher than 2.3 g/cm.sup.3.

2. The glass microspheres according to claim 1, wherein the nuclide oxide is any one of Y.sub.2O.sub.3, Lu.sub.2O.sub.3, Ho.sub.2O.sub.3 or P.sub.2O.sub.5.

3. The glass microspheres according to claim 2, wherein the glass microsphere bodies further contain any one of Al.sub.2O.sub.3, SiO.sub.2 and B.sub.2O.sub.3.

4. The glass microspheres according to claim 3, wherein the glass microspheres have a density of 1.4-2.3 g/cm.sup.3.

5. The glass microspheres according to claim 4, wherein the glass microspheres have a nuclide loading rate of 15-40 wt %.

6. The glass microspheres according to claim 5, wherein the glass microspheres have a density of 1.6-1.9 g/cm.sup.3 and a nuclide loading rate of 33-36 wt %.

7. The glass microspheres according to claim 6, wherein the glass microspheres contain, by molar percentage, 0-40% of Al.sub.2O.sub.3, 20-80% of SiO.sub.2, 0-20% of B.sub.2O.sub.3 and 10-30% of a nuclide oxide, and have a particle size of 10-100 ?m.

8. The glass microspheres according to claim 7, wherein the glass microspheres contain, by molar percentage, 18-22% of Al.sub.2O.sub.3, 45-63% of SiO.sub.2 and 0-10% of B.sub.2O.sub.3.

9. A method for preparing the radioactive glass microspheres for embolization according to claim 1, comprising the following steps: (1) preparing glass microsphere bodies, mixing the glass microsphere bodies with a foaming agent to obtain a mixture, and melting the mixture by heating to obtain a glass matrix; (2) cooling the glass matrix, followed by curing to form a glass block, and then grinding the glass block to obtain glass particles; and (3) melting the glass particles by heating to obtain glass microspheres, and decomposing the foaming agent in the glass microspheres to generate gases so as to form cavities in the glass microspheres.

10. The method according to claim 9, wherein the glass microsphere bodies contain any one of Al.sub.2O.sub.3, SiO.sub.2 and B.sub.2O.sub.3, and a nuclide oxide.

11. The method according to claim 10, wherein the nuclide oxide is any one of Y.sub.2O.sub.3, Lu.sub.2O.sub.3, Ho.sub.2O.sub.3 or P.sub.2O.sub.5.

12. The method according to claim 7, wherein the foaming agent in step (1) comprises one or more of Na.sub.2SO.sub.4, MgSO.sub.4, Na.sub.2CO.sub.3, CaSO.sub.4, K.sub.2CO.sub.3, Li.sub.2CO.sub.3 and SrCO.sub.3.

13. The method according to claim 7, wherein during the melting by heating in step (1), the heating is performed at a temperature of 1,000-1,600? C.; and during the melting by heating in step (3), the heating is performed at a temperature of 1,600-1,800? C.

14. The method according to claim 9, wherein the method further comprises a step (4): screening glass microspheres with a suitable particle size of 10-100 ?m and a density of 1.4-2.3 g/cm.sup.3.

15. A method for preparing the radioactive glass microspheres for embolization according to claim 1, comprising the following steps: (a) preparing glass microsphere bodies, and melting the glass microsphere bodies by heating to obtain a glass matrix; (b) cooling the glass matrix, followed by curing to form a glass block, adding a foaming agent for mixing, and then performing grinding to obtain glass particles so as to make the foaming agent adsorbed on the surfaces of the glass particles; and (c) melting the glass particles by heating, and decomposing the adsorbed foaming agent to generate gases so as to form cavities in the glass microspheres.

16. The method according to claim 15, wherein the glass microsphere bodies contain any one of Al.sub.2O.sub.3, SiO.sub.2 and B.sub.2O.sub.3, and a nuclide oxide.

17. The method according to claim 16, wherein the nuclide oxide is any one of Y.sub.2O.sub.3, Lu.sub.2O.sub.3, HO.sub.2O.sub.3 or P.sub.2O.sub.5.

18. The method according to claim 15, wherein the foaming agent in step (b) comprises any one or more of polyethylene glycol and polyvinyl alcohol.

19. The method according to claim 15, wherein during the melting by heating in step (a), the heating is performed at a temperature of 1,000-1,600? C.; and during the melting by heating in step (c), the heating is performed at a temperature of 1,600-1,800? C.

20. The method according to claim 15, wherein the method further comprises a step (d): screening glass microspheres with a suitable particle size of 10-100 ?m and a density of 1.4-2.3 g/cm.sup.3.

Description

BRIEF DESCRIPTION OF THE DRAWINGS

[0059] FIG. 1 shows optical microscope photographs (50 ?m) of solid glass microspheres (A) and hollow glass microspheres (B) in Example 1.

[0060] FIG. 2 shows scanning electron microscope photographs (50 ?m) of solid glass microspheres (A) and hollow glass microspheres (B) in Example 1.

[0061] FIG. 3 shows an optical microscope image (A) (50 ?m) and a scanning electron microscope photograph (B) (20 ?m) of glass microspheres for embolization obtained after density screening in Example 2.

[0062] FIG. 4 shows comparison of sedimentation effects of hollow microspheres and solid microspheres in a PBS solution at different time points in Example 3, wherein the left figure shows the sedimentation effect (A) when t is 0 second, and the right figure shows the sedimentation effect (B) when t is 1 minute.

[0063] FIG. 5A to FIG. 5E are images showing vascular embolization effects of solid microspheres, in which FIG. 5A is a distribution and angiography image of overall blood vessels before vascular embolization; FIG. 5B is an angiography image of blood vessels in an embolization area (without solid microspheres); FIG. 5C is an angiography image of overall blood vessels after vascular embolization;

[0064] FIG. 5D is a locally enlarged image of an angiography image of blood vessels in an embolization area before embolization (in a white dotted line box of FIG. 5B); and FIG. 5E is a locally enlarged image of blood vessels after embolization (in a white dotted box of FIG. 5C).

[0065] FIG. 6A to FIG. 6E are images showing vascular embolization effects of hollow microspheres of the present invention, in which FIG. 6A is a distribution and angiography image of overall blood vessels before vascular embolization; FIG. 6B is an angiography image of blood vessels in an embolization area (without solid microspheres); FIG. 6C is an angiography image of overall blood vessels after vascular embolization; FIG. 6D is a locally enlarged image of an angiography image of blood vessels in an embolization area before embolization (in a white dotted line box of FIG. 6B); and FIG. 6E is a locally enlarged image of blood vessels after embolization (in a white dotted box of FIG. 6C).

DETAILED DESCRIPTION OF THE INVENTION

[0066] The present invention is described in further detail below in conjunction with examples. It is to be noted that the examples below are intended to facilitate understanding of the present invention, rather than to limit the present invention in any manner. Reagents not specifically identified in the examples are known products and are obtained by purchasing commercially available products.

Example 1 Preparation of Radioactive Glass Microspheres for Embolization Provided by the Present Invention

[0067] A method for preparing radioactive glass microspheres for embolization is provided in this example. The method includes the following steps.

[0068] Certain quantities of Y.sub.2O.sub.3, SiO.sub.2, Al.sub.2O.sub.3 and B.sub.2O.sub.3 were weighed, placed in a quartz grinder (specific proportions are as shown in Table 1) and fully ground for 10 minutes for uniform mixing. A uniformly mixed microsphere raw material powder was transferred to a platinum crucible and heated to 1,000-1,600? C. in a Muffle furnace. 20 minutes later, a melted glass mixture was stirred with a quartz rod and heated again for 10 minutes. A certain quantity of Na.sub.2SO.sub.4 or K.sub.2CO.sub.3 was taken, placed in a quartz grinder and fully ground for 10 minutes. The melted glass mixture was poured, stirred with a quartz rod, heated for 5 minutes, then taken out and slowly poured into water for water quenching. Then, a prepared glass material was ground into a glass powder with an irregular shape and a particle size of 1-100 ?m with a ball mill. The glass powder was subjected to further particle size sorting through an ultrasonic vibrating screen (vibrating for 20 minutes) equipped with a 10 ?m filter screen and a 40 ?m filter screen, and a glass powder on the 10 ?m filter screen was collected. The glass powder was transferred into a flame spheroidization furnace with nitrogen as a carrier gas and an oxygen-acetylene flame as a spheroidization flame (the flame has a temperature of greater than 3,000? C., and the furnace has a temperature of about 1,600-1,800? C.). The glass powder with an irregular shape was melted in a spherical shape, and a foaming agent inside was decomposed to release gases so as to form cavities. Microspheres were collected with a collector at the bottom of the flame spheroidization furnace. The obtained microspheres were first sieved through an ultrasonic vibrating sieve (vibrating for 20 minutes) equipped with a 20 ?m filter and a 50 ?m filter, and then microspheres on the 20 ?m filter were collected.

TABLE-US-00001 TABLE 1 Molar percentages of various components of radioactive glass microspheres with sample numbers S101-S104 and H101 to H111 Y.sub.2O.sub.3/ Al.sub.2O.sub.3/ SiO.sub.2/ B.sub.2O.sub.3/ Na.sub.2SO.sub.4/ K.sub.2CO.sub.3/ molar molar molar molar molar molar Sample % % % % % % S101 18 18 64 0 0 0 S102 19 18 63 0 0 0 S103 20 22 58 0 0 0 S104 20 22 48 10 0 0 H101 18 18 63 0 1 0 H102 18 18 62 0 2 0 H103 18 18 61 0 3 0 H104 18 18 63 0 0 1 H105 18 18 62 0 0 2 H106 18 18 61 0 0 3 H107 18 18 62 0 2 0 H108 19 22 57 0 2 0 H109 20 22 46 10 2 0 H110 20 22 49 7 2 0 H111 20 22 51 5 2 0

[0069] The glass transition temperature of 14 kinds of glass microsphere samples in Table 1 was measured by a differential scanning calorimeter (DSC3, Mettler Toledo) in Example 1 of the present invention, and specific results are as shown in Table 2. In addition, the density of the glass microsphere samples in Table 1 was measured, and the results are as shown in Table 2. The signal intensity of corresponding nuclides in the glass microsphere samples-in Table 1 was measured by inductively coupled plasma-mass spectrometry (ICP-quadrupole-MS, Varian 810-MS, USA) and compared with standard curves of the corresponding nuclides to determine the final nuclide content. Nuclide loading rate (%)=mass of nuclide/total mass of microspheres for embolization?100%, and the results are as shown in Table 2. 100 mg of the samples in Example 1 were subjected to neutron irradiation for 6 hours (the neutron flux is about 5?10.sup.13 neutrons/cm.sup.2.Math.s) respectively, and the radiation dose of each sample was measured by a dose calibrator (Atomlab 100). The S104 and H109 microspheres prepared were suspended in a 0.1% Tween 20 solution and then dropped into a hemocytometer, and optical photographs of the microspheres were taken with a microscope. As shown in FIG. 1, the left figure in FIG. 1 is a microscope photograph of solid glass microspheres, and the right figure is a microscope photograph of hollow glass microspheres. A scanning electron microscope image in FIG. 2 shows that the hollow microspheres have smooth and complete surfaces, and cavities are only present in the glass microspheres, which have no impact on flowing of the glass microspheres in catheters or blood vessels and have no impact on the integrity of embolization.

TABLE-US-00002 TABLE 2 Density, glass transition temperature, nuclide loading rate and radiation dose of glass microsphere samples Nuclide Density/ T.sub.g/? loading Radiation Sample g/cm.sup.3 C. rate/wt % dose/MBq S101 3.56 882 33.7% 2480 S102 3.61 895 35.6% 2500 S103 3.67 905 35.8% 2510 S104 3.59 893 34.2% 2490 H101 2.13 885 33.5% 3190 H102 1.96 887 34.7% 3280 H103 1.73 884 34.1% 3460 H104 1.93 882 33.5% 3450 H105 1.66 885 34.7% 3410 H106 1.41 892 33.9% 3470 H107 2.28 887 34.1% 3470 H108 2.34 899 34.2% 3400 H109 1.76 857 36.4% 3800 H110 1.88 864 36.0% 3890 H111 1.93 873 36.2% 3860

[0070] It can be seen from Table 2 that compared with solid glass microspheres (S101-S104), the density of glass microspheres (H101-H111) added with a foaming agent is significantly decreased and is generally about 1.4-2.3 g/cm.sup.3, which is much lower than that of the solid microspheres (greater than 3.5 g/cm.sup.3). The reason is that after a foaming agent is added, the overall glass microspheres are more loose in texture and have more cavities therein, and the density is greatly decreased in comparison with the solid glass microspheres, which is more similar to the density of blood. Thus, the hollow glass microspheres are more suitable for use as radioactive glass microspheres for embolization. The hollow glass microspheres are not quickly sedimentated in liver blood vessels after injection, but can be uniformly and stably distributed in the liver blood vessels to achieve better distribution and deposition effects and a better embolization effect, thereby significantly improving the therapeutic effect.

[0071] Compared with the solid glass microspheres (S101-S104), the glass microspheres (H101-H111) added with a foaming agent have little change in glass transition temperature, a slightly increased nuclide loading rate and an obviously different radiation dose, which is increased from about 2,500 MBq to about 3,600 MBq. The reason may be that the glass microspheres (H101-H111) added with a foaming agent are loose in texture and contain many bubbles and cavities therein. After neutron activation of a nuclide in the glass microspheres, a ?-ray emitted by yttrium-90 is more likely to radiate from a loose glass matrix with cavities and can produce a higher radiation dose and kill surrounding tumor cells more effectively.

[0072] Through comparison of glass matrix formulas of the two kinds of glass microspheres, it can be seen that in the glass microspheres (H101-H111) added with a foaming agent, when the glass matrix contains B.sub.2O.sub.3, the nuclide loading rate is high, and the radiation dose is obviously higher. After analysis of the microspheres, the reason may be that as the glass microspheres containing B.sub.2O.sub.3 have better properties, convenience is provided for foaming of the foaming agent to further improve the texture and fix more nuclide oxides, and radiation of a ?-ray is more facilitated.

[0073] In addition, two different foaming agents including Na.sub.2SO.sub.4 or K.sub.2CO.sub.3 have no obviously different foaming effects in preparation of the glass microspheres. With increase of the-amount of the foaming agent Na.sub.2SO.sub.4 or K.sub.2CO.sub.3, the density of the prepared glass microspheres is further decreased, but the nuclide loading rate and the radiation dose are not continuously increased. Therefore, the added amount of Na.sub.2SO.sub.4 or K.sub.2CO.sub.3 is preferably 2 molar %.

[0074] Therefore, in order to improve comprehensive performance of radioactive glass microspheres for embolization, a foaming agent is required to be added for preparing glass microspheres with cavities. B.sub.2O.sub.3 is required to be added in a glass matrix formula, and 2 molar % Na.sub.2SO.sub.4 or K.sub.2CO.sub.3 can be used as a foaming agent.

Example 2 Density Screening of Radioactive Glass Microspheres for Embolization

[0075] In this example, in order to further reduce density differences between microspheres, density screening is performed on the microspheres. The microspheres are placed in a solvent with a specific density for centrifugal separation, a precipitated part includes microspheres with a density greater than that of the solvent, and a supernatant part is the part with a density less than that of the solvent. Specific operations are as follows.

[0076] 10 g of H102 microspheres (prepared in Example 1) were weighed, added into 40 mL of 1,2-dibromoethane (with a density of 2.17 g/cm.sup.3) and shaken for 30 seconds for uniform mixing, followed centrifugation for 10 minutes (at 5,000?g), and 15 mL of an emulsion on the upper layer was collected. Then, the microspheres were added into 35 mL of 1,2-dibromoethane and shaken for 30 seconds for uniform mixing, followed by centrifugation for two times for 10 minutes (at 5,000?g), and 10 mL of an emulsion on the upper layer was collected. The obtained microspheres were placed in an oven for drying at 60? C. for more than 2 hours. The dried microspheres were added into 40 mL of a 3 M fluorinated liquid FC40 (with a density of 1.85 g/cm.sup.3) and shaken for 30 seconds for uniform mixing, followed by centrifugation for 10 minutes (at 5,000 g), and 35 mL of a solution on the upper layer was removed. Then, the microspheres were added into 35 mL of a 3 M fluorinated liquid FC40 and shaken for 30 seconds for uniform mixing, followed by centrifugation for 10 minutes (at 5,000?g), and 35 mL of a solution on the upper layer was removed. The microspheres at the bottom were placed in an oven for drying at 60? C. for more than 2 hours to make the residual FC40 completely volatilized. The obtained microspheres are as shown in FIG. 3, which have a density of less than 2.17 g/cm.sup.3 and greater than 1.85 g/cm.sup.3.

Example 3 Comparison in Sedimentation Velocity

[0077] In order to evaluate the sedimentation velocity of hollow microspheres, 40 mg of solid microspheres (S101) and hollow microspheres prepared in Example 2 were weighed and added into 5 mL of PBS for uniform mixing, followed by standing for 1 minute, respectively, and natural sedimentation photographs of the microspheres in PBS were taken, as shown in FIG. 4.

[0078] It can be seen from FIG. 4 that 1 minute later, the solid microspheres are basically sedimentated to the bottom completely due to a high density, while the hollow microspheres are only sedimentated to ? of a liquid column height.

[0079] Thus, it can be seen that due to a high density, existing solid glass microspheres are quickly sedimentated to every corner of the bottoms of blood vessels after each injection and are difficult to be accurately located for achieving a good vascular embolization effect. However, the glass microspheres with cavities, which are prepared by foaming with a foaming agent and provided by the present invention, are not immediately sedimentated to the bottoms of blood vessels after injection, but can be uniformly distributed on upper sides, lower sides, left sides and right sides of vertical interfaces in the blood vessels and accurately accumulate in sites requiring vascular embolization until vascular embolization is realized, so as to achieve a better therapeutic effect.

Example 4 Comparison with Glass Microspheres on the Market

[0080] 10 mg of the microspheres obtained in Example 2 were taken, suspended in 500 ?L of a 0.1% Tween 20 solution and dropped into a hemocytometer, and an optical photograph of the microspheres was taken with a microscope. The microspheres have one or more cavity structures. The particle size of the microspheres was analyzed and measured by image processing software Image J. The microspheres have an average diameter of 26.8 ?m. The nuclide loading rate of the microspheres for embolization was measured by inductively coupled plasma-mass spectrometry. 5 mg of the microspheres for embolization prepared in Example 2 were weighed, and the signal strength of corresponding nuclides was measured by inductively coupled plasma-mass spectrometry (ICP-quadrupole-MS, Varian 810-MS, USA) and compared with standard curves of the corresponding nuclides to determine the final nuclide content. Nuclide loading rate (%)=mass of nuclides/total mass of microspheres for embolization?100%. Through calculation and analysis, the nuclide loading rate is 34.8%. Test results are as shown in Table 3.

TABLE-US-00003 TABLE 3 Comparison of parameters between microspheres for embolization with cavities prepared in Example 2 and TheraSphere? solid microspheres for embolization Diameter (?m) Density (g/cm.sup.3) Loading rate (%) Example 2 26.8 1.85-2.07 34.8 TheraSphere 25 3.6 31.5

[0081] It can be seen from Table 3 that compared with TheraSphere? glass microspheres, the hollow glass microspheres for embolization of the present invention have the advantages that as cavities are formed on the glass microspheres, the density of the glass microspheres for embolization is effectively decreased, and the hollow glass microspheres have good distribution and deposition effects during injection. Moreover, it can also be ensured that the glass microspheres provided by the present invention have a high nuclide loading rate.

Example 5 Animal Experiment on Hollow Microspheres of the Present Invention and Solid Microspheres

1. Materials and Reagents

[0082] A Sumianxin II injection for animals, pentobarbital sodium, an animal fixing frame, an animal dissection plate, a 1 mL syringe, a 5 mL syringe, a 10 mL syringe, an animal shaver, a surgical blade, surgical vessel forceps, surgical scissors, a surgical suture needle, tweezers, a needle holder, a 4-0 surgical suture, an arterial puncture needle, a 0.038 inch radifocus guide wire, a 2% lidocaine injection, a 1.7F Ev3 microcatheter with a guide wire, microspheres for embolization (hollow microspheres prepared by the present invention and solid microspheres on the market: TheraSphere? glass microspheres), ioversol, a disposable surgical drape, iodophor, sterile surgical gloves, heparin sodium and normal saline were used.

2. Anesthesia

[0083] A rabbit was fixed onto an animal fixing frame, 0.2 mL of a Sumianxin II injection for animals was intramuscularly injected into a leg, and then 0.8 mL/kg of a 3% pentobarbital solution was intravenously injected into the margin of an ear.

3. Femoral Artery Puncture and Cannulation

[0084] (1) After the rabbit was anesthetized, four limbs were opened and fixed onto an animal dissection plate to fully expose an inner side surface of one hind limb, hair on an inner side of the leg was shaved with an animal shaver, the inner side was disinfected with iodophor for 3 times, and then a disposable surgical drape was laid. [0085] (2) After subcutaneous layered injection of a 2% lidocaine hydrochloride injection at a site where pulsation of a femoral artery was touched, an epidermal layer and a muscle fascia layer were cut layer by layer with a surgical blade in a pulsation direction of the femoral artery, and a section of the femoral artery was bluntly separated layer by layer with vessel forceps at a site near a vagina vasorum of the femoral artery. [0086] (3) A distal end of the femoral artery was ligated with a suture to make a proximal end fully dilated, an arterial puncture needle was gently punctured into the proximal end in the direction of the femoral artery to send a puncture needle cannula sheath into the femoral artery while a needle core was removed. Bright red arterial blood spilling after the needle core was removed indicated that arterial cannulation was successful. Then, a radifocus guide wire was quickly sent into the femoral artery. The guide wire was observed to enter the aorta by fluoroscopy, which once again confirmed that femoral artery puncture and cannulation were successful. The cannula sheath was fixed in the femoral artery with a suture.

4. Hepatic Arteriography

[0087] The radifocus guide wire was removed, and a 1.7F Ev3 microcatheter and a micro-guide wire were sent. An abdominal artery near a T12 centrum was found, and an ioversol contrast agent diluted with normal saline containing heparin sodium at a ratio of 1:1 was injected to develop a common hepatic artery and a proper hepatic artery. After the 1.7F Ev3 microcatheter was cannulated into the common hepatic artery, digital subtraction angiography was performed to fully display blood supply conditions of hepatic arteries.

5. Embolization of a Hepatic Artery

[0088] In the case of angiography, equal quantities of solid microspheres and hollow microspheres for embolization were fully suspended in diluted ioversol and slowly injected into a target artery for embolization. Flowing conditions of the contrast agent in the artery branch were carefully observed, and embolization was stopped when reverse flowing occurred. Hepatic arteriography was performed again to determine embolization conditions of blood vessels.

6. Completion of Surgery

[0089] The microcatheter and the micro-guide wire were pulled out, the cannula sheath was removed, the proximal end of the femoral artery was quickly ligated, the muscle layer and the epidermal layer of the thigh of the rabbit were sutured layer by layer with a disposable suture needle and a suture and disinfected, and surgery was completed.

7. Results and Analysis

[0090] FIG. 5A to FIG. 5E are images showing embolization of solid glass microspheres, in which FIG. 5A is an angiography image of overall blood vessels before embolization, and it can be seen that the blood vessels are complete and clear; FIG. 5B is an enlarged image of a selected embolization area of solid glass microspheres, and it can be seen that blood vessels in the selected embolization area are complete and clear; FIG. 5C is a locally enlarged image of a selected embolization area; FIG. 5D is an angiography image of solid glass microspheres in a selected embolization area; and FIG. 5E is a locally enlarged image of an angiography image of solid glass microspheres in a selected embolization area. Through comparison between FIG. 5E and FIG. 5C, it can be clearly seen that when the solid glass microspheres are used for vascular embolization, the embolization is not complete, white angiography only appears locally, and blood still flows in some blood vessels, indicating that the solid microspheres cannot have a good embolization effect on blood vessels. The reason may be that due to a large density, the solid microspheres are difficult to flow, thus increasing the possibility of incomplete therapy caused by too early sedimentation in blood vessels. In addition, due to a relatively high density, the probability that the microspheres fall back into a gastroduodenal artery is increased, resulting in possible abdominal pain, vomiting and even gastroduodenal perforation.

[0091] In contrast, when the hollow glass microspheres of the present invention are used for vascular embolization in an embolization area, basically all blood vessels are filled with the hollow glass microspheres. Through comparison between FIG. 6B and FIG. 6C (or comparison between locally enlarged images FIG. 6D and FIG. 6E) as well as FIG. 6A, which is an image of blood vessels without embolization, it can be seen that all blood vessels are filled with the hollow microspheres, and the microspheres are uniformly distributed. When tumor tissues near the blood vessels are found, the hollow microspheres can effectively kill the tumor cells during follow-up radiation therapy. Moreover, due to a relatively lower density, the probability that the microspheres fall back into the gastroduodenal artery is greatly decreased, and complications obtained after embolization surgery are reduced to a maximum extent.

[0092] All patents and publications referred to in the specification of the present invention indicate that these patents and publications are open technologies in the art and can be used in the present invention. All the patents and publications cited herein are also listed in references as each publication is specifically cited separately. The present invention described herein may be realized under the conditions of absence of any one or more elements and presence of one or more limitations, and the limitations are not specified herein. For example, in each instance, the terms contain, substantially composed of . . . and composed of . . . can be replaced by either one of the remaining 2 terms. The so-called one herein only means one and can also mean 2 or above without excluding the meaning of only including one. The terms and expressions used herein are description manners, and the present invention is not limited thereto. Any intentions indicating that the terms and interpretations described herein exclude any equivalent features are also unavailable herein. However, it is to be understood that any suitable changes or modifications can be made within the scope of the present invention and the claims. It is to be understood that the examples described in the present invention are preferred examples and characteristics, some alternations and changes can be made by any person of general skill in the art according to the essence of descriptions of the present invention, and all these alternations and changes are also considered as falling within the scope of the present invention and the scope limited by the independent claims and the dependent claims.