WO2022134408A1 - Radioactive glass microsphere injection, preparation method, and use - Google Patents

Abstract

A radioactive glass microsphere injection, a preparation method, and a use. Per 1 ml radioactive glass microsphere injection contains: 0.1-100 mg of radioactive glass microspheres and 1-0.95 ml of a hydrogel. The injection is used for preparing a drug for treating a tumor, and can be directly injected into the tumor in an intervention manner, the radioactive dose of the radioactive glass microspheres is determined directly according to the administration volume, and the hydrogel reaching the tumor can form a gel in the tumor with calcium ions, thereby more uniformly dispersing and defining the radioactive glass microspheres in the tumor, such that the radioactive glass microspheres provide high-dose local radiation therapy to achieve the treatment of solid tumors, and the injection has broad application prospects in the treatment of solid tumors.

Description

A kind of radioactive glass microsphere injection and preparation method and use technical field

The invention relates to the technical field of medicine, in particular to a radioactive glass microsphere injection and a preparation method and application thereof.

Background technique

The current clinically used radioactive microsphere products mainly include yttrium [ ⁹⁰ Y] resin microspheres SIR-Spheres® (Sirtex Medical Limited, Australia) and yttrium [ ⁹⁰ Y] glass microspheres TheraSphere® (BTG, UK) and are undergoing clinical trials. The holmium [ ¹⁶⁶ Ho] resin microspheres (QuriemSphere®) studied in the experiment, these three microsphere products are all radioactive microsphere products dispersed in sterile water for injection or 0.9% sodium chloride injection solution. The rapid sedimentation in the middle is prone to needle blockage, which makes it impossible for this type of product to be administered directly by a syringe. In order to achieve the convenience of administration and the purpose of radiation shielding, the administration needs to use the perfusion administration device shown in Figure 1. This administration method requires 20-60ml of injection solution for flushing and the radioactive microspheres along the The catheter is carried into the body. Although this method can achieve better administration, it has obvious limitations. 1. It cannot be used for intratumoral administration due to the large administration volume and can only be used for intravascular administration; 2. It cannot be used according to the drug delivered to the body. The volume of the liquid is used to achieve the purpose of quantitative administration of the radioactive microspheres. These limitations make SIR-Spheres® and TheraSphere® only applicable for the treatment of solid tumors with abundant arterial blood supply by means of interventional administration through arterial cannulation, and cannot be used for other solid tumors by direct intratumoral injection The treatment of tumors has severely restricted the expansion of its indications.

The density of glass microspheres is generally 2.0-3.0g/cm ³ . In order to achieve the purpose of direct injection of radioactive glass microspheres, some researchers use glycerol, 40% lipiodol, etc. as dispersion medium for radioactive glass microspheres. It is prepared as a suspension injection, and then administered to animals or humans by direct injection. Although this method of using a high-viscosity dispersion medium can achieve the purpose of relatively uniformly dispersing the glass microspheres, this preparation also has several shortcomings: 1. The viscosity of this type of injection generally exceeds 100mPa·S, and the high viscosity not only It makes the mixing process before injection difficult, and bubbles are easily wrapped in the injection during the mixing process and are not easy to remove; 2. The injection process is also difficult to inject due to the large mass transfer resistance and the drug injected into the tissue is not easy to distribute evenly; 3. The used The large amount of excipients increases the burden on metabolism and may bring safety risks; 4. The mixed glass microspheres will settle to different degrees with the placement time; 5. It is difficult to dose the radioactive microspheres by the dosed volume. Make accurate calculations.

SUMMARY OF THE INVENTION

In order to solve the technical problems in the background art, the present invention provides a radioactive glass microsphere injection and a preparation method and application, wherein the radioactive glass microsphere injection has low viscosity and good fluidity, and the radioactive glass microspheres are dispersed in a medium. It is uniform and does not settle for a long time, and can be used for direct injection.

In a first aspect, the present invention also provides a radioactive glass microsphere injection.

The applicant found in the research that a certain concentration of sodium alginate solution has a certain suspending effect on the dispersion of glass microspheres in water, but the glass microspheres dispersed in the sodium alginate solution will completely settle within 10 minutes. The combination of sodium alginate and divalent metal ions to form a gel can not only disperse the glass microspheres uniformly, but also disperse the glass microspheres uniformly for a long time without sedimentation in the gel with the optimized formulation.

Specifically, a radioactive glass microsphere injection, each 1 ml of the radioactive glass microsphere injection contains: 0.1-100 mg of radioactive glass microspheres, and 1-0.95 ml of hydrogel.

Further research found that by optimizing the ratio and dosage of sodium alginate and divalent metal ions, the glass microsphere injection can maintain good fluidity while ensuring that the glass microspheres do not settle, which can be achieved by direct injection. Dosing. By adding a small amount of divalent metal ions, the viscosity of sodium alginate solution decreases significantly. For example, the viscosity of 0.2% sodium alginate solution is about 30 mPa·S. The viscosity of the hydrogel is also different. When the mass ratio of sodium alginate to divalent metal ion is 1:0.05-0.15, the viscosity of the hydrogel formed is 5-20mPa·S. The decrease in viscosity makes the resistance of the injection process smaller, the needle adaptability is better, the injection becomes easier, the air bubbles in the injection are easier to discharge, and more importantly, the viscosity decreases while the radioactive glass microspheres are in the hydrogel. The dispersion becomes more uniform and the radioactive glass microspheres do not settle for a long time.

Specifically, the mass ratio of the sodium alginate to the divalent metal ion is 1:(0.02-0.3), preferably 1:(0.05-0.15).

Further, the viscosity of the hydrogel is between 1-100 mPa·S, preferably 5-20 mPa·S.

Further, the divalent metal ion refers to a divalent metal ion with good biocompatibility, which can be combined with the sodium alginate solution to react instantaneously to form a hydrogel, such as calcium ion, strontium ion, preferably calcium ion.

Further, the radionuclides loaded on the radioactive glass microspheres include but are not limited to: yttrium [ ⁹⁰ Y], holmium [ ¹⁶⁶ Ho], phosphorus [ ³² P], rhenium [ ¹⁸⁶ Re], rhenium [ ¹⁸⁸ Re], Any one or more of zirconium [ ⁸⁹ Zr] and copper [ ⁶⁴ Cu], these nuclides are supported on glass microspheres by any method to obtain radioactive glass microspheres.

Further research found that the radioactive glass microsphere injection is macroscopically homogeneous, that is, an equal volume of the injection contains substantially the same amount of radioactive glass microspheres and radioactive dose. Therefore, accurate quantitative administration of the radioactive glass microspheres can be achieved by controlling the volume of the injection.

Further research found that the dose of radioactivity contained in a unit volume can be adjusted within the range of 0-5GBq/ml, but when the radioactivity dose of the radioactive glass microspheres exceeds 5GBq/ml, the hydrogel undergoes radiation degradation in a short time, which makes the The viscosity of the composition dropped significantly and the homogeneity was destroyed.

Specifically, the radioactivity of the radioactive glass microspheres is 0-5 GBq per milliliter of the injection, so that the radioactive concentration of the radioactive glass microspheres can be adjusted within a certain range.

Further research found that the particles of the radioactive glass microspheres with a particle size of less than 1 μm can be uniformly and stably dispersed in the aqueous solution of the macromolecular suspending agent such as sodium carboxymethyl cellulose, while the particles with a particle size of 1-1000 μm in the ordinary high Molecular suspending agent solution cannot be uniformly and stably dispersed for a long time, but can be uniformly and stably dispersed for a long time in calcium alginate hydrogel. However, when the particle size of glass microspheres is larger than 300 μm, it is difficult to be administered by direct injection, and the particles with particle size less than 20 μm are easy to migrate to other tissues and organs in vivo.

Specifically, the particle size of the radioactive glass microspheres is 1-1000 μm, preferably 20-300 μm, so that the radioactive glass microspheres are uniformly dispersed in the hydrogel system.

Further research found that radioactive glass microspheres prepared by different materials, such as silicate, borosilicate, aluminosilicate, apatite, phosphate or different methods, can be stable in calcium alginate hydrogel. , evenly dispersed.

Further, the radioactive glass microspheres comprise radioactive glass microspheres prepared by any method, including but not limited to: yttrium [ ⁹⁰ Y] glass microspheres, holmium [ ¹⁶⁶ Ho] glass microspheres, phosphorous [ ³² P] glass microspheres Any one or more of microspheres, rhenium [ ¹⁸⁶ Re/ ¹⁸⁸ Re] glass microspheres, zirconium [ ⁸⁹ Zr] glass microspheres, and copper [ ⁶⁴ Cu] glass microspheres.

In the second aspect, the present invention also provides a method for preparing a radioactive glass microsphere injection, including the following two preparation methods:

In a specific embodiment, the radioactive glass microspheres and the hydrogel are directly mixed uniformly, and the specific steps include:

(1) Dissolve a certain amount of sodium alginate in an appropriate amount of sterile water for injection, filter and sterilize the filter membrane, and then add a certain amount of filter-sterilized calcium chloride solution, and mix well to obtain calcium alginate hydrogel , for A1 agent;

(2) Dispense a certain amount of radioactive glass microsphere aqueous solution, and sterilize it with moist heat, that is, it is B1 agent;

(3) Before use, use a syringe to mix agent A1 and agent B1, mix well, and let stand for a while to remove air bubbles in the preparation.

In order to facilitate clinical use, in another specific embodiment, the radioactive glass microsphere solution containing divalent metal ions and the sodium alginate solution are uniformly mixed, and the specific steps include:

(1) Dissolve a certain quality of sodium alginate in an appropriate amount of sterile water for injection, filter and sterilize it, then package and seal to obtain a sterile sodium alginate solution, which is agent A2;

(2) Disperse a certain amount of radioactive glass microspheres in a certain amount of calcium chloride solution, sub-pack, and sterilize by moist heat at 121°C for 15 minutes to obtain a sterile calcium ion-containing radioactive glass microsphere solution, which is B2 agent;

(3) Use a syringe to inject the A2 agent obtained above into the B2 agent, mix well, and let it stand for a while to remove the air bubbles in the preparation.

In a specific embodiment, the filter membrane is preferably a sterile filter membrane with a pore size of 0.22 μm.

When the present invention is in use, it is preferable to package the A1 agent and the B1 agent together, or to send the A2 agent and the B2 agent combined package as a complete set of products to the hospital to be mixed and formulated by the hospital before use.

The method of the second aspect of the present invention is a method of preparing the radioactive glass microsphere injection of the first aspect of the present invention.

In the third aspect, the present invention also provides the radioactive glass microsphere injection according to the first aspect of the present invention and the radioactive glass microsphere injection prepared by the method according to the second aspect of the present invention, which are used in the preparation of the tumor treatment. application in medicine. The tumors include, but are not limited to, solid tumors such as pancreatic cancer, liver cancer, breast cancer, and prostate cancer.

Further, the drug contains radioactive glass microspheres and hydrogels.

Further, the medicine comprises sodium alginate and radioactive glass microspheres containing divalent metal ions.

Further research found that the calcium alginate hydrogel of the present invention and the calcium ions in the tumor tissue can further react to generate calcium alginate gel. The calcium alginate gel is different from the hydrogel, and its viscosity is much larger than that of the hydrogel. It has no fluidity in the tissue, and it is not easy to move in the tissue after being fixed. This method is beneficial for the radioactive glass microsphere product to be fixed in the solid tumor and not easily transferred to other tissues and organs, which can further reduce the potential safety risk of the radioactive glass microsphere product during the treatment process.

The radioactive glass microsphere injection of the present invention can be administered by direct injection, or can be administered by injection after intervention by a puncture needle.

Specifically, when the tumor is a superficial or superficial tumor, the drug is administered intralesional by direct injection; while deep solid tumors such as pancreatic cancer, liver cancer, and glioma can be guided by ultrasound Under the puncture needle intervention or under the guidance of endoscopic ultrasonography for intratumoral injection. The killing and killing of solid tumors are achieved by local high-dose radioactive radiation to achieve tumor treatment.

The drug can be used for local direct injection of the tumor, and after the drug reaches the lesion site, it can react with calcium ions in the tissue fluid to form a gel, so that the hydrogel gradually loses its fluidity, which is beneficial to fix the radioactive glass microspheres on the site. and reduce the toxic and side effects to other tissues or organs during local radiotherapy.

Compared with the prior art, the present invention has the following beneficial effects:

The present invention significantly reduces the viscosity of the sodium alginate solution by preparing the sodium alginate solution into a hydrogel, so that the injection is not easy to generate bubbles or the bubbles are easily discharged, and the needle adaptability is improved while improving the radioactive glass microspheres in the liquid medium. The dispersion is uniform and does not settle in the liquid phase for a long time. At the same time, the purpose of fixing the radioactive glass microspheres in the tumor is achieved through the further in situ gelation of the hydrogel in the tumor. On the premise of in vivo distribution of the microspheres, the safety risk of its clinical use is reduced.

The radioactive glass microspheres of the present invention are used to prepare a drug for treating tumors, the drug is directly injected into the tumor, and the drug can react with calcium ions in the tissue fluid after reaching the lesion site to form a gel, so that the hydrogel gradually loses The fluidity is beneficial to fix the radioactive glass microspheres at the lesion site and reduce the toxic and side effects to other tissues or organs during local radiotherapy.

The radioactive glass microsphere injection of the present invention can significantly reduce the amount of excipients used and ensure the uniform dispersion of the glass microspheres. The amount of excipients used per 10ml of the novel injection: sodium alginate is about 10mg, calcium chloride is about 5mg, and the rest are Bacterial water for injection can greatly reduce the burden of metabolism and safety risks (conventional dispersion medium: glycerol as an example, 10ml of injection contains about 10g of glycerol), and has a good application prospect. The problem that the radioactive glass microspheres are not easy to be injected directly and the radioactive dose quantification cannot be directly performed by the administration volume during the administration of the radioactive glass microspheres is well solved.

Description of drawings

Fig. 1 is the perfusion administration device of radioactive microspheres in the background technology;

Figure 2 is a comparison diagram of the dispersion state when each sample is shaken up and left for 1min, 10min, 30min, and 60min in Example 11 of the present invention;

Fig. 3 is a diagram of interventional administration under ultrasound guidance of an in situ model of rabbit liver cancer in Example 12 of the present invention.

Detailed ways

The specific embodiments of the present invention will be further described below with reference to the embodiments and the accompanying drawings. It should be noted here that the descriptions of these embodiments are used to help the understanding of the present invention, but do not constitute a limitation of the present invention. In addition, the technical features involved in the various embodiments of the present invention described below can be combined with each other as long as they do not conflict with each other.

Example 1

A method for preparing yttrium [ ⁹⁰ Y] glass microsphere injection, the method comprising the following steps:

Dissolve 20 mg of sodium alginate in 10 ml of sterile water for injection, pass through a 0.22 μm sterile filter membrane, add 10 ml of 0.45 g/L sterile calcium chloride solution, and mix to obtain a viscosity of 16.6 mPa·S (about 20 ℃) calcium alginate hydrogel, which is agent A1; 50 mg of yttrium [ ⁹⁰ Y] glass microspheres are dispersed in 1 ml of sterile water for injection, packaged, and sterilized by moist heat at 121 ℃-15min for later use, which is agent B1 ; Add the A1 agent obtained above into the B1 agent, and mix well. The radioactive glass microspheres did not start to settle within 2 hours of the injection.

Example 2

A method for preparing yttrium [ ⁹⁰ Y] glass microsphere injection, the method comprising the following steps:

Dissolve 20 mg of sodium alginate in 10 ml of sterile water for injection, pass through a 0.22 μm sterile filtration membrane, and encapsulate it for later use as agent A2; 100 mg of yttrium [ ⁹⁰ Y] glass microspheres are dispersed in 1 ml of 5 mg of calcium chloride In the sterilized water for injection, encapsulated, sterilized by moist heat at 121°C-15min for later use, it is agent B2; the agent A2 obtained above is added to agent B2, and it is obtained by mixing. The radioactive glass microspheres did not start to settle within 2 hours of the injection.

Example 3

A method for preparing a holmium [ ¹⁶⁶ Ho] glass microsphere injection, the method comprising the following steps:

Dissolve 20 mg of sodium alginate in 10 ml of sterile water for injection, pass through a 0.22 μm sterile filtration membrane, and encapsulate it for later use as agent A2; 300 mg of holmium [ ¹⁶⁶ Ho] glass microspheres are dispersed in 1 ml of 5 mg of calcium chloride In the sterilized water for injection, encapsulated, sterilized by moist heat at 121°C-15min for later use, it is agent B2; the agent A2 obtained above is added to agent B2, and it is obtained by mixing. The radioactive glass microspheres did not start to settle within 2 hours of the injection.

Example 4

A method for preparing phosphorus [ ³² P] glass microsphere injection, the method comprising the following steps:

Dissolve 20 mg of sodium alginate in 10 ml of sterile water for injection, pass through a 0.22 μm sterile filter membrane, add 10 ml of 0.6 g/L sterile calcium chloride solution, and mix to obtain a viscosity of 8.4 mPa·S (approximately 20°C) calcium alginate hydrogel, which is agent A1; 100 mg of phosphorus [ ³² P] glass microspheres are dispersed in 1ml of sterile water for injection, packaged, and sterilized by moist heat at 121°C-15min for later use, which is agent B1; Add the A1 agent obtained above to the B1 agent and mix well. The radioactive glass microspheres did not start to settle within 2 hours of the injection.

Example 5

A method for preparing copper [ ⁶⁴ Cu] glass microsphere injection, the method comprises the following steps:

Dissolve 20 mg of sodium alginate in 10 ml of sterile water for injection, pass through a 0.22 μm sterile filter membrane, add 10 ml of 0.6 g/L sterile calcium chloride solution, and mix to obtain a viscosity of 8.4 mPa·S (approximately 20°C) calcium alginate hydrogel, which is agent A1; 200 mg of copper [ ⁶⁴ Cu] glass microspheres are dispersed in 1ml of sterile water for injection, packaged, sterilized by moist heat at 121°C-15min for use, which is agent B1; Add the A1 agent obtained above to the B1 agent and mix well. The radioactive glass microspheres did not start to settle within 3 hours of the injection.

Example 6

A method for preparing a zirconium [ ⁸⁹ Zr] glass microsphere injection, the method comprising the following steps:

Dissolve 20 mg of sodium alginate in 10 ml of sterile water for injection, pass through a 0.22 μm sterile filter membrane, add 10 ml of 0.6 g/L sterile calcium chloride solution, and mix to obtain a viscosity of 8.4 mPa·S (approximately 20 ℃) calcium alginate hydrogel, which is agent A1; 5 mg of zirconium [ ⁸⁹ Zr] glass microspheres are dispersed in 1 ml of sterile water for injection, packaged, and then sterilized by moist heat at 121 ℃-15min for use, which is agent B1; Add the A1 agent obtained above to the B1 agent and mix well. The radioactive glass microspheres did not start to settle within 3 hours of the injection.

Example 7

A method for preparing an integrated rhenium [ ¹⁸⁶ Re/ ¹⁸⁸ Re] glass microsphere injection for diagnosis and treatment, the method comprising the following steps:

Dissolve 20 mg of sodium alginate in 10 ml of sterile water for injection, pass through a 0.22 μm sterile filter membrane, add 10 ml of 0.5 g/L sterile calcium chloride solution, and mix to obtain a viscosity of 8.0 mPa·S (approx. 20 ℃) calcium alginate hydrogel, which is agent A1; 100 mg of rhenium [ ¹⁸⁶ Re/ ¹⁸⁸ Re] glass microspheres are dispersed in 1 ml of sterile water for injection, packaged, and sterilized by moist heat at 121 ℃-15min for later use. B1 agent; add the A1 agent obtained above into the B1 agent, and mix well. The radioactive glass microspheres did not start to settle within 3 hours of the injection.

Example 8

A method for preparing an integrated radioactive glass microsphere injection for diagnosis and treatment, the method comprising the following steps:

Dissolve 20 mg of sodium alginate in 10 ml of sterile water for injection, pass through a 0.22 μm sterile filter membrane, add 10 ml of 0.5 g/L sterile calcium chloride solution, and mix to obtain a viscosity of 8.0 mPa·S (approx. 20℃) calcium alginate hydrogel, which is agent A1; Disperse 100mg of yttrium [ ⁹⁰ Y] glass microspheres and 20mg of copper [ ⁶⁴ Cu] glass microspheres in 1ml of sterile water for injection, encapsulate, 121℃-15min After moist heat sterilization, it is used as agent B1; add agent A1 obtained above into agent B1, and mix well. The radioactive glass microspheres did not start to settle within 2 hours of the injection.

Other types of radioactive glass microsphere injections can also be obtained by the same or similar methods and processes described above, and will not be described one by one here.

Example 9

To study the injection and needle suitability of different radioactive glass microsphere injection types in tissues:

Take fresh chicken breast meat purchased from the market, cut it into pieces (about 3*3*2cm), use a 1ml syringe to draw 0.5ml of the glass microsphere suspension for injection, insert the needle from the surface (depth 1cm), and insert the syringe vertically , all samples were injected slowly at a single point. Experiments show that the dispersibility and suspension properties of glass microspheres in glycerol solutions of different concentrations are much better than those of sodium alginate solutions of the same concentration. Therefore, the new formulation and glycerol solution are used as suspending agents for comparative research. The injections in Example 1 and Example 2, as well as the radioactive glass microspheres dispersed in 25% glycerol solution, 50% glycerol solution, 75% glycerol solution, and various injections in glycerol, were sequentially administered by chicken tissue injection. During the administration process, the needle suitability was judged according to whether the injection was smooth and the glass microspheres remained on the needle. The results are shown in Table 1. During the test, it was found that the viscosity of 50% glycerol solution is about 55 mPa·S, which can be injected, but the radioactive glass microspheres will settle soon and cannot be administered smoothly. No obvious sedimentation occurred in the inside, but the viscosity of glycerin exceeded 1200 mPa·S, it was difficult to suck it into the syringe using a syringe, and the needle fit test could not be completed. However, both Example 1 and Example 2 showed good needle adaptability.

Table 1. Needle suitability studies and excipient dosage data for different types of injections

.

It can be seen from Table 1 that the amount of excipients used in the unit volume of the radioactive glass microsphere injection of the embodiment of the present invention is much lower than that of the currently used preparation using glycerol as a dispersion medium.

Example 10

Study on the homogeneity of different radioactive glass microsphere injection types:

Take 10ml of the injections of Examples 1-6 and place them in a 10ml measuring cylinder, then sample 500 μL at 10, 8, 6, 4, and 2ml scales and use a radioactivity meter to measure the activity, and carry out 2 samplings at each scale. Test and take the average value, the activities obtained by sampling at different scales are shown in Table 2.

Table 2. Uniformity test of the distribution of radioactive glass microspheres for different injection formulations

.

The results in Table 2 show that the activities of the sampling tests in Examples 1-6 are basically the same, and the differences are all within 5%, which proves that the radioactive glass microsphere injection itself is uniform in the examples, and the volume of the liquid medicine can be used Perform accurate calculations of radioactivity.

Example 11

Study on the sedimentation time of different radioactive glass microsphere injection types:

About 4ml of radioactive glass microspheres of different injection types were placed in a 10ml vial, shaken well and left to stand, and the time when the glass microspheres completely settled on the bottom of the bottle was recorded. Example 1, Example 2 and 100mg of radioactive glass microspheres were dispersed in 10ml of radioactive glass microspheres were respectively studied in 25% glycerol solution, 50% glycerol solution, 75% glycerol solution, glycerol, and after fully shaking Settling time was recorded. The results are shown in Table 3. Figure 2 shows the comparison of the dispersion state of each injection after shaking well for a certain period of time. The samples in Figure 2 correspond to the glass microspheres dispersed in the 6 media from top to bottom in Table 3 from left to right.

Table 3. Sedimentation studies and viscosity of radioactive glass microspheres in different solution media

.

From the data in Table 3 and Figure 2, it can be seen that the glass microspheres of the radioactive glass microsphere injection prepared in Example 1 and Example 2 are uniformly dispersed in the liquid medium and do not settle for a long time. The time for uniform dispersion without sedimentation all exceeded 2 hours. Glass microspheres dispersed in pure glycerol can also achieve long-term suspension of glass microspheres, but their viscosity exceeds 1200 mPa·S and cannot be injected through a syringe.

Example 12

Study on the administration of radioactive glass microsphere injection to New Zealand tumor-bearing rabbits:

Ultrasound-guided interventional drug administration test was performed on 4 New Zealand rabbits with liver cancer orthotopic model; tumor size: 3.5-8.6 cm ³ ; dosing volume: 8% of the tumor volume, about 0.28-0.69 ml, radioactive The amount of glass microspheres is about 2.8-6.9 mg/piece, and the activity of yttrium [ ⁸⁹ Y] is about 0.03-0.07 mCi. Under the guidance of ultrasound, the tumor was localized and the puncture needle was inserted. When the puncture needle reached the target site, a certain volume of the injection in Example 2 was injected.

The test results show that: the tumor in the deep body can be directly injected through the puncture needle under the guidance of ultrasound, and the drug administration process is smooth without encountering the problem of needle blockage. It is difficult to inject at some points, but the injection can be successfully injected after adjusting the injection point. . The new formulation exhibited good needle suitability. Figure 3 is a diagram of the interventional drug delivery guided by ultrasound in an in situ model of rabbit liver cancer. In the figure, it can be seen that the obvious bright parts in the black circle are the radioactive glass microspheres after injection. The bright spots produced by the reflection prove that the drug was successfully injected into the tumor.

Finally, it should be noted that: the above embodiments are only used to illustrate the technical solutions of the present invention, but not to limit it; although the present invention has been described in detail with reference to the foregoing embodiments, those of ordinary skill in the art should understand: It is still possible to modify the technical solutions recorded in the foregoing embodiments, or perform equivalent replacements to some or all of the technical features; and these modifications or replacements do not make the essence of the corresponding technical solutions deviate from the technical solutions of the embodiments of the present invention. range.

Claims (16)

1. A radioactive glass microsphere injection, characterized in that each 1 ml of the radioactive glass microsphere injection comprises: 0.1-100 mg of radioactive glass microspheres and 1-0.95 ml of hydrogel.
2. The radioactive glass microsphere injection according to claim 1, wherein the radioactivity of the radioactive glass microspheres is 0-5 GBq of radioactive glass microspheres per milliliter of the injection.
3. The radioactive glass microsphere injection according to claim 1 or 2, wherein the radionuclides loaded on the radioactive glass microspheres include but are not limited to: yttrium [ ⁹⁰ Y], holmium [ ¹⁶⁶ Ho], phosphorus [ Any one or more of ³² P], rhenium [ ¹⁸⁶ Re], rhenium [ ¹⁸⁸ Re], zirconium [ ⁸⁹ Zr], and copper [ ⁶⁴ Cu].
4. The radioactive glass microsphere injection according to claim 1, wherein the radioactive glass microspheres can be glass of different materials such as silicate, borosilicate, aluminosilicate, apatite, and phosphate. .
5. The radioactive glass microsphere injection according to claim 1, wherein the hydrogel is prepared by a mixed reaction of sodium alginate solution and divalent metal ions with good biocompatibility.
6. The radioactive glass microsphere injection according to claim 5, wherein the mass ratio of the sodium alginate to the divalent metal ion is 1:(0.02-0.3), preferably 1:(0.05-0.15).
7. The radioactive glass microsphere injection according to claim 5 or 6, wherein the viscosity of the hydrogel is 1-100 mPa·S, preferably 5-20 mPa·S.
8. A method for preparing a radioactive glass microsphere injection, characterized in that the method comprises uniformly mixing the radioactive glass microspheres and the hydrogel.
9. A method for preparing a radioactive glass microsphere injection, characterized in that the method comprises: uniformly mixing a radioactive glass microsphere solution containing divalent metal ions and a sodium alginate solution.
10. A radioactive glass microsphere injection prepared by the method according to claim 8 or 9.
11. The application of the radioactive glass microsphere injection according to any one of claims 1-7 and 10 in the preparation of a medicament for treating tumors.
12. The use of claim 11, wherein the drug comprises radioactive glass microspheres and hydrogels.
13. The application of claim 11, wherein the drug comprises sodium alginate and radioactive glass microspheres containing divalent metal ions.
14. The application according to any one of claims 11-13, wherein when the tumor is a superficial or superficial tumor, the drug is administered intralesional by direct injection, and local high-dose radioactivity is used for intralesional administration. Radiation achieves killing and killing of solid tumors to achieve tumor treatment.
15. The application according to any one of claims 11-13, wherein when the tumor is a deep-body solid tumor, the drug is injected into the tumor through ultrasound-guided puncture needle intervention or endoscopic ultrasound-guided intratumoral injection. Drugs can kill and kill solid tumors through local high-dose radioactive radiation to achieve tumor treatment.
16. The application according to claim 11, wherein the drug can be in situ gelled in the tumor to achieve the function of confining the radioactive glass microspheres in the tumor, and avoid radioactive glass microspheres during local radiotherapy. The distribution of the ball outside the tumor tissue causes damage to other tissues.