WO2023082219A1

WO2023082219A1 - Method for efficiently preparing nano-composite material in which metal-organic framework is loaded with selenium atoms and use thereof

Info

Publication number: WO2023082219A1
Application number: PCT/CN2021/130492
Authority: WO
Inventors: 贺利贞; 陈填烽; 陈义康; 袁中文; 李海伟; 许宇龙
Original assignee: 广东暨创硒源纳米研究院有限公司
Priority date: 2021-11-13
Filing date: 2021-11-13
Publication date: 2023-05-19

Abstract

A method for efficiently preparing a nano-composite material in which a metal-organic framework is loaded with selenium atoms and a use thereof. A preparation method therefor comprises the following steps: (1) weighing ZIF-67 powder and selenium powder, the mass ratio of the ZIF-67 powder to the selenium powder being equal to 1-50:1, or weighing ZIF-8 powder and selenium powder, the mass ratio of the ZIF-8 powder to the selenium powder being equal to 1-50:1, uniformly mixing then pouring the mixture into a heating container, vacuuming the heating container to reach a vacuum state, sealing at a high temperature and heating to 230-280°C, maintaining at a constant temperature for a period of time, taking out the heating container after automatically cooling, pouring out the mixture to obtain a nano-composite material in which a metal-organic framework is loaded with selenium atoms. The nano-composite material in which a metal-organic framework is loaded with selenium atoms has an improved protective effect on human neuroblastoma cells and has an excellent effect in the treatment of cerebral apoplexy.

Description

A kind of nanocomposite material method and application of highly efficient preparation of metal organic framework loaded with selenium atoms

technical field

This patent relates to the technical field of chemical material preparation, in particular to a metal organic framework loaded selenium atom nanocomposite material and its preparation method and application.

Background technique

Metal-organic frameworks (MOFs), with catalytic centers at the molecular/atomic level, high porosity, large surface area, high loading capacity, and uniform structure, as a class of two-dimensional or three-dimensional porous crystal materials, have become rapidly emerging in the past 10 years. and one of the most promising materials for important catalyst design. It shows great potential in biomedical molecular storage, heterogeneous catalysis, biomedical delivery, gas separation, and energy storage applications. As one of the essential trace elements for human body, selenium plays a great role in supporting health maintenance and disease prevention. The combination of MOF and selenium will hopefully open up more possibilities in the field of biomedicine.

ZIF-67 is the framework material of imidazole molecular sieve, which is a porous metal organic framework material, and Zif-8 is a zeolite imidazole framework material, which is a new type of porous material, which combines the high stability of inorganic molecular sieves and the high performance of MOFS. Porosity and organic functionality.

At present, the combination preparation method of MOF and selenium is mainly through physical stirring to achieve in-situ encapsulation. The yield of this method is usually low and uncontrollable, and it is difficult to achieve large-scale or large-scale production. Specifically, the method of synthesizing MOF is used to realize the encapsulation of selenium nanomaterials, and the selenium nanomaterials are evenly mixed with the metal salt solution forming MOF, and then the ligand is added to start the reaction of MOF formation. This method is affected by the size of selenium nanomaterials, and only small sizes can be used for synthesis. At the same time, the selenium content of materials prepared by different MOFs will also vary.

In addition, the existing preparation technology also adopts the tube furnace vapor deposition method, which is to obtain selenium vapor by heating selenium powder at one end of the tube, and drive the selenium gas to the other section of the tube under the flow of nitrogen or argon to carry the selenium gas. A method of depositing selenium doping on the material in the lower temperature region at the end. In this method, a large amount of selenium gas is often discharged with nitrogen or argon gas flow, and most of the selenium is lost with the gas, so the selenium doping amount is as low as 5-16%, most of the selenium is lost with the gas, the doping amount is uncontrollable and the selenium gas It is easy to cause pollution of the tube furnace tube, the maintenance cost is high, and it has an important relationship with the setting of the temperature range, and it is not easy to control large-scale production.

Therefore, it is necessary to improve the preparation process of MOF-based selenium-containing materials to obtain selenium-containing materials based on metal organic frameworks with better performance.

Contents of the invention

Aiming at the deficiencies of the prior art, the primary purpose of the present invention is to provide a method for efficiently preparing a nanocomposite material with selenium atoms supported by a metal organic framework.

Another object of the present invention is to provide a nanocomposite material in which selenium atoms are loaded on a metal organic framework.

Another object of the present invention is to provide the nano-composite material of the metal-organic framework loaded with selenium atoms in anti-oxidation therapy and biopharmaceutical applications.

The object of the present invention is achieved through the following technical solutions:

A method for efficiently preparing a nanocomposite material with a metal-organic framework loaded with selenium atoms, comprising the steps of:

Take by weighing ZIF-67 powder and selenium powder, its mass ratio ZIF-67 powder: selenium powder=1-50:1, pour in heating container after mixing, described heating container is evacuated into vacuum state, high temperature sealing is heated to 230-280 ° C, and keep the constant temperature for a period of time, take out the heating container after automatic cooling, and pour out the mixture to obtain a nanocomposite material with metal organic framework supporting selenium atoms (ie Se/ZIF-67 composite system material);

Or, take by weighing ZIF-8 powder and selenium powder, its mass ratio ZIF-8 powder: selenium powder=1-50:1, pour into heating container after mixing, described heating container is pumped into vacuum state, high-temperature sealing Heating to 230-280°C, keeping the temperature constant for a period of time, taking out the heating container after automatic cooling, and pouring out the mixture to obtain a nanocomposite material (ie Se/ZIF-8 composite system material) with metal organic framework supporting selenium atoms.

Further, the heating container is a quartz glass tube, and the evacuated quartz glass tube is sealed at high temperature by a hydrogen flame, and the sealed quartz glass tube is placed in a high-temperature furnace, heated to 230-280°C, and kept at a constant temperature of 0.5-1.5°C. Hour.

Specifically, use a vacuum sealing system to evacuate the quartz glass tube to vacuum, use a hydrogen flame to heat the quartz glass tube for 3-5 minutes, and the inner glass plug is attached to the glass wall until the seal is intact.

Further, the preparation method of the nanocomposite material with selenium atoms supported by the metal organic framework also includes the step of preparing ZIF-67 powder or ZIF-8 powder,

To prepare ZIF-67 powder, pour cobalt nitrate hexahydrate into beaker A, add methanol and mix; in addition, pour 2-methylimidazole into beaker B, add methanol and mix; the solutions in the above-mentioned beaker A and beaker B are respectively in the ultrasonic Fully dissolve under treatment; then pour the solutions in beaker A and beaker B into a large beaker and mix them together, seal the mouth of the beaker and react under vigorous stirring for 6-10 hours, centrifuge and spin, collect the product and wash it with methanol, and get ZIF after drying -67 powder;

To prepare ZIF-8 powder, pour zinc nitrate hexahydrate into beaker A, add methanol and mix; in addition, pour 2-methylimidazole into beaker B, add methanol and mix; Then, pour the solution in beaker A and beaker B into a large beaker and mix them together, seal the mouth of the beaker and react under vigorous stirring for 1-2 hours, centrifuge and spin, collect the product and wash it with methanol, and dry it to get ZIF- 8 powder.

Further, according to controlling the mixing ratio of ZIF-67 powder and nano-selenium powder, or according to controlling the mixing ratio of ZIF-8 powder and nano-selenium powder, the selenium doping content of the nanocomposite material of the metal-organic framework loaded with selenium atoms can be adjusted Up to 35-48%.

The invention also provides a nanocomposite material in which metal organic framework supports selenium atoms, which is obtained by adopting the above preparation method. Specifically, a Se/ZIF-67 composite system material or a Se/ZIF-8 composite system material is obtained. The nano-composite material containing selenium has anti-oxidation effect.

The present invention also provides the application of the above-mentioned preparation method in biopharmaceuticals to obtain a nanocomposite material with selenium atoms supported by the metal organic framework.

The metal-organic framework-loaded nanocomposite material with selenium atoms has a protective effect on human neuroblastoma cells, and can be made into an oral agent drug or intravenous injection drug with the effect of treating stroke; the metal-organic framework-loaded nanometer composite material with selenium atoms Composite materials can also be used in biocatalytic therapeutic applications.

Compared with the prior art, the solution of the present invention has the following advantages and effects:

(1) The nano-composite material of metal-organic framework loaded selenium atom that the preparation method of the present invention obtains, such as Se/ZIF-67 composite system material, or Se/ZIF-8 composite system material, is the MOF nanomaterial with catalytic ability Combined with selenium, nano-selenium has the functions of anti-oxidation, free radical scavenging and anti-inflammation, and the advantages of metal-organic framework materials such as large specific surface area and high porosity. The composite material has a large loading capacity. Through elemental analysis under a high-resolution transmission electron microscope, it is found that selenium is evenly distributed in the MOF, and the surface is successfully doped with selenium. Moreover, the MOF basically maintains the original morphology framework, which is better than the existing preparation methods of MOF and MOF. The binding material of selenium is more excellent.

(2) Contrasting the existing two preparation methods based on MOF containing selenium, the preparation method of the present invention especially adopts the form of vacuum sealing tube so that selenium will not be discharged when heated at high temperature. Sealed and heated to 230-280°C, and kept at a constant temperature for a period of time, the fusion reaction effect of ZIF-8 powder or ZIF-67 powder and nano-selenium powder is the best, and the selenium and MOF are realized in a closed space as the temperature decreases. More than 95% of the materials are closely combined without leakage, and the selenium doping content of the composite material reaches 35-48%.

The inventor found that the high-temperature vacuum sealing heating to 230-280 ° C can prevent the material from reacting with oxygen in the air, improve the material purity and catalytic rate, and the selection of the heating temperature range value is the best value obtained through a large number of innovative experiments. If the temperature is low At 230°C, MOF and selenium cannot combine well; if the temperature is higher than 280°C, the porosity of the composite material becomes smaller and the catalytic rate is low.

In addition, the preparation method of the present invention can conveniently control the mixing ratio of the MOF material and selenium powder, adjust the content of loaded selenium according to the needs of pharmaceuticals, and overcome the shortcoming of the small synthesis scale of the physical stirring method, which can effectively reduce the waste of raw materials and realize efficient conversion and utilization. Realize the best use of everything and provide an innovative solution for the large-scale synthesis of selenium MOF nanomaterials. It can also overcome the loss of most of the selenium with the gas caused by the existing preparation method (tube furnace vapor deposition method), the low selenium doping amount is only 5-16%, the doping amount is uncontrollable and the selenium gas is easy to cause the tube furnace Pollution of the pipe, the disadvantages of high maintenance costs.

(3) The present invention selects two typical MOF materials, and uses these two typical MOF materials as the carrier of nano-selenium, and uses the method of vacuum sealing to innovatively prepare the composite nano-material of selenium MOF, and loads nano-selenium for other MOF materials. Selenium provides a reference, a reference for loading other elements on MOF, and a technical reference for loading dual or multi-element substances on MOF.

(4) The present invention also provides the application of the above-mentioned preparation method to obtain a nanocomposite material of a metal organic framework loaded with selenium atoms in biopharmaceuticals, and the nanocomposite material of the metal organic framework loaded with selenium atoms can be made into a drug for treating brain diseases Agent drug taken orally or given intravenously; used especially in the treatment of stroke. The nano-composite material with selenium atoms supported by the metal-organic framework can also be used in biocatalysis applications, which greatly expands the application field of the selenium-containing nano-composite material based on the metal-organic framework, and has broad application prospects in medicine and medicine.

The raw materials of composite materials are cheap and easy to obtain, the synthesis and operation steps are highly operable, and there is no pollution to the environment. The synthesis scale can be immediately expanded to realize the commercialization and application of drugs.

Description of drawings

Fig. 1: is the transmission electron micrograph and powder photo of ZIF-67 powder and Se/ZIF-67 composite system material doped with different selenium content of the present invention.

Fig. 2: is the transmission electron micrograph and powder photo of ZIF-8 powder and Se/ZIF-8 composite system material doped with different selenium content of the present invention.

Fig. 3: It is the nanocomposite material of the metal-organic framework of the present invention loaded with selenium atoms, corresponding to the elemental analysis spectrum when Se:ZIF-67=1:5.

Fig. 4: It is the nanocomposite material of the metal-organic framework of the present invention loaded with selenium atoms, corresponding to the elemental analysis spectrum when Se:ZIF-8=1:5.

Fig. 5: It is the nanocomposite material of the metal-organic framework of the present invention loaded with selenium atoms, corresponding to the XRD patterns of different mass ratios (Se:ZIF-67).

Fig. 6: It is the nanocomposite material of the metal organic framework supporting selenium atoms of the present invention, corresponding to the XRD patterns of different mass ratios (Se:ZIF-8).

Figure 7: It is a comparison chart of detection using ABTS total antioxidant capacity detection method.

Figure 8: Comparison of the protective effects of the metal-organic framework-supported nanocomposite material of the present invention on human brain neuroblastoma cells (SH-SY5Y).

Detailed ways

The present invention will be further described in detail below in conjunction with the embodiments and the accompanying drawings, but the embodiments of the present invention are not limited thereto.

The invention provides a method for preparing a nanocomposite material in which a metal organic framework supports selenium atoms, comprising the steps of:

Take by weighing ZIF-67 powder and selenium powder, its mass ratio ZIF-67 powder: selenium powder=1-50:1, pour in the heating container after mixing evenly, nano-selenium powder is purchased from Aladdin (article number: S105193; Purity: 99.9%), the heating container is evacuated into a vacuum state, such as utilizing the vacuum sealing system of Guangzhou Shanzhun Instrument Co., Ltd. to evacuate the quartz glass tube to a vacuum (-15Pa), and heat it to 230-280 ° C with high temperature sealing, and keep Constant temperature for 0.5-1.5 hours, take out the heating container after automatic cooling, and pour out the mixture to obtain a selenium-containing nanocomposite material based on a metal organic framework (ie Se/ZIF-67 composite system material);

Or, take ZIF-8 powder and nano-selenium powder, its mass ratio ZIF-8 powder: selenium powder=1-50:1, pour in the heating container after mixing, described heating container is pumped into vacuum state, high temperature Seal and heat to 230-280°C, and keep at a constant temperature for 0.5-1.5 hours, take out the heating container after automatic cooling, and pour out the mixture to obtain a nanocomposite material (i.e. Se/ZIF-8 composite system material) with metal organic framework supporting selenium atoms .

The heating container is a quartz glass tube, and the evacuated quartz glass tube is sealed at high temperature by a hydrogen flame. The sealed quartz glass tube is placed in a high-temperature furnace, heated to 230-280° C., and kept at a constant temperature for 0.5-1.5 hours. Specifically, the quartz glass tube can be evacuated to a vacuum using a vacuum sealing system, and the quartz glass tube can be heated with a hydrogen flame for 3-5 minutes, and the inner glass plug is bonded to the glass wall until the seal is intact.

Of course, existing purchased ZIF-67 powder or ZIF-8 powder can be used, or ZIF-67 powder or ZIF-8 powder can be prepared according to the following steps.

To prepare ZIF-67 powder, pour cobalt nitrate hexahydrate into beaker A, add methanol and mix; in addition, pour 2-methylimidazole into beaker B, add methanol and mix; the above solutions in beaker A and beaker B are ultrasonically treated Then, pour the solution in beaker A and beaker B into a large beaker and mix them together, seal the mouth of the beaker and react under vigorous stirring for 6-10 hours, centrifuge and spin, collect the product and wash it with methanol, and get ZIF- 67 powder;

Embodiment 1, a method for preparing a nanocomposite material with selenium atoms supported by a metal organic framework, comprising the steps of:

(1) Preparation of ZIF-67

Weigh 0.733g cobalt nitrate hexahydrate into 100mL beaker A, add 50mL methanol, put 1.623g 2-methylimidazole into another 100mL beaker B, add 50mL methanol. The solutions in the above-mentioned beaker A and beaker B were fully dissolved under ultrasonic treatment respectively. Then pour the solutions in beaker A and beaker B into a large beaker and mix together, seal the mouth of the beaker and react under vigorous stirring for 8 hours. Finally, the product was collected by centrifugation at 12000 rpm, washed three times with methanol, and dried in a 60° C. drying oven to obtain ZIF-67 powder.

(2) Preparation of Se/ZIF-67

Weigh 50mg of ZIF-67 powder and selenium powder with different mass ratios (such as ZIF-67:selenium powder=10:1), mix them evenly and pour them into a quartz glass tube, and use the vacuum sealing system to evacuate the quartz glass tube to vacuum (-15Pa), and then use the hydrogen oxygen machine to prepare the hydrogen flame. In the vacuum state, the hydrogen flame seals the quartz glass tube at high temperature, and the inner glass plug is attached to the glass wall until the seal is intact. Finally, place the sealed quartz tube in a muffle furnace, raise the temperature to 230°C at 5°C/min, and keep it at a constant temperature for 1h. After automatic cooling, the quartz glass tube was taken out to obtain the Se/ZIF-67 composite system material.

(3) Preparation of ZIF-8

Weigh 1.2g zinc nitrate hexahydrate into 100mL beaker A, add 41mL methanol; weigh 2.65g 2-methylimidazole into another 100mL beaker B, add 41mL methanol. The solutions in the above-mentioned beaker A and beaker B were fully dissolved under ultrasonic treatment respectively. Then pour the solutions in beaker A and beaker B into a large beaker and mix together, seal the mouth of the beaker and react under vigorous stirring for 1 h. Finally, the product was collected by centrifugation at 12000 rpm, washed three times with methanol, and dried in a 60° C. drying oven to obtain ZIF-8 powder.

(4) Preparation of Se/ZIF-8

Weigh 50mg of ZIF-8 powder and selenium powder with different mass ratios (such as ZIF-8: selenium powder = 10:1), mix well and pour into the quartz glass tube, and use the vacuum sealing system to evacuate the quartz glass tube to vacuum (-15Pa), and then use the hydrogen oxygen machine to prepare the hydrogen flame. In the vacuum state, the hydrogen flame seals the quartz glass tube at high temperature, and the inner glass plug is attached to the glass wall until the seal is intact. Finally, place the sealed quartz tube in a muffle furnace, raise the temperature to 230°C at 5°C/min, and keep it at a constant temperature for 1h. After automatic cooling, the quartz glass tube was taken out to obtain the Se/ZIF-8 composite system material.

Embodiment 2, a method for preparing a nanocomposite material with selenium atoms supported by a metal organic framework, comprising the steps of:

(1) Preparation of ZIF-67

Weigh 0.9g cobalt nitrate hexahydrate into 100mL beaker A, add 50mL methanol, put 1.8g 2-methylimidazole into another 100mL beaker B, add 50mL methanol. The solutions in the above-mentioned beaker A and beaker B were fully dissolved under ultrasonic treatment respectively. Then pour the solutions in beaker A and beaker B into a large beaker and mix together, seal the mouth of the beaker and react under vigorous stirring for 10 h. Finally, the product was collected by centrifugation at 12000 rpm, washed three times with methanol, and dried in a 60° C. drying oven to obtain ZIF-67 powder.

(2) Preparation of Se/ZIF-67

Take by weighing 50mg ZIF-67 powder and the selenium powder of different mass ratios (such as ZIF-67: selenium powder=1:1), pour into diameter 14mm after mixing evenly, in the quartz glass tube of long 280mm, utilize vacuum sealing tube system to The quartz glass tube is evacuated to a vacuum (-15Pa), and then a hydrogen flame is prepared by using an oxygen hydrogen machine. In a vacuum state, the hydrogen flame seals the quartz glass tube at high temperature, and the inner glass plug is bonded to the glass wall until the seal is intact. Finally, place the sealed quartz tube in a muffle furnace, raise the temperature to 260°C at 5°C/min, and keep the temperature constant for 1.5h. After automatic cooling, the quartz glass tube was taken out to obtain the Se/ZIF-67 composite system material.

(3) Preparation of ZIF-8

Weigh 1.5g zinc nitrate hexahydrate into 100mL beaker A, add 43mL methanol; weigh 2.8g 2-methylimidazole into another 100mL beaker B, add 43mL methanol. The solutions in the above-mentioned beaker A and beaker B were fully dissolved under ultrasonic treatment respectively. Then pour the solutions in beaker A and beaker B into a large beaker and mix together, seal the mouth of the beaker and react under vigorous stirring for 2 hours. Finally, the product was collected by centrifugation at 12000 rpm, washed three times with methanol, and dried in a 60° C. drying oven to obtain ZIF-8 powder.

(4) Preparation of Se/ZIF-8

Take by weighing 50mg ZIF-8 powder and the selenium powder (such as ZIF-8:selenium powder=1:1) of different mass ratios, pour into diameter 14mm after mixing evenly, in the quartz glass tube of long 280mm, utilize vacuum sealing tube system to The quartz glass tube is evacuated to a vacuum (-15Pa), and then a hydrogen flame is prepared by using an oxygen hydrogen machine. In a vacuum state, the hydrogen flame seals the quartz glass tube at high temperature, and the inner glass plug is bonded to the glass wall until the seal is intact. Finally, place the sealed quartz tube in a muffle furnace, raise the temperature to 260°C at 5°C/min, and keep the temperature constant for 1.5h. After automatic cooling, the quartz glass tube was taken out to obtain the Se/ZIF-8 composite system material.

The nanocomposite material of the metal-organic framework loaded with selenium atoms obtained by the above preparation method was tested by experiment.

Fig. 1 is a transmission electron microscope image and a powder photo of ZIF-67 powder and Se/ZIF-67 composite system material doped with different selenium contents of the present invention. Get mass ratio ZIF-67: selenium powder=1:1 respectively, ZIF-67: selenium powder=5:1, ZIF-67: selenium powder=10:1, ZIF-67: selenium powder=20:1, ZIF- 67: Selenium powder = 40:1. It can be seen that the lower right corner of the powder photo is a histogram of the mass percentage of selenium, which is detected by an atomic fluorescence spectrometer. On the one hand, it proves that the inventors have realized the technology of controllable selenium doping content. On the other hand, it proves that the selenium content of the composite material of the present invention is higher than that of the existing metal-organic frameworks. When the mass ratio ZIF-67:selenium powder=1:1, the mass percentage of selenium reaches 46.7%.

Fig. 2 is a transmission electron micrograph and a powder photo of ZIF-8 powder and Se/ZIF-8 composite system material doped with different selenium contents of the present invention. Get mass ratio ZIF-8: selenium powder=1:1 respectively, ZIF-8: selenium powder=5:1, ZIF-8: selenium powder=10:1, ZIF-8: selenium powder=20:1, ZIF- 8: Selenium powder = 40:1, it can be seen that the lower right corner of the powder photo is the bar graph of the mass percentage of selenium, which is detected by an atomic fluorescence spectrometer. On the one hand, it proves that the inventors have realized the technology of controllable selenium doping content. On the other hand, it proves that the selenium content of the composite material of the present invention is higher than that of the existing metal-organic frameworks. When the mass ratio ZIF-8:selenium powder=1:1, the mass percentage of selenium reaches 47.6%.

Fig. 3 is the nanocomposite material with selenium atoms supported by the metal organic framework of the present invention, corresponding to the elemental analysis spectrum when Se:ZIF-67=1:5. Fig. 4 is the nanocomposite material with selenium atoms supported by the metal organic framework of the present invention, corresponding to the elemental analysis spectrum when Se:ZIF-8=1:5. It can be seen that the combination of selenium and MOF is very good from the overlapping results of the spectra of the selenium element and the ligand N element in the MOF and the corresponding metal elements.

Fig. 5 is a nanocomposite material with selenium atoms supported by the metal organic framework of the present invention, corresponding to XRD patterns of different mass ratios (Se:ZIF-67). Fig. 6 is a nanocomposite material with selenium atoms supported by a metal organic framework of the present invention, corresponding to XRD patterns of different mass ratios (Se:ZIF-8).

From the X-ray diffraction patterns in Fig. 5 and Fig. 6, the characteristic crystal plane information of the composite material of the present invention can be analyzed, that is, different materials have different crystal plane information. By analyzing and comparing the crystal plane information corresponding to MOF materials with or without selenium doping, it was found that the basic crystal plane information of MOF after selenium doping was preserved, and no new crystal plane information was displayed, indicating that the composite material was successfully doped with selenium.

Figure 7 is the use of the ABTS total antioxidant capacity detection method to detect the antioxidant capacity of different mass ratios (Se:ZIF-67) based on metal-organic framework selenium-containing nanocomposites. It can be seen that the selenium-containing nanocomposites based on metal-organic frameworks have Significant antioxidant capacity, 100ug/mL can achieve close to 95% removal effect.

In addition, using the ABTS total antioxidant capacity detection method, sodium selenite, sodium selenate, selenocysteine, selenomethionine, chitosan-modified nano-selenium, lentinan-modified nano-selenium, and metal-organic framework-based selenium-containing The antioxidant capacity of the nanocomposites was tested. Among them, sodium selenite, sodium selenate, selenocysteine, selenomethionine, chitosan-modified nano-selenium, and lentinan-modified nano-selenium all showed an antioxidant effect lower than 5-10%.

Figure 8 is the selection of the human brain neuroblastoma cell line (SH-SY5Y) as the object of the cell model, by adding 20 μM tert-butyl hydroperoxide to simulate the free radicals produced by the cells, and finally detecting the SH-SY5Y by flow cytometry The apoptosis ratio of SY5Y cells was used to evaluate the protective effect of metal organic framework nanocomposites loaded with selenium atoms on SH-SY5Y cells in the free radical damage model versus cell damage model. It can be seen from the photo of the cells in Figure 8 that the apoptosis ratio of cells after tert-butyl hydroperoxide injury is about 50-70%, and the apoptosis ratio of the composite system is significantly lower than that of the injury group and the MOF alone group. Obviously, it shows that the nanocomposite material of metal-organic framework loaded with selenium atoms can effectively protect cells from damage caused by free radicals.

The present invention also provides the application of the above-mentioned preparation method in biopharmaceuticals to obtain a nanocomposite material with a metal-organic framework loaded with selenium atoms. The nano-composite material of the metal-organic framework loaded with selenium atoms can be made into an oral reagent drug or an intravenous drug for the treatment of stroke, which greatly expands the application field of the selenium-containing nano-composite material based on the metal-organic framework, and has broad medical applications. Pharmaceutical application prospects.

(1) The nano-composite material of metal-organic framework loaded selenium atom that the preparation method of the present invention obtains, such as Se/ZIF-67 composite system material, or Se/ZIF-8 composite system material, is the MOF nanomaterial with catalytic ability Combined with selenium, nano-selenium has the functions of anti-oxidation, free radical scavenging and anti-inflammation, and the advantages of metal-organic framework materials such as large specific surface area and high porosity. The composite material has a large specific surface area and a large loading capacity. Through elemental analysis under a high-resolution transmission electron microscope, it is found that selenium is evenly distributed in the MOF, and the surface is successfully doped with selenium, and the MOF basically maintains the original morphology framework, which is better than the existing preparation. The combined material of MOF and selenium is more excellent.

The inventors have found that high-temperature vacuum sealing heating to 230-280°C can prevent the material from reacting with oxygen in the air, improve the material purity and catalytic rate, and if the temperature is lower than 230°C, MOF and selenium cannot be well combined; if the temperature is higher than 280°C °C, the porosity of the composite material becomes smaller and the catalytic rate is lower.

(3) The metal-organic framework-loaded nanocomposite material with selenium atoms prepared by the inventor has a high utilization rate of selenium atoms, reaching 80-95%. Compared with the selenium MOF material fired in a tube furnace, the selenium utilization rate is increased by 20% -70%, can effectively reduce the waste of raw materials to achieve efficient conversion and utilization, and provide an innovative solution for large-scale synthesis of selenium MOF nanomaterials.

(4) Compared with the selenium MOF composite material prepared by the inventor, the metal organic framework loaded with selenium atoms has better water solubility, water dispersibility, and better antioxidant effect. Under the condition of selenium content, the antioxidant activity increases by 30-70%.

(5) The metal-organic framework-supported nanocomposite material prepared by the inventors has a better protective effect on human neuroblastoma cells than the single nano-selenium, MOF or the selenium-MOF composite material prepared above 700 °C, It has a good therapeutic effect in the treatment of stroke.

Claims

A method for efficiently preparing a nanocomposite material with metal-organic frameworks loaded with selenium atoms, characterized in that it comprises the steps of:

Take by weighing ZIF-67 powder and nano-selenium powder, its mass ratio ZIF-67 powder: selenium powder=1-50:1, pour in the heating container after mixing, described heating container is pumped into vacuum state, high-temperature sealing heating to 230-280°C, and keep the constant temperature for a period of time, take out the heating container after automatic cooling, and pour out the mixture to obtain a nanocomposite material with selenium atoms supported by a metal organic framework;

Or, take by weighing ZIF-8 powder and nano-selenium powder, its mass ratio ZIF-8 powder: selenium powder=1-50:1, pour into heating container after mixing, described heating container is pumped into vacuum state, high temperature Sealing and heating to 230-280° C., and maintaining a constant temperature for a period of time, taking out the heating container after automatic cooling, and pouring out the mixture to obtain a nanocomposite material with selenium atoms supported by a metal organic framework.
According to claim 1, a method for efficiently preparing a nanocomposite material of metal-organic framework loaded with selenium atoms is characterized in that, the heating container is a quartz glass tube, and the vacuumed quartz glass tube is sealed at high temperature by a hydrogen flame, and the sealed A good quartz glass tube is placed in a high-temperature furnace, heated to 230-280°C, and kept at a constant temperature for a period of time.
According to claim 1, a method for efficiently preparing a nanocomposite material of metal-organic frameworks loaded with selenium atoms, is characterized in that the quartz glass tube is evacuated to a vacuum using a vacuum sealing system, and the quartz glass tube is heated by a hydrogen flame for 3-5 minutes , the inner glass plug is attached to the glass wall until the seal is intact.
According to claim 1, a method for efficiently preparing a nanocomposite material with metal-organic frameworks loaded with selenium atoms is characterized in that it also includes the step of preparing ZIF-67 powder or ZIF-8 powder,

To prepare ZIF-67 powder, pour cobalt nitrate hexahydrate into beaker A, add methanol and mix; in addition, pour 2-methylimidazole into beaker B, add methanol and mix; the solutions in the above-mentioned beaker A and beaker B are respectively in the ultrasonic Fully dissolve under treatment; then pour the solutions in beaker A and beaker B into a large beaker and mix them together, seal the mouth of the beaker and react under vigorous stirring for 6-10 hours, centrifuge and spin, collect the product and wash it with methanol, and get ZIF after drying -67 powder;

To prepare ZIF-8 powder, pour zinc nitrate hexahydrate into beaker A, add methanol and mix; in addition, pour 2-methylimidazole into beaker B, add methanol and mix; Then, pour the solution in beaker A and beaker B into a large beaker and mix them together, seal the mouth of the beaker and react under vigorous stirring for 1-2 hours, centrifuge and spin, collect the product and wash it with methanol, and dry it to get ZIF- 8 powder.
According to claim 1, a kind of nano-composite method for efficiently preparing metal-organic framework-loaded selenium atoms is characterized in that, according to controlling the mixing ratio of ZIF-67 powder and nano-selenium powder, or according to controlling ZIF-8 powder and nano-selenium powder The mixing ratio of the selenium powder can adjust the selenium doping content of the nano-composite material with selenium atoms loaded on the metal organic framework to reach 35-48%.
A nanocomposite material with selenium atoms supported by a metal organic framework, characterized in that it is obtained by any one of the preparation methods in claims 1-5.
According to claim 6, the nanocomposite material with selenium atoms supported by metal organic framework is characterized in that it is a Se/ZIF-67 composite system material, or a Se/ZIF-8 composite system material.
According to claim 6, the nanocomposite material with selenium atoms supported by metal organic framework is characterized in that, the nanocomposite material with selenium atoms supported by metal organic framework has anti-oxidation effect.
By adopting any one of the preparation methods in claims 1-5, the application of a nanocomposite material with selenium atoms supported by a metal organic framework in brain diseases and biopharmaceuticals is obtained.
According to the application according to claim 9, it is characterized in that the nanocomposite material of the metal organic framework loaded with selenium atoms has a protective effect on human neuroblastoma cells, and can be made into an oral agent drug or intravenous injection with the effect of treating cerebral apoplexy Drugs; or the nanocomposite material of the metal organic framework supporting selenium atoms can be used in biocatalytic therapeutic applications.