A method for preparing a cyclodextrin metal-organic framework material assisted by supercritical carbon dioxide and application thereof

Abstract

This invention relates to a method for preparing cyclodextrin metal-organic framework materials using supercritical carbon dioxide, comprising: dissolving γ-cyclodextrin and potassium salt in water, filtering the solution through a filter membrane into a container, adding methanol to achieve a methanol-to-water volume ratio of 3-7:1-5, obtaining a reaction solution; transferring the reaction solution to a high-pressure reactor for preheating; introducing CO2 to a pressure of 8-14 MPa for heating and stirring; after the reaction is completed, allowing the high-pressure reactor to cool naturally to room temperature before depressurizing, transferring the reactants from the reactor, adding PEG20000 methanol solution to mix with the reactants, and allowing the mixture to stand in cold water for 2-4 hours; centrifuging at 5000-10000 rpm, collecting the precipitate, washing, and drying to obtain the cyclodextrin metal-organic framework material CD-MOF. This invention can reduce the amount of methanol used, significantly shorten the process time, reduce the risk of leakage caused by prolonged methanol vapor diffusion, and improve the yield and preparation efficiency of CD-MOF.

Description

Technical Field

[0001] This invention relates to the field of drug delivery carrier technology, specifically to a method and application for preparing cyclodextrin metal-organic framework materials using supercritical carbon dioxide. Background Technology

[0002] Metal-organic frameworks (MOFs) are a novel class of porous materials that self-assemble from organic ligands and metal ions through coordination interactions, and they have application value in many fields. However, their potential toxicity and non-degradability limit their application in the food and pharmaceutical industries. Cyclodextrin-metal-organic frameworks (γ-clodextrin-metal-organic frameworks, CD-MOFs), as a novel cyclodextrin derivative, have advantages such as simple synthesis methods and food-grade raw materials, making them a green and edible class of MOFs. They have already been applied in many fields such as drug delivery, gas storage, separation, and catalysis. Currently, the main synthesis methods for CD-MOFs include vapor diffusion, solvothermal methods, microwave-assisted methods, ultrasonic-assisted methods, and seed growth methods. These methods generally suffer from technical problems such as long reaction times, large amounts of organic solvents used, poor environmental friendliness, and high time and energy consumption. For example, CN116712567A discloses a vapor diffusion method for preparing γ-CD-MOF, comprising: dissolving γ-cyclodextrin and a water-soluble potassium salt in water to obtain a mixed solution; filtering the mixed solution through a filter membrane into a reaction vessel; placing the reaction vessel in a methanol vapor atmosphere; allowing the methanol vapor to diffuse into the solution for 3-8 hours; removing the supernatant; adding hexadecyltrimethylammonium bromide and methanol to the supernatant; incubating the resulting suspension at room temperature for another 3-8 hours; then centrifuging to collect the precipitate; washing the collected precipitate with methanol; and vacuum drying at 40-60℃ for 8-12 hours to obtain crystalline γ-CD-MOF. This method is time-consuming, complex, requires a large amount of methanol, and involves methanol vapor diffusion for 3-8 hours, which can easily lead to methanol leakage. Meanwhile, supercritical CO2 fluid (SC-CO2) has attracted widespread attention due to its non-toxicity, non-polluting nature, non-flammability, low cost, chemical inertness, recyclability, and the combined characteristics of supercritical fluids. However, there are no reports in the existing technology on the application of SC-CO2 technology to the preparation process of CD-MOF. Summary of the Invention

[0003] (a) Technical problems to be solved

[0004] In view of the above-mentioned shortcomings and deficiencies of the prior art, the present invention provides a method and application for preparing cyclodextrin metal-organic framework materials using supercritical carbon dioxide assisted preparation, wherein supercritical CO2 is introduced into a container filled with methanol vapor and containing K + In a closed reactor containing a mixed solution of K and γ-cyclodextrin, K... +Highly stable nanoscale CD-MOF materials were prepared by coordination with γ-cyclodextrin. This method can reduce the amount of methanol used, greatly shorten the process time, reduce the risk of leakage caused by long-term methanol vapor diffusion, and improve the yield and preparation efficiency of CD-MOF.

[0005] (II) Technical Solution

[0006] In a first aspect, the present invention provides a method for preparing cyclodextrin metal-organic framework materials using supercritical carbon dioxide-assisted synthesis, comprising:

[0007] S1. Dissolve γ-cyclodextrin and water-soluble potassium salt in water to obtain a mixed solution. Filter the mixed solution through a filter membrane into a container, add methanol to make the volume ratio of methanol to water 3-7:1-5, and obtain the reaction solution.

[0008] S2. Transfer the reaction solution to a high-pressure reactor and preheat it.

[0009] S3. Introduce CO2 into the high-pressure reactor until the pressure reaches 8-14 MPa, then heat and stir the reaction for 15-120 min.

[0010] S4. After the reaction is complete, allow the high-pressure reactor to cool naturally to room temperature, then depressurize it, transfer the reactants from the high-pressure reactor, add PEG20000 methanol solution to mix with the reactants, and place it in cold water to stand for 2-4 hours.

[0011] S5. Centrifuge at 5000-10000 rpm, collect the precipitate, wash and dry it to obtain the cyclodextrin metal-organic framework material CD-MOF.

[0012] According to a preferred embodiment of the present invention, in S1, the water-soluble potassium salt is potassium hydroxide; in the mixed solution, the molar ratio of γ-cyclodextrin to potassium ions is 1:6-10, preferably 1:8; and the concentration of potassium ions in the mixed solution is 0.2-1 mol / L.

[0013] According to a preferred embodiment of the present invention, in S1, the mixed solution is filtered into a container using a filter membrane with a pore size of 0.45 μm, methanol is added, and the mixture is sonicated for 3-8 min to completely dissolve the γ-cyclodextrin in the filtrate and to ensure that the methanol and the filtrate are mixed evenly.

[0014] According to a preferred embodiment of the present invention, in S2, an oil bath is used for preheating at 40-70°C. In S2, it is preferable to transfer the reaction liquid to a high-pressure reactor with a volume 2-4 times that of the reaction liquid. If the volume of the high-pressure reactor is too large, more high-pressure CO2 needs to be added for the reaction, resulting in a large consumption of high-pressure CO2 gas. Therefore, a high-pressure reactor with an appropriate volume should be selected.

[0015] According to a preferred embodiment of the present invention, in S4, the concentration of the PEG20000 methanol solution is 5-15 mg / mL, preferably 8 mg / mL. Preferably, the cold water temperature is 4-25°C, more preferably 10-25°C. Preferably, the volume of the PEG20000 methanol solution is 0.5-2 times the volume of the reactants, and the added volume is related to the concentration of the PEG20000 methanol solution. The amount of PEG20000 added is 0.3-0.5 times the mass of γ-CD. Preferably, the volume of the PEG20000 methanol solution is equal to the volume of the reactants transferred from the high-pressure reactor.

[0016] PEG20000 plays a crucial role in the size of CD-MOF crystals. When PEG20000 is added to the crystallization medium, PEG20000 molecules cover the surface of the CD-MOF crystals, thereby slowing down the crystal growth rate and reducing the final crystal size.

[0017] According to a preferred embodiment of the present invention, in step S5, the product is washed several times with isopropanol and ethanol respectively; the product is dried by blowing air at 60°C for 5 hours.

[0018] According to a preferred embodiment of the present invention, in S5, the reactants in the high-pressure reactor are transferred out and centrifuged at 8000 rpm for 5 min to collect the precipitate.

[0019] Secondly, the present invention provides a method for preparing a drug-loaded cyclodextrin metal-organic framework material, which includes a preparation process for the cyclodextrin metal-organic framework material, the preparation process of which is as described in any of the above embodiments.

[0020] Preferably, the preparation method includes: dissolving and mixing the drug with CD-MOF in a methanol solution, stirring and reacting under water bath heating conditions, collecting the product by centrifugation, washing, and drying to obtain a drug-loaded cyclodextrin metal-organic framework material.

[0021] Preferably, the drug is a natural drug molecule, such as quercetin, silymarin, curcumin, luteolin, paclitaxel, etc.

[0022] Preferably, the drug-to-CD-MOF mass ratio is 3-5:10, the water bath heating temperature is 40-60℃, the stirring speed is 600-1000 rpm, the reaction time is 15-120 min, and the product is collected by centrifugation at 8000 rpm for 5 min. The product is washed three times with methanol and then placed in an oven to dry at 50℃ for 4 h to obtain the drug-loaded cyclodextrin metal-organic framework material.

[0023] (III) Beneficial Effects

[0024] The method of this invention innovatively uses a mixture of SC-CO2 and the organic solvent methanol as the organic solvent. Based on the basic principle of vapor diffusion, under mild operating conditions, it synthesizes highly stable nanoscale CD-MOF materials through coordination. This invention effectively improves the problems of traditional methods, such as long time consumption, large amount of organic solvent used, low yield, high time and energy consumption, and easy leakage of toxic organic solvents.

[0025] This invention uses potassium ions (K) + As a metal salt ion, γ-cyclodextrin (γ-CD) acts as an organic ligand. During the preparation process, CO2 exhibits both gaseous diffusion properties and liquid solubility. Utilizing this property of supercritical CO2, methanol vapor diffusion is assisted to promote the coordination of potassium ions with γ-CD to synthesize nanoscale CD-MOF materials. These CD-MOF materials possess advantages such as high stability and good drug loading capacity. Due to the excellent organic solubility of supercritical CO2, it can replace part of the methanol, reducing methanol consumption and increasing the preparation rate. This invention has advantages such as mild preparation conditions, simple process, low energy consumption, and environmental friendliness. Attached Figure Description

[0026] Figure 1 The images show SEM images of CD-MOFs prepared at different reaction temperatures in Example 1.

[0027] Figure 2 SEM images of CD-MOFs prepared under different reaction pressures in Example 2.

[0028] Figure 3 SEM images of CD-MOFs prepared at different reaction times in Example 3.

[0029] Figure 4 The image shows SEM images of CD-MOFs prepared with different water / methanol ratios in Example 4.

[0030] Figure 5 The image shows the XRD pattern of the CD-MOF prepared in Example 5.

[0031] Figure 6 The XRD results show the stability of the CD-MOF prepared in Example 5 in solvents such as N,N-dimethylformamide, ethanol, dichloromethane, and isopropanol.

[0032] Figure 7 XRD patterns of CD-MOF and QUE@CD-MOF before drug loading.

[0033] Figure 8 SEM images of CD-MOF and QUE@CD-MOF before drug loading.

[0034] Figure 9The results are BET assays of CD-MOF and QUE@CD-MOF before drug loading.

[0035] Figure 10 The dissolution rate curves of QUE and QUE@CD-MOF in solutions with pH = 1.2, 6.8 and 7.4 are shown. Detailed Implementation

[0036] To better explain and facilitate understanding of the present invention, the present invention will be described in detail below with reference to the accompanying drawings and specific embodiments.

[0037] Example 1

[0038] This embodiment provides a method for preparing cyclodextrin metal-organic framework materials using supercritical carbon dioxide, the steps of which are as follows:

[0039] (1) Weigh 0.648 g of γ-cyclodextrin (0.5 mmol) and 0.224 g of potassium hydroxide (0.004 mol), dissolve them in 4 mL of water, filter using a 0.45 μm filter, add 28 mL of methanol, and sonicate for 5 min until the solid reagent in the solution is completely dissolved; the molar ratio n(γ-CD):n(KOH) = 1:8.

[0040] (2) Transfer the mixed solution to a 50 mL high-pressure reactor, place it in an oil bath, and preheat it fully under the four conditions of 40℃, 50℃, 60℃ and 70℃.

[0041] (3) After preheating, CO2 is introduced until the pressure reaches and is maintained at 12 MPa, and the reaction is heated and stirred for 2 hours;

[0042] (4) After the reactor is naturally cooled to room temperature, the pressure is released, and 30 mL of 8 mg / mL PEG20000 methanol solution is added to the reaction system and mixed. The mixture is then allowed to stand in cold water for 3 hours.

[0043] (4) Centrifuge at 8000 rpm for 5 min and collect the precipitate;

[0044] (5) The obtained product particles were washed several times with isopropanol and ethanol, and dried at 60°C for 5 hours. The product obtained was CD-MOF.

[0045] like Figure 1 As shown, where Figure 1 Image A is a 10kx SEM image of the CD-MOF product prepared by reacting at 12 MPa and 40 °C for 2 h. Figure 1 Image B is a 10kx SEM image of the CD-MOF product prepared by reacting at 12 MPa and 50 °C for 2 h. Figure 1C is a 10kx SEM image of the product CD-MOF prepared by reacting at 12 MPa and 60 °C for 2 h. Figure 1 The image D is a 10kx SEM image of the CD-MOF product prepared by reacting at 12 MPa and 70℃ for 2 h. As shown in the figure, the higher the reaction temperature, the more uniform the particle size distribution of the product, the closer the shape of the nanosheet product is to a regular cubic structure, and the higher the product dispersion. Among them, the CD-MOF product prepared by reacting at 12 MPa and 70℃ for 2 h has the best microstructure.

[0046] Example 2

[0047] In this embodiment, the step (3) is changed from "CO2 pressure maintained at 12 MPa" to "CO2 pressure maintained at 8, 10, 12, or 14 MPa" for 2 hours. Other conditions and preparation steps are described in Example 1.

[0048] like Figure 2 As shown, where Figure 2 E is a 10kx SEM image of the CD-MOF product prepared by reacting at 8 MPa and 70℃ for 2 h. Figure 2 F is a 10kx SEM image of the CD-MOF product prepared by reacting at 10 MPa and 70 °C for 2 h. Figure 2 G is a 10kx SEM image of the CD-MOF product prepared by reacting at 12 MPa and 70 °C for 2 h. Figure 2 H is a 10kx SEM image of the CD-MOF product prepared by reacting at 14 MPa and 70℃ for 2 h. As shown in the figure, the higher the reaction pressure, the more uniform the particle size distribution of the product, the closer the shape of the nanosheet product is to a regular cubic structure, and the higher the product dispersion; among them, the CD-MOF product prepared under the condition of reacting at 14 MPa and 70℃ for 2 h has the best microstructure.

[0049] Example 3

[0050] In this embodiment, "heating and stirring for 2 hours" in step (3) is changed to "heating and stirring for 15 minutes, 30 minutes, 1 hour, and 2 hours". For other conditions and preparation steps, please refer to Example 1.

[0051] like Figure 3 As shown, where Figure 3 Image I is a 10kx SEM image of the product CD-MOF prepared by charging CO2 to a pressure of 14 MPa and reacting for 15 min. Figure 3 G is a 10kx SEM image of the product CD-MOF prepared by charging CO2 to a pressure of 14 MPa and reacting for 30 min. Figure 3K is a 10kx SEM image of the product CD-MOF prepared by charging CO2 to a pressure of 14 MPa and reacting for 1 h. Figure 3 L is a 10K-fold SEM image of the CD-MOF product prepared by reacting with CO2 at a pressure of 14 MPa for 2 hours. Comparison shows that the longer the reaction time, the more uniform the particle size distribution of the product, the closer the shape of the nanosheet product is to a regular cubic structure, and the higher the product dispersion. Among them, the CD-MOF product prepared by reacting with CO2 at a pressure of 14 MPa and 70℃ for 2 hours has the best microstructure.

[0052] Example 4

[0053] In this embodiment, the "4 mL water, 28 mL methanol" in step (1) is changed to "10.6 mL water, 21.2 mL methanol; water:methanol = 1:2", "8 mL water, 24 mL methanol; water:methanol = 1:3", "6.4 mL water, 25.6 mL methanol; water:methanol = 1:4", and "4 mL water, 28 mL methanol; water:methanol = 1:7", respectively. Other conditions and preparation steps are the same as in Example 1.

[0054] like Figure 4 As shown, where Figure 4 M is a 300x SEM image of the product CD-MOF prepared by reacting at 10.6 mL water, 21.4 mL methanol, 14 MPa, and 70 °C for 2 h. Figure 4 N is a 300x SEM image of the CD-MOF product prepared in "8 mL water, 24 mL methanol". Figure 4 The image shown is a 5kx SEM image of the CD-MOF product prepared using the mixture of 6.4 mL water and 25.6 mL methanol. Figure 4 The image shows a 10kx SEM image of the CD-MOF product prepared using the "4 mL water, 28 mL methanol" method. As shown in the figure, the higher the methanol:water ratio, the smaller the particle size and the higher the product dispersion. The CD-MOF product prepared under the "4 mL water, 28 mL methanol" condition has the smallest particle size and the highest product dispersion.

[0055] Example 5

[0056] This embodiment provides a method for preparing cyclodextrin metal-organic framework materials using supercritical carbon dioxide, the steps of which are as follows:

[0057] (1) Weigh 0.648g of γ-cyclodextrin and 0.224g of potassium hydroxide, dissolve them in 4mL of water, filter using a 0.45μm filter, add 28mL of methanol, and sonicate for 5min until the solid reagents in the solution are completely dissolved.

[0058] (2) Transfer the mixed solution to a 50 mL high-pressure reactor and preheat it in an oil bath at 70 °C.

[0059] (3) After preheating, CO2 is introduced until the pressure reaches and is maintained at 14 MPa, and the reaction is heated and stirred for 2 hours;

[0060] (4) After the reactor is naturally cooled to room temperature, the pressure is released, and 30 mL of 8 mg / mL PEG20000 methanol solution is added to the reaction system and mixed. The mixture is then allowed to stand in cold water for 3 hours.

[0061] (4) Centrifuge at 8000 rpm for 5 min and collect the precipitate;

[0062] (5) The obtained product particles were washed several times with isopropanol and ethanol, and dried at 60°C for 5 hours. The product obtained was CD-MOF.

[0063] As can be seen from the above examples, the product particles are cubic in shape, and as the temperature increases, the pressure increases, the time increases, and the water-to-alcohol ratio decreases, the particle size becomes smaller and the dispersion becomes higher. The optimal preparation conditions are to react at 14 MPa and 70°C for 2 hours.

[0064] The product prepared in this embodiment was characterized by XRD, such as... Figure 5 As shown in the figure, CD-MOF exhibits clear diffraction peaks at 4°, 5.7°, 6.9°, 13.4°, and 16.7°, consistent with the calculated simulation results, indicating that CD-MOF possesses a complete crystal structure and a good crystal form.

[0065] The CD-MOF prepared in Example 5 was dispersed in N,N-dimethylformamide, ethanol, dichloromethane, and isopropanol, soaked for 12 hours under normal temperature and pressure, centrifuged, dried in a forced-air environment at 60°C, and subjected to XRD analysis to confirm the stability of CD-MOF in different solvents; the test results are as follows. Figure 6 As shown, after solvent treatment, CD-MOF exhibits good stability in isopropanol and ethanol, while its stability in N,N-dimethylformamide and dichloromethane is slightly worse. However, overall, CD-MOF showed corresponding characteristic diffraction peaks in XRD before and after different solvent treatments, indicating good stability in all four solvents.

[0066] Example 6

[0067] In this example, the CD-MOF prepared in Example 5 was used as a drug carrier for drug loading.

[0068] Quercetin (QUE) is a representative compound of flavonols with high medicinal value and biological activity, but its poor water solubility severely limits its application in drug therapy. To improve drug dispersibility and utilization, this study prepared quercetin-loaded cyclodextrin metal-organic framework drug-loaded microparticles, denoted as QUE@CD-MOF, using an impregnation method. The experimental method is as follows:

[0069] (1) 40 mg of quercetin and 100 mg of CD-MOF (prepared in Example 5) were accurately measured and dissolved in 20 mL of methanol solution. The mixture was sonicated for 10 min to ensure complete dissolution. Then, it was transferred to a round-bottom flask and reacted in a water bath at a set temperature of 50 °C and a rotation speed of 800 rpm for 1 h. The reaction was then completed.

[0070] (2) After the reaction is complete, remove the reaction product from the round-bottom flask and transfer it to a centrifuge tube. Centrifuge at 8000 rpm for 5 min. After centrifugation, remove the supernatant from the centrifuge tube and wash it three times with methanol solution.

[0071] (3) After washing, the precipitate obtained by centrifugation was placed in an oven and dried at 50°C for 4 hours to obtain QUE@CD-MOF drug-loaded microparticles.

[0072] XRD analysis was performed on QUE@CD-MOF and pre-loaded CD-MOF, and the results are as follows: Figure 7 As shown, CD-MOF exhibits clear diffraction peaks at 4°, 5.7°, 6.9°, 13.4°, and 16.7°. QUE shows characteristic diffraction peaks at 5.36°, 10.76°, 12.46°, 16.13°, 23.88°, and 27.42°, with the strongest characteristic diffraction peak appearing at 12.46°. This indicates that QUE has a good crystal structure. QUE@CD-MOF shows characteristic peaks of CD-MOF at 4°, 5.7°, 6.9°, 13.4°, and 16.7°. Compared to CD-MOF alone, the characteristic peak intensities of QUE@CD-MOF show slight variations, but overall there is no significant difference. This proves that QUE enters the CD-MOF cavity in an amorphous state, and indicates that the drug loading process does not affect the crystal structure of CD-MOF, providing a basis for its use as a drug carrier.

[0073] like Figure 8The images show SEM images of CD-MOF before and after drug loading, where A and B are SEM images before drug loading, and C and D are SEM images of QUE@CD-MOF after drug loading. As can be seen from the images, the morphology of the QUE-loaded CD-MOF particles is not significantly different from that of the standalone CD-MOF; both exhibit a uniform cubic structure. This indicates that drug loading does not affect the overall structure of the CD-MOF material.

[0074] BET detection was performed on the QUE@CD-MOF of this embodiment, and it was compared with the CD-MOF before drug loading. The detection results are as follows. Figure 9 As shown, the nitrogen adsorption / desorption isotherms of the drug-loaded QUE@CD-MOF and the unloaded CD-MOF are shown in A, and the pore size distribution diagrams of the drug-loaded QUE@CD-MOF and the unloaded CD-MOF are shown in B. After drug loading, the specific surface area of ​​the material (m²) 2 The pore size (nm) and pore volume (cc / g) of the CD-MOF have all decreased significantly, indicating that QUE has been loaded into the porous structure of the CD-MOF. Specific comparison results are as follows:

[0075] <![CDATA[Specific surface area (m 2 / g)]]> Aperture (nm) Pore ​​volume (cc / g) Before drug loading 894.120 1.442 0.138 After drug loading 575.741 1.411 0.119

[0076] Example 7

[0077] This embodiment further conducts a drug dissolution experiment on the QUE@CD-MOF drug-loaded microparticles prepared in Example 6, and the method is as follows:

[0078] (1) Prepare the following solution:

[0079] (A) Take 117 mL of concentrated hydrochloric acid and dilute it in a 500 mL graduated cylinder. Then transfer 24 mL to a 1000 mL graduated cylinder and dilute with degassed water. The pH is 1.2. Solution (A) can simulate the gastric juice environment.

[0080] (B) Weigh 6.9g of sodium dihydrogen phosphate and 0.9g of sodium hydroxide solid, dissolve them in 1000mL of water, pH=6.8. Solution (B) can simulate the small intestinal environment.

[0081] (C) Weigh 1.36 g of potassium dihydrogen phosphate, add 79 mL of 0.1 mol / L sodium hydroxide solution, and dilute with water to 200 mL, pH = 7.4. Solution (C) can simulate the blood environment.

[0082] (2) Dissolution of QUE and QUE@CD-MOF was determined by slurry method using three buffer solutions (A), (B) and (C).

[0083] Weigh QUE and QUE@CD-MOF samples using 2.5 mg QUE as a baseline. Take 500 mL each of buffer solutions (A), (B), and (C). Add the samples to the buffer solutions. Set the equipment temperature to 37℃ and the rotation speed to 100 rpm. Take samples at different time intervals to measure the QUE concentration in the solution. Take samples 11 times in total (2, 5, 8, 13, 20, 30, 40, 55, 75, 100, 130 min), taking 10 mL each time and replenishing with 10 mL of the solution. Filter the collected samples through a 0.45 μm microporous membrane before entering the sampling tube. After all sampling is completed, measure the absorbance of the sample at 372 nm using a UV spectrophotometer. Calculate the dissolution rate by substituting the values ​​into the standard curve. The test results are as follows: Figure 10 As shown.

[0084] As shown in the figure, at each moment under the same pH conditions, the dissolution rate of drug QUE in the drug-loaded microparticles of QUE@CD-MOF is much greater than that of drug QUE. After 40 minutes of dissolution experiment, under three conditions of pH=1.2, 6.8 and 7.4, the dissolution rate of QUE stabilized at 20% and could not continue to increase, while the drug dissolution rate of QUE@CD-MOF reached more than 70% after 40 minutes. In particular, under the condition of pH=7.4, the drug dissolution rate of QUE@CD-MOF reached 96.28%.

[0085] In summary, by loading QUE with CD-MOF, this invention can greatly improve the effective dissolution rate of QUE and effectively promote the bioavailability of QUE.

[0086] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention, and not to limit them; although the present invention has been described in detail with reference to the foregoing embodiments, those skilled in the art should understand that modifications can still be made to the technical solutions described in the foregoing embodiments, or equivalent substitutions can be made to some or all of the technical features; and these modifications or substitutions do not cause the essence of the corresponding technical solutions to deviate from the scope of the technical solutions of the embodiments of the present invention.

Claims

1. A method for preparing a drug-loaded cyclodextrin metal-organic framework material, characterized in that, It includes: The drug and CD-MOF were dissolved and mixed in methanol solution, and the reaction was carried out under water bath heating with stirring. The product was collected by centrifugation, washed, and dried to obtain a drug-loaded cyclodextrin metal-organic framework composite material. The drug was quercetin. The preparation method of the CD-MOF is as follows: S1. Dissolve γ-cyclodextrin and water-soluble potassium salt in water to obtain a mixed solution. Filter the mixed solution through a filter membrane into a container, add methanol to make the volume ratio of methanol to water 3-7:1-5, and obtain the reaction solution. S2. Transfer the reaction solution to a high-pressure reactor and preheat it. S3. Charge CO2 into the high-pressure reactor until the pressure reaches 8-14MPa, then heat and stir the reaction for 15-120 minutes. S4. After the reaction is complete, allow the high-pressure reactor to cool naturally to room temperature, then depressurize it, transfer the reactants from the high-pressure reactor, add PEG20000 methanol solution to mix with the reactants, and place it in cold water to stand for 2-4 hours. S5. Centrifuge at 5000-10000 rpm, collect the precipitate, wash and dry it to obtain the cyclodextrin metal-organic framework material CD-MOF.

2. The preparation method according to claim 1, characterized in that, In S1, the water-soluble potassium salt is potassium hydroxide; in the mixed solution, the molar ratio of γ-cyclodextrin to potassium ions is 1:6-10; and the concentration of potassium ions in the mixed solution is 0.2-1 mol / L.

3. The preparation method according to claim 1, characterized in that, In S1, the mixed solution is filtered into a container using a filter membrane with a pore size of 0.45 μm. Methanol is added, and the mixture is sonicated for 3-8 minutes to completely dissolve the γ-cyclodextrin and potassium hydroxide in the filtrate and to ensure that the methanol and filtrate are mixed evenly.

4. The preparation method according to claim 1, characterized in that, In S2, an oil bath is used to preheat the reaction at 40-70°C.

5. The preparation method according to claim 1, characterized in that, In S4, the concentration of the PEG20000 methanol solution is 5-15 mg / mL; the PEG20000 methanol solution is mixed with the reactants in equal volumes.

6. The preparation method according to claim 1, characterized in that, In S5, the product is washed several times with isopropanol and ethanol respectively during washing; the product is dried by blowing air at 60°C for 5 hours.

7. The preparation method according to claim 1, characterized in that, The mass ratio of the drug to CD-MOF is 3-5:10, the water bath heating temperature is 40-60℃, the stirring speed is 600-1000 rpm, the reaction time is 15-120 min, and the product is collected by centrifugation at 8000 rpm for 5 min.

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