A UiO-66-supported tetracycline hydrochloride material and its preparation method
By using UiO-66 to load tetracycline hydrochloride, the problems of poor biocompatibility and low drug loading of nanoparticle drug carriers were solved, achieving efficient loading and controllable release of tetracycline hydrochloride, thus improving the therapeutic effect and safety of the drug.
Patent Information
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- ZHAOQING UNIV
- Filing Date
- 2026-04-29
- Publication Date
- 2026-07-03
AI Technical Summary
Existing nanoparticle drug carriers suffer from poor biocompatibility during preparation, low drug loading, and unsatisfactory sustained-release effects, which limits their application in disease treatment.
Using metal-organic framework material UiO-66 as a carrier, tetracycline hydrochloride was loaded into its pores by impregnation. The UiO-66-loaded tetracycline hydrochloride material was formed by van der Waals forces and hydrogen bonding, avoiding organic solvent residue and achieving efficient adsorption and stable binding of tetracycline hydrochloride.
This method achieves efficient loading and controlled release of tetracycline hydrochloride in UiO-66 channels, avoiding the drug burst release effect, ensuring high concentration and long-term stable release in the lesion area, and improving biocompatibility and sustained-release effect.
Smart Images
Figure CN122321172A_ABST
Abstract
Description
Technical Field
[0001] This invention belongs to the field of sustained-release drug preparation technology, specifically relating to a UiO-66-loaded tetracycline hydrochloride material and its preparation method. Background Technology
[0002] Currently, the overuse of antibiotics has caused serious environmental pollution, leading to the persistence of drug resistance genes in the environment and contributing to bacterial resistance. Tetracycline hydrochloride is a widely used tetracycline antibiotic in clinical practice with significant efficacy, but it also has certain side effects, causes environmental pollution, and contributes to drug resistance. Therefore, improving the therapeutic effect of tetracycline hydrochloride while reducing its toxic side effects has become a focus of attention in the field of medical research.
[0003] The development of sustained-release drug technology has provided new solutions to the aforementioned problems. Among these, using nanoparticle drug carriers as drug delivery systems or active antibacterial agents can protect the carried antibiotics from biodegradation and inhibit efflux pump activity, thereby effectively combating bacterial resistance. Furthermore, nanoparticle drug carriers can achieve controlled and sustained drug release, prolonging the effective duration of therapeutic action. This allows for the use of lower doses of antibacterial agents while ensuring efficacy, minimizing potential toxic side effects on healthy cells and tissues.
[0004] However, existing nanoparticle drug carriers, such as liposomes, quantum dots, carbon dots, polymer nanoparticles, and micelles, often rely on organic solvents during preparation, resulting in poor biocompatibility of the drug composites. Furthermore, existing preparation processes often lead to surface adsorption as the binding mode between the nanoparticle drug carrier and the drug, resulting in low drug loading and poor sustained-release effects, which greatly limits the application of the prepared drug composites in disease treatment. Summary of the Invention
[0005] To address the poor biocompatibility of existing drug composite materials prepared from nanoparticle drug carriers, as well as the low drug loading and poor sustained-release effects resulting from current preparation methods, this invention provides a UiO-66-loaded tetracycline hydrochloride and its preparation method. In this invention, using a metal-organic framework material UiO-66 as a carrier in an aqueous solvent, tetracycline hydrochloride is loaded onto the pore walls of the UiO-66 metal-organic framework material via an impregnation method, relying on van der Waals forces and hydrogen bonds, thus obtaining a UiO-66-loaded tetracycline hydrochloride material.
[0006] To achieve the above objectives, the technical solution of the present invention is as follows.
[0007] The first objective of this invention is to provide a method for preparing a UiO-66-supported tetracycline hydrochloride material, comprising the following steps: Using metal-organic framework material UiO-66 as a carrier, the carrier was mixed with an aqueous solution of tetracycline hydrochloride and impregnated to load tetracycline hydrochloride into the pores of metal-organic framework material UiO-66, thus obtaining UiO-66-loaded tetracycline hydrochloride material.
[0008] The loading of tetracycline hydrochloride is 11.2 wt% to 20.9 wt% based on the mass of the metal-organic framework material UiO-66.
[0009] As a preferred embodiment, the metal-organic framework material UiO-66 has a pore size of 0.6 nm to 1.2 nm.
[0010] In a preferred embodiment, the mass ratio of UiO-66 to tetracycline hydrochloride is 1:1 / 3 to 1.
[0011] In a preferred embodiment, the aqueous solution of tetracycline hydrochloride is obtained by dissolving tetracycline hydrochloride in water; the concentration of the aqueous solution of tetracycline hydrochloride is 0.5 mg / mL to 1 mg / mL.
[0012] As a preferred embodiment, the metal-organic framework material UiO-66 is prepared by: adding benzoic acid to an organic solvent, using terephthalic acid and a zirconium source as raw materials, ultrasonically dissolving the mixture, and then hydrothermally reacting it at 115℃~125℃ for 12h~24h to obtain the UiO-66 material. The zirconium source is zirconium tetrachloride.
[0013] In a preferred embodiment, the mixing and impregnation is carried out by stirring after ultrasonic mixing; the ultrasonic power is 100W to 300W and the time is 2min to 10min.
[0014] In a preferred embodiment, the stirring speed is 600 rpm to 900 rpm and the time is 20 min to 360 min.
[0015] The second objective of this invention is to provide a UiO-66 tetracycline hydrochloride material prepared by the aforementioned method for preparing UiO-66 supported tetracycline hydrochloride material.
[0016] Compared with the prior art, the beneficial effects of the present invention are as follows: This invention employs a green and environmentally friendly water system and uses the metal-organic framework material UiO-66 as a carrier to load tetracycline hydrochloride onto UiO-66. The tetracycline hydrochloride material is formed by the interaction between UiO-66 and the pore walls through van der Waals forces or hydrogen bonds, thus avoiding organic solvent residue and solving the problem of poor biocompatibility in traditional preparation methods.
[0017] Metal-organic frameworks (UiO-66) possess a large specific surface area and exhibit excellent thermal stability, remaining stable in acidic and alkaline aqueous solutions. This invention utilizes a non-covalent bond between tetracycline hydrochloride and the UiO-66 framework. Through intermolecular interactions, tetracycline hydrochloride molecules are better embedded in the channels or framework of UiO-66, forming a UiO-66-loaded tetracycline hydrochloride material. UiO-66 exhibits excellent drug loading capacity and controlled release performance. Even after loading with tetracycline hydrochloride, the original framework stability is maintained, and there is no "burst release effect" in drug release. The structure remains stable, ensuring a high concentration of tetracycline hydrochloride in the lesion area.
[0018] Based on the synergistic effect of physical barriers and chemical bonds, UiO-66 achieves a sustained-release effect for tetracycline hydrochloride (TC). Physically, the nanoscale pore size (approximately 0.6 nm to 1.2 nm) of UiO-66 significantly sieving and spatially confining TC molecules of similar size (hydrated diameter approximately 1.3 nm to 1.5 nm), and the three-dimensional tortuous channels greatly extend the diffusion path and time of the molecules, forming the basis for sustained release. Chemically, TC is firmly bound to the framework through multiple hydrogen bonds and π-π stacking non-covalent interactions. The stepwise dissociation of these bonds is a dynamic process requiring energy input, thus becoming the core of regulating the release rate and achieving long-term stable release, and contributing to a typical sustained-release platform in the later stages of release. Attached Figure Description
[0019] Figure 1 Figure 1 shows the standard curve of tetracycline hydrochloride aqueous solution and the drug loading of UiO-66-loaded tetracycline hydrochloride material at different times in Example 1 of this invention. Specifically, Figure 1a is the standard curve of tetracycline hydrochloride aqueous solution; Figure 2b is the drug loading of UiO-66-loaded tetracycline hydrochloride material obtained in Example 1 at different times.
[0020] Figure 2 The results of the sustained-release experiment of tetracycline hydrochloride on the UiO-66-loaded tetracycline hydrochloride material obtained in Example 1 of this invention are shown. Figure a is the standard curve of tetracycline hydrochloride in PBS solution; Figure b is the release rate of tetracycline hydrochloride on the UiO-66-loaded tetracycline hydrochloride material obtained in Example 1.
[0021] Figure 3 The XRD comparison diagrams show the synthesized UiO-66 and UiO-66-supported tetracycline hydrochloride material (UiO-66@TC) in Example 1 of the present invention and the UiO-66&TC obtained in Comparative Example 1.
[0022] Figure 4The images show the infrared spectra of TC, UiO-66, UiO-66@TC from Example 1 of the present invention and UiO-66&TC obtained from Comparative Example 1. Specifically, Figure a is a comparison of the infrared spectra of TC, UiO-66, UiO-66@TC from Example 1 and UiO-66&TC obtained from Comparative Example 1; Figure b is the infrared spectrum of UiO-66@TC obtained from Example 1.
[0023] Figure 5 The thermogravimetric analysis comparison diagram of UiO-66-loaded tetracycline hydrochloride material (UiO-66@TC), TC, UiO-66 and its UiO-66-loaded tetracycline hydrochloride material (UiO-66@TC) during drug release (UiO-66@TC-rel) obtained in Example 1 of the present invention. Detailed Implementation
[0024] To enable those skilled in the art to better understand and implement the technical solutions of this invention, the invention is further described below with reference to specific embodiments. However, the embodiments are not intended to limit the invention. Unless otherwise specified, the following test methods and detection methods are conventional methods; unless otherwise specified, the reagents and raw materials are commercially available.
[0025] Existing nanoparticle drug carriers, such as liposomes, quantum dots, carbon dots, polymer nanoparticles, and micelles, often rely on organic solvents during preparation, resulting in poor biocompatibility of the drug composites. Furthermore, the binding mechanism between nanoparticle drug carriers and drugs is mostly surface adsorption, leading to low drug loading and poor sustained-release effects, which greatly limits the application of the prepared drug composites in disease treatment.
[0026] The technical solution of the present invention will be analyzed in detail below.
[0027] This invention provides a method for preparing a UiO-66-loaded tetracycline hydrochloride material. Using a metal-organic framework (MOF) UiO-66 as a carrier, the carrier is mixed with an aqueous solution of tetracycline hydrochloride and impregnated to load the tetracycline hydrochloride into the pores of the MOF UiO-66, thus obtaining the UiO-66-loaded tetracycline hydrochloride material. The loading amount of the tetracycline hydrochloride is 11.2 wt% to 20.9 wt% based on the mass of the MOF UiO-66.
[0028] In the above technical solution, this invention adopts a green and environmentally friendly water system and uses the metal-organic framework material UiO-66 as a carrier to load tetracycline hydrochloride onto UiO-66. Relying on van der Waals forces or hydrogen bonds and interactions with the pore walls, a UiO-66-loaded tetracycline hydrochloride material is formed, avoiding the problem of poor biocompatibility caused by residual organic solvents. In the preparation method of the UiO-66-loaded tetracycline hydrochloride material proposed in this invention, tetracycline hydrochloride (TC) can be efficiently adsorbed by UiO-66. The core lies in the series of synergistic non-covalent bonds between TC molecules and the porous framework of UiO-66: electrostatic interactions first pull the tetracycline hydrochloride molecules closer to the surface of the loading material, followed by π-π stacking, hydrogen bonding, coordination and acid-base interactions, and pore filling and physical adsorption, which firmly bind it within the pores.
[0029] Furthermore, UiO-66 possesses excellent drug loading capacity and controlled release performance. Even after loading tetracycline hydrochloride, it maintains the stability of its original framework, exhibiting no "burst release effect" and ensuring high concentrations of tetracycline hydrochloride at the lesion site. The sustained-release mechanism of UiO-66 for tetracycline hydrochloride (TC) is based on the synergistic effect of physical barriers and chemical bonds. Physically, its nanoscale pore size (approximately 0.6 nm to 1.2 nm) significantly sieving and spatially confining TC molecules of similar size (hydrated diameter approximately 1.3 nm to 1.5 nm), and the three-dimensional tortuous channels greatly extend the diffusion path and time of the molecules, forming the basis for sustained release. Chemically, TC is firmly bound to the framework through multiple hydrogen bonds and π-π stacking non-covalent interactions. The stepwise dissociation of these bonds is a dynamic process requiring energy input, thus becoming the core of regulating the release rate and achieving long-term stable release, and contributing to a typical sustained-release platform in the later stages of release.
[0030] The technical solution of the present invention will be further illustrated below through the following embodiments and comparative examples.
[0031] Determination of the standard curve for tetracycline hydrochloride aqueous solution: Preparation of S1, 1 mg / mL tetracycline hydrochloride standard solution: Weigh 2.5 g tetracycline hydrochloride, add 20 mL of purified water, and stir to dissolve. After complete dissolution, transfer to a 250 mL volumetric flask and dilute to volume.
[0032] S2, Determining the maximum absorption wavelength: Transfer 1 mL of 1 mg / mL tetracycline hydrochloride standard solution to a 25 mL volumetric flask, dilute to volume, shake thoroughly, and let stand for a period of time. Transfer 5 mL of the solution to a cuvette and perform a full-wavelength scan in the range of 200 nm to 900 nm, determining the maximum absorption wavelength to be 351 nm.
[0033] S3. Take 1 mg / mL of tetracycline hydrochloride and perform serial dilutions to obtain tetracycline hydrochloride aqueous solutions with concentrations of 0.040 mg / mL, 0.035 mg / mL, 0.030 mg / mL, 0.025 mg / mL, 0.020 mg / mL, and 0.015 mg / mL. Place the solutions of different concentrations into cuvettes sequentially and measure the absorbance at 351 nm to plot a standard curve.
[0034] Example 1 A method for preparing a UiO-66-supported tetracycline hydrochloride material includes the following steps: S1, weigh 0.0129 mol zirconium tetrachloride, 0.0129 mol terephthalic acid, and 0.2575 mol benzoic acid into a 300 mL beaker, add 2.2066 mol N,N-dimethylformamide (DMF) solvent, and ultrasonically vibrate for 10 min (after vibration, check if the solution is clear and transparent; if any solid is not completely dissolved, vibrate again). Transfer the solution to a polytetrafluoroethylene-lined container, place it in a sealed 500 mL hydrothermal reactor, and then place it in an electrically heated constant-temperature drying oven. Set the temperature to 120 °C within 4 hours, maintain a constant temperature of 120 °C for 24 hours, and then cool to room temperature. Remove the reactor, centrifuge the suspension, retain the solid, wash with DMF and ethanol, and vacuum dry at 120 °C to obtain the organometallic framework UiO-66.
[0035] S2, Weigh 0.3g of tetracycline hydrochloride into a 500mL beaker (based on the mass of the metal-organic framework material UiO-66, the loading of the tetracycline hydrochloride is 20.9wt%), add 300mL of purified water, and sonicate until the solution becomes clear to obtain a tetracycline hydrochloride aqueous solution; Transfer 50mL of the tetracycline hydrochloride aqueous solution to add 50mg of the metal-organic framework UiO-66, sonicate for 2min to make the system more homogeneous, and stir at 900rpm for 60min to obtain the UiO-66-loaded tetracycline hydrochloride material, denoted as UiO-66@TC.
[0036] Example 2 A method for preparing a UiO-66-supported tetracycline hydrochloride material includes the following steps: S1, weigh 0.0129 mol zirconium tetrachloride, 0.0129 mol terephthalic acid, and 0.2575 mol benzoic acid into a 300 mL beaker, add 2.2066 mol N,N-dimethylformamide (DMF) solvent, and ultrasonically vibrate for 10 min (after vibration, check if the solution is clear and transparent; if any solid is not completely dissolved, vibrate again). Transfer the solution to a polytetrafluoroethylene-lined container, place it in a sealed 500 mL hydrothermal reactor, and then place it in an electrically heated constant-temperature drying oven. Set the temperature to 120 °C within 4 hours, maintain a constant temperature of 120 °C for 24 hours, and then cool to room temperature. Remove the reactor, centrifuge the suspension, retain the solid, wash with DMF and ethanol, and vacuum dry at 120 °C to obtain the organometallic framework UiO-66.
[0037] S2, Weigh 0.3g of tetracycline hydrochloride (TC) into a 300mL beaker (based on the mass of the metal-organic framework material UiO-66, the loading of the tetracycline hydrochloride is 20.9wt%), add 300mL of purified water, and sonicate until the solution becomes clear to obtain a tetracycline hydrochloride aqueous solution; Transfer 50mL of the tetracycline hydrochloride aqueous solution to add 25mg of the metal-organic framework UiO-66, sonicate for 2min to make the system more homogeneous, and stir at 800rpm for 180min to obtain the UiO-66-loaded tetracycline hydrochloride material, denoted as UiO-66@TC.
[0038] Example 3 A method for preparing a UiO-66-supported tetracycline hydrochloride material includes the following steps: S1, weigh 0.0129 mol zirconium tetrachloride, 0.0129 mol terephthalic acid, and 0.2575 mol benzoic acid into a 300 mL beaker, add 2.2066 mol N,N-dimethylformamide (DMF) solvent, and ultrasonically vibrate for 10 min (after vibration, check if the solution is clear and transparent; if any solid is not completely dissolved, vibrate again). Transfer the solution to a polytetrafluoroethylene-lined container, place it in a sealed 500 mL hydrothermal reactor, and then place it in an electrically heated constant-temperature drying oven. Set the temperature to 120 °C within 4 hours, maintain a constant temperature of 120 °C for 24 hours, and then cool to room temperature. Remove the reactor, centrifuge the suspension, retain the solid, wash with DMF and ethanol, and vacuum dry at 120 °C to obtain the organometallic framework UiO-66.
[0039] S2, Weigh 0.3g of tetracycline hydrochloride (TC) into a 300mL beaker (based on the mass of the metal-organic framework material UiO-66, the loading of the tetracycline hydrochloride is 20.9wt%), add 300mL of purified water, and sonicate until the solution becomes clear to obtain a tetracycline hydrochloride aqueous solution; Transfer 50mL of the tetracycline hydrochloride aqueous solution to 100mg of the metal-organic framework UiO-66, sonicate for 2min to make the system more homogeneous, and stir at 700rpm for 120min to obtain the UiO-66-loaded tetracycline hydrochloride material, denoted as UiO-66@TC.
[0040] To further illustrate the effects of the present invention, comparative examples are also provided, as follows: Comparative Example 1 A method for preparing a UiO-66 physically mixed tetracycline hydrochloride composite material includes the following steps: Weigh 0.3 g of tetracycline hydrochloride (TC) into a 300 mL beaker, add 300 mL of purified water, and sonicate until the solution becomes clear to obtain a tetracycline hydrochloride aqueous solution. Transfer 50 mL of the tetracycline hydrochloride aqueous solution to 100 mg of organometallic framework UiO-66, sonicate for 2 min to make the system more homogeneous, and stir at 900 rpm for 5 min under magnetic conditions at room temperature to obtain a UiO-66 physical mixed tetracycline hydrochloride composite material, denoted as UiO-66&TC.
[0041] Drug loading performance test: Weigh 0.300 g of tetracycline hydrochloride and add it to a 300 mL beaker. Then, add 300 mL of purified water to the beaker using a pipette. Agitate the solution with an ultrasonic cleaner until it becomes clear, obtaining a tetracycline hydrochloride aqueous solution. Transfer 50 mL of the tetracycline hydrochloride aqueous solution to a beaker and add 50 mg of organometallic framework UiO-66. No UiO-66 was added to the blank control group. Agitate the solution with an ultrasonic cleaner for 2 minutes to ensure homogeneity. Then, stir the solution with a magnetic stirrer at 900 rpm for 2 hours. Every 20 minutes, transfer 1 mL of the solution to a 25 mL volumetric flask, dilute to volume with purified water, shake thoroughly, allow to stand, filter through a 0.45 μm filter membrane, collect the filtrate, and measure the absorbance at 351 nm. Record the data, calculate the tetracycline hydrochloride loading, and determine the optimal drug loading time.
[0042] Figure 1Figure 1 shows the standard curve of the tetracycline hydrochloride aqueous solution and the drug loading of the UiO-66-loaded tetracycline hydrochloride material at different times in Example 1 of this invention. Figure 1a shows the standard curve of the tetracycline hydrochloride aqueous solution, with the formula y = -0.01967 + 24x, exhibiting good linear regression. Figure 2b shows the drug loading of the UiO-66-loaded tetracycline hydrochloride material obtained in Example 1 at different times. It can be seen that when the stirring speed is 900 rpm and the ratio of UiO-66 to tetracycline hydrochloride is 1:1, from 0 min to 70 min, the drug loading increases with increasing stirring time, reaching a maximum of 20.9 wt% at 70 min. It then begins to decrease from 70 min to 120 min. From 120 min to 360 min, the drug loading continues to increase with increasing stirring time, reaching a maximum of 18.6 wt% at 180 min, and then begins to decrease to equilibrium.
[0043] Sustained-release performance test: Weigh 20 mg of the UiO-66-loaded tetracycline hydrochloride material obtained in the examples and comparative examples into a dialysis bag and perform sustained release in 100 mL of PBS (phosphate buffered saline). Stir at 100 rpm and take samples at 0 h, 0.5 h, 1 h, 3 h, 6 h, 8 h, 12 h, and 24 h. Take 2 mL of each sample in a cuvette, measure its absorbance, and record the data. Calculate the amount of tetracycline hydrochloride released.
[0044] Figure 2 The results of the sustained-release experiment of tetracycline hydrochloride on the UiO-66-loaded tetracycline hydrochloride material obtained in Example 1 of this invention are shown. Figure a is the standard curve of tetracycline hydrochloride PBS solution, with the standard curve being y = 0.01118 + 19.29143x, R... 2 =0.99979, indicating good linear regression. Figure b shows the release rate of tetracycline hydrochloride from the UiO-66-loaded tetracycline hydrochloride material obtained in Example 1. The release rate increases with time, reaching a maximum of 59.11% at 22 hours.
[0045] X-ray powder diffraction characterization: After vacuum drying, the UiO-66-loaded tetracycline hydrochloride material was ground into powder in an agate mortar, transferred to a beryllium plate, and laid flat for injection. The parameters were set on the computer: 2θ = 5°~50°, voltage 40kV, current 40mA. The XRD powder diffraction pattern of the UiO-66-loaded tetracycline hydrochloride material was obtained by scanning with an X-ray powder diffractometer (Bruck AXS, D8ADVANCE, Germany).
[0046] Figure 3The XRD patterns of the UiO-66 synthesized in Example 1, the UiO-66-supported tetracycline hydrochloride material UiO-66@TC, and the sustained-release process of UiO-66@TC obtained in Example 1 are compared with those of UiO-66@TC obtained in Comparative Example 1. The diffraction peaks of UiO-66@TC in the figure do not show the characteristic peaks of TC. Compared with the diffraction peaks of synthesized UiO-66, the peak intensity of the UiO-66 diffraction peaks is larger, which may be due to the loading of TC on UiO-66. UiO-66&TC is obtained by physically mixing UiO-66 and TC. The characteristic peaks of TC appear in the XRD pattern. Compared with the diffraction peaks of synthesized UiO-66, it shows the diffraction peaks of UiO-66, and there are some additional diffraction peaks. The peak intensity changes little, indicating that the loading process of UiO-66@TC is not a simple physical mixing, but rather TC is adsorbed into the pores of UiO-66. UiO-66@TC-rel is the slow-release process of UiO-66@TC obtained in Example 1. Its peak intensity is about the same as that of synthesized UiO-66, which shows that the slow-release process of UiO-66@TC does not affect the stability of its crystal structure.
[0047] Infrared spectral characterization: The KBr pellet method was used to vacuum dry the sample. Then, the sample was ground into powder with potassium bromide at a ratio of 1:200 using an agate mortar. The infrared spectrum was obtained at room temperature using a Tianjin Gangdong Technology FTIR-650S Fourier transform infrared spectrometer, with a wavenumber range of 4000. -1 ~400cm -1 .
[0048] Figure 4 The images show the infrared spectra of TC, UiO-66, UiO-66@TC from Example 1 of this invention, and UiO-66&TC from Comparative Example 1. Figure a is a comparison of the infrared spectra of TC, UiO-66, UiO-66@TC from Example 1, and UiO-66&TC from Comparative Example 1; Figure b is the infrared spectrum of UiO-66@TC from Example 1. Comparing UiO-66@TC and TC, it can be seen that at 2850 cm⁻¹... -1 ~3000cm -1 The absorption peak at 1600 cm⁻¹ is attributed to the stretching vibration of the C-H bond on the methyl group in TC. The presence of this peak in UiO-66@TC indicates successful TC loading by UiO-66. Furthermore, the infrared spectra of UiO-66 and UiO-66@TC are largely consistent, with the main characteristic peaks of UiO-66 remaining unchanged, indicating that the structure of UiO-66 did not undergo significant changes before and after drug loading, and its structure remained stable. The infrared spectrum after sustained release shows that the peak at 1600 cm⁻¹... -1 ~500cm -1The presence of large and broad peaks within the range indicates that the TC drug molecule structure in UiO-66@TC partially enters the Uio-66 pores (producing the infrared spectrum peaks of TC), generating strong interaction forces and further enhancing thermal stability, which is further reflected by thermogravimetric analysis.
[0049] Thermogravimetric analysis characterization: The thermal stability of UiO-66-loaded tetracycline hydrochloride material was characterized using a differential thermogravimetric analyzer (DTG-60H, Shimadzu Corporation, Japan). The thermal properties of the compound and the corresponding mass change as a function of temperature were obtained during the temperature control process. 3-5 mg of sample was weighed, and the gas environment was nitrogen. The experimental temperature was raised to 800 °C at a rate of 10 °C / min.
[0050] Figure 5 The thermogravimetric analysis comparison diagram shows the sustained release process of UiO-66@TC, TC, UiO-66 and its UiO-66-loaded tetracycline hydrochloride material (UiO-66@TC-rel) obtained in Example 1 of the present invention. The thermal stability of TC, UiO-66, and their composite material UiO-66@TC was compared in the range of 20℃ to 800℃. Approximately 17% of the mass loss of UiO-66@TC in the range of 20℃ to 88℃ was attributed to the evaporation of water or solvent adsorbed by the porous material. A sharp drop of 14.4% in UiO-66@TC from 88℃ to 466℃ corresponds to the decomposition of the organic components of TC. The further 20.2% loss in UiO-66@TC from 466℃ to 589℃ may be related to the collapse of the UiO-66 framework. The results indicate that UiO-66@TC retains 48.4% of its mass at high temperatures, exhibiting superior thermal stability. Furthermore, the slope at 466℃ is smaller compared to pure UiO-66, suggesting that the interaction between TC and UiO-66 slows down the decomposition process, demonstrating a synergistic effect. UiO-66@TC-rel exhibits the best thermal stability, possibly due to the increased interaction forces between the TC molecule and the Uio-66 pores. These forces collectively influence thermal stability, including coordination interactions (the interaction between the hydroxyl and amino groups on the drug molecule and the Zr metal ions on Uio-66). 4+ The interactions include coordination effects, hydrogen bonding (hydroxyl and amino groups on the drug molecule forming hydrogen bonds with the carboxyl oxygen group on Uio-66), π-π stacking (non-covalent stacking of the benzene ring of the drug molecule with the benzene ring of the organic ligand on Uio-66), and electrostatic interactions (interactions between the positive charge present in the pores of Uio-66 and the negative charge of the drug molecule).
[0051] Obviously, those skilled in the art can make various modifications and variations to this invention without departing from its spirit and scope. Therefore, if these modifications and variations fall within the scope of the claims of this invention and their equivalents, this invention also intends to include these modifications and variations.
Claims
1. A method of preparing a UiO-66 supported tetracycline hydrochloride material, characterized in that, Includes the following steps: Using metal-organic framework material UiO-66 as a carrier, the carrier was mixed with an aqueous solution of tetracycline hydrochloride and impregnated to load tetracycline hydrochloride into the pores of metal-organic framework material UiO-66, thus obtaining UiO-66 loaded with tetracycline hydrochloride material. The loading of tetracycline hydrochloride is 11.2 wt% to 20.9 wt% based on the mass of the metal-organic framework material UiO-66.
2. The method of preparing UiO-66 supported tetracycline hydrochloride composite according to claim 1, characterized in that, The metal-organic framework material UiO-66 has a pore size of 0.6 nm to 1.2 nm.
3. The method for preparing the UiO-66-supported tetracycline hydrochloride material according to claim 1, characterized in that, The mass ratio of UiO-66 to tetracycline hydrochloride is 1:1 / 3 to 1.
4. The method for preparing the UiO-66-supported tetracycline hydrochloride composite material according to claim 1, characterized in that, The aqueous solution of tetracycline hydrochloride is obtained by dissolving tetracycline hydrochloride in water; the concentration of the aqueous solution of tetracycline hydrochloride is 0.5 mg / mL to 1 mg / mL.
5. The preparation method of the UiO-66-supported tetracycline hydrochloride composite material according to claim 1, characterized in that, The preparation method of the metal-organic framework material UiO-66 is as follows: In an organic solvent, terephthalic acid and a zirconium source are added, benzoic acid is added and ultrasonically dissolved, followed by a hydrothermal reaction at 115℃~125℃ for 12h~24h to obtain the UiO-66 material. The zirconium source is zirconium tetrachloride.
6. The method for preparing the UiO-66-supported tetracycline hydrochloride material according to claim 1, characterized in that, The mixing and impregnation process involves ultrasonic mixing followed by stirring; the ultrasonic power is 100W to 300W, and the time is 2min to 10min.
7. The method for preparing the UiO-66 supported tetracycline hydrochloride material according to claim 6, characterized in that, The stirring reaction is carried out at a speed of 600 rpm to 900 rpm for a time of 20 min to 360 min.
8. A UiO-66-supported tetracycline hydrochloride material, characterized in that, It was prepared using the preparation method of UiO-66 loaded with tetracycline hydrochloride as described in any one of claims 1 to 7.