ASIV-MOFs nano-enzyme medicine for eye direct current as well as preparation method and application of ASIV-MOFs nano-enzyme medicine
By preparing ASⅣ-MOFs nanoenzymes with positive potential and using direct current delivery technology, the problem of low bioavailability of ASⅣ in the eyes was solved, and the efficient targeted drug delivery and treatment effect of ASⅣ in the eyes was achieved.
Patent Information
- Application Number
- CN202510593563.4
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2025-05-09
- Publication Date
- 2025-08-01
AI Technical Summary
In the prior art, AS IV has low bioavailability in the eyes and is difficult to effectively pass through the blood eye barrier, resulting in insufficient drug concentration when treating posterior ocular diseases such as macular degeneration and retinopathy.
ASⅣ is modified by the porous coordination polymer CeO2-MOFs nanoenzyme composed of cerium metal cluster nodes and organic ligands, and ASⅣ-MOFs nanoenzymes with positive potential are prepared, and delivered to the target organ of the ocular target through direct current, and targeted drug delivery is achieved using direct current ion introduction technology.
It improves the permeability and retention time of ASⅣ in the eyes, increases the bioavailability of drugs in the eyes, reduces the side effects of other drug delivery routes and drug waste, and achieves precise guidance and efficient treatment.
Smart Images
Figure CN120392792A_ABST
Abstract
Description
Technical Field
[0001] The present invention relates to the field of biomedical technologies, and particularly to an ASⅣ-MOFs nanozyme drug for direct current in the eye, a preparation method and an application thereof. Background Art
[0002] Astragaloside Ⅳ (AS-Ⅳ) is the main active ingredient extracted from the traditional Chinese medicine Astragalus membranaceus, belonging to triterpenoid saponin compounds, and has various pharmacological effects such as anti-inflammatory, antioxidant, anti-apoptotic, immunomodulatory and vascular protection. In recent years, its research in the treatment of eye diseases has gradually increased, and it has shown potential application value especially in the fields of dry eye, glaucoma, diabetic retinopathy, age-related macular degeneration and cataract.
[0003] Metal-organic frameworks (MOFs) nanozymes are novel hybrid materials assembled by metal ions and organic ligands through coordination bonds, and have characteristics such as a clear and distinct structure, a high specific surface area and pore size, high loadability, dispersibility and biocompatibility. MOFs nanozymes have been widely used in drug delivery, immunoradiotherapy, photodynamic therapy, and moreover, the internal surface chemistry properties thereof can be adjusted and are easy to modify. The optimized nanozymes have excellent superoxide dismutase activity, can achieve antioxidant effects by regulating the P38 protein kinase, reduce oxidative stress, and achieve therapeutic effects. Hemolysis experiments and cytotoxicity experiments suggest that MOFs have good biocompatibility and low toxicity. In addition, the accumulation toxicity of MOFs can be reduced or eliminated by changing the structural units and preparation conditions of MOFs. Therefore, MOFs nanozymes can play a synergistic role with ASⅣ to reduce inflammatory reactions and oxidative stress to treat eye-related diseases.
[0004] Direct current iontophoresis technology is a biophysical method that uses a direct current to introduce drug ions into the skin or mucosa via electrodes, so as to enter local tissues or the blood circulation, and is a transdermal drug delivery technology with broad application prospects. This technology applies a low-intensity current to the skin through an iontophoresis device to push drug molecules into the skin, which helps the transdermal delivery of drug molecules. Currently, this treatment method usually uses neutral drug molecules for local introduction, and the research on directly introducing charged traditional Chinese medicine MOFs nanozymes into eye tissues through direct current is still blank. If ASⅣ is encapsulated in MOFs to construct a charged ASⅣ-MOFs nanozyme and delivered to the eye target organ through direct current to construct a novel eye drug delivery system, it will greatly improve the permeability of ASⅣ in the eye, increase its residence time in the eye, and effectively improve the bioavailability of the drug in the eye through the synergistic effect of the drug delivery carrier.
[0005] The blood-eye barrier is a physiological barrier unique to eye tissues, mainly divided into the blood-aqueous barrier and the blood-retinal barrier. Its core function is to restrict the free entry of substances in the blood into the eye, thereby protecting the stability of the intraocular microenvironment. However, this barrier also significantly affects the intraocular absorption of drugs. The physicochemical properties of drugs, such as molecular weight, liposolubility, charge state, etc., will all affect their ability to pass through the blood-eye barrier. Especially when treating posterior segment eye diseases such as macular degeneration and retinopathy, it is necessary to select a targeted drug delivery strategy. For example, systemic administration (oral or intravenous injection) usually has difficulty achieving an effective intraocular concentration because the drug needs to cross the blood-eye barrier, while local administration (such as eye drops) may be effective in the anterior segment but has limited effect on posterior segment diseases.
[0006] Therefore, there is provided an ASⅣ-MOFs nanozyme drug for ocular direct current, a preparation method and an application thereof. Summary of the Invention
[0007] The purpose of the present invention is to provide an ASⅣ-MOFs nanozyme drug for ocular direct current, a preparation method and an application thereof to overcome the existing defects, and solve the problem of low bioavailability of ASⅣ in the eye.
[0008] The technical solution to achieve the above purpose is:
[0009] An ASⅣ-MOFs nanozyme drug for ocular direct current according to one of the present inventions, wherein the ASⅣ-MOFs nanozyme is a porous coordination polymer CeO2-MOFs nanozyme composed of cerium metal cluster nodes and organic ligands connected regularly and modified with ASⅣ.
[0010] Preferably, the Zeta potential of the ASⅣ-MOFs nanozyme solution is +12.4 mV.
[0011] A preparation method of an ASⅣ-MOFs nanozyme drug for ocular direct current according to a second aspect of the present invention includes:
[0012] Step S1, at room temperature, weigh Ce(NO3)3·6H2O and place it in a NaOH solution, and stir at room temperature to make the solution mix evenly;
[0013] Step S2, transfer the mixed solution into a high-pressure reaction kettle, seal the kettle, react at 180 °C for 24 h, take out the reaction kettle after it cools down, and centrifuge at 9000 rpm for 15 min at room temperature to obtain the precipitate;
[0014] Step S3, wash the precipitate alternately with deionized water and absolute ethanol 3 times, then dry and calcine it to finally obtain CeO2-MOFs nanozyme powder;
[0015] Step S4: At room temperature, weigh ASⅣ and CeO2-MOFs nanozyme powder, add absolute ethanol, stir magnetically at 500 rpm at room temperature, and stir and react for 24 h;
[0016] Step S5: Centrifuge the solution obtained in Step S4 at 9000 rpm for 15 min at room temperature, take the precipitate, and wash it alternately with deionized water and absolute ethanol three times;
[0017] Step S6: Dry the washed solution and disperse it in deionized water to form a suspension, and then obtain the ASⅣ-MOFs nanozyme solution.
[0018] Preferably, in Step S1, the mass of Ce(NO3)3·6H2O is 0.977 g, and the NaOH solution is a strong alkaline solution with a concentration of 0.1 M, a volume of 45 ml, and a pH of 13.
[0019] Preferably, in Step S3, drying and calcination are carried out by drying in an oven at 80 °C and calcining in a muffle furnace at 400 °C for 4 h.
[0020] Preferably, in Step S4, the mass ratio of ASⅣ to CeO2-MOFs nanozyme is 1:9; the volume of the absolute ethanol solution is 20 ml.
[0021] Preferably, in Step S6, targeted drug delivery is completed with the ASⅣ-MOFs nanozyme solution, and the process is as follows:
[0022] Place two special dressings soaked with the ASⅣ-MOFs nanozyme solution on the upper eyelids of both eyes respectively;
[0023] Cover the direct current introduction electrode eye mask on the dressing, and place the auxiliary electrode on the gauze soaked with physiological saline on the occipital part;
[0024] Turn on the power supply, with a voltage of 0.5 - 2.0 V, a current intensity of 1 - 2 mA, and an introduction time of 20 min, and targeted drug delivery can be completed.
[0025] Application of an ASⅣ-MOFs nanozyme drug for eye direct current in the treatment of eye diseases according to the third aspect of the present invention.
[0026] Preferably, the ASⅣ-MOFs nanozyme is used as a drug reservoir required for direct current targeted introduction for transdermal drug delivery to the eyes.
[0027] The beneficial effects of the present invention are:
[0028] The present invention first prepares ASⅣ-MOFs nanozymes through a simple hydrothermal synthesis method. The ASⅣ-MOFs nanozymes prepared by modifying ASⅣ with CeO2-MOFs nanozymes have advantages such as high electric field responsiveness, synergistic therapeutic effects, high stability, and long-lasting effects. This method is simple to operate, green and safe, and low in cost, which is conducive to large-scale application and the promotion of clinical transformation;
[0029] The CeO2-MOFs nanozymes prepared in the present invention are porous coordination polymers composed of cerium metal cluster nodes and organic ligands connected regularly. They have characteristics such as small particle size, positive potential, high specific surface area and pore size, high loading capacity, dispersibility, and biocompatibility. Moreover, through their excellent superoxide dismutase activity, they can scavenge reactive oxygen species, reduce oxidative stress, and achieve therapeutic effects, making them excellent nano-carriers for ASⅣ;
[0030] The present invention innovatively delivers charged-polarity ASⅣ-MOFs nanozymes to the ocular target organ through direct current, which has the characteristics of "precision guidance and targeted drug delivery". Using this drug delivery system not only increases the local drug bioavailability in the target organ but also reduces the multi-site side effects and drug waste caused by other drug delivery routes. Description of the Drawings
[0031] Figure 1 is a flow chart of the preparation method of the ASⅣ-MOFs nanozyme drug for ocular direct current in the present invention;
[0032] Figure 2 is a representative transmission electron microscope image of CeO2-MOFs nanozymes in the examples of the present invention;
[0033] Figure 3 is the X-ray diffraction pattern characterization of MOFs nanozymes in the examples of the present invention;
[0034] Figure 4 is a representative scanning electron microscope image of CeO2-MOFs nanozymes in the examples of the present invention;
[0035] Figure 5 is a representative scanning electron microscope image of ASⅣ-MOFs nanozymes in the examples of the present invention;
[0036] Figure 6 is a histogram of the particle size of CeO2-MOFs nanozymes in the examples of the present invention;
[0037] Figure 7 is a histogram of the particle size of ASⅣ-MOFs nanozymes in the examples of the present invention;
[0038] Figure 8 is the Zeta potential diagram of MOFs nanozymes in double-distilled water in the examples of the present invention;
[0039] Figure 9 It is the result diagram of the in vitro hydroxyl radical scavenging experiment of MOFs nanozyme in the embodiments of the present invention;
[0040] Figure 10 It is the result diagram of the cell survival rate of human corneal epithelial cells treated with dimethyl sulfoxide (DMSO), ASⅣ, CeO2-MOFs nanozyme, and ASⅣ-MOFs nanozyme for 24 h evaluated by using a CCK-8 kit in the embodiments of the present invention;
[0041] Figure 11 It is a representative transmission electron microscope diagram of the targeted drug delivery of ASⅣ-MOFs nanozyme through direct current iontophoresis through the rabbit eyelid skin into the conjunctival tissue in the embodiments of the present invention. Detailed implementation manners
[0042] Next, the technical solutions of the present invention will be clearly and completely described in conjunction with the accompanying drawings. In the description of the present invention, it should be noted that the orientation or positional relationship indicated by the terms "center", "upper", "lower", "left", "right", "vertical", "horizontal", "inner", "outer", etc. is based on the orientation or positional relationship shown in the accompanying drawings. It is only for the convenience of describing the present invention and simplifying the description, rather than indicating or implying that the device or element referred to must have a specific orientation, be constructed and operated in a specific orientation, and therefore should not be construed as a limitation to the present invention. In addition, the terms "first", "second", and "third" are only used for descriptive purposes and cannot be construed as indicating or implying relative importance.
[0043] Next, the present invention will be further described in conjunction with the accompanying drawings.
[0044] An ASⅣ-MOFs nanozyme drug for eye direct current, wherein the ASⅣ-MOFs nanozyme is a porous coordination polymer CeO2-MOFs nanozyme composed of cerium metal cluster nodes and organic ligands regularly connected and modified with ASⅣ.
[0045] In the embodiment, the Zeta potential of the ASⅣ-MOFs nanozyme solution is +12.4 mV.
[0046] As Figure 1 shown, a preparation method of an ASⅣ-MOFs nanozyme drug for eye direct current includes:
[0047] Step S1, at room temperature, weigh Ce(NO3)3·6H2O and place it in a NaOH solution, and stir at room temperature to make the solution mix evenly.
[0048] In the embodiment, the mass of Ce(NO3)3·6H2O is 0.977 g, and the NaOH solution is a strong alkaline solution with a concentration of 0.1 M, a volume of 45 ml, and a pH of 13.
[0049] Step S2: Transfer the mixed solution into a high-pressure reactor, seal the reactor, react at 180 °C for 24 h, take out the reactor after it cools down, and centrifuge at 9000 rpm for 15 min at room temperature to obtain the precipitate.
[0050] Step S3: Wash the precipitate alternately with deionized water and absolute ethanol three times, then dry and calcine it to finally obtain CeO2-MOFs nanozyme powder.
[0051] In the example, drying and calcination are carried out by drying in an oven at 80 °C and calcining in a muffle furnace at 400 °C for 4 h.
[0052] Step S4: At room temperature, weigh ASⅣ and CeO2-MOFs nanozyme powder, add absolute ethanol, and stir magnetically at 500 rpm at room temperature for 24 h.
[0053] In the example, the mass ratio of ASⅣ to CeO2-MOFs nanozyme is 1:9; the volume of the absolute ethanol solution is 20 ml.
[0054] Step S5: Centrifuge the solution obtained in Step S4 at 9000 rpm for 15 min at room temperature, and wash the precipitate alternately with deionized water and absolute ethanol three times.
[0055] Step S6: Dry the washed solution and disperse it in deionized water to form a suspension, and then obtain the ASⅣ-MOFs nanozyme solution, dry and calcine it to finally obtain the ASⅣ-MOFs nanozyme.
[0056] In the example, targeted drug delivery is completed through the ASⅣ-MOFs nanozyme solution, and the process is as follows:
[0057] Place two special dressings soaked with the ASⅣ-MOFs nanozyme solution on the upper eyelids of both eyes respectively;
[0058] Cover the imported electrode eye mask of direct current on the dressing, and place the auxiliary electrode on the gauze soaked with physiological saline on the occipital part;
[0059] Turn on the power supply, with a voltage of 0.5 - 2.0 V, a current intensity of 1 - 2 mA, and an import time of 20 min, and targeted drug delivery can be completed.
[0060] Application of an ASⅣ-MOFs nanozyme drug for direct current in the eyes in the treatment of eye diseases; The ASⅣ-MOFs nanozyme is used as a drug reservoir required for direct current targeted import for transdermal drug delivery in the eyes.
[0061] Preparation method and performance characterization of the ASⅣ-MOFs nanozyme direct current targeted drug delivery system in Example 1
[0062] At room temperature, 0.977 g of Ce(NO3)3·6H2O was accurately weighed and placed in 45 ml of NaOH (0.1 M, pH 13) solution. The solution was stirred at room temperature to mix evenly.
[0063] The obtained solution was transferred into a high-pressure reactor, and the reactor was sealed. The reaction was carried out at 180 °C for 24 h. After the reactor cooled down, it was taken out. The precipitate was collected by centrifugation at 9000 rpm for 15 min at room temperature.
[0064] The obtained precipitate was washed alternately with deionized water and absolute ethanol three times, then dried in an oven at 80 °C and calcined in a muffle furnace at 400 °C for 4 h to finally obtain CeO2-MOFs nanozyme powder.
[0065] At room temperature, 5 mg of ASⅣ and 45 mg of CeO2-MOFs nanozyme were accurately weighed and added to 20 ml of absolute ethanol. The mixture was stirred at 500 rpm with a magnetic stirrer for 24 h.
[0066] The obtained solution was centrifuged at 9000 rpm for 15 min at room temperature. The precipitate was washed alternately with deionized water and absolute ethanol three times.
[0067] The washed solution was dried in an oven at 80 °C and then dispersed in deionized water to form a suspension, thus obtaining the ASⅣ-MOFs nanozyme solution.
[0068] Two special dressings sized 2×3 cm soaked with ASⅣ-MOFs nanozyme solution were respectively placed on the upper eyelids of both eyes. Then, a direct current introduction electrode (anode) eye mask was covered on the dressings, and an auxiliary electrode (cathode) with a gauze soaked in normal saline was placed on the occipital part. The power was turned on, with a voltage of 0.5 - 2.0 V, a current intensity of 1 - 2 mA, and an introduction time of 20 min, and targeted drug delivery could be completed.
[0069] The electron microscope characterization of the ASⅣ-MOFs nanozyme prepared in this example for the eye is as Figure 2 - 7 shown. The Zeta potential of the MOFs nanozyme in double-distilled water is as Figure 8 shown. The results of the in vitro hydroxyl radical scavenging experiment of the MOFs nanozyme are as Figure 9 shown. The results of the cell viability of human corneal epithelial cells treated with DMSO, ASIV, CeO2-MOFs nanozyme, and ASⅣ-MOFs nanozyme for 24 h evaluated using a CCK-8 kit are as Figure 10 shown.
[0070] In Example 2, the charged-polarity ASⅣ-MOFs nanozyme was delivered to the eye target organ by direct current to verify the ASIV penetration and biological performance effects. The specific process is as follows:
[0071] In vitro hydroxyl radical scavenging experiment of MOF nanozymes, prepare relevant reagents: phosphate buffer solution (PBS, 0.01 M, pH 7.4), salicylic acid solution: 1 mM (dissolved in PBS), FeSO4 solution: 1 mM (dissolved in PBS), H2O2 solution: 1 mM (dissolved in PBS). Prepare ASIV, CeO2-MOF nanozyme, and ASIV-MOF nanozyme solutions with different concentrations.
[0072] Establish a reaction system: Add the following reagents to a test tube in sequence: 0.5 mL of FeSO4 solution, 0.5 mL of H2O2 solution, 0.5 mL of the sample to be tested (ASIV, CeO2-MOF nanozyme, ASIV-MOF nanozyme solution), 0.5 mL of salicylic acid solution, and 1 mL of PBS (pH 7.4). After mixing, react in a water bath at 37 °C for 30 minutes, and measure the absorbance. Seed human corneal epithelial cells (HECEs) into a 96-well plate, incubate with DMSO, ASIV, CeO2-MOF nanozyme, and ASIV-MOF nanozyme solutions in an incubator for 24 h, measure the absorbance, and calculate the cell viability.
[0073] Select 30 healthy New Zealand rabbits of ordinary grade, with a body weight of 1.5 kg - 2.5 kg, and divide them into a blank group (CON group), an ASIV-MOF nanozyme eye drop group (ASIV-M group), and an ASIV-MOF nanozyme direct current group (ASIV-M-E group). The CON group is fed normally without any intervention; the ASIV-M group is instilled with eye drops at an equivalent dose (10 μM), 4 times a day for 5 consecutive days; the ASIV-M-E group is given direct current iontophoresis of the same concentration solution as the ASIV-M group.
[0074] Adopt the eye-occipital iontophoresis method. First, place two special dressings sized 2×3 cm soaked in astragaloside IV aqueous solution on the eyes of the rabbits respectively; then cover the direct current introduction electrode (anode) eye mask on the dressing, and place the auxiliary electrode (cathode) on the gauze soaked in physiological saline on the occipital part of the rabbit; turn on the power supply, with a voltage of 0.5 - 2.0 V and a current intensity of 1 - 2 mA, and the introduction time each time is 20 min, 2 times a day for 5 consecutive days.
[0075] Collect specimens from all rabbits 2 h after the last administration for ASIV penetration and biological performance detection.
[0076] Experimental results
[0077] Figure 2 The transmission electron microscope images confirm that the CeO2-MOF nanozyme prepared in Example 1 is a porous coordination polymer composed of small-sized cerium metal cluster nodes and organic ligands connected regularly.
[0078] Figure 3The X-ray diffraction pattern (FTIR-infrared spectrum) characterization of the MOFs nanozyme confirmed that the ASⅣ-MOFs nanozyme prepared in Example 1 had stretching vibration peaks of OH, C-H, C=O, and Ce-O at 3396 cm-1, 2939 cm-1, 1650 cm-1, and 1046 cm-1 respectively, proving successful drug loading.
[0079] Figure 4 , Figure 5 Representative scanning electron micrographs of the CeO2-MOFs nanozyme and ASIV-MOFs nanozyme and Figure 6 , Figure 7 The histogram of the particle size of the MOFs nanozyme confirmed that the average particle size of the CeO2-MOFs nanozyme was 100 nm; and the particle size of the ASIV-MOFs nanozyme prepared in Example 1 increased, with an average particle size of 124 nm.
[0080] Figure 8 The Zeta potential diagram of the MOFs nanozyme in double-distilled water showed that the CeO2-MOFs nanozyme was positively charged with a potential of 12.4 mV. This indicated that there was an electron transfer phenomenon in the ASⅣ-MOFs nanozyme system, enhancing the response ability of ions under the action of the electric field force.
[0081] Figure 9 The results of the in vitro hydroxyl radical scavenging experiment of the MOFs nanozyme showed that ASⅣ, CeO2-MOFs nanozyme, and ASⅣ-MOFs nanozyme solutions all had antioxidant effects at different concentrations, and among them, the ASⅣ-MOFs nanozyme had the best antioxidant effect.
[0082] Figure 10 The results of the HECEs cell survival rate showed that in human corneal epithelial cells, the four groups of DMSO, ASⅣ, CeO2-MOFs nanozyme, and ASⅣ-MOFs nanozyme all had good cell activity, and the results were not significantly different.
[0083] Figure 11 The representative transmission electron micrograph of the ASⅣ-MOFs nanozyme after targeted drug delivery into the conjunctival tissue through direct current iontophoresis through the rabbit eyelid skin confirmed that the charged ASⅣ-MOFs nanozyme was delivered to the ocular target organ through direct current, with the characteristics of "precision guidance and targeted drug delivery".
[0084] In summary, the present invention provides an ASⅣ-MOFs nanozyme drug for ophthalmic direct current, a preparation method and an application. The first prepared CeO2-MOFs nanozyme is a porous coordination polymer composed of cerium metal cluster nodes and organic ligands connected regularly. It has characteristics such as small particle size, positive potential, high specific surface area and pore size, high loading capacity, dispersibility and biocompatibility. Moreover, through its excellent superoxide dismutase activity, it can scavenge reactive oxygen species, reduce oxidative stress, and achieve a therapeutic effect, making it an excellent nano-carrier for ASⅣ. Secondly, CeO2-MOFs nanozyme is modified with ASⅣ by a simple hydrothermal synthesis method to prepare ASⅣ-MOFs nanozyme, which has advantages such as high electric field responsiveness, synergistic therapeutic effect, high stability and long-term effect. This method is simple to operate, green, safe and low-cost, which is conducive to large-scale application and promoting clinical transformation. Finally, the present invention pioneered the delivery of charged-polarity ASⅣ-MOFs nanozyme to the ocular target organ through direct current, with the characteristics of "precision guidance and targeted drug delivery". Using the drug not only increases the local drug bioavailability of the target organ, but also reduces the multi-site side effects and drug waste brought by other drug delivery routes. The research results will surely provide assistance for the development of innovative drug delivery methods for ophthalmic diseases.
[0085] The above embodiments are only used to illustrate the technical solutions of the present invention, rather than to limit them; although the present invention has been described in detail with reference to the foregoing embodiments, those of ordinary skill in the art should understand that: they can still modify the technical solutions recorded in the foregoing embodiments, or perform equivalent replacements on some or all of the technical features; and these modifications or replacements do not make the essence of the corresponding technical solutions deviate from the scope of the technical solutions of the embodiments of the present invention.
Claims
1. An ASⅣ-MOFs nanozyme drug for direct current in the eye, characterized in that, The ASⅣ-MOFs nanozyme is CeO2-MOFs nanozyme modified ASⅣ, a porous coordination polymer composed of cerium metal cluster nodes and organic ligands connected regularly.
2. The ASⅣ-MOFs nanozyme drug for direct current of eyes according to claim 1, wherein The Zeta potential of the ASⅣ-MOFs nanozyme solution is +12.4 mV.
3. Preparation method of ASⅣ-MOFs nanozyme drug for direct current of eyes, characterized in that, Including: Step S1, at room temperature, weigh Ce(NO3)3·6H2O and place it in the NaOH solution, stir at room temperature to mix the solution evenly; Step S2, transfer the mixed solution into a high-pressure reaction kettle, seal the kettle, react at 180 °C for 24 h, take out the reaction kettle after it cools down, centrifuge at 9000 rpm for 15 min at room temperature to obtain the precipitate; Step S3, wash the precipitate alternately with deionized water and absolute ethanol 3 times, then dry and calcine it to finally obtain CeO2-MOFs nanozyme powder; Step S4, at room temperature, weigh ASⅣ and CeO2-MOFs nanozyme powder, add absolute ethanol, stir magnetically at 500 rpm at room temperature, and stir and react for 24 h; Step S5, centrifuge the solution obtained in Step S4 at 9000 rpm for 15 min at room temperature, take the precipitate and wash it alternately with deionized water and absolute ethanol 3 times; Step S6, dry the washed solution and disperse it in deionized water to form a suspension, and then obtain the ASⅣ-MOFs nanozyme solution.
4. The preparation method of an ASⅣ-MOFs nanozyme drug for eye direct current according to claim 3, characterized in that, In Step S1, the mass of Ce(NO3)3·6H2O is 0.977 g, and the NaOH solution is a strong alkaline solution with a concentration of 0.1 M, a volume of 45 ml, and a pH of 13.
5. The preparation method of an ASⅣ-MOFs nanozyme drug for ocular direct current according to claim 3, characterized in that, In Step S3, drying and calcining are carried out by drying in an 80 °C oven and calcining in a muffle furnace at 400 °C for 4 h.
6. The preparation method of an ASⅣ-MOFs nanozyme drug for direct current of eyes according to claim 3, characterized in that, In Step S4, the mass ratio of ASⅣ to CeO2-MOFs nanozyme is 1:9; The volume of the absolute ethanol solution is 20 ml.
7. The preparation method of an ASⅣ-MOFs nanozyme drug for ocular direct current according to claim 3, characterized in that In Step S6, targeted drug delivery is completed with the ASⅣ-MOFs nanozyme solution, and the process is as follows: Place two special dressings soaked with the ASⅣ-MOFs nanozyme solution on the upper eyelids of both eyes respectively; Cover the conductive electrode eye mask of direct current on the dressing, and place the auxiliary electrode on the gauze soaked with physiological saline on the occipital part; Turn on the power supply, with a voltage of 0.5 - 2.0 V, a current intensity of 1 - 2 mA, and an introduction time of 20 min, and targeted drug delivery can be completed.
8. Application of an ASⅣ-MOFs nanozyme drug for direct current in the eyes in the treatment of eye diseases.
9. Use of an ASⅣ-MOFs nanozyme drug for direct current of eyes according to claim 8 in the treatment of eye diseases, characterized in that, The ASⅣ-MOFs nanozyme is used as a drug reservoir required for transdermal delivery of direct current for transdermal drug delivery to the eyes.