Curcumin microneedle patch and preparation method and application thereof

Abstract

The application discloses a curcumin microneedle patch and a preparation method and application thereof, and belongs to the technical field of medical materials, and the preparation method comprises the following steps: adding ammonia water, tetraethyl orthosilicate and magnesium nitrate into a cetyltrimethylammonium solution in sequence, stirring and reacting, collecting and calcining a precipitate, and preparing mesoporous magnesium ion silicon dioxide; placing the mesoporous magnesium ion silicon dioxide in a curcumin solution, stirring and reacting, and preparing mesoporous magnesium ion silicon dioxide nanoparticles loaded with curcumin; adding a photoinitiator and the mesoporous magnesium ion silicon dioxide nanoparticles into a methylacrylated gelatin solution, and preparing a needle tip stock solution; injecting the needle tip stock solution into a mold with a microneedle structure, performing photostyling, injecting a PVA solution into the mold, and air-drying to obtain the microneedle patch. The microneedle patch has solubility, can deliver drugs to a dermis layer to play a therapeutic role, has the advantages of high transdermal efficiency, and has controllable release effect, and effectively solves the problems in the prior art.

Description

Technical Field

[0001] This invention belongs to the field of medical materials technology, specifically relating to a curcumin microneedle patch, its preparation method, and its application. Background Technology

[0002] Diabetic ulcers are difficult-to-heal wounds caused by a combination of factors, including peripheral neuropathy, local ischemia, and infection. Clinically, they manifest as local erosion, ulceration, and necrosis. The fact that these wounds do not heal for a long time is one of the main complications of diabetes.

[0003] Currently, the initial treatment of diabetic ulcers mainly relies on topical dressings. Traditional wound dressings include gauze and bandages, whose primary function is to absorb exudate and secretions from open wounds. Some drug-loaded dressings have low transdermal efficiency and are not very effective; they also tend to adhere to newly formed tissue, causing pain upon removal. Furthermore, gauze dressings require frequent changes to prevent infiltration into adjacent healthy tissue, which not only increases medication costs but also adds to patient discomfort and the difficulty of care.

[0004] Modern wound dressings include foams, hydrocolloids, and hydrogels. Modern wound dressings keep the wound moist, thus achieving moist wound healing. However, these dressings only remain on the wound surface and cannot solve the problem of low drug transdermal efficiency. Furthermore, these dressings tend to adhere to newly formed tissue, causing pain upon removal. Summary of the Invention

[0005] To address the aforementioned shortcomings in the prior art, this invention provides a curcumin microneedle patch, its preparation method, and its application. This microneedle patch is soluble and can deliver drugs to the dermis to exert therapeutic effects, exhibiting the advantage of high transdermal efficiency. Simultaneously, it has a controllable release effect, effectively solving the problems existing in the prior art.

[0006] To achieve the above objectives, the technical solution adopted by the present invention to solve its technical problem is as follows: A method for preparing curcumin microneedle patches includes the following steps: (1) Add ammonia, tetraethyl orthosilicate and magnesium nitrate sequentially to a hexadecyltrimethylammonium solution, stir to react, collect the precipitate and calcine to obtain magnesium ion silica; (2) Place magnesium ion silica in curcumin solution and stir to react to obtain curcumin-loaded magnesium ion silica nanoparticles. (3) Add a photoinitiator and magnesium ion silica nanoparticles to a methacrylamide gelatin solution to prepare a needle tip stock solution; (4) Inject the needle tip stock solution into the mold with microneedle structure to cover the hole of the needle tip. After removing the air bubbles, continue to inject the needle tip stock solution into the mold. After light curing, inject PVA solution into the mold and air dry to obtain the product.

[0007] Furthermore, in step (1), the ratio of hexadecyltrimethylammonium, ammonia, tetraethyl orthosilicate and magnesium nitrate is 0.45-0.55g:10-14ml:4.5-5ml:10-10.5g.

[0008] Furthermore, in step (1), the stirring reaction time is 20-30h; the calcination temperature is 600-700℃, and the calcination time is 2-4h.

[0009] Furthermore, in step (2), the solvent for the curcumin solution is anhydrous ethanol, and the concentration of the curcumin solution is 4-6 mg / ml; the stirring reaction time is 45-50 h.

[0010] Further, in step (3), the concentration of the methacrylamide gelatin solution is 90-110 mg / ml, the amount of photoinitiator in each milliliter of methacrylamide gelatin solution is 1.5-2.5 mg, and the amount of magnesium ion silica nanoparticles in each milliliter of methacrylamide gelatin solution is 2.5-3.5 mg.

[0011] Furthermore, the concentration of the PVA solution in step (4) is 18-22 W / V.

[0012] Furthermore, in step (4), the microneedles on the microneedle patch are 800 μm long, 340 μm in diameter, and the center-to-center distance between two adjacent microneedles is 500 μm.

[0013] A curcumin microneedle patch was prepared using the method described above.

[0014] The above-mentioned curcumin microneedle patch is used as a dressing for diabetic wounds.

[0015] The beneficial effects of this invention are as follows: The magnesium ion-modified silica of this invention has a mesoporous structure and is biodegradable. Curcumin is physically adsorbed or encapsulated within the mesopores of the magnesium ion-modified silica. When the microneedle comes into contact with the skin tissue fluid, the silica gradually degrades, and the structure is gradually destroyed. Curcumin is slowly released along with the carrier degradation, avoiding rapid leakage of free curcumin and improving the bioavailability of curcumin. In addition, magnesium ions are released during the degradation process, which work synergistically with curcumin to exert an antibacterial effect.

[0016] The microneedle tip of this invention is composed of GelMA (methacrylamide gelatin) hydrogel, whose three-dimensional network structure can further restrict the diffusion rate of curcumin. GelMA swells slowly in the physiological environment, allowing curcumin to be released gradually through diffusion. This synergizes with the degradation rate of the magnesium ion silica carrier to achieve a "dual controlled release" effect.

[0017] Curcumin can be delivered directly to the dermis via microneedle patches, avoiding the first-pass effect of the liver and improving its bioavailability. At the same time, the slow release prolongs the local action time, reduces rapid metabolic loss, and improves bioavailability. The microneedle patch in this invention exhibits a photothermal effect, enabling antibacterial activity and accelerating wound healing. Specifically, curcumin is a typical electron-conjugated compound with a β-diketone structure, readily undergoing enol tautomerism. Curcumin coordinates with magnesium ions via a bidentate chelate configuration to form a stable six-membered ring with strong fluorescence, serving as a natural photosensitizer and playing a crucial role in photothermal therapy (PTT). Attached Figure Description

[0018] Figure 1 Images of different microneedles; Figure 2 Microscopic structures of different microneedles; Figure 3 A is a statistical graph of microneedle stress-strain; B is an image of the microneedles after Rhodamine staining. Figure 4 This is a drug release curve. Figure 5 A shows images of different groups of microneedles clearing intracellular ROS; B is a quantitative statistical graph of ROS clearance capacity using flow cytometry. Figure 6 Photothermal effect diagrams of different microneedles; Figure 7 A shows the temperature curves of different microneedles; B shows the photothermal stability curve of SMC-MN; C shows the thermal imaging of SMC-MN in a living environment. Figure 8 The images show the antibacterial results of the microneedle patch. A is the LB-agar colony map of Staphylococcus aureus after different microneedle treatments; B is the quantitative survival rate of Staphylococcus aureus after different microneedle treatments. Detailed Implementation

[0019] To make the objectives, technical solutions, and advantages of this invention clearer, the invention will be further described in detail below with reference to embodiments. It should be understood that the specific embodiments described herein are only for explaining the invention and are not intended to limit the invention; that is, the described embodiments are merely some embodiments of the invention, and not all embodiments.

[0020] Therefore, the following detailed description of the embodiments of the present invention is not intended to limit the scope of the claimed invention, but merely to illustrate selected embodiments of the invention. All other embodiments obtained by those skilled in the art based on the embodiments of the present invention without inventive effort are within the scope of protection of the present invention.

[0021] It should be noted that relational terms such as "first" and "second" are used merely to distinguish one entity or operation from another, and do not necessarily require or imply any such actual relationship or order between these entities or operations. Furthermore, the terms "comprising," "including," or any other variations thereof are intended to cover non-exclusive inclusion, such that a process, method, article, or apparatus that comprises a list of elements includes not only those elements but also other elements not expressly listed, or elements inherent to such a process, method, article, or apparatus. Unless otherwise specified, an element defined by the phrase "comprising one..." does not exclude the presence of other identical elements in the process, method, article, or apparatus that includes that element.

[0022] The features and performance of the present invention will be further described in detail below with reference to the embodiments and accompanying drawings. Example 1

[0023] A curcumin microneedle patch, the preparation method of which includes the following steps: (1) Dissolve 0.51 g cetyltrimethylammonium (CTAB) in 300 mL dd water, add 12 mL ammonia water, heat to 80 °C and stir for 30 min until clear, then add 4.8 mL tetraethyl orthosilicate (TEOS), continue stirring for 30 min, then add 10.25 g magnesium nitrate and stir for 25 hours; after centrifugation, wash the precipitate three times with anhydrous ethanol and water respectively, and calcine at 650 °C for 3 h to obtain biodegradable magnesium ion silica nanoparticles (SM); (2) Dissolve 50 mg of curcumin in 50 mL of anhydrous ethanol, sonicate to dissolve, add the prepared magnesium ion silica nanoparticles, stir at room temperature for 50 h to obtain silica nanoparticles (SMC) loaded with curcumin. (3) Dissolve 10g of gelatin in 100 mL of PBS solution at 45℃, then slowly add 3 mL of methacrylic anhydride to the reaction solution, and continue to stir vigorously at 45℃ for 2 h. Dialyze the product in pure water at 40℃ for 7 days to remove unreacted impurities and byproducts, and obtain methacrylamide gelatin (GelMA). (4) Add 20 g of polyvinyl alcohol (PVA) to 100 mL of deionized water and stir at 90°C until the PVA is completely dissolved. After the solution cools, let it stand overnight to remove air bubbles to obtain a 20% PVA solution for later use. Weigh 100 mg GelMA, add it to 1 mL of deionized water, and dissolve it in a 40°C water bath. Weigh 2 mg of photoinitiator LAP and add it to the above solution. Stir until completely dissolved and mixed evenly to obtain a 10% GelMA solution. Add 3 mg SMC to 1 mL of GelMA solution to obtain the SMC-MN needle tip stock solution. (5) A microneedle mold was obtained by precisely preparing holes on the surface of polydimethylsiloxane material using laser etching technology. The microneedles were 800 μm long and 340 μm in diameter, with a center-to-center distance of 500 μm between adjacent microneedles. The needle tip solution was injected into the surface of the mold with the microneedle structure using a syringe so that it could just cover the holes on the mold. Then the mold was placed in a vacuum drying oven, the vacuum was drawn to 0.08 MPa, and the vacuum was broken quickly after 10 min. The mold was then removed. 300 µL of needle tip solution was added, and the mixture was concentrated at 30 °C for 1 h. This process was repeated 3 times. The mold was then cured by irradiation with visible light for 10 min. Finally, 20% PVA solution was added, and the mold was air-dried at room temperature for 24 h. The microneedle patch was then peeled off from the mold and trimmed to obtain a complete microneedle patch (SMC-MN). Example 2

[0024] A curcumin microneedle patch, the preparation method of which includes the following steps: (1) Dissolve 0.45 g cetyltrimethylammonium (CTAB) in 300 mL dd water, add 10 mL ammonia water, heat to 80 °C and stir for 30 min until clear, then add 4.5 mL tetraethyl orthosilicate (TEOS), continue stirring for 30 min, then add 10 g magnesium nitrate and stir for 20 hours; after centrifugation, wash the precipitate three times with anhydrous ethanol and water respectively, and calcine at 600 °C for 4 h to obtain biodegradable magnesium ion silica nanoparticles (SM). (2) Dissolve 25 mg of curcumin in 50 mL of anhydrous ethanol, sonicate to dissolve, add the prepared magnesium ion silica nanoparticles, stir at room temperature for 48 h to obtain silica nanoparticles (SMC) loaded with curcumin. (3) Dissolve 10g of gelatin in 100 mL of PBS solution at 45℃, then slowly add 3 mL of methacrylic anhydride to the reaction solution, and continue to stir vigorously at 45℃ for 2 h. Dialyze the product in pure water at 40℃ for 7 days to remove unreacted impurities and byproducts, and obtain methacrylamide gelatin (GelMA). (4) Add 18 g of polyvinyl alcohol (PVA) to 100 mL of deionized water and stir at 90°C until the PVA is completely dissolved. After the solution cools, let it stand overnight to remove air bubbles to obtain an 18% PVA solution for later use. Weigh 90 mg of GelMA and add it to 1 mL of deionized water. Dissolve the solution in a 40°C water bath. Weigh 1.5 mg of photoinitiator LAP and add it to the above solution. Stir until completely dissolved and mixed to obtain a GelMA solution. Add 2.5 mg of SMC to 1 mL of GelMA solution to obtain the SMC-MN needle tip stock solution. (5) A microneedle mold was obtained by precisely preparing holes on the surface of polydimethylsiloxane material using laser etching technology. The microneedles were 800 μm long and 340 μm in diameter, with a center-to-center distance of 500 μm between adjacent microneedles. The needle tip solution was injected into the surface of the mold with the microneedle structure using a syringe so that it could just cover the holes on the mold. Then the mold was placed in a vacuum drying oven, the vacuum was drawn to 0.08 MPa, and the vacuum was broken quickly after 10 min. The mold was then removed. 300 µL of needle tip solution was added, and the mixture was concentrated at 30 °C for 1 h. This process was repeated 3 times. The mold was then cured by irradiation with visible light for 10 min. Finally, 20% PVA solution was added, and the mold was air-dried at room temperature for 24 h. The microneedle patch was then peeled off from the mold and trimmed to obtain a complete microneedle patch (SMC-MN). Example 3

[0025] A curcumin microneedle patch, the preparation method of which includes the following steps: (1) Dissolve 0.55 g cetyltrimethylammonium (CTAB) in 300 mL dd water, add 14 mL ammonia water, heat to 80 °C and stir for 30 min until clear, then add 5 mL tetraethyl orthosilicate (TEOS), continue stirring for 30 min, then add 10.5 g magnesium nitrate and stir for 25 hours; after centrifugation, wash the precipitate three times with anhydrous ethanol and water respectively, and calcine at 700 °C for 2 h to obtain biodegradable magnesium ion silica nanoparticles (SM); (2) Dissolve 75 mg of curcumin in 50 mL of anhydrous ethanol, sonicate to dissolve, add the prepared magnesium ion silica nanoparticles, stir at room temperature for 48 h to obtain silica nanoparticles (SMC) loaded with curcumin. (3) Dissolve 10g of gelatin in 100 mL of PBS solution at 45℃, then slowly add 3 mL of methacrylic anhydride to the reaction solution, and continue to stir vigorously at 45℃ for 2 h. Dialyze the product in pure water at 40℃ for 7 days to remove unreacted impurities and byproducts, and obtain methacrylamide gelatin (GelMA). (4) Add 22 g of polyvinyl alcohol (PVA) to 100 mL of deionized water and stir at 90°C until the PVA is completely dissolved. After the solution cools, let it stand overnight to remove air bubbles to obtain a 22% PVA solution for later use. Weigh 110 mg of GelMA and add it to 1 mL of deionized water. Dissolve the solution in a 40°C water bath. Weigh 2.5 mg of photoinitiator LAP and add it to the above solution. Stir until completely dissolved and mixed evenly to obtain a GelMA solution. Add 3.5 mg of SMC to 1 mL of GelMA solution to obtain the SMC-MN needle tip stock solution. (5) A microneedle mold was obtained by precisely preparing holes on the surface of polydimethylsiloxane material using laser etching technology. The microneedles were 800 μm long and 340 μm in diameter, with a center-to-center distance of 500 μm between adjacent microneedles. The needle tip solution was injected into the surface of the mold with the microneedle structure using a syringe so that it could just cover the holes on the mold. Then the mold was placed in a vacuum drying oven, the vacuum was drawn to 0.08 MPa, and the vacuum was broken quickly after 10 min. The mold was then removed. 300 µL of needle tip solution was added, and the mixture was concentrated at 30 °C for 1 h. This process was repeated 3 times. The mold was then cured by irradiation with visible light for 10 min. Finally, 20% PVA solution was added, and the mold was air-dried at room temperature for 24 h. The microneedle patch was then peeled off from the mold and trimmed to obtain a complete microneedle patch (SMC-MN).

[0026] Test case Using the methods in steps (3) and (4) of Example 1, SMC was replaced with SM to obtain unloaded curcumin microneedle patch (SM-MN); using the methods in steps (3) and (4) of Example 1, the addition of SMC was removed to obtain blank microneedle patch (G-MN). I. Taking SM-MN microneedle patches, G-MN microneedle patches, and the SMC-MN microneedle patch in Example 1 as examples, the morphology and color characterization of different microneedle patches were observed using a digital camera. The results are shown in […]. Figure 1 The results showed that the G-MN microneedle patch was transparent, indicating that it did not contain any drugs; the SM-MN microneedle patch was light yellow; while the SMC-MN microneedle patch was a darker yellow due to the presence of curcumin inside.

[0027] II. The morphology and composition of different groups of microneedle patches were observed and analyzed, and the specific results are as follows: Figure 2As shown, the microneedles are all composed of a square pyramid array. The G-MN needle tip surface is smooth and without obvious defects, indicating that the substrate was not damaged during the preparation process and maintained good structural integrity. The surface roughness of the SM-MN and SMC-MN needle tips is significantly increased, which is due to the introduction of nanoparticles. The elemental distribution of SMC-MN was characterized by energy-dispersive spectroscopy (EDS). From the EDS elemental distribution diagram, it can be clearly observed that magnesium (Mg), oxygen (O), and silicon (Si) are uniformly distributed throughout the entire structure of SMC-MN, without obvious agglomeration.

[0028] III. The mechanical properties of the SMC-MN microneedle patch were characterized using a universal testing machine. For example... Figure 3 As shown in Figure A, no obvious fracture or inflection point was observed in the stress-strain diagram within the displacement range of 0-700 μm. The maximum stress value reached by SMC-MN at a displacement of 600 μm was 0.42 N·needle. -1 .

[0029] To visually evaluate the skin penetration performance of microneedles, Rhodamine 6G was used as a fluorescent marker, loaded onto microneedle patches, and then inserted into the skin tissue of hair-removed rats. The skin tissue was observed using a digital microscope. Figure 3 Results B showed regular red pits on the skin surface, which were residual Rhodamine 6G within the skin tissue, indicating that the microneedles had successfully penetrated the stratum corneum and achieved local drug delivery. The uniform and regular distribution of the red pits on the skin surface indicated that the microneedle array maintained good alignment consistency during insertion, without significant deviation or breakage. Quantitative analysis showed an insertion rate of 100%, indicating that all microneedles successfully penetrated the skin tissue, demonstrating that the microneedle patch possesses sufficient mechanical strength to penetrate the stratum corneum.

[0030] IV. Drug Release Kinetics Experiment: Five SMC-MN tablets were placed in a dialysis bag, sealed, and placed in 10 mL of PBS solution. 10% w / v Tween 80 was added to the PBS buffer to improve the dispersion stability of curcumin in the medium. The bag was placed in a constant-temperature shaker at 37 ℃ and 200 r / min. 3 mL of the release solution was collected at different time points, and isothermal and equal-volume phosphate buffer was added simultaneously. The absorbance at 425 nm was measured using a UV spectrophotometer. All experiments were repeated three times. Results are shown below. Figure 4The results showed that curcumin exhibited rapid release characteristics within the initial 24 hours, with a cumulative release of 10.4 ± 0.1 µg. This was mainly attributed to the physical adsorption of curcumin molecules on the surface of the microneedles. Subsequently, the curcumin concentration gradually increased with the degradation of the nanosheets. During the 14-day release period, SMC-MN demonstrated good sustained release performance, with a cumulative release of 29.2 ± 1.2 µg. This not only meets the need for high drug concentrations in the early stages of wound healing but also maintains effective drug concentrations at the treatment site through sustained release, providing an ideal drug delivery system for promoting the healing of diabetic ulcers.

[0031] V. To evaluate the intracellular anti-inflammatory effect of SMC-MN, an inflammation model was established by stimulating RAW 264.7 macrophages with lipopolysaccharide (LPS), and intracellular reactive oxygen species (ROS) levels were detected using the DCFH-DA fluorescent probe. Fluorescence microscopy showed that LPS stimulation significantly increased intracellular ROS levels in macrophages, manifesting as bright green fluorescence. Figure 5 As shown in Figure A, compared with the LPS group, the green fluorescence intensity of the G-MN extract treatment group did not change significantly, the fluorescence intensity of the SM-MN extract treatment group was slightly weakened, while the fluorescence intensity of the SMC-MN extract treatment group decreased significantly, indicating that SMC-MN can effectively inhibit LPS-induced ROS generation.

[0032] To further quantify the ROS scavenging ability of SMC-MN, flow cytometry was used to analyze the cells in each group. Figure 5 (B) The results showed that, compared with the LPS group, the ROS clearance rates of the SM-MN group and the SMC-MN group were 29.2±1.5% and 42.9±0.9%, respectively. Among them, the ROS clearance rate of the SMC-MN group was significantly higher than that of the SM-MN group, which further verified its excellent anti-inflammatory properties.

[0033] The anti-inflammatory effects of G-MN, SM-MN, and SMC-MN were evaluated using a DPPH (1,1-diphenyl-2-trinitrophenylhydrazine) radical scavenging assay. The results are as follows: Figure 5 As shown in Figure C, the DPPH scavenging rate of SMC-MN is significantly higher than that of G-MN and SM-MN.

[0034] VI. Measurement of the photothermal effect of the material; results are shown below. Figure 6The results showed that SMC-MN exhibited a significant photothermal effect when irradiated with an 808 nm near-infrared (NIR) laser. Under constant laser power, the temperature of the SMC-MN patch increased rapidly with prolonged irradiation time, rising by 27°C within 5 minutes. In contrast, the temperatures of G-MN and SM-MN did not change significantly under the same conditions. This result demonstrates that SMC-MN can efficiently convert NIR light energy into heat energy.

[0035] To further evaluate the photothermal stability of SMC-MN, three NIR laser on / off cycle experiments were conducted. The laser power was 1.0 W / cm². -2 Under the specified conditions, SMC-MN rapidly heated up within 1 minute and cooled down to room temperature quickly after the laser was turned off. The maximum temperature of SMC-MN remained almost consistent across the three cycles, indicating excellent cyclic stability and repeatability of its photothermal behavior.

[0036] To verify the photothermal response performance of SMC-MN in a live environment, microneedle patches were placed on wounds of SD rats and irradiated with an 808 nm NIR laser. The results showed that under laser irradiation, the temperature of SMC-MN rapidly increased, reaching a maximum of 51.7℃. This result indicates that even in humid conditions, SMC-MN can efficiently convert NIR light energy into heat energy, exhibiting excellent photothermal conversion performance.

[0037] VII. To verify the photothermal antibacterial effect of microneedles (MN), Staphylococcus aureus was selected as a model strain, and an in vitro antibacterial experiment was established. See details below. Figure 8 The experiment was divided into a Control group (untreated), a G-MN group, a SM-MN group, a SMC-MN group, and a SMC-MN+NIR group. Figure 8 Observation of bacterial growth on LB agar plates revealed that the G-MN group had almost no antibacterial effect. Figure 8 B showed that the antibacterial rate of the SM-MN group was only 20%, while the antibacterial rate of the SMC-MN group was about 44%. However, the SMC-MN+NIR group had the fewest colonies and an antibacterial rate of 94%, which was significantly higher than the other groups.

Claims

1. A method for preparing curcumin microneedle patches, characterized in that, Includes the following steps: (1) Add ammonia, tetraethyl orthosilicate and magnesium nitrate sequentially to a hexadecyltrimethylammonium solution, stir to react, collect the precipitate and calcine to obtain magnesium ion silica; (2) Place magnesium ion silica in curcumin solution and stir to react to obtain curcumin-loaded magnesium ion silica nanoparticles. (3) Add a photoinitiator and magnesium ion silica nanoparticles to a methacrylamide gelatin solution to prepare a needle tip stock solution; (4) Inject the needle tip stock solution into the mold with microneedle structure to cover the hole of the needle tip. After removing the air bubbles, continue to inject the needle tip stock solution into the mold. After light curing, inject PVA solution into the mold and air dry to obtain the product.

2. The method for preparing curcumin microneedle patches as described in claim 1, characterized in that, In step (1), the ratio of hexadecyltrimethylammonium, ammonia, tetraethyl orthosilicate and magnesium nitrate is 0.45-0.55g:10-14ml:4.5-5ml:10-10.5g.

3. The method for preparing curcumin microneedle patches as described in claim 1, characterized in that, In step (1), the stirring reaction time is 20-30h; the calcination temperature is 600-700℃ and the calcination time is 2-4h.

4. The method for preparing curcumin microneedle patches as described in claim 1, characterized in that, In step (2), the solvent for the curcumin solution is anhydrous ethanol, and the concentration of the curcumin solution is 0.5-1.5 mg / ml; the stirring reaction time is 45-50 h.

5. The method for preparing curcumin microneedle patches as described in claim 1, characterized in that, In step (3), the concentration of the methacrylamide gelatin solution is 90-110 mg / ml, the amount of photoinitiator in each milliliter of methacrylamide gelatin solution is 1.5-2.5 mg, and the amount of magnesium ion silica nanoparticles in each milliliter of methacrylamide gelatin solution is 2.5-3.5 mg.

6. The method for preparing curcumin microneedle patches as described in claim 1, characterized in that, In step (4), the concentration of the PVA solution is 18-22 W / V.

7. The method for preparing curcumin microneedle patches as described in claim 1, characterized in that, The microneedles on the microneedle patch in step (4) are 800 μm long and 340 μm in diameter, and the center-to-center distance between two adjacent microneedles is 500 μm.

8. A curcumin microneedle patch, characterized in that, It is prepared by any one of claims 1-7.

9. The use of the curcumin microneedle patch as described in claim 8 as a wound dressing for diabetes.

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