Microneedle patch capable of sequentially releasing medicines and preparation method of microneedle patch

Abstract

The invention belongs to the field of medical apparatus and instruments, and particularly relates to a microneedle patch capable of sequentially releasing drugs and a preparation method of the microneedle patch. The microneedle patch capable of sequentially releasing the medicine comprises a substrate layer, a plurality of microneedles are arranged on the substrate layer, each microneedle comprises a separation layer and a needle tip layer, magnesium powder is filled in the separation layer, and raw materials of the separation layer comprise polyvinyl alcohol and the blood activating medicine; the needle tip layer is prepared from the following raw materials: chitosan, polyvinylpyrrolidone and a tendon and bone strengthening medicine. Drug delivery can be carried out to the corium layer in a minimally invasive mode, and compared with an existing drug means, the drug delivery system has the advantages that the bioavailability is high, drugs can be continuously released, and adverse side effects are reduced to a large extent. Due to the structure of the needle body, the two loaded traditional Chinese medicine active ingredients can be released in sequence and have a synergistic effect, so that rapid healing of fracture is promoted.

Description

Technical Field

[0001] The present invention belongs to the field of medical devices, and in particular relates to a microneedle patch for sequentially releasing drugs and a preparation method thereof. Background Art

[0002] A fracture is a disruption of bone continuity and integrity. The fracture healing process can be divided into three phases, sequentially including: the hematoma-inflammatory phase, the callus formation phase, and bone remodeling. In the initial fracture phase, bleeding occurs at the affected site, forming a hematoma accompanied by a large infiltration of immune cells. This is the hematoma-inflammatory phase. During the callus formation phase, mesenchymal stem cells that have migrated to the affected area differentiate into osteoblasts, which promote bone formation, or chondrocytes, which promote cartilage formation. This subsequently forms an avascular soft callus, providing additional strength to the fracture site. Once a relatively mechanically stable environment is established, chondrocyte differentiation proceeds, the cartilage extracellular matrix mineralizes, and vascularization of the cartilage matrix is promoted. New woven bone replaces the cartilage matrix, forming a hard callus. During the bone remodeling phase, after continuous bone resorption by osteoclasts and bone deposition by osteoblasts, the immature woven bone undergoes significant remodeling into lamellar bone, restoring the mechanical properties of the bone to pre-injury levels, and completing the fracture healing cycle.

[0003] During clinical treatment, doctors need to reduce the fracture and fix the fracture area to ensure that the broken ends remain stable and do not shift during the healing process. Currently, commonly used auxiliary tools in clinical practice include external fixation devices based on splints and plasters, or internal fixators based on intramedullary nails and steel plates. The specific plan depends on the patient's general condition, fracture type, and soft tissue conditions. In addition, it is necessary to combine vitamin D, calcium supplements, bone healing agents and other drugs for auxiliary treatment. Oral medications have a slow effect due to the long process of digestion and absorption. External ointments and plasters have the disadvantage of being difficult to break through the stratum corneum barrier. There is an urgent need to find a new drug delivery method with high drug delivery efficiency.

[0004] Microneedles, an emerging drug delivery tool with promising applications, offer reduced invasiveness and enhanced bioavailability. They can deliver drugs that are less effective at low doses without disrupting skin nerve endings. Microneedles are micrometer-sized needles used for drug delivery or biosensing. They are typically fabricated in arrays and applied as patches. Their tips can penetrate the epidermis and reach the dermis without damaging blood vessels and nerves within the dermis, enabling the delivery of therapeutic agents to specific areas through the dermis for therapeutic effects. Advances in materials science and advancements in microfabrication equipment have enabled the fabrication of microneedles in a variety of forms. Currently, microneedles can be categorized into five major types: solid microneedles, coated microneedles, hollow microneedles, biodegradable microneedles, and hydrogel microneedles. The latter two types are currently the most widely researched in the field of drug delivery. Microneedles loaded with target drugs are constructed from biodegradable biofunctional materials. Upon insertion into the skin, the tips partially degrade and release the drug, achieving sustained and effective drug delivery. By selecting materials with different degradation cycles and constructing different microneedle morphologies and structures, it is possible to regulate the drug release behavior of microneedles. One idea is to design the microneedle into a detachable structure, by introducing a separation layer with different mechanical properties between the needle tip layer and the substrate to achieve easy separation under shear or tension. The drug-loaded needle tip layer is then implanted subcutaneously to achieve long-term drug release. Another idea is to construct a "shell-core" structure, that is, the microneedle body has an outer shell and an inner core, and the outer shell wraps the inner core. The two are made of different materials. By adjusting the degradation cycle of the outer shell and inner core materials, controlled and sustained release of the loaded drug can be achieved.

[0005] The application of microneedles in the treatment of orthopedic diseases is relatively less than in other fields. Currently, almost all published literature focuses on the management and treatment of rheumatoid arthritis, osteoarthritis and osteoporosis, and this trend has continued to rise in the past few years. Summary of the Invention

[0006] The object of the present invention is to provide a method for preparing a microneedle patch for sequentially releasing drugs.

[0007] Another object of the present invention is to provide a microneedle prepared by the above method.

[0008] Another object of the present invention is to provide applications of the above-mentioned microneedles.

[0009] According to a specific embodiment of the present invention, the method for preparing a microneedle comprises the following steps: The needle tip layer aqueous solution, magnesium powder, separation layer solution and base layer solution are sequentially added into the microneedle mold, and after demoulding, the microneedle.

[0010] According to a specific embodiment of the present invention, the method for preparing a microneedle comprises the following steps: (1) Preparation of the needle tip layer: adding the needle tip layer aqueous solution to a mold, immersing the mold in an alkaline solution to make the needle tip gel, removing the residual alkaline solution, and drying to obtain the needle tip layer; (2) Filling magnesium powder: adding magnesium powder into the mold treated in step (1); (3) Preparing the separation layer: adding the separation layer aqueous solution to the mold treated in step (2) and allowing it to dry at room temperature; after the water in the separation layer solution is completely evaporated, adding the base layer solution; (4) Preparing the base layer: adding the base layer solution to the mold treated in step (3), standing and drying at room temperature, and demolding to obtain the microneedle patch.

[0011] The volume ratio of the tip layer solution, the separation layer solution, and the base layer solution is (10-15): (15-20): (60-100).

[0012] According to the microneedle preparation method of a specific embodiment of the present invention, in the needle tip layer aqueous solution, the chitosan (CS) concentration is 1-5% W / V, the polyvinyl pyrrolidone (PVP) concentration is 1-5% W / V, and the OTF concentration is 20-30% W / V.

[0013] Preferably, the concentration of CS and PVP is 1:1, so that the needle tip layer has better mechanical properties and is easy to penetrate the skin.

[0014] According to the microneedle preparation method of a specific embodiment of the present invention, in the separation layer aqueous solution, the concentration of polyvinyl alcohol (PVA) is 10-20% W / V, and the concentration of PNS is 20-30% W / V.

[0015] According to the microneedle preparation method of a specific embodiment of the present invention, the PVP concentration in the base layer solution is 10-20% W / V.

[0016] The amounts of the tip layer solution, separation layer solution, base layer solution, and magnesium powder can be adjusted based on the size of the microneedle mold to ensure that the tip layer solution, magnesium powder, and base layer solution fully fill the microneedle mold. For a 1 cm × 1 cm mold, the volume ratio of the tip layer solution, separation layer solution, and base layer solution is (10-15):(15-20):(60-100). The amount of magnesium powder required to fully fill the mold should be no less than 0.005 g.

[0017] In Traditional Chinese Medicine (TCM), fractures are divided into three stages: early, middle, and late. Based on this, a "three-stage dialectical" treatment theory has been proposed. The early stage of fracture generally refers to one week after the fracture. TCM theory posits that the pathogenesis during this stage lies in qi stagnation and blood stasis. Therefore, blood-activating drugs are needed to dissipate blood stasis, promote new blood circulation, reduce swelling, and relieve pain. The present invention utilizes Panax notoginseng saponins (PNS) for this period. The middle stage of fracture generally refers to two to three weeks after the fracture. TCM theory posits that tendon-strengthening and bone-strengthening drugs should be used to strengthen tendons and bones, harmonize the meridians, and relieve pain. The present invention utilizes Drynaria fortunei total flavonoids (OTF) for this period. The late stage of fracture generally refers to four weeks after the fracture. At this time, drugs such as Chinese angelica and Atractylodes macrocephala should be used to nourish qi and blood, and strengthen the foundation and replenish the vital energy.

[0018] In the present invention, the separation layer of the microneedles is loaded with Panax notoginseng saponins (PNS), corresponding to the early stage of fracture in Traditional Chinese Medicine (TCM). The tip layer is loaded with total flavonoids from Drynaria fortunei (OTF), corresponding to the mid-stage of fracture in TCM. Furthermore, the separation layer of the microneedle structure contains magnesium powder, which not only allows for rapid peeling of the tip layer but also allows for rapid early release of the PNS from the separation layer. The tip layer is then implanted into the dermis for long-term release of the OTF. This invention leverages the different solubility properties of the separation and tip layers of the microneedles, utilizes magnesium powder to accelerate the separation of the separation and tip layers, and combines this with appropriate medicinal ingredients to achieve the therapeutic effect of first promoting blood circulation and removing blood stasis, then promoting osteogenesis, consistent with TCM's "three-stage dialectics" theory.

[0019] Preferably, for the needle tip implanted in the skin, a medical polymer material with good biocompatibility can be selected, including but not limited to one or more of chitosan, trehalose, cellulose, hyaluronic acid and carboxymethyl cellulose.

[0020] Preferably, the separation layer and the base layer can be made of hydrophilic polymer materials, including but not limited to one or more of polyvinyl alcohol (PVA), polyvinyl pyrrolidone (PVP), polylactic acid (PLA), polyglycolic acid (PGA), and polylactic-glycolic acid (PLGA).

[0021] The solvent can be selected from water or ethanol according to the properties of the polymer material.

[0022] Preferably, the magnesium powder can be 200 mesh or 400 mesh.

[0023] According to a specific embodiment of the present invention, a microneedle patch for sequential drug release comprises a base layer, a plurality of microneedles are arranged on the base layer, each of the microneedles comprises a separation layer and a needle tip layer, magnesium powder is filled in the separation layer, wherein, The raw materials of the needle tip layer include chitosan, polyvinyl pyrrolidone and muscle and bone strengthening drugs; The raw materials of the separation layer include polyvinyl alcohol and blood-activating drugs.

[0024] According to a specific embodiment of the present invention, the microneedle patch for sequential drug release comprises chitosan, polyvinyl pyrrolidone and muscle and bone strengthening drugs in a mass ratio of (1-5): (1-5): (20-30) in the needle tip layer.

[0025] According to the microneedle patch for sequential drug release according to a specific embodiment of the present invention, in the separation layer, the blood-activating drug is selected from Panax notoginseng saponins.

[0026] Preferably, the blood-activating drugs suitable for use within one week after a fracture can also be replaced with extracts or effective active ingredients of traditional Chinese medicinal materials such as astragalus, salvia miltiorrhiza, and angelica.

[0027] According to a specific embodiment of the present invention, in the microneedle patch for sequential drug release, the mass ratio of polyvinyl alcohol to the blood-activating drug in the separation layer is (10-20): (20-30).

[0028] According to the microneedle patch for sequential drug release according to a specific embodiment of the present invention, in the needle tip layer, the muscle and bone strengthening drug is selected from total flavonoids of Drynaria fortunei.

[0029] Preferably, the muscle and bone strengthening drugs suitable for use within two to three weeks after a fracture can also be replaced with extracts or effective active ingredients of traditional Chinese medicinal materials such as Acanthopanax acanthopanax, Black Tiger, and Morus alba.

[0030] According to the microneedle patch for sequential drug release according to a specific embodiment of the present invention, the magnesium powder is selected from 200 mesh or 400 mesh magnesium powder.

[0031] According to a specific embodiment of the present invention, the substrate layer of the sequential drug-releasing microneedle patch is selected from one or more of polyvinyl alcohol, polyvinyl pyrrolidone, polylactic acid, polyglycolic acid, and polylactic-co-glycolic acid. Preferably, the substrate layer is selected from PVP, and the PVP is prepared into a substrate layer solution with a concentration of 10-20% W / V.

[0032] Beneficial effects of the present invention: After the microneedles of the present invention are inserted into the skin, the separation layer, made of a more water-soluble PVA material than the needle tip layer, and the magnesium powder's ability to rapidly react in the presence of small amounts of water to generate H₂ bubbles, creates a cavity within the separation layer, increasing the surface area in contact with the skin. This allows the blood-activating components (e.g., PNS) carried by the separation layer to be preferentially released, achieving the therapeutic goal of promoting blood circulation and removing blood stasis in the early stages of fractures. Simultaneously, as the separation layer gradually disintegrates, the needle tip made of CS / PVP material is implanted in the skin and separated from the base, allowing the long-term release of muscle-strengthening and bone-strengthening components (e.g., OTF) to promote osteogenesis in the mid-stage of fractures. BRIEF DESCRIPTION OF THE DRAWINGS

[0033] In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the following briefly introduces the drawings required for use in the embodiments or the description of the prior art. Obviously, the drawings described below are only some embodiments of the present invention. For ordinary technicians in this field, other drawings can be obtained based on these drawings without paying any creative work.

[0034] Figure 1 Schematic diagram of the microneedle structure, where 1 is the base layer, 2 is the separation layer, and 3 is the tip layer.

[0035] Figure 2 Schematic diagram of the microneedle preparation process.

[0036] Figure 3 This is the result of microneedle morphology characterization; (a) Microneedle patch; (b) Microneedle tip arrangement under a microscope, scale 1000 μm; (c) Tip morphology under a microscope, scale 500 μm.

[0037] Figure 4 Shows the separation results of the microneedle tip in water; (a) Microneedle patch before immersion in water, scale bar 500 μm; (b) Light microscopy image of the microneedle patch after immersion in water for 600 s; Figure 5 The results show the separation of the microneedle tip in pig skin; (a) Separation of the microneedle patch on the pig skin surface, scale 500 μm; (b) Paraffin section of pig skin tissue.

[0038] Figure 6 Showing the in vitro drug release profile of the microneedles; (a) PNS release curve of the separation layer; (b) OTF release curve of the needle tip layer. DETAILED DESCRIPTION

[0039] To make the objectives, technical solutions, and advantages of the present invention more apparent, the technical solutions of the present invention will be described in detail below. Obviously, the embodiments described are only some of the embodiments of the present invention, not all of them. Based on the embodiments of the present invention, all other implementations obtained by those of ordinary skill in the art without inventive effort are within the scope of protection of the present invention.

[0040] Example 1 Preparation of microneedles 1.1 The microneedles of this embodiment include the following components: A. Prepare the needle tip layer aqueous solution: chitosan (CS) concentration is 1% W / V, polyvinylpyrrolidone (PVP) concentration is 1% W / V, OTF concentration is 20% W / V, and the needle tip layer aqueous solution is obtained. B. Prepare the separation layer aqueous solution: polyvinyl alcohol (PVA) concentration is 10% W / V, and PNS concentration is 20% W / V; C. Prepare the basal layer solution: PVP concentration is 10% W / V.

[0041] 1.2 The microneedles of this embodiment include the following components: A. Prepare the needle tip layer aqueous solution: chitosan (CS) concentration is 3% W / V, polyvinylpyrrolidone (PVP) concentration is 3% W / V, OTF concentration is 25% W / V, and the needle tip layer aqueous solution is obtained. B. Prepare the separation layer aqueous solution: polyvinyl alcohol (PVA) concentration is 15% W / V, and PNS concentration is 25% W / V; C. Prepare the basal layer solution: PVP concentration is 15% W / V.

[0042] 1.3 The microneedles of this embodiment include the following components: A. Prepare the needle tip layer aqueous solution: chitosan (CS) concentration is 5% W / V, polyvinylpyrrolidone (PVP) concentration is 5% W / V, OTF concentration is 30% W / V, and the needle tip layer aqueous solution is obtained. B. Prepare the separation layer aqueous solution: polyvinyl alcohol (PVA) concentration is 20% W / V, and PNS concentration is 30% W / V; C. Prepare the basal layer solution: PVP concentration is 20% W / V.

[0043] The microneedles of the above embodiment can be prepared by the following method: To prepare microneedles using the multilayer perfusion method, add 100-150 μL of the tip layer solution to a 1 cm × 1 cm mold. Vacuum the solution until it completely fills the pinhole, then scrape off any excess. Repeat the same process for the separation layer solution, adding 150-200 μL. Finally, pipette 600-1000 μL of the base layer solution to evenly cover the mold. This involves the following steps: (1) Add the needle tip layer aqueous solution to the PDMS mold, evacuate the mold using a vacuum drying dish, and remove bubbles. After scraping off the excess solution, soak the mold in a 10% w / v NaOH solution to allow the chitosan solution at the needle tip to gel. Then, slowly rinse the mold groove with running water to completely remove any residual NaOH. Then dry it.

[0044] (2) Add sufficient Mg powder (at least 0.005 g for a 1 cm × 1 cm mold to ensure that each pinhole in the microneedle mold is completely covered by magnesium powder) to the dried microneedle concave mold and flatten it. Then add the separation layer aqueous solution and let it dry at room temperature. (3) After the water in the separation layer solution is completely evaporated, add the base layer solution and let it stand to dry at room temperature; (4) After the solvent in the substrate solution is completely evaporated, demoulding is performed and the prepared microneedles are taken out to obtain the microneedle structure as shown in FIG. Figure 1 The preparation process is as shown in Figure 2 shown.

[0045] The microneedle morphology was investigated and the characterization results were as follows: Figure 3 shown.

[0046] like Figure 3 As shown, the overall dimensions of the microneedle patch are approximately 1 cm × 1 cm. The needles are regular quadrangular pyramids, arranged in a neat array. The brownish-brown color of the needles is due to the loading of active Chinese medicine powder, which contrasts significantly with the unloaded, transparent base layer. The needle tips exhibit excellent light transmittance, and black magnesium particles are evenly distributed in the separation layer at the lower half of the needles.

[0047] Example 2 Investigation of the performance of microneedles 1. Results of needle tip separation in water The prepared microneedle was fixed to the bottom of a glass dish with the true tip facing upwards and observed under an optical microscope. A sufficient amount of deionized water was then poured into the dish, and the separation of the microneedle tip in the water was recorded.

[0048] The results are as follows Figure 4 As shown in the figure, the microneedle tip layer separated after immersion in water for 600 seconds. The black powder at the end of the quadrangular pyramid tip that fell off the backing is magnesium powder. Bubbles formed immediately after immersion in water. After 60 seconds, a large number of bubbles were generated, a cavity formed in the separation layer, and the tip gradually tilted. After 120 seconds, the tip began to detach from the base layer. After 300 seconds, the microneedle tip had detached significantly, and a cavity formed at the corresponding location in the base layer. This indicates that the tip detachment was caused by the disintegration of the separation layer due to the presence of magnesium powder, rather than the rapid dissolution of the base layer. After 600 seconds, the microneedle tip was completely floating in the water, completely separated from the base layer. Figure 4 (b) shows the tip of a microneedle detaching from the center of the patch and floating to the edge. This separation clearly demonstrates that the complete separation of the tip layer is achieved by the magnesium in the separation layer creating bubbles upon contact with water.

[0049] 2. Pigskin needle tip separation results The microneedles were pressed into the skin of a pig cadaver. The puncture area on the skin surface was moistened with deionized water. After 15 minutes, the microneedles were gently peeled off, and the arrangement of the needle tips implanted in the skin was observed under an optical microscope. The pig skin at the puncture area was then fixed in 4% histological fixative for 24 hours, dehydrated, infiltrated, embedded in paraffin, and sectioned.

[0050] The results are as follows Figure 5 As shown, Figure 5 (a) shows the needle tip separated and fully implanted in the pig skin. The black particles are magnesium powder, which indirectly confirms that microneedle separation is achieved by the magnesium powder in the separation layer generating bubbles when it comes into contact with water, causing the separation layer to disintegrate. Figure 5 The paraffin section results in b also showed that the needle tip completely penetrated the pig skin.

[0051] Example 3 Investigating the release of microneedles in vitro OTF standards were serially diluted, and the absorbance was measured at 285 nm by UV-visible spectrophotometry to generate a standard absorbance curve. Magnesium-containing microneedles with or without OTF loaded on the tips were prepared. The microneedles were immersed in 10 mL of 1× PBS (pH 7.4) at 37°C. 500 μL of PBS was collected at 1, 2, 4, 8, 12, 24, 48, 72, 96, 120, 144, 168, 192, 216, 240, 264, 288, 312, and 336 h, and the absorbance was measured at 285 nm by UV-visible spectrophotometry. After each sampling, 500 μL of fresh PBS was added to the system. Drug release profiles from the tip layer were plotted by comparison with the standard curve. The experiment was repeated three times for each microneedle group.

[0052] A PNS standard was serially diluted, and the absorbance was measured at 277 nm by UV-visible spectrophotometry to generate a standard absorbance curve. Magnesium-containing and magnesium-free microneedles with only the basal drug were prepared. The microneedles were immersed in 10 mL of 1× PBS (pH 7.4) at room temperature. 500 μL of PBS was sampled at the 2nd, 5th, 10th, 15th, 20th, 25th, 30th, 35th, 40th, 45th, 50th, 55th, and 60th intervals, and the absorbance was measured at 277 nm by UV-visible spectrophotometry. After each sample, 500 μL of fresh PBS was added to the system. The basal drug release curve was plotted by comparison with the standard curve. The experiment was repeated three times for each microneedle group. like Figure 6As shown, the tip layer and separation layer exhibit different timescales of drug release. The separation layer drug was fully released within 1 hour, while the tip layer drug required 14 days to achieve complete release. For microneedles with magnesium powder added, the drug release rate from the separation layer was significantly accelerated within 5-20 minutes compared to microneedles without magnesium powder. Similarly, compared to microneedles without magnesium powder, microneedles with magnesium powder added exhibited more rapid tip layer drug release within the first hour, while after 1 hour, the drug release curves showed no significant difference. This suggests that the difference in drug release within the first hour is due to the faster detachment of the microneedle tips with magnesium powder added, increasing the surface area of the fallen tips in contact with the PBS solution and accelerating drug release. However, after 1 hour, due to the complete dissolution of the basal layer and separation layer in water, the tips of both microneedle groups completely detached, and there was no significant difference in drug release behavior.

[0053] In summary, the microneedles of the present invention can achieve rapid drug release from the separation layer and long-term sustained release from the needle tip layer, thereby achieving sequential release of the two drugs, thereby effectively cooperating with traditional Chinese medicine theory for treatment.

[0054] The above description is merely a specific embodiment of the present invention, but the scope of protection of the present invention is not limited thereto. Any modifications or substitutions that can be easily conceived by a person skilled in the art within the technical scope disclosed in the present invention should be included in the scope of protection of the present invention. Therefore, the scope of protection of the present invention should be based on the scope of protection of the claims.

Claims

1. A microneedle patch for sequential drug release, characterized in that: The microneedle patch includes a base layer, a plurality of microneedles are arranged on the base layer, each of the microneedles includes a separation layer and a needle tip layer, and magnesium powder is filled in the separation layer, wherein, The raw materials of the separation layer include polyvinyl alcohol and blood-activating drugs; The raw materials of the needle tip layer include chitosan, polyvinyl pyrrolidone and muscle and bone strengthening drugs.

2. The sequential drug release microneedle patch according to claim 1, characterized in that: In the needle tip layer, the mass ratio of chitosan, polyvinyl pyrrolidone and muscle and bone strengthening drugs is (1-5): (1-5): (20-30).

3. The microneedle patch for sequential drug release according to claim 1, characterized in that: In the separation layer, the blood-activating drug is selected from Panax notoginseng saponins.

4. The sequential drug release microneedle patch according to claim 1, characterized in that: In the separation layer, the mass ratio of polyvinyl alcohol to the blood-activating drug is (10-20): (20-30).

5. The sequential drug release microneedle patch according to claim 1, characterized in that: In the needle tip layer, the muscle and bone strengthening drug is selected from the total flavonoids of Drynaria fortunei.

6. The microneedle patch for sequential drug release according to claim 1, characterized in that: The magnesium powder is selected from 200 mesh or 400 mesh magnesium powder.

7. The sequential drug release microneedle patch according to claim 1, characterized in that: The base layer is selected from one or more of polyvinyl alcohol, polyvinyl pyrrolidone, polylactic acid, polyglycolic acid, and polylactic acid-glycolic acid.

8. The method for preparing the sequential drug release microneedle patch according to any one of claims 1 to 7, characterized in that: The preparation method comprises the following steps: The needle tip layer aqueous solution, magnesium powder, separation layer solution, and base layer solution are sequentially added to the microneedle mold. After demolding, the microneedle patch is obtained, wherein the microneedle patch includes a base layer, a plurality of microneedles are arranged on the base layer, each of the microneedles includes a separation layer and a needle tip layer, and magnesium powder is filled in the separation layer.

9. The preparation method according to claim 8, characterized in that The method comprises the following steps: (1) Preparing the needle tip layer: adding the needle tip layer aqueous solution to a mold, soaking the mold in an alkaline solution to make the needle tip gel, removing the residual alkaline solution, and drying to obtain the needle tip layer; (2) Filling magnesium powder: adding magnesium powder into the mold treated in step (1); (3) Preparing the separation layer: After vacuuming, add the separation layer aqueous solution to the mold treated in step (2), and let it stand and dry at room temperature; after the water in the separation layer solution is completely evaporated, add the base layer solution; (4) Preparing the base layer: adding the base layer solution to the mold treated in step (3), standing and drying at room temperature, and demolding to obtain the microneedle patch.

Images