Self-heating microneedle acupoint patch

Abstract

The application discloses a self-heating microneedle acupoint patch, which comprises a drug delivery layer; the drug delivery layer is a sheet with a plurality of microneedles on one side; the drug delivery layer comprises a front surface and a back surface, the microneedles are located on the front surface of the drug delivery layer, and the microneedles are loaded with drugs; the back surface of the drug delivery layer is provided with a self-heating layer, and the self-heating layer is a porous self-heating metal layer. The drug delivery layer is obtained by solidification, demolding, annealing and hydrogen reduction treatment of metal slurry, and finally loaded with drugs. The self-heating layer is made by setting the self-heating metal under the inert gas flow in a staggered and opposite manner to the drug delivery layer, and depositing the self-heating metal on the back surface of the drug delivery layer by laser sputtering. The acupoint patch can improve the drug loading capacity, self-heating and heat preservation, and the heat can promote drug penetration and enhance acupoint stimulation, so that the acupoint treatment effect can be improved and the treatment time can be shortened.

Description

Technical Field

[0001] This invention relates to the field of medical device technology, specifically to a self-heating microneedle acupoint patch. Background Technology

[0002] Acupoint patch therapy, based on the theory of meridians in Traditional Chinese Medicine, involves placing medication on acupoint patches and applying them directly to acupoints and affected areas to treat diseases—a non-invasive and painless acupoint therapy. The mechanism of action of acupoint patch therapy is complex and not fully understood, but the generally accepted mechanisms are as follows: first, the stimulation and regulation of acupoints; second, the pharmacological effect after drug absorption; and third, the combined effect of both. Acupoint patch therapy directly stimulates acupoints with medication, and through transdermal absorption, the local drug concentration is significantly higher than in other areas, resulting in a more direct effect. It avoids gastrointestinal administration, thus preventing damage to the spleen and stomach. Acupoint patch therapy is simple to learn, requires no special medical equipment or instruments, and is easy to promote. It combines the advantages of acupuncture and drug therapy, with significant therapeutic effects. Because acupoint patches do not cause trauma to the body and the drug release site is precise, it has become a new drug delivery method increasingly adopted by many people.

[0003] Acupoint patches have been widely used and promoted due to the aforementioned advantages, but some problems still exist, limiting their efficacy: ordinary acupoint patches work by stimulating acupoints with drugs for transdermal absorption. Since acupoint patches directly contact the stratum corneum of the skin, drug penetration is poor. To enhance drug penetration, acupoint patches generally need to be applied for several hours, reducing convenience and comfort, and potentially causing allergic reactions in people with sensitive skin. Appropriate heating of the acupoint patch can promote drug absorption and reduce application time. For example, the paper "Smart hydrothermally responsive microneedle for topical tumor treatment" (Rengui Xu et al., Journal of Controlled Release 358 (2023) 566–578) discloses a smart hydrothermally responsive microneedle for local tumor treatment. This microneedle has a hydrothermally responsive substance added to one side to achieve heating: after optimizing the composition by adding appropriate amounts of Fe, AC, sodium chloride, anhydrous magnesium sulfate, and calcium oxide, the self-heating boiling pack can raise the water temperature to 60-70℃. However, this microneedle has two main problems: first, the drug loading capacity is limited, which prolongs the application time; second, the water-heating temperature is too high, which can easily cause burns to the skin. Therefore, there is a need for an acupoint patch with microneedles that can increase the drug loading capacity, shorten the application time, appropriately heat the microneedles, and prevent heat loss. Summary of the Invention

[0004] In view of the above-mentioned prior art, the purpose of this invention is to provide a self-heating microneedle acupoint patch. The self-heating metal nanoparticles on the back surface of the acupoint patch of this invention are small in size and highly active, making them prone to oxidation. The oxidation process releases heat, causing the acupoint patch to heat up rapidly. Simultaneously, the oxide nanomaterials formed by the oxidation of the surface metal nanoparticles can prevent heat from being transmitted to the air, allowing most of the heat generated by oxidation to be conducted to the human body through the metal microneedles. Furthermore, because the self-heating nanoparticles on the back surface of the acupoint patch are arranged in a porous manner, the oxidation of the surface does not hinder the contact between the air and the underlying metal nanoparticles, allowing for continuous oxidation and heat release. The acupoint patch of this invention is self-heating and heat-retaining; the heat can promote drug penetration and enhance acupoint stimulation, thereby improving the therapeutic effect of acupoint therapy and shortening treatment time.

[0005] To achieve the above objectives, the present invention adopts the following technical solution: This invention provides a self-heating microneedle acupoint patch, comprising a drug delivery layer; the drug delivery layer is a thin sheet with a plurality of microneedles on one side; the drug delivery layer includes a front side and a back side, the microneedles are located on the front side of the drug delivery layer, and the microneedles are loaded with drugs; a self-heating layer is provided on the back side of the drug delivery layer, the self-heating layer is a porous self-heating metal layer; the porous self-heating metal layer is located on the back side of the drug delivery layer.

[0006] Preferably, the microneedle is a porous microneedle; the thickness of the sheet is 0.1~0.5mm; and the height of the microneedle is 200μm~2mm.

[0007] Preferably, the method for preparing the drug delivery layer is as follows: An organic slurry containing metal is filled into a microneedle template, cured, and then demolded to obtain a metal sheet with microneedles. The metal sheet with microneedles is then annealed, followed by heat treatment in a reducing atmosphere. Finally, the drug is loaded onto the microneedles to obtain a drug delivery layer.

[0008] The microneedle template is made of PDMS, which is cast onto a 3D-printed microneedle array, cured, and then demolded. The curing temperature is 80~120℃, and the time is 0.5~2h. The microneedle template is a 3D-printed microneedle array, which can be made of PMMA; then a mixture of PDMS and a curing agent is cast onto the PMMA microneedle array, vacuum dried, and cured. After demolding, a PDMS microneedle template is obtained. The curing agent is RTV615.

[0009] The metal-containing organic slurry is an organic slurry containing silver, copper, titanium, iron, gold, or nickel, or is obtained by mixing powders of silver, copper, titanium, iron, gold, or nickel with a dispersant and a plasticizer. The dispersant is Solsperse 17000; the plasticizer is at least one of dibutyl phthalate and an acetic acid solution of chitosan.

[0010] Preferably, the annealing temperature is 700 °C and the annealing time is 3 h; the reducing atmosphere is Ar / H2, and the heat treatment temperature is 600 °C and the time is 2 h.

[0011] Preferably, the method for loading the drug onto the microneedle is as follows: The microneedles are immersed in a drug solution or the drug solution is sprayed onto the microneedles, and then the microneedles are dried to load the drug onto the microneedles.

[0012] The method for microneedle drug immersion is as follows: place the microneedle in a drug solution, load the drug solution onto the microneedle, and then dry the drug-loaded microneedle to obtain a drug-loaded drug delivery surface; The method for spraying drugs onto microneedles is as follows: spray the drug solution onto the microneedles, and after drying, obtain acupoint patches loaded with drugs; Preferably, the porous self-heating metal layer is made of at least one of silver, copper, titanium, iron, and tantalum; and the thickness of the porous self-heating metal layer is 1-20 µm.

[0013] Preferably, the porous self-heating metal layer is prepared by the following method: (1) Press the self-heating metal powder into tablets to obtain self-heating metal sheets; (2) Take a transparent sealed container with an air inlet and an air outlet at both ends. Inert gas is introduced into the air inlet of the transparent sealed container. Place the drug delivery layer at the top of the transparent sealed container and at one end of the air outlet. Place the self-heating metal sheet at the bottom of the transparent sealed container, facing the back of the drug delivery layer. The distance between the self-heating metal sheet and the air outlet is greater than the distance between the drug delivery layer and the air outlet. (3) In an inert gas flow, a laser is directed at the upper surface of the self-heating metal sheet to irradiate it. The laser sputters out self-heating metal nanoclusters, which are deposited on the back side of the drug delivery layer above to form a porous self-heating metal layer with micro-nano structure.

[0014] Preferably, in step (1), the particle size of the self-heating metal powder is 1~20μm.

[0015] Preferably, in step (2), the projection of the drug delivery layer on the bottom of the transparent sealed container does not coincide with the self-heating metal sheet; the distance between the projection of the drug delivery layer on the bottom of the transparent sealed container and the self-heating metal sheet is 5~20mm. The inert gas is argon.

[0016] Preferably, in step (3), the velocity of the inert airflow is 5-40 cm. 3 / min.

[0017] Laser irradiation is performed using a fiber laser with a wavelength of 1064nm and a maximum power of 50W at a speed of 700-900mm / s, a line spacing of 0.001-0.005mm, and a power of 35-50W.

[0018] The acupoint patches are vacuum-packed immediately after preparation to prevent self-heating metal oxidation.

[0019] The beneficial effects of this invention are: (1) The present invention uses porous metal microneedles with a height of 200µm-2mm to load drugs. The microneedles can just penetrate the stratum corneum of the skin and reach the dermis. The drugs loaded on the microneedles penetrate into the body, achieving the superimposed effect of acupoint stimulation and direct drug penetration, thus enhancing the therapeutic effect. At the same time, the microneedles only penetrate the stratum corneum of the skin, so there will be no obvious pain during the treatment process, thus avoiding the pain of treatment.

[0020] (2) The present invention uses a template to prepare the drug delivery layer. The template can be reused repeatedly and can be prepared in large quantities at low cost. The microneedles have micropores, which can greatly increase the drug loading and improve the therapeutic effect.

[0021] (3) During use, when air comes into contact with the self-heating layer of the acupoint patch of this invention, the self-heating metal nanoparticles, due to their small size and high activity, are easily oxidized. The heat released during the oxidation process causes the acupoint patch to heat up rapidly. Furthermore, because the nanoparticles in the self-heating metal layer on the back of the acupoint patch are arranged in a porous manner, the oxidation of the surface layer does not hinder the contact between the air and the underlying metal nanoparticles, allowing for continuous oxidation and heat release. The self-heating metal layer oxidizes from the outside to the inside; the external oxidation into oxides acts as a heat-insulating layer, reducing heat loss from the self-heating metal layer to the outside air, thus allowing rapid conduction to the skin via the metal microneedles. The self-heating layer is composed of micro- and nano-metal particles, with a small total amount of self-heating metal, resulting in a moderate heating temperature that will not damage the skin. The acupoint patch of this invention is self-heating and heat-insulating; the heat can promote drug penetration and enhance acupoint stimulation, thereby improving the therapeutic effect of acupoints and shortening the treatment time. Attached Figure Description

[0022] Figure 1 Example 1: Structural diagram of acupoint patch, wherein 1-microneedle (silver needle), 2-metal sheet (silver sheet), 3-self-heating metal layer (copper micro / nano particles). Figure 2 Photograph of the PMMA template used in Example 1; Figure 3 Photographs of the PDMS template prepared in Example 1; Figure 4SEM images of silver needles at different magnifications; where (a) is a SEM image of a silver needle at a scale of 400 μm, (b) is a SEM image of the top of a silver needle at a scale of 50 μm, (c) is a SEM image of the lower part of a silver needle at a scale of 50 μm, and (d) is a SEM image of a silver needle at a scale of 5 μm. Figure 5 Example 1 shows the EDS characterization of the silver needles prepared, where (a) is the EDS characterization of the silver needles before annealing, and (b) is the EDS characterization of the silver needles after annealing. Figure 6 : Schematic diagram of the self-heating layer preparation device in Example 1, wherein, 1-quartz tube, 2-air inlet, 3-air outlet, 4-copper sheet (pressed tablet), 5-drug administration layer, 6-laser; Figure 7 SEM image of the self-heating copper nanoparticles prepared in Example 1; Figure 8 Infrared camera image of the acupoint patch in Example 1 taken from the side with the silver needle; Figure 9 Example 1: Temperature change of acupoint patch over time, measured from one side of the silver needle using an infrared camera; Figure 10 SEM image of the self-heating copper nanoparticles prepared in the comparative example. Detailed Implementation

[0023] It should be noted that the following detailed descriptions are illustrative and intended to provide further explanation of this application. Unless otherwise specified, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this application pertains.

[0024] As introduced in the background section, existing self-heating microneedle drug delivery devices have the following two problems: First, the microneedle structure is simple and the drug load is small; second, the self-heating material is basically the same as the material used in commonly used heat packs, and the heating temperature is too high. For metal acupoint patches, the metal conducts heat too quickly, which can easily cause burns.

[0025] Based on this, the purpose of this invention is to provide a self-heating microneedle acupoint patch. This invention first pours a metal organic slurry into a mold to obtain a metal sheet loaded with microneedles. Then, the microneedles are annealed. Annealing serves two purposes: first, it enhances the strength and hardness of the microneedles; second, the high temperature volatilizes and removes the organic compounds in the microneedles, leaving micropores and increasing the drug loading capacity. Under a hydrogen atmosphere, the microneedles are treated at high temperature to remove the oxide layer on their surface, resulting in porous metal microneedles, ensuring rapid heat conduction through the self-heating layer. Then, under a protective atmosphere, the self-heating metal tablet is irradiated with a laser, causing the self-heating metal to be sputtered and deposited onto the back of the drug delivery layer, forming a porous micro / nano structure, i.e., the self-heating metal layer. Because the porous insulating micro / nano layer has micropores, air passes through these micropores, oxidizing the self-heating metal in the underlying self-heating metal layer and releasing heat. Because self-heating metal is made of metal and dissipates heat quickly, without an insulation layer, heat would be lost to the surrounding air in addition to being transferred through the metal microneedles, resulting in excessive heat loss, shorter self-heating time, and poorer heating effect. However, the porous self-heating metal layer oxidizes from the outside in during the oxidation process. The outermost layer, in contact with the outside air, oxidizes into a metal oxide layer, which can prevent heat release into the air during subsequent oxidation. This avoids excessive heat loss, allowing heat to be mainly transferred through the metal drug delivery layer, promoting drug penetration, enhancing acupoint stimulation, improving the therapeutic effect of acupoints, and shortening treatment time.

[0026] Using other methods, it is difficult to prepare a porous micro / nano-structured self-heating metal layer on the back side of the self-heating layer. While laser irradiation is effective, if the compressed self-heating metal sheet is placed directly above the back of the drug delivery layer, the laser irradiation requires extremely high energy to penetrate the compressed metal sheet (greater than 100 µm) to sputter metal particles onto the drug delivery layer. Typical laser parameter settings are insufficient to penetrate the compressed sheet. High laser energy results in large, high-velocity sputtered metal particles, leading to larger particles reaching the drug delivery layer. Simultaneously, the small relative distance between the compressed metal sheet and the drug delivery layer results in minimal lateral diffusion, causing most particles to move forward at high speeds onto the drug delivery layer. This prevents the preparation of a porous self-heating metal layer on the drug delivery layer, resulting in a solid self-heating metal layer. Only the portion in contact with air is oxidized, failing to oxidize the entire self-heating metal layer and thus affecting the heating effect. If the self-heating metal sheet in the tablet is replaced with a self-heating metal sheet, using the method of this invention, the dense structure of the metal sheet makes it difficult for the laser to bombard the metal particles, reducing the amount of metal particles generated and thus reducing the metal content of the self-heating layer. If the self-heating metal sheet is placed above the drug delivery layer and the laser irradiates the self-heating metal sheet to project the self-heating metal onto the drug delivery layer, the resulting self-heating layer metal particles are larger. When the acupoint patch is used, the self-heating layer only oxidizes the surface metal upon contact with air, significantly reducing the self-heating effect. The laser energy required for laser sputtering of the metal sheet is higher than that for metal tablets. The high laser energy will trigger additional thermal effects, causing the metal particles to grow, resulting in larger self-heating metal particles.

[0027] Research has shown that by staggering the back of the drug delivery layer and the self-heating metal sheet after tableting, when the laser is irradiated from top to bottom, only the self-heating metal sheet is irradiated, not the drug delivery layer. Under an inert atmosphere, the laser only irradiates the surface of the self-heating metal sheet. By controlling the laser parameters, the self-heating metal sheet sputters metal nanoclusters, which, with the assistance of an inert gas flow, are deposited onto the drug delivery layer above, forming a self-heating metal layer with a microporous structure on the back of the drug delivery layer.

[0028] To enable those skilled in the art to better understand the technical solution of this application, the technical solution of this application will be described in detail below with reference to specific embodiments.

[0029] The test materials used in the embodiments of this invention are all conventional test materials in the art and can be purchased through commercial channels.

[0030] Example 1: (1) Preparation of the drug delivery layer: ① A polymethyl methacrylate (PMMA) microneedle array was prepared using 3D printing technology, such as... Figure 2As shown, the microneedle height is 1mm and the needle spacing is 1mm; ② Mix PDMS and RTV615 curing agent evenly at a mass ratio of 10:1, place in a vacuum drying oven to remove air bubbles from the mixture, pour onto a PMMA microneedle array, and cure in a vacuum drying oven at 80℃ for 1.5 hours. Demold to obtain the PDMS pinhole array template, as shown below. Figure 3 As shown; ③ The purchased silver paste solution (purchased from Guangzhou Kaixiang Electronic Products Co., Ltd., model and specification CD-03, 10g) was evenly filled onto the PDMS pinhole array template, ultrasonicated for 10 minutes, and cured in a vacuum drying oven at 120℃ for 1 hour to obtain the silver microneedle array. ④ Anneal the prepared silver microneedle array in air at 700 °C to remove organic matter from the silver paste, and reduce it at 600 °C for 2 h in an Ar / H2 atmosphere (V(Ar):V(H2)=10:1) to obtain a porous silver microneedle array sheet.

[0031] Depend on Figure 4 As can be seen, a silver needle with a height of 1 mm was successfully prepared; according to Figure 4 (b) It can be seen that the metal needle has a porous structure.

[0032] Depend on Figure 5 As you can see, the organic matter in the silver needle has been removed, which creates micropores on the silver needle.

[0033] ⑤ Prepare a loxoprofen sodium aqueous solution. Invert the porous silver needle with the drug delivery surface into the loxoprofen sodium aqueous solution. Store the loxoprofen sodium aqueous solution in the porous silver needle and dry it to obtain the drug delivery surface loaded with loxoprofen sodium.

[0034] (2) Preparation of the self-heating metal layer, such as Figure 6 As shown: ① Take 500mg of copper powder with a particle size of 3µm and compress it into tablets to obtain copper sheets.

[0035] ② Ar is continuously introduced into the air inlet of the quartz tube for 15 minutes beforehand to purge air. The pressed copper sheet is placed at the bottom of the quartz tube, and the drug delivery layer is fixedly placed on the top of the quartz tube wall near the air outlet, with the back of the drug delivery layer exposed downwards. The projection of the drug delivery layer on the bottom of the quartz tube does not coincide with the copper sheet, and the distance from the right end of the copper sheet to the air outlet of the quartz tube is greater than the distance from the left end of the drug delivery layer to the outlet, with a spacing of 10 mm.

[0036] ③ The airflow velocity of Ar is 20 cm. 3 The copper sheet was irradiated with a laser at a speed of 900 mm / s, a line spacing of 0.005 mm, and a power of 40 W. The laser sputtered copper nanoclusters were deposited onto the back of the acupoint patch to form a self-heating copper layer with a microporous structure.

[0037] ⑤ Place the quartz container inside the glove box and vacuum-pack the acupoint patch. See the structural diagram of the acupoint patch. Figure 1 .

[0038] (3) Usage: The medication side with porous silver needles is applied to the affected area and gently pressed. The porous silver needles penetrate the stratum corneum to reach the dermis. Loxoprofen sodium, loaded on the porous silver needles, penetrates into the dermis, providing rapid pain relief. Simultaneously, air comes into contact with the microporous self-heating copper layer (self-heating metal layer). For example... Figure 7 As shown, the self-heating metal layer contains numerous micropores. The copper nanoparticles, with a size of tens of nanometers, are small, highly reactive, and prone to oxidation. This oxidation generates heat, which heats the acupoint patch. Simultaneously, the copper oxide formed on the surface provides excellent insulation, preventing heat from escaping into the air. This allows most of the heat generated by the oxidation of the copper nanoparticles to be conducted to the body through the silver needles. This provides warmth and comfort to the affected area, accelerates drug diffusion, and further enhances the analgesic effect.

[0039] (4) Remove the acupoint patch from its vacuum packaging and test the temperature change using an infrared camera, such as... Figure 8 As shown, the temperature measured from the silver needle side reaches 38.5℃, providing warmth to the affected area and accelerating drug diffusion, further enhancing the analgesic effect. The temperature measured around the self-heating layer is not significantly different from the ambient temperature, indicating the heat-insulating effect of the oxidized self-heating metal layer.

[0040] like Figure 7 As shown, the copper nanoparticles exhibit a porous arrangement. Therefore, after the surface copper contacts air and forms copper oxide, air can enter through the pores and react with the underlying copper nanoparticles, causing an exothermic oxidation reaction. This ensures that the acupoint patch maintains a relatively uniform temperature over a longer period. Furthermore, due to the low content of copper nanoparticles, the temperature will not be excessively high, eliminating concerns about skin burns from overheating. To further test the self-heating effect of the acupoint patch, after removing the vacuum packaging, an infrared camera was used to continuously monitor temperature changes from the silver needle side. Figure 9 As shown, the temperature of the acupoint patch can rise to 38℃ within 30 seconds, and remains relatively constant for the next 20 minutes before starting to decrease. Because the silver microneedles conduct heat quickly, this time is sufficient for the medication to be fully released. Compared to ordinary acupoint patches, this accelerates treatment time and improves therapeutic efficacy.

[0041] Example 2 The difference from Example 1 is that in step (1), titanium paste is used to prepare porous titanium microneedles. Titanium powder (46wt%) with an average diameter of 3-5μm, acetic acid solution of chitosan (1wt%) and butyl phthalate (6.4wt%) are used as plasticizers, Solsperse 170000 (0.6wt%) is used as a dispersant and ethanol solution (46wt%) is used as a volatile organic solvent to cast the titanium paste; in step (2), iron powder is used to prepare the self-heating layer.

[0042] Comparative Example The difference from Example 1 is that a dense copper sheet with a thickness of 20 μm was taken and placed on top of the drug delivery layer. Both were placed at the bottom of a quartz tube, with the copper sheet and the back side of the drug delivery layer facing each other. The quartz tube was filled with argon gas, and the copper sheet was irradiated with the same laser parameters as in Example 1 to prepare a self-heating metal layer on the back side of the drug delivery layer. The SEM image of the self-heating metal layer is shown below. Figure 10 As shown, the copper particles have a relatively large size, around 5 µm, and the oxidation process only occurs on the copper surface, which severely reduces the self-heating efficiency.

[0043] The above description is merely a preferred embodiment of this application and is not intended to limit this application. Various modifications and variations can be made to this application by those skilled in the art. Any modifications, equivalent substitutions, improvements, etc., made within the spirit and principles of this application should be included within the protection scope of this application.

Claims

1. A self-heating microneedle acupoint patch, characterized in that, It includes a drug delivery layer; the drug delivery layer is a thin sheet with several microneedles on one side; the drug delivery layer includes a front side and a back side, the microneedles are located on the front side of the drug delivery layer, and the microneedles are loaded with drugs; the back side of the drug delivery layer is provided with a self-heating layer, the self-heating layer is a porous self-heating metal layer; The porous self-heating metal layer is made of at least one of silver, copper, titanium, iron, and tantalum; the thickness of the porous self-heating metal layer is 1-20 µm. The porous self-heating metal layer is prepared by the following method: (1) Press the self-heating metal powder into tablets to obtain self-heating metal sheets; (2) Take a transparent sealed container with an air inlet and an air outlet at both ends. Inert gas is introduced into the air inlet of the transparent sealed container. Place the drug delivery layer at the top of the transparent sealed container and at one end of the air outlet. Place the self-heating metal sheet at the bottom of the transparent sealed container and opposite to the back of the drug delivery layer. The distance between the self-heating metal sheet and the air outlet is greater than the distance between the drug delivery layer and the air outlet. (3) In an inert gas flow, a laser is directed at the upper surface of the self-heating metal sheet to irradiate it. The laser sputters out self-heating metal nanoclusters, which are deposited on the back side of the drug delivery layer above to form a porous self-heating metal layer with micro-nano structure.

2. The self-heating microneedle acupoint patch according to claim 1, characterized in that, The microneedles are porous microneedles; the thickness of the sheet is 0.1~0.5mm; the height of the microneedles is 200μm~2mm.

3. The self-heating microneedle acupoint patch according to claim 2, characterized in that, The method for preparing the drug delivery layer is as follows: An organic slurry containing metal is filled into a microneedle template, cured, and then demolded to obtain a metal sheet with microneedles. The metal sheet with microneedles is then annealed, followed by heat treatment in a reducing atmosphere. Finally, the drug is loaded onto the microneedles to obtain a drug delivery layer.

4. The self-heating microneedle acupoint patch according to claim 3, characterized in that, The annealing temperature is 700 °C and the annealing time is 3 h; the reducing atmosphere is Ar / H2, and the heat treatment temperature is 600 °C and the time is 2 h.

5. The self-heating microneedle acupoint patch according to claim 3, characterized in that, The method for loading the drug onto the microneedles is as follows: The microneedles are immersed in a drug solution or the drug solution is sprayed onto the microneedles, and then the microneedles are dried to load the drug onto the microneedles.

6. The self-heating microneedle acupoint patch according to claim 1, characterized in that, In step (1), the particle size of the self-heating metal powder is 1~20μm.

7. The self-heating microneedle acupoint patch according to claim 1, characterized in that, In step (2), the projection of the drug delivery layer on the bottom of the transparent sealed container does not coincide with the self-heating metal sheet; the distance between the projection of the drug delivery layer on the bottom of the transparent sealed container and the self-heating metal sheet is 5~20mm.

8. The self-heating microneedle acupoint patch according to claim 1, characterized in that, In step (3), the velocity of the inert airflow is 5~40 cm. 3 / min; Laser irradiation is performed using a fiber laser with a wavelength of 1064nm and a maximum power of 50W at a speed of 700~900mm / s, a line spacing of 0.001~0.005mm, and a power of 35~50W.

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