Preparation method and application of lappaconitine analgesic hydrogel microneedle

Abstract

The invention discloses a preparation method and application of lappaconitine analgesic hydrogel microneedles, which are used in the field of external application drugs, and the preparation method comprises the following steps: dissolving methylacryloylated sodium hyaluronate in a photocuring initiator 2, 4, 6-trimethylbenzoyl phenyl ethyl phosphonate to obtain a hyaluronic acid gel solution; the preparation method comprises the following steps: dissolving methacrylated chondroitin sulfate in a photocuring initiator 2, 4, 6-trimethylbenzoyl phenyl ethyl phosphonate to obtain a solution mixed with the methacrylated chondroitin sulfate; pre-filling an outer PDMS mold with the obtained hyaluronic acid gel solution to obtain an outer microneedle structure; the preparation method comprises the following steps: ultrasonically dissolving lappaconitine in a solution mixed with methacrylated chondroitin sulfate; and uniformly filling the lappaconitine solution into the obtained outer layer PDMS mold with the outer layer microneedle structure. Through the microneedle structure, lappaconitine can permeate into skin tissue more directly and more quickly.

Description

Technical Field

[0001] The present invention relates to the field of external application medicines, and in particular to a preparation method and application of lappaconitine analgesic hydrogel microneedles. Background Art

[0002] Pain, a functional or substantial feeling felt by the body, can have a significant impact on life when it is severe. For example, arthritis, cancer, and neuropathic pain not only cause severe physical torture to patients, but also mental suffering. Conventional analgesic methods, such as oral medications, transdermal injections, and intravenous administration, often have problems such as large side effects, high difficulty in operation, and the need for professional personnel to administer the drugs, as well as complications such as nodules or infections at the injection site.

[0003] Microneedle technology, as an innovative transdermal drug delivery method, consists of an array of hundreds of micron-sized microneedles. It can effectively penetrate the stratum corneum without touching the subcutaneous nerve endings and release the drug into the dermis. The advantages of microneedle drug delivery are obvious: no pain, efficient transmission, high flexibility, easy to use, strong customizability, reduced side effects and good portability. Aconitine, due to its excellent analgesic and anti-inflammatory effects, has been used to treat various body pains and inflammations.

[0004] The drug is released too quickly, causing the drug effect to be too concentrated, making it impossible to achieve long-term continuous analgesia; the drug's absorption efficiency on the skin is low, and some active ingredients cannot be fully utilized, affecting the overall analgesic effect; the drug's analgesic effect lasts too short to meet the need for long-term pain relief, and patients need to change patches frequently, which increases the cost and inconvenience of use.

[0005] Currently, no effective solution has been proposed for the problems in the related technologies. Summary of the invention

[0006] In order to overcome the above problems, the present invention aims to propose a method for preparing and applying a lappa lactamase analgesic hydrogel microneedle, with the aim of solving the problems that the drug release rate is too fast, resulting in the drug effect being too concentrated and unable to achieve long-term continuous analgesia; the drug absorption efficiency on the skin is low, and some active ingredients cannot be fully utilized, affecting the overall analgesic effect; the drug analgesic duration is too short to meet the demand for long-term pain relief, and patients need to frequently change patches, thereby increasing the cost and inconvenience of use.

[0007] To this end, the specific technical solution adopted by the present invention is as follows:

[0008] According to one aspect of the present invention, a method for preparing lappaconitine analgesic hydrogel microneedles is provided, and the method for preparing lappaconitine analgesic hydrogel microneedles comprises the following steps:

[0009] S1, dissolving methacrylated sodium hyaluronate in a photocuring initiator 2,4,6-trimethylbenzoylphenylphosphonic acid ethyl ester, and ensuring complete dissolution by controlling the dissolution temperature and stirring time to obtain a hyaluronic acid gel solution;

[0010] S2, dissolving methacryloyl chondroitin sulfate in a photocuring initiator, 2,4,6-trimethylbenzoylphenylphosphonic acid ethyl ester; ensuring complete dissolution by controlling the dissolution temperature and stirring time to obtain a solution mixed with methacryloyl chondroitin sulfate;

[0011] S3, pre-filling the obtained hyaluronic acid gel solution into the outer PDMS mold, performing vacuum treatment under vacuum conditions; performing centrifugal treatment, and irradiating under blue ultraviolet light to obtain an outer microneedle structure;

[0012] S4, dissolving lappaconitine in a solution mixed with methacryloylated chondroitin sulfate by ultrasonication, controlling the ultrasonic power and time, to obtain a lappaconitine solution;

[0013] S5, evenly filling the lappaconitine solution into the outer PDMS mold of the outer microneedle structure obtained, and repeatedly drying the mold; and irradiating the mold under ultraviolet light to form a double-layer microneedle structure;

[0014] S6. Place the double-layer microneedle structure in a vacuum drying oven and remove residual moisture.

[0015] Optionally, the dissolving temperature is 40-50°C.

[0016] Optionally, the stirring time is 30 minutes.

[0017] Optionally, the outer PDMS mold has a height of 900 μm, a base width of 300 μm, and a needle tip spacing of 700 μm.

[0018] Optionally, performing vacuum treatment under vacuum conditions includes performing vacuum treatment for 10 minutes under a vacuum condition of less than 200 Pa.

[0019] Optionally, the centrifugation comprises centrifugation at 3000 rpm for 10 minutes.

[0020] Optionally, the ultrasonic power is 80 W and the ultrasonic time is 10 minutes.

[0021] Optionally, the lappaconitine solution is evenly filled into the outer PDMS mold of the outer microneedle structure that has been obtained and repeatedly dried for 10 minutes.

[0022] Optionally, the double-layer microneedle structure is placed in a vacuum drying oven with a vacuum degree controlled below 100 Pa and maintained for 4 hours.

[0023] According to another aspect of the present invention, a method for preparing lappaconitine analgesic hydrogel microneedles and its application in lappaconitine analgesic hydrogel microneedles are also provided.

[0024] Compared with the prior art, this application has the following beneficial effects:

[0025] 1. The present invention adopts an ingenious double-layer structure design, in which the outer layer is formed by a PDMS mold to form a microneedle structure, and the inner layer is formed by a lappaconitine solution to form a microneedle structure containing drug components, which not only improves the mechanical strength and stability of the microneedle, but also realizes the effective load and slow release of the drug, thereby enhancing the analgesic effect; in the preparation process, by accurately controlling key parameters such as dissolution temperature, stirring time, vacuum treatment, centrifugal treatment and light curing irradiation time, the complete dissolution and uniform mixing of each component and the precise formation of the microneedle structure are ensured, the controllability and repeatability of the preparation process are improved, and the quality and performance of the microneedle are ensured; the selected materials such as methacryloyl sodium hyaluronate, methacryloyl chondroitin sulfate and PDMS have good biocompatibility and can reduce the stimulation and rejection reaction to human tissues. At the same time, lappaconitine, as a compound with biological activities such as analgesia and anti-inflammatory, further enhances the biomedical application value of microneedles.

[0026] 2. Through the microneedle structure of the present invention, lappaconitine can penetrate into the skin tissue more directly and quickly, thereby improving the delivery efficiency and utilization rate of the drug, which not only reduces the waste and side effects of the drug, but also achieves precise treatment of the painful area. BRIEF DESCRIPTION OF THE DRAWINGS

[0027] The above characteristics, features and advantages of the present invention and their implementation methods and methods will become more clearly understood in conjunction with the following description of the embodiments, which are described in detail in conjunction with the accompanying drawings. Herein, a schematic diagram is shown:

[0028] Figure 1 This is a flow chart of a method for preparing lappaconitine analgesic hydrogel microneedles according to an embodiment of the present invention;

[0029] Figure 2 This is a picture of lappaconitine analgesic hydrogel microneedles prepared in a method for preparing lappaconitine analgesic hydrogel microneedles according to an embodiment of the present invention. DETAILED DESCRIPTION

[0030] In order to enable those skilled in the art to better understand the solution of the present application, the technical solution in the embodiments of the present application will be clearly and completely described below in conjunction with the drawings in the embodiments of the present application. Obviously, the described embodiments are only part of the embodiments of the present application, not all of the embodiments. Based on the embodiments in the present application, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of this application.

[0031] According to an embodiment of the present invention, a method for preparing and using a lappaconitine analgesic hydrogel microneedle is provided.

[0032] The present invention is further described with reference to the accompanying drawings and specific embodiments. Figure 1-Figure 2 As shown, according to one embodiment of the present invention, a method for preparing lappaconitine analgesic hydrogel microneedles is provided, and the method for preparing lappaconitine analgesic hydrogel microneedles comprises the following steps:

[0033] S1. Dissolve methacrylated sodium hyaluronate in a photocuring initiator, ethyl 2,4,6-trimethylbenzoylphenylphosphonate, and ensure complete dissolution by controlling the dissolving temperature and stirring time to obtain a hyaluronic acid gel solution.

[0034] Preferably, the dissolution temperature is 40-50°C.

[0035] Preferably, the stirring time is 30 minutes.

[0036] It should be explained that sodium methacrylated hyaluronate is a chemically modified hyaluronic acid with a methacryloyl group, which enables it to undergo free radical polymerization. Hyaluronic acid itself is a natural polysaccharide with good biocompatibility and moisturizing properties. After modification, its properties are further expanded and can be used to prepare biomedical materials such as hydrogels. The photocuring initiator 2,4,6-trimethylbenzoylphenylphosphonic acid ethyl ester is a commonly used photocuring initiator that can generate free radicals under ultraviolet or visible light irradiation, thereby initiating polymerization reactions. Its selection should be based on factors such as its photosensitivity, solubility, and compatibility with monomers.

[0037] The dissolving temperature is 40-50℃, and the stirring time is 30 minutes. The appearance of the solution is used to determine whether it is completely dissolved. A completely dissolved solution should be transparent and free of granular substances. If there are undissolved particles or turbidity, it means that the solution is not completely dissolved and it is necessary to continue stirring or adjust the dissolving conditions.

[0038] S2, dissolving methacryloyl chondroitin sulfate in the photocuring initiator 2,4,6-trimethylbenzoylphenylphosphonic acid ethyl ester; ensuring complete dissolution by controlling the dissolving temperature and stirring time to obtain a solution mixed with methacryloyl chondroitin sulfate.

[0039] Chondroitin sulfate in methacrylylated chondroitin sulfate is a natural polysaccharide. After methacrylylation, polymerizable groups are introduced into its molecular chain, enabling it to undergo free radical polymerization. This modified chondroitin sulfate has a wide range of applications in the biomedical field, such as in the preparation of biomaterials such as hydrogels and films.

[0040] The dissolving temperature is 40-50℃, the stirring time is 30 minutes, and the complete dissolution is judged by observing the appearance of the solution. A completely dissolved solution should be transparent and free of granular substances. If there are undissolved particles or turbidity, it means that the dissolution is incomplete and it is necessary to continue stirring or adjust the dissolution conditions.

[0041] S3. Pre-fill the obtained hyaluronic acid gel solution into the outer PDMS mold, and perform vacuum treatment under vacuum conditions; and perform centrifugal treatment, and place it under blue ultraviolet light for irradiation to obtain the outer microneedle structure.

[0042] Preferably, the centrifugation comprises centrifugation at 3000 rpm for 10 minutes.

[0043] Preferably, the outer PDMS mold has a height of 900 μm, a base width of 300 μm, and a needle tip spacing of 700 μm.

[0044] Preferably, performing vacuum treatment under vacuum conditions includes performing vacuum treatment for 10 minutes under a vacuum condition of less than 200 Pa.

[0045] It should be explained that, first of all, the outer PDMS (polydimethylsiloxane) mold needs to be prepared. PDMS is a commonly used biomedical material with good biocompatibility and processability. In this step, the specifications of the outer PDMS mold are preferably 900 μm high, 300 μm base width, and 700 μm needle tip spacing. These dimensions are designed to meet the specific requirements of the microneedle structure. The hyaluronic acid gel solution obtained previously is carefully injected into the outer PDMS mold. Avoid bubbles during injection and ensure that the solution is evenly distributed.

[0046] The filled PDMS mold is placed in a vacuum chamber and vacuum treated under a vacuum degree of less than 200 Pa. The purpose of the vacuum treatment is to remove bubbles in the solution and ensure the uniformity and integrity of the microneedle structure. The preferred vacuum treatment time is 10 minutes, which is enough to remove most bubbles.

[0047] The centrifugal treatment is to further remove bubbles and impurities in the solution and make the solution more evenly distributed in the PDMS mold. The preferred centrifugal parameters are 3000 rpm for 10 minutes. The selection of this speed and time is based on experimental experience and material properties.

[0048] The centrifuged PDMS mold is placed under ultraviolet light for irradiation. Ultraviolet light can excite the photocuring initiator to produce free radicals, thereby initiating the polymerization reaction of the hyaluronic acid gel solution. The irradiation time depends on factors such as the type and concentration of the photocuring initiator, the thickness of the solution, and the desired microneedle structure. Through the photocuring process, a microneedle structure with a specific shape and size can be obtained.

[0049] PDMS (polydimethylsiloxane) mold: PDMS is a commonly used microfluidic and microfabrication material with good biocompatibility, plasticity and transparency. It can be used to prepare microstructures with complex shapes, such as microneedles and microchannels, through mold replication technology.

[0050] S4. Dissolve lappaconitine in a solution mixed with methacryloylated chondroitin sulfate by ultrasonication, control the ultrasonic power and time, and obtain a lappaconitine solution.

[0051] Preferably, the ultrasonic power is 80W and the ultrasonic time is 10 minutes.

[0052] It should be explained that lappaconitine: lappaconitine is a compound with analgesic, anti-inflammatory and other biological activities, and is commonly used in the preparation of pharmaceutical preparations. In this step, lappaconitine is added to the solution as an active ingredient.

[0053] Solution mixed with methacryloyl chondroitin sulfate: This is the solution prepared in the previous step, which contains methacryloyl chondroitin sulfate and a photocuring initiator. This solution has good biocompatibility and polymerizability and is suitable for preparing biomedical materials such as microneedles.

[0054] Ultrasonic power and time control: Lappaconitine is added to a solution mixed with methacryloylated chondroitin sulfate and dissolved by ultrasound. Ultrasound is a high-frequency vibration wave that can produce strong cavitation and mechanical effects, thereby accelerating the dissolution of the solute. In this step, the preferred ultrasonic power is 80W and the ultrasonic time is 10 minutes. The selection of these two parameters is based on experimental experience and material properties, aiming to ensure that Lappaconitine is completely dissolved in the solution while avoiding degradation or destruction of the material.

[0055] Dissolution process: Under the action of ultrasound, the lappaconitine molecules are gradually broken and dispersed in the solution, and are fully mixed with methacryloyl chondroitin sulfate and photocuring initiator. By controlling the ultrasonic power and time, it can be ensured that the lappaconitine is completely dissolved in the solution to form a uniform solution.

[0056] After ultrasonic dissolution, we obtained a uniform solution containing lappaconitine, methacryloyl chondroitin sulfate and photocuring initiator. This solution can be used to prepare biomedical materials such as microneedles with analgesic function in subsequent steps.

[0057] Methacryloyl Chondroitin Sulfate: Methacryloyl Chondroitin Sulfate is a chemically modified chondroitin sulfate with polymerizable groups and specific biological activity. In the preparation of biomedical materials, Methacryloyl Chondroitin Sulfate can be added to the material as a matrix material or active ingredient to improve the performance of the material or give the material specific biological functions.

[0058] S5. The lappaconitine solution is evenly filled into the outer PDMS mold of the outer microneedle structure obtained and dried repeatedly for multiple times; and then irradiated under blue ultraviolet light to form a double-layer microneedle structure.

[0059] Preferably, the lappaconitine solution is evenly filled into the outer PDMS mold of the outer microneedle structure that has been obtained and the irradiation time for repeated drying is 10 minutes.

[0060] It should be explained that the lappaconitine solution is a uniform solution containing lappaconitine, methacryloyl chondroitin sulfate and photocuring initiator prepared in the previous step.

[0061] Outer PDMS mold of outer microneedle structure: This is the PDMS mold with outer microneedle structure prepared in the previous step. This mold has been formed into a microneedle shape by photocuring technology, and now it needs to be used as a container filled with lappa acetamiprid solution.

[0062] Carefully inject the lappaconitine solution into the outer PDMS mold of the outer microneedle structure. Make sure the solution is evenly distributed during injection and avoid creating bubbles. Tools such as a micropipette or syringe can be used for precise injection.

[0063] The filled PDMS mold is placed in a drying oven and dried repeatedly. The purpose of drying is to remove the solvent in the solution, leaving solid components such as lappaconitine and methacryloyl chondroitin sulfate in the mold to form a stable microneedle structure.

[0064] Each drying time is 10 minutes. Repeated drying can ensure that the solvent in the solution is completely removed while avoiding degradation or damage to the material. The number and time of drying can be adjusted according to the specific situation to achieve the best effect.

[0065] The dried PDMS mold is placed under ultraviolet light for irradiation. The ultraviolet light can excite the photocuring initiator to produce free radicals, thereby initiating a polymerization reaction in the lappa urea solution. Through the photocuring process, a microneedle with a double-layer structure can be formed.

[0066] The irradiation time depends on factors such as the type and concentration of the photocuring initiator, the thickness of the solution, and the desired microneedle structure. By adjusting the irradiation time, the shape and size of the microneedles can be controlled.

[0067] After the above steps, a microneedle with a double-layer structure is obtained. The outer layer is a microneedle structure formed by a PDMS mold, and the inner layer is a microneedle structure containing drug components formed by a lappaconitine solution. This double-layer microneedle structure has broad application prospects in the biomedical field, such as for drug delivery, pain treatment, etc.

[0068] S6. Place the double-layer microneedle structure in a vacuum drying oven and remove residual moisture.

[0069] Preferably, the double-layer microneedle structure is placed in a vacuum drying oven with a vacuum degree controlled below 100 Pa and maintained for 4 hours.

[0070] It should be explained that the double-layer microneedle structure is a microneedle with a double-layer structure prepared in the previous step, the outer layer is a microneedle structure formed by a PDMS mold, and the inner layer is a microneedle structure containing drug ingredients formed by a lappa 11 solution.

[0071] The double-layer microneedle structure is carefully placed in a vacuum drying oven. A vacuum drying oven is a commonly used device for removing residual moisture and solvents from materials. By reducing the air pressure in the oven, the evaporation and removal of moisture can be accelerated.

[0072] In the vacuum drying oven, the vacuum degree is controlled below 100 Pa by adjusting the working parameters of the vacuum pump. The selection of this vacuum degree is based on experimental experience and consideration of material properties, aiming to ensure that moisture can be effectively removed from the microneedle structure while avoiding structural damage or performance loss of the material.

[0073] The double-layer microneedle structure is kept in a vacuum drying oven for 4 hours. This time is chosen to ensure that the residual moisture in the microneedle structure can be fully removed to achieve the desired drying effect. The length of the holding time can be adjusted according to the specific situation to achieve the best effect.

[0074] In a vacuum drying oven, the evaporation rate of water will be accelerated due to the reduction of air pressure. At the same time, the vacuum environment can also reduce oxidation and contamination on the surface of the material, and improve the purity and performance of the material. By maintaining a certain time and vacuum degree, it can ensure that the residual water in the double-layer microneedle structure is effectively removed.

[0075] The examples are outlined below:

[0076] This example aims to prepare a hydrogel microneedle containing a lappaconitine analgesic ingredient. The microneedle consists of an outer PDMS microneedle structure and an inner lappaconitine drug layer, and has a double-layer structure for pain treatment.

[0077] The specific steps are as follows:

[0078] 1) Preparation of hyaluronic acid gel solution:

[0079] 1 g of methacrylated sodium hyaluronate was dissolved in 10 mL of photocuring initiator 2,4,6-trimethylbenzoylphenylphosphonic acid ethyl ester.

[0080] Stir at 45°C for 30 minutes to ensure complete dissolution to obtain a transparent, particle-free hyaluronic acid gel solution.

[0081] 2) Preparation of a solution mixed with methacrylylated chondroitin sulfate:

[0082] 1 g of methacryloyl chondroitin sulfate was dissolved in 10 mL of photocuring initiator 2,4,6-trimethylbenzoylphenylphosphonic acid ethyl ester.

[0083] The mixture was stirred at 45°C for 30 minutes to ensure complete dissolution and obtain a transparent solution.

[0084] 3) Preparation of outer microneedle structure:

[0085] The outer PDMS mold was prepared with specifications of 900 μm in height, 300 μm in base width, and 700 μm in needle tip spacing.

[0086] Pre-fill the outer PDMS mold with the hyaluronic acid gel solution, avoiding bubbles.

[0087] The vacuum treatment was performed for 10 minutes at a vacuum degree of less than 200 Pa to remove air bubbles.

[0088] The mixture was centrifuged at 3000 rpm for 10 minutes to further remove bubbles and impurities.

[0089] The microneedle is placed under blue ultraviolet light for irradiation, and the irradiation time is adjusted according to the specific situation until an outer microneedle structure with a specific shape and size is obtained.

[0090] 4) Preparation of lappaconitine solution:

[0091] 0.5 g of lappaconitine was dissolved by ultrasonication in the previously prepared solution mixed with methacryloylated chondroitin sulfate.

[0092] The ultrasonic power was 80 W and the ultrasonic time was 10 min to ensure that lappaconitine was completely dissolved to form a uniform solution.

[0093] 5) Formation of a double-layer microneedle structure:

[0094] The lappaconitine solution was evenly filled into the outer PDMS mold of the outer microneedle structure that had been obtained.

[0095] Repeat the drying process several times, with each drying time lasting 10 minutes, to ensure that the solvent in the solution is completely removed.

[0096] The microneedles are placed under blue ultraviolet light for irradiation, and the irradiation time is adjusted according to the specific situation until a microneedle with a double-layer structure is formed.

[0097] 6) Remove residual moisture:

[0098] The double-layer microneedle structure was carefully placed in a vacuum drying oven.

[0099] Adjust the working parameters of the vacuum pump to control the vacuum degree below 100Pa.

[0100] Keep it for 4 hours to ensure that the residual water in the microneedle structure is fully removed.

[0101] According to another embodiment of the present invention, a method for preparing lappaconitine analgesic hydrogel microneedles and applying the same in lappaconitine analgesic hydrogel microneedles are provided.

[0102] In summary, with the aid of the above technical scheme of the present invention, the present invention adopts an ingenious double-layer structure design, in which the outer layer is formed of a PDMS mold to form a microneedle structure, and the inner layer is formed of a lappa quinone solution to form a microneedle structure containing drug components, which not only improves the mechanical strength and stability of the microneedles, but also realizes the effective loading and slow release of drugs, thereby enhancing the analgesic effect; in the preparation process, by accurately controlling key parameters such as dissolution temperature, stirring time, vacuum treatment, centrifugal treatment and light curing irradiation time, the complete dissolution and uniform mixing of each component and the precise formation of the microneedle structure are ensured, thereby improving the controllability and Repeatability ensures the quality and performance of the microneedles; the selected materials such as sodium methacrylated hyaluronate, methacrylated chondroitin sulfate and PDMS have good biocompatibility and can reduce irritation and rejection reactions to human tissues; at the same time, lappaconitine, as a compound with analgesic, anti-inflammatory and other biological activities, further enhances the biomedical application value of the microneedles; through the microneedle structure of the present invention, lappaconitine can penetrate into the skin tissue more directly and quickly, thereby improving the delivery efficiency and utilization rate of the drug, which not only reduces the waste and side effects of the drug, but also realizes the precise treatment of the painful area.

[0103] Although the present invention has been disclosed as above with preferred embodiments, the embodiments are merely examples for the convenience of description and are not intended to limit the present invention. Those skilled in the art may make several changes and modifications without departing from the spirit and scope of the present invention. The scope of protection claimed by the present invention shall be based on the claims.

Claims

1. A method for preparing lappaconitine analgesic hydrogel microneedles, characterized in that: The method for preparing the lappaconitine analgesic hydrogel microneedle comprises the following steps: S1, dissolving methacrylated sodium hyaluronate in a photocuring initiator 2,4,6-trimethylbenzoylphenylphosphonic acid ethyl ester, and ensuring complete dissolution by controlling the dissolution temperature and stirring time to obtain a hyaluronic acid gel solution; S2, dissolving methacryloyl chondroitin sulfate in a photocuring initiator, ethyl 2,4,6-trimethylbenzoylphenylphosphonate; ensuring complete dissolution by controlling the dissolution temperature and stirring time, to obtain a solution mixed with methacryloyl chondroitin sulfate; S3, pre-filling the obtained hyaluronic acid gel solution into the outer PDMS mold, performing vacuum treatment under vacuum conditions; performing centrifugal treatment, and irradiating under blue ultraviolet light to obtain an outer microneedle structure; S4, dissolving lappaconitine in a solution mixed with methacryloylated chondroitin sulfate by ultrasonication, controlling the ultrasonic power and time, to obtain a lappaconitine solution; S5, evenly filling the lappaconitine solution into the outer PDMS mold of the outer microneedle structure obtained, and repeatedly drying the mold; and irradiating the mold under ultraviolet light to form a double-layer microneedle structure; S6. Place the double-layer microneedle structure in a vacuum drying oven and remove residual moisture.

2. The method for preparing a lappaconitine analgesic hydrogel microneedle according to claim 1, characterized in that: The dissolving temperature is 40-50°C.

3. The method for preparing a lappaconitine analgesic hydrogel microneedle according to claim 2, characterized in that: The stirring time is 30 minutes.

4. The method for preparing a lappaconitine analgesic hydrogel microneedle according to claim 3, characterized in that: The outer PDMS mold has a height of 900 μm, a base width of 300 μm, and a needle tip spacing of 700 μm.

5. The method for preparing a lappaconitine analgesic hydrogel microneedle according to claim 4, characterized in that: The vacuum treatment under vacuum conditions includes performing vacuum treatment for 10 minutes under a vacuum condition of less than 200 Pa.

6. The method for preparing lappaconitine analgesic hydrogel microneedle according to claim 5, characterized in that: The centrifugation treatment includes centrifugation at 3000 rpm for 10 minutes.

7. The method for preparing lappaconitine analgesic hydrogel microneedle according to claim 6, characterized in that: The ultrasonic power is 80W, and the ultrasonic time is 10 minutes.

8. The method for preparing lappaconitine analgesic hydrogel microneedle according to claim 7, characterized in that: The irradiation time for uniformly filling the lappaconitine solution into the outer PDMS mold of the outer microneedle structure obtained and repeatedly drying the mold is 10 minutes.

9. The method for preparing lappaconitine analgesic hydrogel microneedle according to claim 8, characterized in that: The double-layer microneedle structure is placed in a vacuum drying oven with a vacuum degree controlled below 100 Pa and maintained for 4 hours.

10. The method for preparing lappaconitine analgesic hydrogel microneedles according to any one of claims 1 to 9 is used in lappaconitine analgesic hydrogel microneedles.

Images