Manufacturing method of silk fibroin hydrogel microneedle and hydrogel microneedle

Abstract

According to the silk fibroin hydrogel microneedle manufacturing method and the hydrogel microneedle, a silk fibroin solution and a riboflavin aqueous solution are evenly mixed to obtain a mixed solution, then a hydrogen peroxide solution is added into the mixed solution to be mixed to obtain a precursor solution, then the precursor solution is poured into a light-transmitting microneedle mold, and the silk fibroin hydrogel microneedle is obtained. Placing a microneedle mold containing the precursor solution into a vacuum pump, performing vacuum pumping treatment, taking out the microneedle mold, placing the microneedle mold under ultraviolet irradiation for illumination to form a gel, drying the gel at room temperature, taking out the gel from the microneedle mold, forming a plurality of convex cones on the outer surface of the gel, and performing vacuum pumping treatment on the cones to obtain the composite microneedle. The silk fibroin hydrogel microneedle is obtained. According to the design, the operation requirement is low, the slow release effect is good, the biocompatibility is high, and efficient carrying of treatment medicine is facilitated.

Description

Technical Field

[0001] The invention relates to a microneedle preparation process, belongs to the field of polymer gel, and particularly relates to a silk fibroin hydrogel microneedle preparation method and the hydrogel microneedle. Background Art

[0002] Microneedles (MNs) are microscale needles used for drug delivery and other targeting. A large number of preclinical studies and a limited number of clinical trials have shown that MNs can be used to deliver oligonucleotides, desmopressin, DNA, vaccines, insulin, and human growth hormone through the skin. In addition, MNs have been widely studied for blood sampling, signal monitoring, intrascleral drug delivery, microneedle-assisted gene transfer, and biosensors.

[0003] Since most polymers are biocompatible, existing polymer microneedles rarely cause serious side effects. However, since most polymers are soft, this may cause catastrophic buckling failure of the microneedles during insertion. It can be seen that in addition to biocompatibility, microneedles must also have high mechanical properties, be able to penetrate into the skin, and destroy the stratum corneum without breaking or buckling failure.

[0004] The invention patent application with application number 201410061578.8 and application date February 24, 2014 discloses a silk fibroin gel microneedle system and its preparation method, wherein a silk fibroin solution with a mass concentration of 3-15% is treated with ultrasonic oscillation, and then cast on a polydimethylsiloxane membrane pinhole mold array obtained by laser drilling, and the mold is placed in a vacuum drying oven to evacuate the solution into the holes, and the vacuum is maintained to dry the mold to a constant weight to obtain a silk fibroin gel microneedle system. Although the design is an insoluble gel microneedle with a certain strength to penetrate the skin, it still has the following defects: This design requires that the silk fibroin solution be treated with ultrasonic vibration first to induce pre-crystallization of the silk fibroin solution, so that gelation can occur after the pre-crystallized silk fibroin solution is poured into the mold to form silk fibroin gel microneedles. The operation requirements are high, and the gelation process is carried out in two stages, making it difficult to ensure the quality of the gel. In addition, the production process of this design means that therapeutic drugs can only be added after the silk fibroin gel microneedles are formed, which undoubtedly increases the difficulty of carrying drugs and also impairs the effect of subsequent drug sustained release.

[0005] The information disclosed in this background technology section is only intended to increase the understanding of the overall background of the application, and should not be regarded as acknowledging or suggesting in any form that the information constitutes the prior art already known to ordinary technicians in this field. Summary of the invention

[0006] The purpose of the present invention is to overcome the defects and problems of the prior art, such as high operating requirements and poor sustained-release effect, and to provide a method for manufacturing a silk fibroin hydrogel microneedle and a hydrogel microneedle with low operating requirements and good sustained-release effect.

[0007] To achieve the above objectives, the technical solution of the present invention is: a method for manufacturing silk fibroin hydrogel microneedles, the manufacturing method comprising the following steps: The first step: firstly, the silk fibroin solution and the riboflavin aqueous solution are uniformly mixed to obtain a mixed solution, and then the hydrogen peroxide solution is added to the mixed solution for mixing to obtain a precursor solution; The second step: first pour the precursor solution into a light-transmitting microneedle mold, then put the microneedle mold containing the precursor solution into a vacuum pump, and then perform a vacuum treatment. Then take out the microneedle mold, and place it under ultraviolet light to form a gel. Then dry it at room temperature, and then take the gel out of the microneedle mold. A plurality of convex cones are formed on the outer surface of the gel. Then peel off the cones on the gel one by one to obtain a plurality of silk fibroin hydrogel microneedles, and one cone corresponds to one silk fibroin hydrogel microneedle.

[0008] In the second step, the microneedle mold includes a top surface and a groove arranged therein, the bottom of the groove is connected to the top ends of a plurality of hollow conical tubes, the bottom ends of the conical tubes extend downward, and the top ends of the conical tubes are wider than the bottom ends of the conical tubes; The pouring of the precursor solution into the light-transmitting microneedle mold means: first pouring the precursor solution into the groove, and then the precursor solution flows into the cone; The step of taking the gel out of the microneedle mold refers to: using tweezers to clamp the gel out of the groove, at which point all the cones are located at the bottom of the gel.

[0009] In the first step, the concentration of the silk fibroin solution is 1.5-7wt%, the concentration of the riboflavin aqueous solution is 0.05-10mmol / L, and the volume ratio between the silk fibroin solution and the riboflavin aqueous solution is 5-20:1.

[0010] In the first step, the volume percentage concentration of the hydrogen peroxide solution is 5-30%, and the volume ratio between the hydrogen peroxide solution and the mixed solution is 1:5-30.

[0011] In the second step, the vacuum condition corresponding to the vacuum treatment is -0.04 to +0.10Mpa.

[0012] In the second step, the operating parameters of the ultraviolet light are: the power of the ultraviolet lamp is 100-900W, and the illumination time is 2-30min.

[0013] In the first step, the silk fibroin solution is prepared according to the following steps: first, the raw silk is placed in a sodium carbonate aqueous solution and heated and immersed for degumming to obtain degummed silk fibroin fibers, and then the degummed silk fibroin fibers are immersed in a LiBr aqueous solution and heated to dissolve to obtain a crude solution, and then the obtained crude solution is placed in a dialysis bag, and then the dialysis bag is placed in deionized water for low-temperature dialysis, the dialysis temperature is 0-4°C, the dialysis time is 1-5d, and then the remaining solution in the dialysis bag after dialysis is filtered to obtain a filtrate, which is the silk fibroin solution.

[0014] The concentration of the sodium carbonate aqueous solution is 0.1-0.5wt%, and the mass volume ratio of raw silk to the sodium carbonate aqueous solution is 1g / 10-100mL; The heating temperature of the degumming treatment is 45-100°C, and the degumming treatment time is 1-8h; The concentration of the LiBr aqueous solution is 1-10 mol / L, and the mass volume ratio of the degummed silk fibroin fiber to the LiBr aqueous solution is 1 g / 1-20 mL; The temperature for heating and dissolving the degummed silk fibroin fibers in the LiBr aqueous solution is 45-85° C., and the heating and dissolving time is 0.5-3 hours.

[0015] In the first step, after obtaining the precursor solution, a therapeutic drug is added to obtain a drug-carrying precursor solution; In the second step, the drug-carrying precursor solution is poured into a light-transmitting microneedle mold, and the resulting silk fibroin hydrogel microneedles contain therapeutic drugs.

[0016] A hydrogel microneedle is prepared according to the above-mentioned method for preparing a silk fibroin hydrogel microneedle.

[0017] Compared with the prior art, the present invention has the following beneficial effects: 1. In a method for manufacturing a silk fibroin hydrogel microneedle and a hydrogel microneedle of the present invention, a silk fibroin solution and a riboflavin aqueous solution are first mixed uniformly to obtain a mixed solution, a hydrogen peroxide solution is added to the mixed solution for mixing to obtain a precursor solution, and then the precursor solution is poured into a light-transmitting microneedle mold, and then the microneedle mold containing the precursor solution is placed in a vacuum pump, and then vacuumized, and then the microneedle mold is taken out and placed under ultraviolet light for illumination to form a gel, and then dried at room temperature, and then the gel is taken out from the microneedle mold, and a plurality of convex cones are formed on the outer surface of the gel, namely the silk fibroin hydrogel microneedle, and the advantages of this design include: First of all, the overall operation only requires mixing, vacuuming, and ultraviolet irradiation, which is easy to operate, especially drying can be done at room temperature, and vacuuming only takes 15min-45min, which is convenient and fast; Secondly, the main raw materials include silk fibroin solution, riboflavin aqueous solution, and hydrogen peroxide solution. Among them, silk fibroin solution and riboflavin aqueous solution have good biocompatibility, and hydrogen peroxide is basically consumed in the gel process, and its content is very small and non-toxic to the human body. Therefore, there is no organic reagent residue in the final microneedle, no biological toxicity, and good biocompatibility. Thirdly, the whole production process only includes the preparation of the precursor solution and the subsequent treatment of the precursor solution. Among them, the preparation process of the precursor solution is conducive to the addition of therapeutic drugs, so that the final microneedles contain therapeutic drugs, rather than additional additions after the microneedles are prepared, which is more conducive to the slow release of therapeutic drugs. First, the three-dimensional hydrogel structure can evenly wrap most of the therapeutic drugs inside it, rather than exposing them to the outside, avoiding drug waste and failure. Secondly, the encapsulation of the therapeutic drugs can synchronize the process of the drugs entering the human body with the process of the hydrogel being degraded by the tissue fluid, thereby achieving a slow release process, which is conducive to the sustained release of the drugs. Therefore, the present invention not only has lower operation requirements and better sustained-release effect, but also has stronger biocompatibility.

[0018] 2. In the method for manufacturing a silk fibroin hydrogel microneedle and the hydrogel microneedle of the present invention, the precursor solution used is a blend of a silk fibroin solution, a riboflavin aqueous solution, and a hydrogen peroxide solution, wherein the silk fibroin is based, and riboflavin and hydrogen peroxide are used as a photocuring system, and the silk fibroin hydrogel is cured under ultraviolet light. During the reaction, hydrogen peroxide decomposes under ultraviolet light to produce oxygen, and riboflavin is first excited to produce a triplet state under ultraviolet light, and then reacts with the oxygen produced by hydrogen peroxide to form oxygen free radicals, which are then The base promotes the mutual entanglement between the silk protein macromolecules to form a gel (that is, riboflavin and H2O2 undergo a continuous photo-crosslinking cycle reaction, promoting the conversion of tyrosine to dityrosine, and playing a role in catalyzing gelation). It can be seen that hydrogen peroxide, as an oxygen source, can provide more oxygen for the photocuring system, continuously promote the continuation of the reaction, greatly shorten the gel formation time, and improve the production efficiency of hydrogel microneedles. At the same time, this rapid gel process is also conducive to safely encapsulating the therapeutic drug in the microneedle to avoid damage due to the production process. Therefore, the present invention not only has a short production time and high production efficiency, but also is conducive to the efficient carrying of therapeutic drugs.

[0019] 3. In the method for manufacturing a silk fibroin hydrogel microneedle and the hydrogel microneedle of the present invention, a therapeutic drug can be added after obtaining a precursor solution to obtain a drug-carrying precursor solution, and then the drug-carrying precursor solution is poured into a light-transmitting microneedle mold, and the finally obtained silk fibroin hydrogel microneedle contains the therapeutic drug. The advantages of this design include: First, before the hydrogel microneedles are formed, an opportunity can be provided for the therapeutic drug to be mixed with the precursor solution, so that the drug is carried during the formation of the microneedles, so that the silk fibroin hydrogel microneedles finally obtained contain therapeutic drugs both inside and on the outer wall, and the therapeutic drugs contained inside the silk fibroin hydrogel microneedles are greater than those contained on the outer wall; Secondly, the short preparation time of the hydrogel microneedles in this design is fully utilized to mix the therapeutic drug with the precursor solution before photopolymerization and curing, so that most of the therapeutic drugs are evenly coated inside the hydrogel microneedles. The microneedles are used as carriers of therapeutic drugs to achieve the purpose of controlled drug delivery, expanding the application of silk fibroin-based hydrogel microneedles in the biomedical field. Therefore, the present invention can not only carry drugs during the process of making microneedles, but also make most of the therapeutic drugs evenly distributed in the microneedles, which is beneficial to the promotion and application in the biomedical field. BRIEF DESCRIPTION OF THE DRAWINGS

[0020] Figure 1 It is a schematic diagram of the structure of the gel in the present invention.

[0021] Figure 2 It is a schematic diagram of the structure of the microneedles on the gel in the present invention.

[0022] Figure 3 It is a schematic diagram of the operation of clamping out the gel in the present invention.

[0023] Figure 4 It is a structural schematic diagram of the mold in the present invention. DETAILED DESCRIPTION

[0024] The present invention is further described in detail below in conjunction with the accompanying drawings and specific implementation methods.

[0025] See also Figure 1 — Figure 4 , a method for manufacturing a silk fibroin hydrogel microneedle, the manufacturing method comprising the following steps: The first step: firstly, the silk fibroin solution and the riboflavin aqueous solution are uniformly mixed to obtain a mixed solution, and then the hydrogen peroxide solution is added to the mixed solution for mixing to obtain a precursor solution; The second step: first pour the precursor solution into a light-transmitting microneedle mold, then put the microneedle mold containing the precursor solution into a vacuum pump, and then perform a vacuum treatment. Then take out the microneedle mold, and place it under ultraviolet light to form a gel. Then dry it at room temperature, and then take the gel out of the microneedle mold. A plurality of convex cones are formed on the outer surface of the gel. Then peel off the cones on the gel one by one to obtain a plurality of silk fibroin hydrogel microneedles, and one cone corresponds to one silk fibroin hydrogel microneedle.

[0026] In the second step, the microneedle mold includes a top surface and a groove arranged therein, the bottom of the groove is connected to the top ends of a plurality of hollow conical tubes, the bottom ends of the conical tubes extend downward, and the top ends of the conical tubes are wider than the bottom ends of the conical tubes; The pouring of the precursor solution into the light-transmitting microneedle mold means: first pouring the precursor solution into the groove, and then the precursor solution flows into the cone; The step of taking the gel out of the microneedle mold refers to: using tweezers to clamp the gel out of the groove, at which point all the cones are located at the bottom of the gel.

[0027] In the first step, the concentration of the silk fibroin solution is 1.5-7wt%, the concentration of the riboflavin aqueous solution is 0.05-10mmol / L, and the volume ratio between the silk fibroin solution and the riboflavin aqueous solution is 5-20:1.

[0028] In the first step, the volume percentage concentration of the hydrogen peroxide solution is 5-30%, and the volume ratio between the hydrogen peroxide solution and the mixed solution is 1:5-30.

[0029] In the second step, the vacuum condition corresponding to the vacuum treatment is -0.04 to +0.10Mpa.

[0030] In the second step, the operating parameters of the ultraviolet light are: the power of the ultraviolet lamp is 100-900W, and the illumination time is 2-30min.

[0031] In the first step, the silk fibroin solution is prepared according to the following steps: first, the raw silk is placed in a sodium carbonate aqueous solution and heated and immersed for degumming to obtain degummed silk fibroin fibers, and then the degummed silk fibroin fibers are immersed in a LiBr aqueous solution and heated to dissolve to obtain a crude solution, and then the obtained crude solution is placed in a dialysis bag, and then the dialysis bag is placed in deionized water for low-temperature dialysis, the dialysis temperature is 0-4°C, the dialysis time is 1-5d, and then the remaining solution in the dialysis bag after dialysis is filtered to obtain a filtrate, which is the silk fibroin solution.

[0032] The concentration of the sodium carbonate aqueous solution is 0.1-0.5wt%, and the mass volume ratio of raw silk to the sodium carbonate aqueous solution is 1g / 10-100mL; The heating temperature of the degumming treatment is 45-100°C, and the degumming treatment time is 1-8h; The concentration of the LiBr aqueous solution is 1-10 mol / L, and the mass volume ratio of the degummed silk fibroin fiber to the LiBr aqueous solution is 1 g / 1-20 mL; The temperature for heating and dissolving the degummed silk fibroin fibers in the LiBr aqueous solution is 45-85° C., and the heating and dissolving time is 0.5-3 hours.

[0033] In the first step, after obtaining the precursor solution, a therapeutic drug is added to obtain a drug-carrying precursor solution; In the second step, the drug-carrying precursor solution is poured into a light-transmitting microneedle mold, and the resulting silk fibroin hydrogel microneedles contain therapeutic drugs.

[0034] A hydrogel microneedle is prepared according to the above-mentioned method for preparing a silk fibroin hydrogel microneedle.

[0035] The supplementary technical features of the present invention are as follows: The LiBr aqueous solution in the present invention refers to a lithium bromide aqueous solution.

[0036] The reason why the concentration of the silk fibroin solution is limited to 1.5-7wt% in the present invention is that if the concentration is too low, the final microspheres will be soft and difficult to form, and if the concentration is too high, it will be difficult to enter the cone tube and form microneedles. In addition, this concentration is also conducive to the final hydrogel microneedles having a suitable density and pore size, so as to facilitate the subsequent smooth release of drugs.

[0037] The reason why the volume ratio of the silk fibroin solution to the riboflavin aqueous solution is limited to 5-20:1 in the present invention is that if it is too low, the gel effect is poor and it is difficult to form, and if it is too high, materials are wasted and costs are increased.

[0038] The reason why the concentration of the hydrogen peroxide solution is limited to 20-30 vol% in the present invention is that if the concentration is too low, the gelation promoting effect cannot be achieved, and if the concentration is too high, materials are wasted and costs are increased.

[0039] The reason why the illumination time is limited to 2-30 minutes in the present invention is that if the time is too short, gel cannot be formed, and if the time is too long, the material will dry out.

[0040] The preferred drying time of the present invention is 12-48 hours.

[0041] The preferred vacuuming time of the present invention is 15 min-45 min.

[0042] Embodiment 1: A method for manufacturing a silk fibroin hydrogel microneedle, the method comprising the following steps: The first step: firstly, the silk fibroin solution and the riboflavin aqueous solution are uniformly mixed to obtain a mixed solution, and then the hydrogen peroxide solution is added to the mixed solution for mixing to obtain a precursor solution; The concentration of the silk fibroin solution is 3wt%, the concentration of the riboflavin aqueous solution is 0.5 mmol / L, and the volume ratio of the silk fibroin solution to the riboflavin aqueous solution is 20:1; the volume percentage concentration of the hydrogen peroxide solution is 30%, and the volume ratio between the hydrogen peroxide solution and the mixed solution is 1:30; Step 2: Pour the precursor solution into a light-transmitting microneedle mold (such as Figure 4 As shown, the pouring position is the groove of the mold, the bottom of the groove is connected to the top of a plurality of hollow conical tubes, the bottom of the conical tubes extends downward, the top of the conical tubes is wider than the bottom of the conical tubes, and the poured precursor solution will flow into the conical tubes), and then the microneedle mold containing the precursor solution is placed in a vacuum pump, and then vacuumized at -0.08Mpa for 30 minutes, and then the microneedle mold is taken out and placed under ultraviolet light for illumination to form a gel, and then dried at room temperature, and then the gel is taken out from the microneedle mold (as shown in FIG. Figure 3 As shown in FIG. 1 ), a plurality of outwardly convex cones (such as Figure 1 Then, the cones on the gel are peeled off one by one to obtain multiple silk fibroin hydrogel microneedles (as shown in Figure 2 ), and one cone corresponds to one silk fibroin hydrogel microneedle.

[0043] A hydrogel microneedle, wherein the hydrogel microneedle is prepared according to the above-mentioned method for preparing a silk fibroin hydrogel microneedle (such as Figure 2 As shown in the figure, the hydrogel microneedles are pyramid-shaped with a smooth surface, forming an 11×11 microneedle array with a height of about 400-800μm and a bottom width of 200-600μm. Microneedles of this height are sufficient to reach the dermis of skin tissue to achieve drug (such as insulin) delivery.

[0044] Embodiment 2: The basic content is the same as that of Example 1, except that: The silk fibroin solution is prepared according to the following steps: first, 30 g of raw silk is placed in 900 mL of a 0.1 wt% sodium carbonate aqueous solution and boiled and soaked for 1.5 hours to perform degumming treatment to obtain degummed silk fibroin fibers, and then the degummed silk fibroin fibers are immersed in 300 mL of a 10 mol / L LiBr aqueous solution and heated to 80° C. to dissolve for 3 hours to obtain a crude solution, and then the crude solution is placed in a dialysis bag, and then the dialysis bag is placed in 0° C. deionized water for 5 days, and then the dialyzed solution is filtered to remove impurities to obtain a silk fibroin solution.

[0045] Embodiment 3: The basic content is the same as that of Example 1, except that: In the second step, the operating parameters of the ultraviolet light are: the power of the ultraviolet lamp is 100-900W, and the illumination time is 2-30min.

[0046] Embodiment 4: The basic content is the same as that of Example 1, except that: In the first step, after obtaining the precursor solution, a therapeutic drug is added to obtain a drug-carrying precursor solution; In the second step, the drug-carrying precursor solution is poured into a light-transmitting microneedle mold, and the resulting silk fibroin hydrogel microneedles contain therapeutic drugs.

[0047] Embodiment 5: The basic content is the same as that of Example 1, except that: In the second step, during the vacuuming process, the precursor solution will flow into the cone tube to the greatest extent and fill the cone tube to facilitate the subsequent gelation into microneedles.

[0048] The above description is only a preferred embodiment of the present invention, and the protection scope of the present invention is not limited to the above embodiment. Any equivalent modifications or changes made by ordinary technicians in this field based on the contents disclosed by the present invention should be included in the protection scope recorded in the claims.

Claims

1. A method for manufacturing a silk fibroin hydrogel microneedle, characterized in that: The manufacturing method comprises the following steps: The first step: firstly, the silk fibroin solution and the riboflavin aqueous solution are uniformly mixed to obtain a mixed solution, and then the hydrogen peroxide solution is added to the mixed solution for mixing to obtain a precursor solution; The second step: first pour the precursor solution into a light-transmitting microneedle mold, then put the microneedle mold containing the precursor solution into a vacuum pump, and then perform a vacuum treatment. Then take out the microneedle mold, and place it under ultraviolet light to form a gel. Then dry it at room temperature, and then take the gel out of the microneedle mold. A plurality of convex cones are formed on the outer surface of the gel. Then peel off the cones on the gel one by one to obtain a plurality of silk fibroin hydrogel microneedles, and one cone corresponds to one silk fibroin hydrogel microneedle.

2. The method for manufacturing a silk fibroin hydrogel microneedle according to claim 1, characterized in that: In the second step, the microneedle mold includes a top surface and a groove arranged therein, the bottom of the groove is connected to the top ends of a plurality of hollow conical tubes, the bottom ends of the conical tubes extend downward, and the top ends of the conical tubes are wider than the bottom ends of the conical tubes; The pouring of the precursor solution into the light-transmitting microneedle mold means: first pouring the precursor solution into the groove, and then the precursor solution flows into the cone tube; The step of taking the gel out of the microneedle mold refers to: using tweezers to clamp the gel out of the groove, at which point all the cones are located at the bottom of the gel.

3. A method for manufacturing a silk fibroin hydrogel microneedle according to claim 1 or 2, characterized in that: In the first step, the concentration of the silk fibroin solution is 1.5-7wt%, the concentration of the riboflavin aqueous solution is 0.05-10mmol / L, and the volume ratio between the silk fibroin solution and the riboflavin aqueous solution is 5-20:

1.

4. A method for manufacturing a silk fibroin hydrogel microneedle according to claim 1 or 2, characterized in that: In the first step, the volume percentage concentration of the hydrogen peroxide solution is 5-30%, and the volume ratio between the hydrogen peroxide solution and the mixed solution is 1:5-30.

5. The method for manufacturing a silk fibroin hydrogel microneedle according to claim 1 or 2, characterized in that: In the second step, the vacuum condition corresponding to the vacuum treatment is -0.04 to +0.10Mpa.

6. The method for manufacturing a silk fibroin hydrogel microneedle according to claim 1 or 2, characterized in that: In the second step, the operating parameters of the ultraviolet light are: the power of the ultraviolet lamp is 100-900W, and the illumination time is 2-30min.

7. A method for manufacturing a silk fibroin hydrogel microneedle according to claim 1 or 2, characterized in that: In the first step, the silk fibroin solution is prepared according to the following steps: First, the raw silk is placed in a sodium carbonate aqueous solution and heated and immersed for degumming to obtain degummed silk fibroin fibers, and then the degummed silk fibroin fibers are immersed in a LiBr aqueous solution and heated to dissolve to obtain a crude solution, and then the obtained crude solution is placed in a dialysis bag, and then the dialysis bag is placed in deionized water for low-temperature dialysis, the dialysis temperature is 0-4°C, the dialysis time is 1-5 days, and then the remaining solution in the dialysis bag after dialysis is filtered to obtain a filtrate, which is a silk fibroin solution.

8. The method for manufacturing a silk fibroin hydrogel microneedle according to claim 7, characterized in that: The concentration of the sodium carbonate aqueous solution is 0.1-0.5wt%, and the mass volume ratio of raw silk to the sodium carbonate aqueous solution is 1g / 10-100mL; The heating temperature of the degumming treatment is 45-100°C, and the degumming treatment time is 1-8h; The concentration of the LiBr aqueous solution is 1-10 mol / L, and the mass volume ratio of the degummed silk fibroin fiber to the LiBr aqueous solution is 1 g / 1-20 mL; The temperature for heating and dissolving the degummed silk fibroin fibers in the LiBr aqueous solution is 45-85° C., and the heating and dissolving time is 0.5-3 hours.

9. The method for manufacturing a silk fibroin hydrogel microneedle according to claim 1 or 2, characterized in that: In the first step, after obtaining the precursor solution, a therapeutic drug is added to obtain a drug-carrying precursor solution; In the second step, the drug-carrying precursor solution is poured into a light-transmitting microneedle mold, and the resulting silk fibroin hydrogel microneedles contain therapeutic drugs.

10. A hydrogel microneedle, characterized in that: The hydrogel microneedle is prepared according to the method for preparing a silk fibroin hydrogel microneedle according to claim 1 or 2.

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