Soluble microneedle for treating skin acne as well as preparation method and application of soluble microneedle

Abstract

The invention belongs to the technical field of microneedle preparations, and particularly discloses a soluble microneedle for treating skin acnes and a preparation method and application thereof.The soluble microneedle comprises a hyaluronic acid compound, iron ions and bisulfite ions, the hyaluronic acid compound comprises aldehyde hyaluronic acid and binary polyphenol, and the iron ions and the bisulfite ions are combined to form the soluble microneedle. The hydroformylated hyaluronic acid is hyaluronic acid subjected to ring opening oxidation. According to the preparation method, hyaluronic acid is subjected to ring-opening oxidation to obtain hyaluronic acid carrying aldehyde groups, dopamine hydrochloride is chemically modified, iron ions are used as bridges to connect bisulfite ions, an antibacterial polymer is developed to serve as a matrix to be used for preparing the soluble microneedle, the soluble microneedle is punctured into the skin in a pressing mode, and the antibacterial effect is achieved. The substrate for manufacturing the microneedle is soluble, so that sharp waste is not generated, and the risk of secondary infection and the cost of biological waste treatment are reduced.

Description

Technical Field

[0001] The invention belongs to the field of microneedle preparations, and specifically relates to a soluble microneedle for treating skin acne, and a preparation method and application thereof. Background Art

[0002] Acne vulgaris is a widespread chronic inflammatory disease of the sebaceous glands and hair follicles. It ranks as the eighth most prevalent disease in the world, affecting about 85% of adolescents and about 12% of adult women in the world. Acne vulgaris is often accompanied by sebum secretion, which can occur anywhere on the body, easily causing discomfort and pain to patients.

[0003] At present, the options for treating acne mainly include anti-inflammatory drugs and antibacterial drugs, including retinoids, antibiotics and antibacterial agents, which are administered through local, systemic or oral routes to achieve the best acne treatment effect. However, the above strategies for treating acne have certain limitations. Oral administration is limited by three major obstacles: gastric acid degradation, mucus clearance and intestinal epithelial cell impermeability, which seriously reduces the utilization of drugs. The topical application of creams, ointments, gels or lotions containing antibiotics or antibacterial agents to treat acne is effective for patients with mild acne, but bacteria will migrate through the epidermis and dermis to the subcutaneous tissue. Due to the presence of the stratum corneum of the skin, the drug permeability is low, and the deep infection source cannot be completely eliminated, which may cause repeated infection. In addition, long-term reliance on antibiotics for treatment will accelerate the development of antibiotic resistance in bacteria, and there may also be safety hazards such as adverse reactions and side effects. Therefore, there is an urgent need to find a new drug delivery method that can overcome these problems and is suitable for clinical application.

[0004] As a minimally invasive, transdermal treatment method, the functional mechanism of microneedles is to penetrate the skin to create micron-level pathways, allowing drugs to directly enter the epidermis or upper dermis, minimizing drug side effects and improving drug utilization, making it very suitable for the treatment of skin acne or other diseases.

[0005] However, the current microneedle treatment of acne still has the following problems: metal microneedles are easy to break and remain in the skin tissue, causing secondary damage to the wound and aggravating the severity of the diseased area. Therefore, it is very practical to prepare a safe and easy-to-use microneedle for the treatment of acne. Summary of the invention

[0006] In view of the above-mentioned problems with microneedles currently used to treat acne, the present invention provides a soluble microneedle for treating skin acne, and a preparation method and application thereof. The soluble microneedle is based on the ring-opening oxidation of hyaluronic acid to hyaluronic acid carrying aldehyde groups, and by chemically modifying dopamine hydrochloride and connecting bisulfite ions with iron ions as a bridge, an antibacterial polymer is developed as a matrix for preparing soluble microneedles, which are inserted into the skin by pressing. Since the substrate for making the microneedles is soluble, no sharp waste is generated, reducing the risk of secondary infection and the cost of biological waste treatment. The specific technical scheme is as follows:

[0007] First, the present invention provides a method for preparing a soluble microneedle for treating skin acne, comprising the following steps:

[0008] S1 prepares a soluble microneedle matrix: hyaluronic acid and an oxidant are mixed and reacted, ethylene glycol is added after the reaction to obtain aldehyde-modified hyaluronic acid, a cross-linking agent is added to the aldehyde-modified hyaluronic acid to obtain a hyaluronic acid complex, and finally the hyaluronic acid complex is conjugated with iron ions and bisulfite ions to obtain a soluble microneedle matrix;

[0009] S2 Preparation of soluble microneedles: First, the mold for preparing microneedles is cleaned, and then the soluble microneedle matrix is ​​filled into the mold, and the soluble microneedles are obtained after centrifugation and drying.

[0010] Furthermore, the step S1 of preparing the soluble microneedle matrix comprises the following steps:

[0011] S110 Hyaluronic acid aldehyde formation: hyaluronic acid is dissolved in water, an oxidant is added thereto, and the reaction is stirred in the dark, and after the reaction is completed, ethylene glycol is added thereto to continue the reaction, and after the reaction is completed, the product is dialyzed and purified to remove unreacted monomers, and finally freeze-dried to obtain aldehyde-formyl hyaluronic acid;

[0012] S120 Preparation of hyaluronic acid complex: dissolving the aldehyde-modified hyaluronic acid obtained in S110 in water, adding a cross-linking agent thereto and stirring at room temperature for reaction, dialysis-purifying the reaction product to remove unreacted monomers, and finally freeze-drying to obtain the hyaluronic acid complex;

[0013] S130 hyaluronic acid complex conjugation: After the hyaluronic acid complex is dissolved in water, iron ions, acetic acid and bisulfite ions are added thereto in sequence, and the reaction is stirred at room temperature. After the reaction is completed, the product is dialyzed and purified to remove unreacted monomers, and finally freeze-dried to obtain a soluble microneedle matrix.

[0014] Furthermore, in the step S110, the oxidant is any one of sodium periodate, potassium periodate and hydrogen peroxide; the mass ratio of the hyaluronic acid to the oxidant is 1:0.5 to 1:3; and the light-proof stirring reaction is for 2 to 3 hours.

[0015] Furthermore, in step S120, the cross-linking agent is any one of dopamine hydrochloride, catechol, and gallic acid; the added mass ratio of the aldehyded hyaluronic acid to the cross-linking agent is 1:0.5 to 1:1; and the room temperature stirring reaction time is 12 to 24 hours.

[0016] Furthermore, in step S130, the iron ions are from any one of ferric chloride and ferric sulfate, and the bisulfite ions are from sodium bisulfite; and the molar ratio of the hyaluronic acid complex to the iron ions and bisulfite ions is 3:1:0.1 to 6:1:0.1.

[0017] Furthermore, the step S2 of preparing the soluble microneedles comprises the following steps:

[0018] S210 mold pretreatment: first the mold is plasma cleaned, then the mold is placed under ventilation and glow conditions, and finally cooled in a vacuum;

[0019] Preparation of S220 soluble microneedles: The soluble microneedle matrix was filled into the mold, and the excess matrix was removed after centrifugation. After drying, the mold was centrifuged again, and then placed under drying conditions overnight to obtain soluble microneedles.

[0020] Furthermore, in step S210, the plasma cleaning pressure is 5 kPa, the cleaning time is 5 min to 10 min, and the ventilation flow rate is 300 to 500 m 3 / h, ventilation time is 5 to 10 minutes; glow treatment time is 1 minute; vacuum cooling time is 3 to 5 minutes.

[0021] Furthermore, in step S220, the mass fraction of hyaluronic acid used to prepare the soluble microneedles is 6% to 12% (w / w); the centrifugal speed is 3000 to 4000 rpm, the centrifugal time is 5 to 10 min; and the drying temperature is 37°C.

[0022] The present invention also provides a soluble microneedle for treating skin acne, which is prepared using any one of the above-mentioned methods for preparing a soluble microneedle for treating skin acne. The soluble microneedle comprises the following components: a hyaluronic acid complex, iron ions and bisulfite ions. The hyaluronic acid complex comprises aldehyde-modified hyaluronic acid and a cross-linking agent. The aldehyde-modified hyaluronic acid is hyaluronic acid that has undergone ring-opening oxidation.

[0023] The present invention also provides an application of the soluble microneedle for treating skin acne, wherein the application includes treating skin acne, fungal infection and tumor.

[0024] Compared with the prior art, the present invention has the following beneficial effects:

[0025] 1) The inventors of the present invention have innovatively proposed a soluble microneedle in response to the problems of existing microneedles for treating acne. Hyaluronic acid is used as a matrix, an oxidant is used to open the ring of hyaluronic acid to form hyaluronic acid carrying an aldehyde group, and a gel network is formed by binary polyphenols, and finally iron ions and bisulfite ions are added to prepare a complete soluble microneedle. The soluble microneedle prepared by combining the hyaluronic acid complex with iron ions and bisulfite ions has both mechanical strength and solubility, can form effective microneedle holes on the skin surface for delivering therapeutic drugs, and can also dissolve naturally without residue in the skin. At the same time, the iron ions and bisulfite ions added in the microneedle can not only be antibacterial after the microneedle is dissolved, but also promote rapid repair of the skin, and will not cause allergic problems such as inflammation.

[0026] 2) The soluble microneedles in the present invention can directly dissolve and release drugs after forming microneedle holes. Compared with existing metal microneedles, they will not leave sharp waste in the skin. Moreover, compared with the technology of using metal microneedles to open skin pores and then applying ointment, it is more environmentally friendly and safer.

[0027] 3) The soluble microneedles of the present invention can be used by themselves when treating skin acne and fungal infections, without the need for trained professionals to operate, which is more convenient and quicker. At the same time, there is no need to purchase subsequent care products after use, thus saving costs. BRIEF DESCRIPTION OF THE DRAWINGS

[0028] Figure 1 Schematic diagram of the preparation process of the soluble microneedle matrix in the present invention;

[0029] Figure 2 Schematic diagram of the preparation process of the soluble microneedle in the present invention;

[0030] Figure 3 The diagram of the antibacterial effect of bacterial plate coating (left) and the statistical diagram of the antibacterial rate (right) in Experimental Example 1 of the present invention are shown;

[0031] Figure 4 This is a scanning effect diagram of the bacterial morphology in Experimental Example 1 of the present invention;

[0032] Figure 5 The force displacement curve of HFS-MNs in Experimental Example 2 of the present invention (left), mouse skin puncture diagram (middle) and microneedle channel skin staining section diagram (right);

[0033] Figure 6 This is a diagram showing the effect of HFS-MNs in treating acne in mice in Experimental Example 3 of the present invention;

[0034] Figure 7 Figure 3 shows the weight change (left) and skin thickness change (right) of mice treated with HFS-MNs for 7 days in Experimental Example 3 of the present invention;

[0035] Figure 8 This is a staining section of mice after 7 days of HFS-MNs treatment in Experimental Example 3 of the present invention. DETAILED DESCRIPTION

[0036] In order to make the purpose, technical solution and advantages of the present invention more clear, the technical solution of the present invention will be clearly and completely described below in conjunction with embodiments and drawings.

[0037] Example 1

[0038] like Figure 1 and Figure 2 As shown, this embodiment provides a method for preparing a soluble microneedle for treating skin acne, comprising the following steps:

[0039] S1 prepares a soluble microneedle matrix: hyaluronic acid and an oxidant are mixed and reacted, ethylene glycol is added after the reaction to obtain aldehyde-modified hyaluronic acid, a cross-linking agent is added to the aldehyde-modified hyaluronic acid to obtain a hyaluronic acid complex, and finally the hyaluronic acid complex is conjugated with iron ions and bisulfite ions to obtain a soluble microneedle matrix;

[0040] Specifically, 1.0 g of hyaluronic acid is completely dissolved in 100 mL of ultrapure water, and then 25 mL of 0.5 mol / L sodium periodate solution is added, and the mixture is stirred in the dark at room temperature for 2 h for oxidation reaction. After the reaction is completed, 1 ml of ethylene glycol is added to the mixed solution to continue the reaction. After the reaction is completed, the product is dialyzed and purified with ultrapure water to remove unreacted monomers, and then freeze-dried to obtain aldehyde-modified hyaluronic acid (AHA).

[0041] 1.0 g AHA was completely dissolved in 100 mL ultrapure water, and then 1.0 g dopamine hydrochloride was added and stirred at room temperature for 12 h to react. After the reaction, the product was dialyzed with ultrapure water to remove unreacted monomers, and then freeze-dried to obtain a hyaluronic acid complex (DAHA).

[0042] 100 mg DAHA was completely dissolved in 10 mL ultrapure water. Then 2 mL 20 mmol / L FeCl3 solution (), acetic acid (5%) solution and 1 mL 4 mmol / L NaHSO3 solution were added in sequence and stirred at room temperature for 12 h. The addition of acetic acid can adjust the solubility of iron ions in the hyaluronic acid complex. The product was purified by ultrapure water dialysis to remove unreacted monomers, and freeze-dried to obtain a soluble microneedle matrix (HFS).

[0043] S2 Preparation of soluble microneedles: First, the mold for preparing microneedles is cleaned, and then the soluble microneedle matrix is ​​filled into the mold, and the soluble microneedles are obtained after centrifugation and drying.

[0044] Specifically, the PDMS mold was laid flat in a plasma cleaning machine, vacuumed to 100 kPa, and maintained for 5 min. The oxygen cylinder was opened and the flow rate was adjusted to 300 m / s. 3 / h to maintain ventilation for 3 minutes. Turn on the glow treatment for 5 minutes. Turn off the glow and ventilation to maintain vacuum cooling for 3 minutes, deflate and remove the mold.

[0045] The soluble microneedle matrix HFS (7%, w / w) was filled into the mold, centrifuged at 3000 rpm for 10 min, and the excess matrix outside the needle was removed with a glass slide, and dried at 37°C for 2 h. After repeating the above steps once more, the soluble microneedle matrix HFS was dried at 37°C overnight, the microneedles were peeled off, and the excess borders were cut off to obtain soluble microneedles (HFS-MNs), which were stored at room temperature for subsequent use.

[0046] The soluble microneedle for treating skin acne prepared in this embodiment includes 100 mg of hyaluronic acid complex, 0.04 mmol of iron ions and 0.004 mmol of bisulfite ions.

[0047] The soluble microneedle for treating skin acne prepared in this embodiment can be used in the treatment of surface skin diseases such as skin acne and fungal infections, and can also be used in the treatment of deep skin diseases such as tumor drug delivery.

[0048] Example 2

[0049] The difference between this embodiment and embodiment 1 is that the content of the prepared soluble microneedle components is different. Specifically, the soluble microneedle prepared in this embodiment includes 200 mg of hyaluronic acid complex, 0.08 mmol of iron ions and 0.008 mmol of bisulfite ions. The other experimental steps and parameters are consistent with those in embodiment 1.

[0050] Example 3

[0051] The difference between this embodiment and embodiment 1 is that the mass ratio of hyaluronic acid to oxidant is 1:1.6. Specifically, in step S1, 1.0 g of hyaluronic acid is completely dissolved in 100 mL of ultrapure water, and then 15 mL of 0.5 mol / L sodium periodate solution is added and stirred in the dark at room temperature for 2 h for oxidation reaction. Other experimental steps and parameters are consistent with those in embodiment 1.

[0052] Experimental Example 1: In vitro antibacterial assay of soluble microneedle matrix (HFS)

[0053] This experiment was conducted to test the in vitro antibacterial effects of HFS and its precursors HA and HF.

[0054] Experimental methods:

[0055] The HFS prepared in Example 1 was taken, and simple hyaluronic acid (HA) and aldehyde-modified hyaluronic acid grafted with iron ions (HF) were prepared as experimental controls, and PBS was used as a blank control group to test the in vitro antibacterial effect of Propionibacterium acnes.

[0056] The experimental results are as attached Figure 3 As shown. Analysis of experimental results: From the experimental results, it can be seen that there are basically no bacteria surviving in the HFS group, showing the most excellent antibacterial performance, with an antibacterial rate of 99.84%. Good anti-Propionibacterium acnes activity is essential for the treatment of acne. At the same time, the experimental results of the HA and HF groups also show that iron ions and sulfur dioxide gas can also be used for synergistic antibacterial effects. In order to explore the antibacterial mechanism of HFS, the bacterial morphology after the material interacted with P. acnes was photographed by TEM. The experimental results are shown in the attached Figure 4 As shown in the figure, the morphology of the bacteria in the PBS group and the single H2O2 group remained intact, indicating that PBS and H2O2 did not cause damage to the bacteria. This also further shows that they have almost no antibacterial activity, which is consistent with the previous plate coating experiment results. However, the morphology of the bacteria in the HFS group changed significantly, and the bacterial cell membrane shrank or ruptured, indicating that after the interaction between HFS and bacteria, Fe 3+ The release of HFS and SO2 can cause oxidative stress in bacteria and lead to bacterial death. The experimental results are consistent with the expected results, that is, one of the antibacterial mechanisms of HFS is to produce ROS to destroy the cell membrane of P. acnes.

[0057] Experimental Example 2: Evaluation of HFS-MNs skin penetration efficiency

[0058] Experimental method: Take the HFS-MNs prepared in Example 1 and prepare simple hyaluronic acid microneedles (HA-MN S ) were used to conduct force displacement tests and mouse skin puncture experiments.

[0059] The experimental results are as attached Figure 5 As shown in the left figure, when the displacement reaches 400 μm, the compression forces of HFS-MNs and HA-MNs are 0.50±0.18N / needle and 0.46±0.11N / needle, respectively, which are much larger than the insertion force of 0.098N required for the microneedle to penetrate the skin barrier, proving that both MNs can penetrate the skin. The reason why the compression force of HFS-MNs is slightly larger may be due to the fact that Fe 3+ The addition of NH4+ increases the mechanical strength of the polymer and thus improves the mechanical strength of HFS-MNs. After applying HFS-MNs to the back skin of mice, it can be observed that an array of pinholes (such as attached Figure 5 As shown in the middle figure). Figure 5As shown in the right figure, the microchannels on the mouse skin are further visible through the hematoxylin & eosin tissue staining section, with a depth of about 300μm. These experimental results verify that the mechanical strength of HFS-MNs is sufficient to penetrate the mouse skin and deliver drugs in situ at the diseased site, providing a basis for subsequent in vivo acne treatment experiments.

[0060] Experimental Example 3: Evaluation of the therapeutic effect of HFS-MNs on acne

[0061] Experimental methods:

[0062] In this example, mice infected with Propionibacterium acnes were used to establish an acne model to evaluate the therapeutic effect of HFS-MNs on acne. Six-week-old Balb / c mice were selected as experimental subjects and randomly divided into 4 groups. HA-MNs and Mentholatum cream (MeL) on the market were used as control groups, HFS-MNs were used as experimental groups, and a blank control group (CK) was set up to treat acne mice. Optical photographs were used to record the changes in the severity of acne in mice within 7 days after treatment, and the changes in the weight and acne thickness of the mice were counted.

[0063] The experimental results are as attached Figure 6 , Attachment Figure 7 and attached Figure 8 shown.

[0064] Analysis of experimental results: From the experimental results, it can be seen that the weight changes of the four groups of mice are within a normal range, and the use of HFS-MNs will not cause adverse effects on the physiological functions of mice. According to the change pattern of acne thickness, the CK group mice did not receive any treatment, and the acne thickness increased over time. The same phenomenon was also observed in the HA group. This shows that HA-MNs lacks effective therapeutic effects on acne, and unmodified HA has almost no antibacterial activity against Propionibacterium acnes. After three courses of treatment, the acne in the MeL group was suppressed to a certain extent on the third day after medication. After observation on the fifth and seventh days, the acne was still not completely cured. Because of the existence of the skin barrier, it is difficult for ointment drugs to penetrate deep into the infection and effectively kill bacteria, which is very similar to the results reported previously. Compared with other groups, the HFS-MNs group showed a very good therapeutic effect on the first day after medication, the acne basically disappeared on the third day, and the wound was basically completely healed on the seventh day.

[0065] The cure of acne in mice was further observed through hematoxylin & eosin tissue staining sections. Compared with other treatment groups, the thickness of skin sections in the HFS-MNs treatment group was thinner than that in other groups, and the skin tissue had fewer inflammatory cells (marked by black arrows). Clear and complete dermis and reticular layer of hair follicle structure can be observed in the skin tissue of the HFS-MNs treatment group, and the tissue staining results after treatment were similar to those of the healthy group mouse skin.

[0066] It is obvious to those skilled in the art that the present invention is not limited to the details of the exemplary embodiments described above, and that the present invention can be implemented in other specific forms without departing from the spirit or essential features of the present invention. Therefore, the embodiments should be regarded as exemplary and non-restrictive from any point of view. In addition, it should be understood that although this specification is described in accordance with the embodiments, it does not contain only one technical solution. This narrative of the specification is only for the sake of clarity. Those skilled in the art should regard the specification as a whole, and the technical solutions in the embodiments can also be appropriately combined to form other embodiments that can be understood by those skilled in the art.

Claims

1. A method for preparing soluble microneedles for treating skin acne, characterized in that: The following steps are involved: S1 Preparation of soluble microneedle matrix: Hyaluronic acid is mixed with an oxidant to react to obtain aldehyde-modified hyaluronic acid. Adding binary polyphenol to the hyaluronic acid to react to obtain a hyaluronic acid complex, and finally conjugating the hyaluronic acid complex with iron ions and bisulfite ions to obtain a soluble microneedle matrix; S2 Preparation of soluble microneedles: First, clean the mold for preparing microneedles, then fill the mold with soluble microneedle matrix, and then After drying, soluble microneedles were obtained.

2. The method for preparing a soluble microneedle for treating skin acne according to claim 1, characterized in that: The step S1 of preparing the soluble microneedle matrix comprises the following steps: S110 Hyaluronic acid aldehyde formation: hyaluronic acid is dissolved in water, an oxidant is added thereto, and the reaction is stirred in the dark. After the reaction is completed, the product is dialyzed and purified to remove unreacted monomers, and finally freeze-dried to obtain aldehyde-formylated hyaluronic acid; S120 Preparation of hyaluronic acid complex: dissolving the aldehyde-modified hyaluronic acid obtained in S110 in water, adding divalent polyphenol thereto and stirring at room temperature for reaction, dialysis purification of the reaction product to remove unreacted monomers, and finally freeze-drying to obtain the hyaluronic acid complex; S130 hyaluronic acid complex conjugation: After the hyaluronic acid complex is dissolved in water, iron ions and bisulfite ions are added thereto in sequence, and the reaction is stirred at room temperature. After the reaction is completed, the product is dialyzed and purified to remove unreacted monomers, and finally freeze-dried to obtain a soluble microneedle matrix.

3. The method for preparing a soluble microneedle for treating skin acne according to claim 2, characterized in that: In the step S110, the oxidant is any one of sodium periodate, potassium periodate and hydrogen peroxide; the mass ratio of the hyaluronic acid to the oxidant is 1:0.5 to 1:3; and the light-proof stirring reaction is for 2 to 3 hours.

4. The method for preparing a soluble microneedle for treating skin acne according to claim 2, characterized in that: In the step S120, the cross-linking agent is any one of dopamine hydrochloride, catechol, and gallic acid; the added mass ratio of the aldehyded hyaluronic acid to the cross-linking agent is 1:0.5 to 1:1; and the room temperature stirring reaction time is 12 to 24 hours.

5. The method for preparing a soluble microneedle for treating skin acne according to claim 2, characterized in that: In step S130, the iron ions come from any one of ferric chloride and ferric sulfate, and the bisulfite ions come from sodium bisulfite; the molar ratio of the hyaluronic acid complex to the iron ions and bisulfite ions is 3:1:0.1 to 6:1:0.

1.

6. A method for preparing a soluble microneedle for treating skin acne according to claim 1, characterized in that: The step S2 of preparing the soluble microneedles comprises the following steps: S210 mold pre-treatment: firstly, the mold is plasma cleaned, and then the mold is placed under ventilation and glow conditions for treatment; Preparation of S220 soluble microneedles: The soluble microneedle matrix was filled into the mold, and the excess matrix was removed after centrifugation. After drying, the mold was centrifuged again, and then placed under drying conditions overnight to obtain soluble microneedles.

7. A method for preparing a soluble microneedle for treating skin acne according to claim 6, characterized in that: The pretreatment of the microneedle mold in step S210 includes vacuuming to 5 kPa for 5 min to 10 min; ventilation flow rate of 300 to 500 m 3 / h, ventilation time is 5 to 10 minutes; glow treatment time is 1 minute; vacuum cooling time is 3 to 5 minutes.

8. The method for preparing a soluble microneedle for treating skin acne according to claim 6, characterized in that: In the step S220, the mass fraction of hyaluronic acid used to prepare the soluble microneedles is 6% to 12% (w / w); the centrifugal speed is 3000 to 4000 rpm, the centrifugal time is 5 to 10 min; and the drying temperature is 37°C.

9. A soluble microneedle for treating skin acne prepared by the preparation method according to any one of claims 1 to 8, characterized in that: The soluble microneedle comprises the following components: a hyaluronic acid complex, iron ions and bisulfite ions. The hyaluronic acid complex comprises aldehyde-modified hyaluronic acid and divalent polyphenol. The aldehyde-modified hyaluronic acid is hyaluronic acid that has undergone ring-opening oxidation.

10. Use of a soluble microneedle prepared by the preparation method according to any one of claims 1 to 8 or according to claim 9 for treating skin acne, characterized in that: The applications include treatment of skin acne, fungal infections and tumors.

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