Soluble microneedle capable of being dried at high temperature, preparation method therefor, and use thereof

Abstract

A soluble microneedle capable of being dried at a high temperature, a preparation method therefor, and use thereof. By screening the prescription of microneedle matrix materials, the drying temperature for the microneedle can be increased to 40 °C to 60 °C, thereby greatly shortening the drying time for the microneedle, and better facilitating batch production. The adopted microneedle preparation process does not need special devices, and only common vacuum drying and high-temperature drying devices are needed. A two-step method is adopted, firstly, a needle tip matrix solution is rapidly loaded into a microneedle mold by means of a vacuum method, then a needle tip matrix solution containing bubbles on an upper layer is removed, a backing layer matrix solution of the prescription is added into the mold and then dried and demolded at 40 °C to 60 °C, and then the microneedle can be obtained. By adopting the above method, the problem that bubbles are difficult to completely eliminate in the process of preparing the microneedle by means of a vacuum method can be well solved.

Description

Soluble microneedle capable of drying at high temperature, preparation method thereof, and use thereof

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS

[0002] This application claims the benefit of Chinese Application No. 202410239468.X, filed on March 4, 2024. Said application No. 202410239468.X is hereby incorporated by reference in its entirety. Technical Field

[0003] The present invention belongs to the technical field of microneedles, and in particular relates to a soluble microneedle that can be dried at high temperature, a preparation method thereof, and uses thereof. Background Art

[0004] Microneedles are micron-scale arrays made of materials such as metal, silicon, and polymers, ranging in length from 25 to 2000 μm, with either symmetrical conical or asymmetrical beveled tips. Although the concept of microneedles was first proposed in the 1970s, the processing and manufacturing of microneedle products did not become a reality until the 1990s, with the development and maturity of microelectromechanical systems (MEMS) technology. Microneedle delivery is a novel transdermal delivery method that allows active ingredients to penetrate the stratum corneum without interfering with the underlying nerves, enabling painless administration of active ingredients. Currently, microneedles are primarily categorized into four types: solid microneedles (which are enhanced by pre-treatment of the skin); coated microneedles (which dissolve the drug subcutaneously after insertion); soluble microneedles (which contain a soluble polymer microneedle containing the drug, which ultimately dissolves subcutaneously); and hollow microneedles (which store the drug in the cavity of the hollow microneedle for subcutaneous injection).

[0005] Currently, the conventional method for preparing soluble microneedle patches involves dissolving the microneedle matrix material and active substance in water to form an aqueous solution, casting the aqueous solution into a negative microneedle mold, and then drying and curing the solution at room temperature or low temperature to release the mold to obtain the soluble microneedles. During the solution casting process, vacuum, pressurization, centrifugation, ultrasound, and other methods are used to assist in filling the mold. The vacuum method is commonly used in production due to its ease of operation and simple equipment. However, there are currently two major problems: drying the microneedles at room temperature or low temperature generally requires more than 12 hours, which is a long time and is not conducive to mass production of microneedles. During the vacuum method preparation process, a large number of bubbles are generated in the microneedle matrix solution. Failure to completely remove these bubbles will affect the appearance of the microneedles and may even lead to incomplete microneedle arrays or deformation of the microneedle matrix after drying.

[0006] Chinese patent CN115400341A provides a method for shortening microneedle drying time. First, a polymer material aqueous solution is pressed into a thin sheet using a compression molding technique at high temperature. The sheet is then placed on a microneedle mold and pressed into the mold using a hot press. The temperature is then lowered and dried to produce soluble microneedles. This method shortens the microneedle production time, but the high temperature required for pressing the sheet (80°C) requires specialized equipment and molds, making the process complex. Furthermore, excessively high temperatures are detrimental to the stability of the active substance. Park et al. (Efficacy and safety of a new microneedle patch for skin brightening, A randomized, split-face, single-blind study) reported another method for shortening microneedle drying time. A high-concentration sodium hyaluronate (HA) solution was added to a microneedle mold, pressurized with 5 tons of pressure for 30 seconds, and dried at 50°C for 1 hour to produce microneedles. This method is similar to the method in Chinese patent CN115400341A, but eliminates the sheet pressing step and adds a high-temperature drying step after pressing. However, this method also requires special pressurizing equipment, and the literature does not indicate the specific specifications of sodium hyaluronate.

[0007] Summary of the Invention

[0008] In order to solve the technical defects existing in the existing soluble microneedle preparation method, the present invention provides a new type of soluble microneedle that can be dried at high temperature, and its preparation method and use.

[0009] The method for preparing soluble microneedles described in the present invention can effectively solve the problems that microneedles take a long time to dry at room temperature and are easily deformed at high temperature, making it difficult to form a complete microneedle array, and that bubbles are difficult to completely eliminate during the vacuum method for preparing microneedles.

[0010] The purpose of the present invention can be achieved by the following technical solutions:

[0011] In a first aspect, the present invention provides a soluble microneedle that can be dried at high temperature, wherein the soluble microneedle is made of a needle tip matrix solution and a backing layer matrix solution, wherein the high temperature is 40°C-60°C, and the needle tip matrix solution or the backing layer matrix solution contains 1-10% by weight of a water-soluble polymer material and 1-10% by weight of a water-soluble small molecule material.

[0012] Preferably, the needle tip matrix solution or the backing layer matrix solution contains 1-5% by weight of a water-soluble high molecular material and 1-5% by weight of a water-soluble low molecular material.

[0013] The water-soluble polymer material is selected from one or more of the following: sodium hyaluronate (HA), sodium carboxymethyl cellulose (CMC), hydroxypropyl methylcellulose (HPMC), chondroitin sulfate, dextran, dextrin, polyvinyl pyrrolidone (PVP), polyvinyl alcohol (PVA), silk protein, chitosan or gelatin.

[0014] Preferably, the water-soluble polymer material is selected from one or more of the following: sodium hyaluronate, polyvinyl alcohol or gelatin.

[0015] Preferably, the needle tip matrix solution or the backing layer matrix solution contains 2% to 3% by weight of water-soluble small molecule materials.

[0016] The water-soluble small molecule material is selected from one or more of the following: glucose, trehalose, lactose, panthenol or vitamin C ethyl ether.

[0017] The molecular weight of the sodium hyaluronate is in the range of 50 kDa to 500 kDa.

[0018] As an optional method, in the above-mentioned soluble microneedles, the water-soluble polymer material is selected from sodium hyaluronate or a combination of sodium hyaluronate and another water-soluble polymer material, the weight ratio of sodium hyaluronate to another water-soluble polymer material is in the range of 1:5-5:1, and the other water-soluble polymer material is selected from: sodium carboxymethyl cellulose, hydroxypropyl methylcellulose, chondroitin sulfate, dextran, dextrin, polyvinyl pyrrolidone, polyvinyl alcohol, silk protein, chitosan or gelatin.

[0019] The molecular weight of the sodium hyaluronate is in the range of 200 kDa to 400 kDa.

[0020] Preferably, the needle tip matrix solution or the backing layer matrix solution contains 5% by weight of sodium hyaluronate.

[0021] Alternatively, preferably, the needle tip matrix solution or the backing layer matrix solution contains 3% by weight of sodium hyaluronate.

[0022] Alternatively, preferably, the needle tip matrix solution or the backing layer matrix solution comprises 3% sodium hyaluronate and 2% polyvinyl alcohol by weight.

[0023] Alternatively, preferably, the needle tip matrix solution or the backing layer matrix solution comprises 3% sodium hyaluronate and 2% gelatin by weight.

[0024] As an optional method, in the above-mentioned soluble microneedles, the needle tip matrix solution or the backing layer matrix solution further contains 1-10% by weight of polyols, polyethylene glycols, poloxamer 188, polyvinyl alcohol, hydroxypropyl methylcellulose or polyvinyl pyrrolidone, wherein the polyols are selected from one or more of the following: pentanediol, butylene glycol or hexylene glycol, and the polyethylene glycols are selected from one or more of the following: polyethylene glycol 400, polyethylene glycol 6000 or polyethylene glycol 8000.

[0025] Preferably, the needle tip matrix solution or the backing layer matrix solution further contains 1-5% by weight of a polyol substance.

[0026] More preferably, the polyol substance is selected from butanediol or hexanediol.

[0027] As an optional method, in the above-mentioned soluble microneedles, the needle tip matrix solution or the backing layer matrix solution further contains 0.1%-2% by weight of a hydrophilic emulsifier, and the hydrophilic emulsifier is selected from one or more of the following: Tween-20, polyvinyl alcohol, gelatin, polyoxyethylene castor oil, polyether silicone oil or poloxamer 188.

[0028] Preferably, the needle tip matrix solution or the backing layer matrix solution further comprises 0.5% Tween-20 by weight.

[0029] Preferably, the needle tip matrix solution or the backing layer matrix solution further contains 1% by weight of polyoxyethylene castor oil.

[0030] Preferably, the needle tip matrix solution or the backing layer matrix solution further contains 1% by weight of polyether silicone oil.

[0031] As an optional embodiment, in the above-mentioned soluble microneedles, the needle tip matrix solution or the backing layer matrix solution further contains 1-10% by weight of an active ingredient, and the active ingredient is selected from one or more of the following: niacinamide, tranexamic acid, arbutin, tripeptide-1 copper, carnosine or acetyl hexapeptide-8.

[0032] As an option, in the above-mentioned soluble microneedles, the needle tip matrix solution or the backing layer matrix solution further comprises water or a mixed solvent consisting of water and other solvents, and the other solvents are selected from one or more of the following: ethanol, propylene glycol or glycerol.

[0033] In a second aspect, the present invention provides a method for preparing the soluble microneedles described in the first aspect, the method comprising the following steps:

[0034] The soluble microneedles are prepared using a two-step method. First, the needle tip matrix solution is quickly loaded into the gap of the microneedle mold, the upper layer of the needle tip matrix solution containing bubbles is removed, and then the backing layer matrix solution is added to the mold and dried at 40-60°C and demolded to obtain the soluble microneedles.

[0035] As an optional manner, in the above preparation method, the method for quickly loading the needle tip matrix solution into the voids of the microneedle mold includes vacuum method, centrifugation method, pressurization method or water bath ultrasound method, and the material of the microneedle mold is selected from one or more of the following: polyethylene, polypropylene, polyvinyl chloride, polyoxymethylene, nylon, polydimethylsiloxane, polycarbonate or polytetrafluoroethylene.

[0036] Preferably, the method for quickly loading the needle tip matrix solution into the voids of the microneedle mold is a vacuum method, specifically, placing the mold in a vacuum drying oven and evacuating at -0.07 MPa for 10 minutes.

[0037] Preferably, the material of the microneedle mold is selected from polydimethylsiloxane (PDMS).

[0038] As an optional manner, in the above preparation method, the drying temperature is 50° C. and the drying time is within 2 hours.

[0039] Preferably, the drying temperature is 50° C. or 60° C., and the drying time is within 1 hour.

[0040] In a third aspect, the present invention provides use of the soluble microneedles described in the first aspect or the soluble microneedles prepared by the preparation method described in the second aspect in preparing a soluble microneedle patch.

[0041] Compared with the prior art, the advantages of the present invention are embodied in the following aspects:

[0042] (1) The present invention screens the microneedle matrix material formula to increase the microneedle drying temperature to 40°C-60°C, significantly shortening the microneedle drying time. The specific drying temperature can be selected based on the stability of the active substance in the microneedle, and the general drying time is 0.5-2 hours. This is more conducive to mass production. The microneedle preparation process used in the present invention does not require special equipment, only ordinary vacuum drying and high-temperature drying equipment.

[0043] (2) The present invention employs a two-step process. First, the tip matrix solution is rapidly loaded into the microneedle mold using a vacuum method. Then, the upper layer of the tip matrix solution containing bubbles is removed. The prescribed backing layer matrix solution is added to the mold, dried at 40-60°C, and then demolded to obtain the microneedles. This method effectively solves the problem of difficulty in completely eliminating bubbles during the vacuum method for preparing microneedles.

[0044] (3) The needle tip matrix of the present invention can be the same as or different from the backing matrix. For example, the needle tip matrix contains active substances while the backing matrix is ​​a blank matrix without active substances. This method can concentrate the active substances at the needle tip, greatly reducing the amount of active substances used. BRIEF DESCRIPTION OF THE DRAWINGS

[0045] Figure 1: Photos of blank microneedles prepared with HA of different average molecular weights.

[0046] Figure 2: Microscope photo of blank microneedles. The average molecular weight of sodium hyaluronate is 200,000-400,000.

[0047] Figure 3: 54×61 microneedle array with deformation (left) and without deformation (right).

[0048] Figure 4: 25×25 array microneedles with localized precipitation of white matter (left) and without precipitation of white matter (right).

[0049] Figure 5: Photograph of microneedles prepared using formulation No. 5 in Example 5. The photo shows good flexibility after shearing.

[0050] Figure 6: Photograph of microneedles prepared using formulation No. 2 in Example 5. The photo shows poor flexibility after shearing.

[0051] Figure 7: Representative photographs of split microneedles with vitamin C ethyl ether and tripeptide-1 copper at the tips.

[0052] Figure 8: Photograph of the integrated microneedle containing vitamin C ethyl ether and tripeptide-1 copper in formulation No. 4 in Example 8.

[0053] Figure 9: Microwell array left by a 10×10 array microneedle patch.

[0054] Figure 10: 24h average cumulative transdermal penetration percentage of acetyl hexapeptide-8 microneedle group and solution group. DETAILED DESCRIPTION

[0055] The present invention will be further described below with reference to specific embodiments. It should be understood that the specific embodiments described herein are only used to illustrate the present invention and are not intended to limit the scope of the present invention.

[0056] If no specific techniques or conditions are specified in the examples, the experiments were carried out according to the techniques or conditions described in the literature in the field or according to the product instructions. If no manufacturer is specified for the reagents or instruments used, they are all conventional products that can be purchased through regular channels.

[0057] The experimental methods in the following examples are conventional methods unless otherwise specified. The experimental materials used in the following examples are commercially available products unless otherwise specified.

[0058] Unless otherwise specified, the percentages (%) of various ingredients in the following examples are by mass.

[0059] Example 1: Preparation of blank microneedles without active substances using sodium hyaluronate (HA) with different average molecular weights

[0060] Weigh the prescribed amount of raw materials and deionized water according to the recipe in Table 1, stir and mix until completely dissolved, centrifuge or vacuum to remove bubbles, and then inject the mixture into a 10×10 array PDMS microneedle mold. Place the mold in a vacuum drying oven at -0.07 MPa for 10 minutes. Remove the mold, remove the air-filled microneedle matrix solution above the mold, and refill with fresh microneedle matrix solution. Dry at 50°C with forced air for 50 minutes. Remove the mold, cool at room temperature for half an hour, and demold. The results are shown in Figure 1.

[0061] Table 1: Different blank microneedle formulations

[0062] The results showed that microneedles prepared with sodium hyaluronate HA with an average molecular weight of 200,000-400,000 did not deform significantly, as shown in Figure 2. Microneedles prepared with other sodium hyaluronates all deformed to varying degrees. In the following examples, the molecular weight of sodium hyaluronate was 200,000-400,000.

[0063] Example 2: Effect of different formulations on the spreading effect of microneedle matrix solution after adding it to the mold

[0064] Weigh the raw materials and deionized water in the amounts specified in Table 1, stir and mix until completely dissolved, centrifuge or vacuum to remove bubbles, and inject the resulting mixture into a 54 × 61 array PDMS microneedle mold. Spread the matrix solution evenly over the mold and let it sit at room temperature for 1 hour. The wetting and spreading effects of the microneedle matrix solution on the large-scale mold were examined. The results are shown in Table 2.

[0065] Table 2: Effects of different formulations on the spreading of microneedle matrix solution after addition to the mold

[0066] The results showed that hydrophilic emulsifiers such as Tween-20, PVA, gelatin, polyoxyethylene castor oil, and polyether silicone oil can increase the wetting effect of the microneedle matrix solution on the PDMS microneedle mold, allowing it to spread evenly on the large-size mold.

[0067] Example 3: Effects of different formulations on the morphology of microneedles after drying

[0068] Weigh the prescribed amounts of raw materials and deionized water according to the recipe in Table 3, stir until completely dissolved, centrifuge or vacuum to remove bubbles, and inject the resulting mixture into a 54×61 array PDMS microneedle mold. Spread the matrix solution evenly over the mold and place it in a vacuum drying oven at -0.07 MPa for 10 minutes. Remove the mold, remove any bubbles of microneedle matrix solution above the mold, and refill with fresh microneedle matrix solution. Dry at 50°C with forced air for 1 hour. Remove the mold, cool it at room temperature for half an hour, and then demold it.

[0069] Table 3: Effects of different formulations on the morphology of microneedles after drying

[0070] The results showed that small molecule sugars (glucose, lactose, trehalose), vitamin C ethyl ether, and panthenol can prevent the microneedle matrix from deforming after drying (see Figure 3).

[0071] Example 4: Effect of different formulations on the presence of solid precipitates on the surface of microneedles containing active substances after drying

[0072] Weigh the raw materials and deionized water in the amounts specified in Table 4, stir until completely dissolved, centrifuge or vacuum to remove bubbles, and inject the mixture into a 10 × 10 array PDMS microneedle mold. Place the mold in a vacuum drying oven at -0.07 MPa for 10 minutes. Remove the mold, remove the air-filled microneedle matrix solution above the mold, and refill with fresh microneedle matrix solution. Dry at 60°C with forced air for 30 minutes. Remove the mold, cool at room temperature for half an hour, and then demold.

[0073] Table 4: Effects of different formulations on the presence of solid precipitates on the surface of microneedles containing active substances after drying

[0074] The results showed that small molecule sugars (glucose, lactose, trehalose), vitamin C ethyl ether, panthenol, etc. can inhibit the precipitation of active substances on the surface of microneedles during the drying process, as shown in Figure 4.

[0075] Example 5: Effect of different formulations on the flexibility of microneedles after drying

[0076] Weigh the raw materials and deionized water in the amounts specified in Table 5, stir until completely dissolved, centrifuge or vacuum to remove bubbles, and inject the resulting mixture into a 10×10 array PDMS microneedle mold. Place the mold in a horizontal centrifuge at 4000 rpm for 5 minutes, remove the mold, and air dry it at 50°C for 50 minutes. Remove the mold, cool it at room temperature for half an hour, and then demold it. Flexibility scores are shown in Table 5.

[0077] Table 5: Effects of different formulations on the flexibility of microneedles after drying

[0078] The results showed that adding substances such as polyvinyl alcohol, hexylene glycol, polyoxyethylene castor oil, and polyether silicone oil to the formulation significantly improved the flexibility of the microneedles after drying. Photos of microneedles with good and poor flexibility are shown in Figures 5 and 6, respectively.

[0079] Example 6: Time required for heating and drying at different temperatures when preparing microneedles using molds of different sizes

[0080] According to recipe No. 5 in Table 5, weigh the raw materials and deionized water in the prescribed amount, stir until completely dissolved, centrifuge or vacuum to remove bubbles, and then inject the resulting mixture into 25×25 and 54×61 array PDMS microneedle molds, respectively. Mold parameters are shown in Table 6. Place the molds in a vacuum drying oven at -0.07 MPa for 10 minutes. Remove the molds, remove any bubbles in the microneedle matrix solution above the molds, and refill with fresh microneedle matrix solution. Blast air drying was performed at 40°C, 50°C, and 60°C. The drying times required for different molds at different temperatures were investigated; the results are shown in Table 7.

[0081] Table 6: PDMS microneedle mold parameters

[0082] Table 7: Drying time of microneedles prepared using different molds at different temperatures

[0083] The results showed that increasing the blast drying temperature significantly shortened the drying time required for microneedles. Microneedles prepared using a 54×61 array mold required longer drying times than those prepared using a 25×25 array mold due to their larger size. At a drying temperature of 40-60°C, the blast drying time for microneedles could be controlled within 20-100 minutes.

[0084] Example 7: Preparation of Split Microneedles Containing Whitening and Anti-wrinkle Active Substances

[0085] According to the recipe in Table 8, weigh the raw materials and deionized water in the prescribed amounts, stir and mix until completely dissolved, centrifuge or vacuum to remove bubbles, and inject the tip matrix solution into a 10×10 PDMS microneedle mold. Spread the tip matrix solution evenly over the mold and place it in a vacuum drying oven at -0.07 MPa for 10 minutes. Remove the mold, remove any bubbles of the tip matrix solution above the mold, add the backing layer matrix solution, and spread the backing layer matrix solution evenly over the mold. Dry it at 50°C for 1 hour. Remove the mold, cool it at room temperature for half an hour, and demold it to obtain split microneedles containing whitening and anti-wrinkle active ingredients. Representative photos of split microneedles with vitamin C ethyl ether and tripeptide-1 copper at the tips (prepared using recipe 1 in Table 8) are shown in Figure 7.

[0086] Table 8: Split microneedle formula containing whitening and anti-wrinkle active substances

[0087] Example 8: Preparation of integrated microneedles containing whitening and anti-wrinkle active substances

[0088] According to the recipe in Table 9, weigh the raw materials and deionized water in the prescribed amounts. Stir and mix until completely dissolved. Centrifuge or vacuum to remove bubbles. Inject the microneedle matrix solution into 54×61 and 25×25 PDMS microneedle molds, respectively. Spread the microneedle matrix solution evenly over the molds and place them in a vacuum drying oven at -0.07 MPa for 10 minutes. Remove the molds, remove any bubbles of microneedle matrix solution above the molds, refill the microneedle matrix solution, spread the microneedle matrix solution evenly over the molds, and air-dry at 50°C for 1 hour. Remove the molds, cool at room temperature for half an hour, and demold. This yields integrated microneedles containing whitening and anti-wrinkle active ingredients. The properties of the dried microneedles are shown in Table 9. A photograph of the integrated microneedles containing vitamin C ethyl ether and tripeptide-1 copper is shown in Figure 8.

[0089] Table 9: All-in-one microneedle formulations containing whitening and anti-wrinkle active ingredients

[0090] Example 9: Microneedle prick test

[0091] A homemade 10×10 microneedle array (prepared according to Recipe 2 in Table 4) was applied to pig skin for a prick test. After staining with trypan blue and observing under a microscope, the micropore array left by the microneedles was visible. The results of the prick test showed that the homemade 10×10 microneedle array left a complete micropore array in the animal skin, with a puncture rate of 100%, as shown in Figure 9.

[0092] Example 10: Microneedle in vitro transdermal diffusion test

[0093] Six small, circular pieces of Bama Xiang pig skin with a diameter of approximately 2.7 cm were taken, thawed, and placed with the stratum corneum facing up. Acetyl hexapeptide-8 microneedles (prepared according to recipe 3 in Table 8) were added to three pieces, and acetyl hexapeptide-8 solution was added to three pieces. After the skin sample was added, the skin was placed in an in vitro transdermal diffusion cell and fixed with a clamp. The upper end of the supply cell was sealed with a sealing film to prevent water evaporation. 8 mL of normal saline was added to the receiving cell, magnetically stirred at 200 rpm, and the temperature was maintained at 37 ± 0.5 ° C. 1 mL of sample was taken 24 hours after transdermal permeation. The sample was filtered through a 0.22 μm microporous filter membrane and detected by high performance liquid chromatography.

[0094] Microneedle sample group: Three 10×10 microneedles were placed on the skin, gently pressed for 1 minute, and then fixed to the skin with double-sided tape. The microneedles contained 75 μg of acetyl hexapeptide-8.

[0095] Solution application group: 75 μL of 1 mg / mL acetyl hexapeptide-8 solution was dripped onto the skin.

[0096] The content of samples in the in vitro transdermal test was determined, and the results showed that the content of samples before 8 hours was lower than the detection limit. The average in vitro transdermal release percentage of the microneedle group at 24 hours was 10.17%, and the average in vitro transdermal release percentage of the solution group was 4.39%. The transdermal release percentage of the microneedle group was significantly higher than that of the solution group, as shown in Table 10 and Figure 10.

[0097] Table 10: 24h cumulative transdermal percentage of acetyl hexapeptide-8 microneedles and solution (%)

[0098] Obviously, those skilled in the art may make various changes and modifications to the present invention without departing from the spirit and scope of the present invention. Thus, if such changes and modifications fall within the scope of the claims and their equivalents, the present invention is intended to include such changes and modifications.

Claims

1. A soluble microneedle that can be dried at high temperature, characterized in that: The soluble microneedles are made of a needle tip matrix solution and a backing layer matrix solution, the high temperature is 40° C.-60° C., and the needle tip matrix solution or the backing layer matrix solution contains 1-10% by weight of a water-soluble polymer material and 1-10% by weight of a water-soluble small molecule material. The water-soluble polymer material is selected from one or more of the following: sodium hyaluronate, sodium carboxymethyl cellulose, hydroxypropyl methylcellulose, chondroitin sulfate, dextran, dextrin, polyvinyl pyrrolidone, polyvinyl alcohol, silk protein, chitosan or gelatin; The water-soluble small molecule material is selected from one or more of the following: glucose, trehalose, lactose, panthenol or vitamin C ethyl ether, The molecular weight of the sodium hyaluronate is in the range of 50 kDa to 500 kDa.

2. The soluble microneedle according to claim 1, wherein: The water-soluble polymer material is selected from sodium hyaluronate or a combination of sodium hyaluronate and another water-soluble polymer material, the weight ratio of the sodium hyaluronate to the other water-soluble polymer material is in the range of 1:5-5:1, and the other water-soluble polymer material is selected from sodium carboxymethyl cellulose, hydroxypropyl methylcellulose, chondroitin sulfate, dextran, dextrin, polyvinyl pyrrolidone, polyvinyl alcohol, silk protein, chitosan or gelatin, The molecular weight of the sodium hyaluronate is in the range of 200 kDa to 400 kDa.

3. The soluble microneedle according to claim 1, wherein: The needle tip matrix solution or the backing layer matrix solution further contains 1-10% by weight of polyols, polyethylene glycols, poloxamer 188, polyvinyl alcohol, hydroxypropyl methylcellulose or polyvinyl pyrrolidone, wherein the polyols are selected from one or more of the following: pentanediol, butylene glycol or hexylene glycol, and the polyethylene glycols are selected from one or more of the following: polyethylene glycol 400, polyethylene glycol 6000 or polyethylene glycol 8000.

4. The soluble microneedle according to claim 1, wherein: The needle tip matrix solution or the backing layer matrix solution further contains 0.1%-2% by weight of a hydrophilic emulsifier, which is selected from one or more of the following: Tween-20, polyvinyl alcohol, gelatin, polyoxyethylene castor oil, polyether silicone oil or poloxamer 188.

5. The soluble microneedle according to claim 1, wherein: The needle tip matrix solution or the backing layer matrix solution further comprises 1-10% by weight of an active ingredient, wherein the active ingredient is selected from one or more of the following: niacinamide, tranexamic acid, arbutin, tripeptide-1 copper, carnosine or acetyl hexapeptide-8.

6. The soluble microneedle according to claim 1, wherein: The needle tip matrix solution or the backing layer matrix solution further comprises water or a mixed solvent consisting of water and other solvents, wherein the other solvents are selected from one or more of the following: ethanol, propylene glycol or glycerol.

7. The method for preparing the soluble microneedle according to any one of claims 1 to 6, characterized in that: The preparation method comprises the following steps: The soluble microneedles are prepared using a two-step method. First, the needle tip matrix solution is quickly loaded into the gap of the microneedle mold, the upper layer of the needle tip matrix solution containing bubbles is removed, and then the backing layer matrix solution is added to the mold and dried at 40-60°C and demolded to obtain the soluble microneedles.

8. The preparation method according to claim 7, characterized in that: In the preparation method, the method for quickly loading the needle tip matrix solution into the gap of the microneedle mold includes vacuum method, centrifugation method, pressurization method or water bath ultrasound method, and the material of the microneedle mold is selected from one or more of the following: polyethylene, polypropylene, polyvinyl chloride, polyoxymethylene, nylon, polydimethylsiloxane, polycarbonate or polytetrafluoroethylene.

9. The preparation method according to claim 7, characterized in that: In the preparation method, the drying temperature is 50° C. or 60° C., and the drying time is within 2 hours.

10. Use of the soluble microneedle according to any one of claims 1 to 6 or the soluble microneedle prepared by the preparation method according to any one of claims 7 to 9 in preparing a soluble microneedle patch.

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