Method for preparing microneedle patch and microneedle patch prepared thereby

Abstract

The present application belongs to the technical field of microneedles and relates to a method for preparing a microneedle patch and a microneedle patch prepared thereby. According to the method for preparing the microneedle patch provided by the present application, one section of an active ingredient solution and two sections of a soluble microneedle skeleton solution are injected into a mold, and a zolmitriptan soluble microneedle with bases uniformly interconnected or independent of each other can be prepared through uniform drying treatment; the drying time of peripheral microneedles and that of inner microneedles in the array tend to be the same during drying, thus avoiding the situation that part of the microneedles are excessively dried and broken after demolding due to uneven drying; the one section of the solution containing the active ingredient and the two sections of the soluble microneedle skeleton solution are more tightly connected, thereby avoiding bubble formation due to the non-uniform overall drying of the solution. Thus, the yield of microneedle preparation is greatly improved.

Description

A method for preparing a microneedle patch and the microneedle patch prepared therefrom

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS

[0002] This application claims priority to Chinese patent application number 202311871287.0, filed with the Patent Office of China on December 29, 2023, entitled “A preparation process for a microneedle patch and the microneedle patch prepared therefrom,” the entire contents of which are incorporated by reference into this application. Technical Field

[0003] The present application belongs to the field of microneedle technology and relates to a method for preparing a microneedle patch and the microneedle patch prepared therefrom. Background Art

[0004] At present, the contact between the gasket and the microneedles of the soluble microneedle patch is mainly through the adhesive layer provided on the gasket and the formed microneedle solution. The adhesive layer is used to bond the microneedles formed in the microneedle female mold, so that the microneedles are fixedly bonded to the adhesive layer, which facilitates the demolding and separation of the cured microneedles from the microneedle female mold to form a soluble microneedle patch.

[0005] However, after the soluble microneedle patch is placed for a long time, the sticky material of the sticky layer can easily penetrate into the contacting microneedles, affecting the stability of the active drugs inside the microneedles. Therefore, a gasket material without sticky material is used to directly contact and fit the microneedles to avoid the penetration and mutual influence between the sticky material and the active drugs in the microneedles.

[0006] Related technology When preparing microneedles with active pharmaceutical ingredients, after the microneedle solution with the active ingredient is filled into the microneedle groove mold, a non-sticky gasket is directly attached to the surface of the microneedle solution when it is in a liquid state, and then the microneedle patch is placed in a normal temperature and humidity environment of the prior art for curing. The microneedle solution is in a liquid state, causing the microneedle solutions on different microneedle grooves to overflow and spread to connect into one piece. However, due to the overflow of the microneedle solution at the root of the microneedle groove, gaps and bubbles are formed in the microneedle base after drying, resulting in poor microneedle formability. In addition, during the drying process, since the gasket has the function of isolating the air, the microneedle solution located on the periphery of the gasket is more fully in contact with the flowing air and dries faster than that located in the center of the gasket. When the microneedle solution of the microneedle in the center of the gasket is dried, the microneedle solution located on the periphery of the gasket is over-dried, so that the microneedles on the periphery of the gasket are easily broken during demolding, resulting in a low yield rate of microneedle preparation. When preparing a microneedle patch, when the surface of the microneedle solution filled into the microneedle groove mold is dried under the normal temperature and humidity environment of the existing technology and then the gasket is attached, the surface of the microneedle solution on the microneedle groove mold that is in contact with the air dries faster than the solution inside the microneedle groove, resulting in uneven drying of the microneedle solution. The solution is easily broken during demolding, resulting in a low yield rate of microneedle preparation.

[0007] In view of this, this application is hereby filed. Summary of the Invention

[0008] Based on the problems and deficiencies in the prior art, the present application provides a method for preparing a microneedle patch and the microneedle patch prepared therefrom. The method for preparing a microneedle patch provided by the present application injects a section of active ingredient solution and two sections of soluble microneedle skeleton solution into a mold, and through uniform drying treatment, can prepare soluble microneedles with bases evenly connected or independent of each other; during the drying process, the drying time of the outer microneedles and the inner microneedles of the array can be made similar, avoiding the situation where some microneedles are over-dried or broken after demolding due to uneven drying; it can make the section of solution containing the active ingredient and the two sections of soluble microneedle skeleton solution more tightly connected, avoiding bubbles formed due to uneven drying of the entire solution; and greatly improving the yield rate of microneedle preparation.

[0009] the term:

[0010] 1. PVP-K17: polyvinylpyrrolidone;

[0011] 2. PVA: polyvinyl alcohol;

[0012] 3. PVP: vinyl pyrrolidone.

[0013] The technical solution of this application is as follows:

[0014] In one aspect, the present application provides a method for preparing a microneedle patch, the method comprising the following steps:

[0015] (1) Injecting a section of active ingredient solution into the mold;

[0016] (2) injecting two sections of soluble microneedle skeleton solution into the mold, so that the two sections of soluble microneedle skeleton solution protrude from the surface of the mold to form protruding droplets;

[0017] (3) uniformly drying the mold filled with the first-stage active ingredient solution and the second-stage soluble microneedle skeleton solution; the uniform drying process includes a first uniform drying process or a first uniform drying process and a second uniform drying process, so that the protruding droplets are sticky gel-like protrusions;

[0018] (4) Pressing the gasket onto the gel-like protrusions in step (3), drying, and demoulding to obtain a soluble microneedle patch.

[0019] In an optional embodiment, the temperature of the first uniform drying treatment in step (3) is 20-30°C.

[0020] In an optional embodiment, the temperature of the first uniform drying treatment in step (3) can also be 0-20°C.

[0021] In an optional embodiment, the humidity of the first uniform drying treatment in step (3) is 80%-95%.

[0022] In an optional embodiment, the first uniform drying treatment time in step (3) is 6-20 hours.

[0023] In an optional embodiment, the temperature of the second uniform drying treatment in step (3) is 20-30°C.

[0024] In an optional embodiment, the temperature of the second uniform drying treatment in step (3) can also be 0-20°C.

[0025] In an optional embodiment, the humidity of the second uniform drying treatment in step (3) is 30-70%.

[0026] In an optional embodiment, the humidity of the second uniform drying treatment in step (3) is 40-60%.

[0027] In an optional embodiment, the second uniform drying treatment time in step (3) is 1-5 minutes.

[0028] In an optional embodiment, the second uniform drying treatment time in step (3) is 3-5 minutes.

[0029] In an optional embodiment, the drying humidity in step (4) is 10%-90%.

[0030] In an optional embodiment, the drying temperature in step (4) is 20-30°C.

[0031] In an optional embodiment, the drying temperature in step (4) can also be 0-20°C.

[0032] In an optional embodiment, the drying time in step (4) is 15-72 hours.

[0033] In an optional embodiment, the mass of the protruding droplets in step (2) is 100-400 nanoliters / droplet; and the spacing between adjacent protruding droplets is 200-400 microns.

[0034] In an optional embodiment, the mass of the protruding droplets in step (2) is 150-350 nanoliters / droplet; and the spacing between adjacent protruding droplets is 250-300 microns.

[0035] In an optional embodiment, the active ingredient solution in step (1) includes but is not limited to the following combinations:

[0036] Combination 1: zolmitriptan, organic acid, and polyvinyl alcohol;

[0037] Combination 2: PVP;

[0038] Combination 3: chondroitin sulfate and dextran;

[0039] Combination 4: dextran and recombinant protein vaccine;

[0040] Combination five: dextran and LNP-mRNA.

[0041] Optionally, the organic acid includes but is not limited to one or more of formic acid, acetic acid, propionic acid, butyric acid, octanoic acid, adipic acid, oxalic acid, malonic acid, succinic acid, maleic acid, tartaric acid, benzoic acid, phenylacetic acid, phthalic acid, terephthalic acid, valeric acid, caproic acid, capric acid, stearic acid, palmitic acid, acrylic acid, glacial acetic acid, succinic acid and citric acid.

[0042] Further optionally, the organic acid includes one or more of tartaric acid, glacial acetic acid, succinic acid and citric acid.

[0043] Optionally, the content of each component in the active ingredient solution is:

[0044] Combination 1: zolmitriptan (30%-45%), organic acid (8%-16%), and polyvinyl alcohol (0.5%-3.0%);

[0045] Combination 2: PVP (10%);

[0046] Combination 3: chondroitin sulfate (5%) and dextran (5%);

[0047] Combination 4: dextran (20%) and recombinant protein vaccine (20%);

[0048] Combination five: dextran (20%) and LNP-mRNA (40%).

[0049] In an optional embodiment, the two-segment soluble microneedle skeleton solution in step (2) is a high molecular polymer solution.

[0050] More specifically, the high molecular polymer solution includes at least two of dextran 70, polyvinyl alcohol, PVP-K17, sucrose and water for injection.

[0051] Optionally, the polymer solution includes but is not limited to the following combinations:

[0052] Combination 1: Dextran 70 and water for injection;

[0053] Combination 2: polyvinyl alcohol, PVP-K17 and water for injection;

[0054] Combination 3: polyvinyl alcohol, sucrose and water for injection;

[0055] Combination 4: polyvinyl alcohol and water for injection;

[0056] Further optionally, the content of each component in the high molecular polymer solution is:

[0057] Combination 1: Dextran 70 (30%-50%) and water for injection (balance);

[0058] Combination 2: polyvinyl alcohol (10%-30%), PVP-K17 (10%-30%) and water for injection (balance);

[0059] Combination 3: polyvinyl alcohol (10%-20%), sucrose (10%-20%) and water for injection (balance);

[0060] Combination 4: polyvinyl alcohol (20%-40%) and water for injection (balance).

[0061] Further optionally, the content of each component in the high molecular polymer solution is:

[0062] Combination 1: Dextran 70 (40%) and water for injection (balance);

[0063] Combination 2: polyvinyl alcohol (20%), PVP-K17 (20%), and water for injection (balance);

[0064] Combination 3: polyvinyl alcohol (18%), sucrose (18%), and water for injection (balance);

[0065] Combination 4: polyvinyl alcohol (30%) and water for injection (balance).

[0066] Specifically, the gasket in step (3) is a TPU gasket.

[0067] On the other hand, the present application provides a zolmitriptan soluble microneedle patch, which is prepared by the above preparation method. The zolmitriptan soluble microneedle patch includes one section of active ingredient solution and two sections of soluble microneedle skeleton solution.

[0068] Specifically, the contents of the components of the first stage active ingredient solution are: zolmitriptan 30%-45%, organic acid 8%-16%, and polyvinyl alcohol 0.5%-3.0%.

[0069] Optionally, the organic acid includes but is not limited to one or more of tartaric acid, glacial acetic acid, succinic acid and citric acid.

[0070] Specifically, the two-stage soluble microneedle skeleton solution is a high molecular polymer solution.

[0071] More specifically, the high molecular polymer solution includes at least two of dextran 70, polyvinyl alcohol, PVP-K17, sucrose and water for injection.

[0072] Optionally, the polymer solution includes but is not limited to the following combinations:

[0073] Combination 1: Dextran 70 and water for injection;

[0074] Combination 2: polyvinyl alcohol, PVP-K17 and water for injection;

[0075] Combination 3: polyvinyl alcohol, sucrose and water for injection;

[0076] Combination 4: polyvinyl alcohol and water for injection;

[0077] Further optionally, the content of each component in the high molecular polymer solution is:

[0078] Combination 1: Dextran 70 (30%-50%) and water for injection (balance);

[0079] Combination 2: polyvinyl alcohol (10%-30%), PVP-K17 (10%-30%) and water for injection (balance);

[0080] Combination 3: polyvinyl alcohol (10%-20%), sucrose (10%-20%) and water for injection (balance);

[0081] Combination 4: polyvinyl alcohol (20%-40%) and water for injection (balance).

[0082] Further optionally, the content of each component in the high molecular polymer solution is:

[0083] Combination 1: Dextran 70 (40%) and water for injection (balance);

[0084] Combination 2: polyvinyl alcohol (20%), PVP-K17 (20%), and water for injection (balance);

[0085] Combination 3: polyvinyl alcohol (18%), sucrose (18%), and water for injection (balance);

[0086] Combination 4: polyvinyl alcohol (30%) and water for injection (balance).

[0087] Furthermore, the present application also provides a vaccine-soluble microneedle patch, which is prepared by the above-mentioned preparation method. The vaccine-soluble microneedle patch includes one section of active ingredient solution and two sections of soluble microneedle skeleton solution.

[0088] The beneficial effects of this application include, for example:

[0089] (1) The method for preparing the microneedle patch provided in the present application can prepare soluble microneedles with bases that are uniformly connected or independent of each other.

[0090] (2) The preparation method of the microneedle patch provided in the present application can achieve the same drying time for the microneedles at the periphery of the TPU gasket and the microneedles at the center of the TPU gasket during the drying process, thereby avoiding the situation where the microneedles at the periphery of the TPU gasket are over-drying and the microneedles are broken after demolding due to uneven drying, and the yield rate reaches more than 95%.

[0091] (3) The preparation method of the microneedle patch can make the first section of microneedle solution containing active ingredients and the second section of soluble microneedle skeleton solution more tightly connected, avoiding bubbles formed due to uneven drying of the entire solution, and making the yield rate reach more than 95%. BRIEF DESCRIPTION OF THE DRAWINGS

[0092] In order to more clearly illustrate the specific embodiments of the present disclosure or the technical solutions in the prior art, the following briefly introduces the drawings required for use in the specific embodiments or the description of the prior art. Obviously, the drawings described below are some embodiments of the present disclosure. For ordinary technicians in this field, other drawings can be obtained based on these drawings without paying any creative work.

[0093] Figure 1 is a diagram of the microneedle patch prepared in Comparative Example 1;

[0094] Figure 2 is a diagram of the microneedle patch prepared in Comparative Example 3;

[0095] FIG3 is a diagram of the microneedle patch prepared in Comparative Example 4;

[0096] FIG4 is a diagram of the microneedle patch prepared in Comparative Example 5;

[0097] FIG5 is a diagram of the microneedle patch prepared in Comparative Example 7;

[0098] FIG6 is a diagram of the base of the microneedle patch prepared in Example 1-14;

[0099] FIG7 is a diagram of the microneedle patch prepared in Example 1-14. DETAILED DESCRIPTION

[0100] The present application is described below with reference to specific examples. The following examples are not intended to limit the present application but are merely intended to illustrate the present application so that the technical solutions of the present application are easier to understand and grasp. The experimental methods described in the following examples are conventional methods unless otherwise specified; the reagents and materials described are commercially available unless otherwise specified.

[0101] Example 1-Example 20

[0102] The formulas of Examples 1 to 20 are shown in Table 1:

[0103] Table 1 Formulations of Examples 1 to 20 Note: In Examples 1-7, 9, 11, 13, 14, 15, 16, and 17, the ideal semi-curing effect can be achieved under the conditions of the first curing. In Examples 8, 10, 12, 18, 19, and 20, the humidity of the first semi-curing is higher than that of Examples 7, 9, and 11, making it difficult to directly achieve the ideal semi-curing state, so a second short-term semi-curing is required.

[0104] Comparative Example 1-Comparative Example 11

[0105] The formulas of Comparative Examples 1 to 11 are shown in Table 2:

[0106] Table 2 Formula table of comparative example 1-comparative example 11

[0107] The preparation methods of Examples 1 to 20 and Comparative Examples 1 to 11 are as follows:

[0108] 1. Inject 1 section of solution into the mold at 25°C and 90% RH for 5-20 minutes;

[0109] 2. Continue to inject the second stage soluble polymer solution into the mold until the second stage soluble polymer solution can completely fill the remaining needle cavity position. Fill the mold at 25°C and 90% RH for 30-180 minutes to obtain a mold filled with the first stage solution and the second stage soluble polymer solution. The mass of the protruding droplets formed by injecting the two stage soluble polymer solutions into the mold is 150-350 nanoliters / drop, and the distance between the protruding droplets is 250-300 microns.

[0110] 3. Perform the first uniform drying process to make the outer part of the raised droplets semi-dry, showing a gel-like state with no fluidity and a certain deformation ability; if the raised droplets still have fluidity after the first uniform drying, perform the second drying process to make the outer part of the raised droplets semi-dry, showing a gel-like state with no fluidity and a certain deformation ability.

[0111] 4. Completely cover the droplets with the TPU gasket, and press the TPU vertically from top to bottom with a force of 1-5N per square centimeter. The raised droplets are pressed into evenly connected droplets, or pressed into an independent circular plane that is not connected to the surrounding droplets.

[0112] 5. Place the mold in an environment with a humidity of 10%-90% and a temperature of 0℃-20℃ or 20℃-30℃ and dry it for 15-72 hours. Use an instrument to separate the TPU from the mold, and the microneedles will adhere to the TPU at the same time.

[0113] The yield rates of Examples 1 to 20 and Comparative Examples 1 to 11 are shown in Table 3.

[0114] Table 3 Yield rate of Examples 1 to 20 and Comparative Examples 1 to 11

[0115] The experimental results show that:

[0116] In Comparative Example 1, due to the low humidity during the first uniform drying treatment, the microneedle solution as a whole dried too quickly, was over-dried, could not be flattened, and bubbles and gaps appeared on the needle body. In Comparative Example 2, due to the low humidity during the first uniform drying treatment and the too short treatment time, it was over-dried, and had no stickiness when attached to the gasket, and could not be bonded to the TPU. The microneedles prepared in Comparative Example 1 are shown in Figure 1. The structure of the microneedles prepared in Comparative Example 2 is similar to that of Comparative Example 1, and Figure 1 can also be referred to. The raised solution on the horizontal surface of the mold was over-dried, resulting in the inability to flatten the raised solution when the gasket was applied, affecting the adhesion of the microneedles to the gasket. At the same time, the mechanical strength of the microneedles whose bases were not flattened will also be affected. The base is uneven, and the microneedles are easy to tip over when applied.

[0117] In Comparative Example 3, the second uniform drying treatment with too high humidity easily leads to individual microneedle gaps and bubbles, which affect the microneedle formability and result in a low microneedle preparation yield, as shown in FIG2 .

[0118] The microneedles prepared in Comparative Example 4 are shown in Figure 3. Since the first uniform drying time is short, the moisture in the microneedles cannot be evaporated and dried evenly, so that the short-term low-humidity drying during the second uniform drying will cause the microneedles to dry unevenly as a whole. The solution raised on the horizontal surface of the mold is semi-solidified, while the solution in the needle cavity is still in a relatively moist state. When the microneedles are dried as a whole after the gasket is applied, the solution in the needle cavity is easy to seep out, causing the solution to spread on the surface of the mold, easily forming bubbles and gaps in the microneedle base, affecting the formability of the microneedles.

[0119] The solutions of Comparative Examples 5 and 6 were relatively dilute, and they spread out when the pad was applied, which easily led to bubbles and gaps in the microneedle base. The microneedles prepared in Comparative Example 5 are shown in Figure 4. The microneedle structure prepared in Comparative Example 6 is similar to that of Comparative Example 5, and Figure 4 can also be used for reference.

[0120] The yield rate of microneedle preparation in Comparative Example 7 is low. Since the humidity of the first uniform drying is high, the moisture in the microneedles cannot be evaporated and dried evenly, so that the short-term low-humidity drying during the second uniform drying causes the microneedles to dry unevenly as a whole. The solution raised on the horizontal surface of the mold is semi-solidified, while the solution in the needle cavity is still in a relatively moist state. After the gasket is applied, when the microneedles are dried as a whole, the solution in the needle cavity is easy to seep out, causing the solution to spread on the surface of the mold, easily forming bubbles and gaps in the microneedle base, affecting the formability of the microneedles, as shown in Figure 5.

[0121] In Comparative Example 9, the proportion of raw materials and auxiliary materials is too high, and the viscosity of the solution obtained is too high. In addition, the solution is easy to dry when preparing microneedles, and the process is unstable, which affects the preparation efficiency. In Comparative Example 10, the excessive amount of PVA will cause the solution viscosity to be too high, and the microneedle preparation method will be more difficult. At the same time, it will increase the drying time of the microneedles. The difficulty in drying the first stage solution will cause the second stage solution to be over-dried when the microneedles are dried as a whole, which will easily lead to broken needles during demolding, affecting the yield rate of microneedle preparation. The first stage solution in Comparative Example 11 has strong hygroscopicity. After the microneedles are prepared, the solution absorbs moisture in the air and easily dissolves, thereby affecting the preparation efficiency of the microneedles.

[0122] Examples 1-20 were all formed normally, indicating that the preparation method of the soluble microneedle patch provided in the present application can prepare microneedles for different soluble microneedle solutions, and achieve uniform semi-cured soluble microneedle patches with uniformly connected bases or independent bases, the outer circle microneedles and the inner circle microneedles having the same drying time (see Figure 6), no bubbles, and continuous needles after demolding (see Figure 7).

[0123] In summary, the method for preparing a microneedle patch provided in this application is capable of preparing soluble microneedles with evenly connected bases or independent bases. During the drying process, the drying time of the microneedles at the periphery of the TPU gasket and the microneedles at the center of the TPU gasket can be made similar, avoiding the situation where the microneedles at the periphery of the TPU gasket are over-dried and break after demolding due to uneven drying. At the same time, it can make the first section of microneedle solution containing the active ingredient more tightly connected with the second section of the soluble microneedle skeleton solution, avoiding the formation of bubbles due to uneven drying of the entire solution, and achieving a yield rate of over 95%.

[0124] The above detailed description is a specific description of one feasible embodiment of the present application, and this embodiment is not intended to limit the scope of the patent of this application. It should be noted that any equivalent implementation or modification that does not depart from the scope of the present application should be included in the scope of the technical solution of this application. Therefore, the scope of protection of the patent of this application shall be based on the attached requirements. Industrial Applicability

[0125] In summary, the present application provides a method for preparing a microneedle patch and the microneedle patch prepared therefrom, wherein a section of active ingredient solution and two sections of soluble microneedle skeleton solution are injected into a mold, and through uniform drying treatment, soluble microneedles with uniformly connected bases or independent bases can be prepared; during the drying process, the drying time of the outer microneedles and the inner microneedles of the array can be made similar, thereby avoiding the situation where some microneedles are over-drying or broken after demolding due to uneven drying; the section of solution containing the active ingredient can be more tightly connected to the two sections of the soluble microneedle skeleton solution, thereby avoiding the formation of bubbles due to uneven drying of the entire solution; and the yield rate of microneedle preparation is greatly improved.

Claims

1. A preparation method of a microneedle patch, characterized in that, The preparation method includes the following steps: (1) Inject a section of active ingredient solution into the mold; (2) Inject a second section of soluble microneedle skeleton solution into the mold, such that the second section of soluble microneedle skeleton solution bulges from the surface of the mold to form a bulging droplet; (3) Perform a uniform drying treatment on the mold injected with the first section of active ingredient solution and the second section of soluble microneedle skeleton solution; the uniform drying treatment includes a first uniform drying treatment or a first uniform drying treatment and a second uniform drying treatment, such that the bulging droplet becomes a viscous colloidal bulge; (4) Press a gasket onto the colloidal bulge obtained in step (3), dry, and demold to obtain a microneedle patch.

2. The preparation method according to claim 1, characterized in that, In step (3), the temperature of the first uniform drying treatment is 20 - 30°C, the humidity is 80% - 95%, and the treatment time is 6 - 20 h.

3. The preparation method according to any one of claims 1-2, characterized in that, In step (3), the temperature of the second uniform drying treatment is 20 - 30°C, the humidity is 30 - 70%, and the treatment time is 1 - 5 min.

4. The preparation method according to any one of claims 1 to 3, characterized in that, In step (4), the humidity for drying is 10% - 90%; the time is 15 - 72 h; the temperature is 20 - 30°C.

5. The preparation method according to any one of claims 1-4, characterized in that, In step (3), the temperature of the first uniform drying treatment is 0 - 20°C, the humidity is 80% - 95%, and the treatment time is 6 - 20 h.

6. The preparation method according to any one of claims 1-5, characterized in that, In step (3), the temperature of the second uniform drying treatment is 0 - 20°C, the humidity is 30 - 70%, and the treatment time is 1 - 5 min.

7. The preparation method according to any one of claims 1-6, characterized in that, In step (4), the humidity for drying is 10% - 90%; the time is 15 - 72 h; the temperature is 0 - 20°C.

8. The preparation method according to any one of claims 1-7, characterized in that, In step (2), the mass of the bulging droplet is 150 - 350 nanoliters per droplet; the distance between adjacent bulging droplets is 250 - 300 micrometers.

9. The preparation method according to any one of claims 1-8, characterized in that, The first section of active ingredient solution includes any one of the following combinations: Combination one: 30% - 45% sumatriptan, 8% - 16% organic acid, and 0.5% - 3.0% polyvinyl alcohol; Combination two: 10% PVP; Combination three: 5% chondroitin sulfate and 5% dextran; Combination four: 20% dextran and 20% recombinant protein vaccine; Combination five: 20% dextran and 40% LNP - mRNA.

10. The preparation method according to claim 9, characterized in that, The organic acid includes one or more of formic acid, acetic acid, propionic acid, butyric acid, caprylic acid, adipic acid, oxalic acid, malonic acid, succinic acid, maleic acid, tartaric acid, benzoic acid, phenylacetic acid, phthalic acid, terephthalic acid, valeric acid, caproic acid, capric acid, stearic acid, palmitic acid, acrylic acid, glacial acetic acid, succinic acid, and citric acid.

11. The preparation method according to claim 9, characterized in that, The organic acid includes one or more of tartaric acid, glacial acetic acid, succinic acid, and citric acid.

12. The preparation method according to any one of claims 1-11, characterized in that, In step (2), the second section of soluble microneedle skeleton solution is a polymer solution.

13. The preparation method according to claim 12, wherein The polymer solution includes any one of the following combinations: Combination one: 30% - 50% dextran 70 and the balance being water for injection; Combination two: 10% - 30% polyvinyl alcohol, 10% - 30% PVP - K17, and the balance being water for injection; Combination three: 10% - 20% polyvinyl alcohol, 10% - 20% sucrose, and the balance being water for injection; Combination Four: 20%-40% polyvinyl alcohol and the balance being water for injection.

14. The preparation method according to any one of claims 1-13, characterized in that, The gasket described in step (4) is a TPU gasket.

15. A sumatriptan soluble microneedle patch, characterized in that, The sumatriptan soluble microneedle patch is prepared by the preparation method according to any one of claims 1-14, and comprises one segment of active ingredient solution and two segments of soluble microneedle matrix solution.

16. A soluble microneedle patch for a vaccine, characterized in that, The vaccine soluble microneedle patch is prepared by the preparation method according to any one of claims 1-14, and comprises one segment of active ingredient solution and two segments of soluble microneedle matrix solution.

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