Multifunctional hydrogel microneedle patch for promoting hair growth as well as preparation method and application of multifunctional hydrogel microneedle patch

Abstract

The invention discloses a multifunctional hydrogel microneedle patch for promoting hair growth and a preparation method and application thereof, and belongs to the technical field of hydrogel microneedle patches. The multifunctional hydrogel microneedle patch takes hyaluronic acid and polyvinyl alcohol as base materials, and contains Chinese yam exosomes loaded with medicines; the mass ratio of the medicine to the Chinese yam exosome is 1: 1. The hydrogel microneedle patch loaded with the medicine-Chinese yam exosome is constructed, so that the cooperation of efficient transdermal delivery of the medicine and active regulation of the hair follicle microenvironment is realized. According to the scheme, the defects that a traditional preparation is low in bioavailability and single in function are effectively overcome, hair follicle angiogenesis and cell proliferation are remarkably promoted, the hair regeneration effect is improved, and a safe and efficient new strategy is provided for alopecia treatment.

Description

Technical Field

[0001] This invention relates to the field of hydrogel microneedle patch technology, and in particular to a multifunctional hydrogel microneedle patch for promoting hair growth, its preparation method, and its application. Background Technology

[0002] In the fields of clinical medicine and tissue engineering, the treatment of hair loss (especially androgenetic alopecia) has long relied on topical medications (such as minoxidil) or oral preparations (such as finasteride). While minoxidil, as a first-line topical medication, has some effect in promoting hair growth, its transdermal absorption efficiency is limited by the natural barrier function of the stratum corneum of human skin, resulting in low bioavailability. Patients need to administer the medication frequently over a long period, and it is often accompanied by adverse reactions such as local irritation, contact dermatitis, or hirsutism, leading to poor treatment compliance and tolerability. Therefore, achieving efficient, controllable, and low-irritation drug delivery has become a key technical challenge that urgently needs to be solved in this field.

[0003] In recent years, transdermal drug delivery systems (TDDS) have gradually become a research hotspot, especially dissolvable microneedles (MNs) technology, which has attracted attention due to its ability to penetrate the stratum corneum painlessly and improve drug delivery efficiency. However, existing microneedle systems are mostly based on single drug loading, with relatively limited functions, and often use chemically synthesized carriers or animal-derived exosomes as delivery media, which have problems such as potential immunogenicity, insufficient biosafety, or complex preparation processes. In addition, traditional microneedles often lack the ability to actively regulate the hair follicle microenvironment after penetration enhancement, making it difficult to achieve multi-mechanism synergistic treatment and affecting their overall efficacy in the treatment of hair loss.

[0004] Furthermore, plant-derived exosomes, as an emerging bioactive delivery carrier, possess advantages such as wide availability, high safety, and the presence of natural active ingredients. However, their application in hair loss treatment is still in its early stages. Currently, there is a lack of integrated systems that combine plant exosomes with microneedle technology to synergistically load commonly used clinical hair growth drugs. Simultaneously, existing technologies still face technical bottlenecks regarding how to stably and efficiently load drugs into plant exosomes and further immobilize them within a hydrogel microneedle matrix with suitable mechanical properties and good biocompatibility. These bottlenecks include difficulties in process integration, easy inactivation of active ingredients, and poor controllability of the drug loading system. This results in existing hair growth stimulant formulations often having limited functionality and insufficient synergistic effects, failing to meet the urgent clinical demand for efficient, safe, and convenient treatments. Summary of the Invention

[0005] The purpose of this invention is to provide a multifunctional hydrogel microneedle patch for promoting hair growth, its preparation method, and its applications, thereby addressing the problems existing in the prior art. This invention achieves synergistic effects of highly efficient transdermal drug delivery and active regulation of the hair follicle microenvironment by constructing a hydrogel microneedle patch loaded with drug-yam exosomes. This approach effectively overcomes the shortcomings of traditional formulations, such as low bioavailability and limited functionality, significantly promoting hair follicle angiogenesis and cell proliferation, enhancing hair regeneration, and providing a safe and efficient new strategy for hair loss treatment.

[0006] To achieve the above objectives, the present invention provides the following solution:

[0007] This invention provides a multifunctional hydrogel microneedle patch for promoting hair growth, using hyaluronic acid and polyvinyl alcohol as matrix materials, and containing yam exosomes loaded with drugs;

[0008] The mass ratio of the drug to the yam exosomes is 1:1.

[0009] Optionally, the drug may include minoxidil or finasteride.

[0010] Optionally, the mass ratio of the hyaluronic acid to the polyvinyl alcohol is (1~3):(5~15).

[0011] Optionally, the concentration of the drug-loaded yam exosomes in the multifunctional hydrogel microneedle patch is 5 mg / mL.

[0012] This invention also provides a method for preparing the aforementioned multifunctional hydrogel microneedle patch, comprising the following steps:

[0013] S1. Preparation of yam exosomes;

[0014] S2. Mix the drug with the yam exosomes obtained in step S1 to prepare a drug-loaded yam exosome solution;

[0015] S3. Mix the hyaluronic acid solution with the polyvinyl alcohol solution to obtain the hydrogel matrix solution;

[0016] S4. Mix the drug-loaded yam exosome solution obtained in step S2 with the hydrogel matrix solution obtained in step S3 to obtain a microneedle precursor mixture.

[0017] S5. Inject the microneedle precursor mixture obtained in step S4 into the microneedle mold to prepare the multifunctional hydrogel microneedle patch.

[0018] Optionally, the method for preparing the yam exosomes includes the following steps:

[0019] After juicing and filtering the yam, the juice was successively centrifuged at 1000×g for 10 min, 3000×g for 15 min, 10000×g for 30 min, and 20000×g for 30 min, and the supernatant was collected. Finally, the supernatant was centrifuged at 120000×g for 2 h, the precipitate was resuspended and filtered through a 0.22 μm filter membrane to obtain the yam exosomes.

[0020] The present invention also provides the use of the aforementioned multifunctional hydrogel microneedle patch in the preparation of products for promoting hair growth, treating hair loss or activating hair follicle cells.

[0021] Optionally, the product may include a drug or a medical device.

[0022] The present invention also provides a product for promoting hair growth, treating hair loss or activating hair follicle cells, comprising the above-mentioned multifunctional hydrogel microneedle patch.

[0023] Optionally, the product may include a drug or a medical device.

[0024] The present invention discloses the following technical effects:

[0025] This invention loads yam exosomes carrying commonly used clinical drugs (such as minoxidil) into hydrogel microneedle patches, constructing a synergistic therapeutic platform integrating efficient transdermal delivery, controlled drug release, and active microenvironment regulation. This design directly addresses the problems of low bioavailability, frequent administration, and easy local irritation associated with traditional minoxidil formulations. Simultaneously, it overcomes the limitations of existing microneedle technology, such as its single function and lack of active regulation of hair follicle ecology, providing a convenient, efficient, and safe innovative delivery solution for hair loss treatment.

[0026] The multifunctional hydrogel microneedle patch of this invention significantly improves the overall efficacy of hair regeneration. In vivo experimental results show that, compared with single-component treatments or traditional delivery methods, the multifunctional hydrogel microneedle patch exhibits a significant synergistic effect, effectively promoting perifollicular angiogenesis (upregulation of CD31 expression) and cell proliferation (upregulation of Ki67 expression), and significantly increasing the number and length of hair follicles. The synergistic effect of yam exosomes and drugs through the microneedle platform enables dual regulation of hair follicle cells and the microenvironment, providing a promising new strategy for the clinical treatment of hair-related diseases such as androgenetic alopecia. Attached Figure Description

[0027] To more clearly illustrate the technical solutions in the embodiments of the present invention or the prior art, the drawings used in the embodiments will be briefly introduced below. Obviously, the drawings described below are only some embodiments of the present invention. For those skilled in the art, other drawings can be obtained based on these drawings without creative effort.

[0028] Figure 1 TEM image of yam exosomes;

[0029] Figure 2 Diagram showing the diameter distribution of yam exosomes;

[0030] Figure 3 SEM image of hydrogel microneedle patch;

[0031] Figure 4 The fluorescence detection image is for the hydrogel microneedle patch.

[0032] Figure 5 Quantitative graphs of hair regeneration (A) and hair coverage (B) in mouse models under different treatments;

[0033] Figure 6 H&E staining images (A) and quantitative images of hair follicle length (B) of skin sections from different treatment groups at the treatment sites;

[0034] Figure 7 Representative immunofluorescence staining images of CD31 (A), representative immunofluorescence staining images of Ki67 (B), and relative fluorescence intensity histograms of CD31 (C) and Ki67 (D) in different treatment groups on day 8. Detailed Implementation

[0035] Various exemplary embodiments of the present invention will now be described in detail. This detailed description should not be considered as a limitation of the present invention, but rather as a more detailed description of certain aspects, features, and embodiments of the present invention.

[0036] It should be understood that the terminology used in this invention is merely for describing particular embodiments and is not intended to limit the invention. Furthermore, with respect to numerical ranges in this invention, it should be understood that each intermediate value between the upper and lower limits of the range is also specifically disclosed. Any stated value or intermediate value within a stated range, as well as each smaller range between any other stated value or intermediate value within said range, is also included in this invention. The upper and lower limits of these smaller ranges may be independently included or excluded from the range.

[0037] Unless otherwise stated, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art. While only preferred methods and materials have been described herein, any methods and materials similar or equivalent to those described herein may be used in the implementation or testing of this invention. All references to this specification are incorporated by way of citation to disclose and describe methods and / or materials associated with those references. In the event of any conflict with any incorporated reference, the content of this specification shall prevail.

[0038] Various modifications and variations can be made to the specific embodiments described in this specification without departing from the scope or spirit of the invention, as will be apparent to those skilled in the art. Other embodiments derived from this specification will also be obvious to those skilled in the art. This specification and embodiments are merely exemplary.

[0039] The terms “include,” “including,” “have,” “contain,” etc., used in this article are all open-ended terms, meaning that they include but are not limited to.

[0040] Example

[0041] A multifunctional hydrogel microneedle patch that promotes hair growth is prepared as follows:

[0042] 1. Preparation of exosomes from Dioscorea opposita

[0043] S1. After peeling the Chinese yam, add 10 times its weight of water and juice it using a juicer to obtain coarse yam liquid. Then filter it multiple times with gauze to remove coarse impurities.

[0044] S2. Centrifuge the filtered juice using a centrifuge: First, centrifuge at 1000×g for 10 minutes, then take the supernatant. Next, centrifuge at 3000×g for 15 minutes, then take the supernatant. Then, centrifuge at 10000×g for 30 minutes, take the supernatant, and finally centrifuge at 20000×g for 30 minutes to gradually remove larger particulate matter.

[0045] S3. Centrifuge the supernatant obtained in S2 at 120000×g for 2h, and then filter it through a 0.22 µm membrane to obtain an exosome solution to enrich yam exosomes.

[0046] The yam exosomes prepared above were observed by TEM, as follows: Figure 1 As shown.

[0047] Dilute the yam exosomes to approximately 1×10⁻⁶ using phosphate-buffered saline (PBS). 8 Particles per milliliter (mL) -1 After dust removal via a 0.22 µm filter membrane, the sample reached equilibrium at 25°C. A precise 10 µL sample was placed in a cuvette, and three rounds of measurements were performed using a dynamic light scattering (DLS) instrument with a backscattering angle of 173° and refractive indices of 1.45 / 1.335. The Z-average particle size was used as the characterization parameter for average particle size; when the polydispersity index (PDI) was less than 0.2, the sample was considered a monodisperse system. After 5 minutes of measurement, the diameter distribution of the yam exosomes was obtained. Figure 2 As shown.

[0048] 2. Preparation of yam exosomes loaded with minoxidil (YEVs@Mi)

[0049] Take 5 mg of the above-mentioned yam exosomes, dissolve them in 900 μL of distilled water, add 100 μL of minoxidil solution with a mass concentration of 50 mg / mL, stir well, and then place in 4℃ in the dark and gently shake for 4 h to obtain yam exosomes (YEVs@Mi) loaded with minoxidil.

[0050] 3. Preparation of microneedle precursor mixture

[0051] Accurately weigh 1g of polyvinyl alcohol (PVA) powder (degree of alcoholysis 87-89%, molecular weight 67 kDa) into a beaker and add 20mL of distilled water. Place the beaker in a 90℃ water bath and stir until the PVA is completely dissolved to obtain a clear and viscous PVA solution. Cool to room temperature for later use.

[0052] Accurately weigh 0.2 g of hyaluronic acid (HA) powder (molecular weight 100 kDa) into another beaker, and add 20 mL of deionized water. Stir at room temperature until the HA is completely dissolved to obtain a clear HA solution.

[0053] PVA solution and HA solution were mixed at a volume ratio of 1:1 to obtain a homogeneous and transparent mixed solution, which is the microneedle precursor solution.

[0054] Take 1 mL of microneedle precursor solution, add 1 mL of YEVs@Mi solution, mix well to obtain microneedle precursor mixture.

[0055] 4. Preparation of microneedle patches

[0056] The prepared microneedle precursor mixture was fixed using a microneedle mold, then concentrated and dried at 37°C for 48 hours to obtain the multifunctional hydrogel microneedle patch YEVs@Mi-MN.

[0057] The morphology of the prepared hydrogel microneedle patch was measured using scanning electron microscopy (SEM), and the results are as follows: Figure 3 As shown. Its fluorescence morphology was measured using laser confocal microscopy, and the results are as follows. Figure 4 As shown.

[0058] Comparative Example 1

[0059] A blank hydrogel microneedle patch containing no active ingredients is prepared as follows:

[0060] Accurately weigh 1g of polyvinyl alcohol (PVA) powder (degree of alcoholysis 87-89%, molecular weight 67 kDa) into a beaker and add 20mL of distilled water. Place the beaker in a 90℃ water bath and stir until the PVA is completely dissolved to obtain a clear and viscous PVA solution. Cool to room temperature for later use.

[0061] Accurately weigh 0.2 g of hyaluronic acid (HA) powder (molecular weight 100 kDa) into another beaker, and add 20 mL of deionized water. Stir at room temperature until the HA is completely dissolved to obtain a clear HA solution.

[0062] PVA solution and HA solution were mixed at a volume ratio of 1:1 to obtain a homogeneous and transparent mixed solution, which is the microneedle precursor solution.

[0063] Take 1 mL of microneedle precursor solution, add 1 mL of PBS solution, mix well, fix through a microneedle mold, then concentrate, and dry at 37°C for 48 h to obtain a blank hydrogel microneedle patch without any active ingredients.

[0064] Comparative Example 2

[0065] A spreadable hydrogel loaded only with yam exosomes is prepared as follows:

[0066] 1. Preparation of exosomes from Dioscorea opposita

[0067] S1. After peeling the Chinese yam, add 10 times its weight of water and juice it using a juicer to obtain coarse yam liquid. Then filter it multiple times with gauze to remove coarse impurities.

[0068] S2. Centrifuge the filtered juice using a centrifuge: First, centrifuge at 1000×g for 10 minutes, then take the supernatant. Next, centrifuge at 3000×g for 15 minutes, then take the supernatant. Then, centrifuge at 10000×g for 30 minutes, take the supernatant, and finally centrifuge at 20000×g for 30 minutes to gradually remove larger particulate matter.

[0069] S3. Centrifuge the supernatant obtained in S2 at 120000×g for 2h, and then filter it through a 0.22 µm membrane to obtain an exosome solution to enrich yam exosomes.

[0070] Take 5 mg of yam exosomes and dissolve them in 900 μL of distilled water to obtain a yam exosome solution.

[0071] 2. Preparation of spreadable hydrogel

[0072] Accurately weigh 1g of polyvinyl alcohol (PVA) powder (degree of alcoholysis 87-89%, molecular weight 67 kDa) into a beaker and add 20mL of distilled water. Place the beaker in a 90℃ water bath and stir until the PVA is completely dissolved to obtain a clear and viscous PVA solution. Cool to room temperature for later use.

[0073] Accurately weigh 0.2 g of hyaluronic acid (HA) powder (molecular weight 100 kDa) into another beaker, and add 20 mL of deionized water. Stir at room temperature until the HA is completely dissolved to obtain a clear HA solution.

[0074] PVA solution and HA solution were mixed at a volume ratio of 1:1 to obtain a homogeneous and transparent mixed solution.

[0075] Take 1 mL of the above mixed solution, add 1 mL of yam exosome solution, stir well, and finally form a hydrogel that can be applied, Hydrogel@YEVs.

[0076] Comparative Example 3

[0077] A hydrogel microneedle patch loaded with yam exosomes is prepared as follows:

[0078] 1. Preparation of exosomes from Dioscorea opposita

[0079] S1. After peeling the Chinese yam, add 10 times its weight of water and juice it using a juicer to obtain coarse yam liquid. Then filter it multiple times with gauze to remove coarse impurities.

[0080] S2. Centrifuge the filtered juice using a centrifuge: First, centrifuge at 1000×g for 10 minutes, then take the supernatant. Next, centrifuge at 3000×g for 15 minutes, then take the supernatant. Then, centrifuge at 10000×g for 30 minutes, take the supernatant, and finally centrifuge at 20000×g for 30 minutes to gradually remove larger particulate matter.

[0081] S3. Centrifuge the supernatant obtained in S2 at 120000×g for 2h, and then filter it through a 0.22 µm membrane to obtain an exosome solution to enrich yam exosomes.

[0082] Take 5 mg of yam exosomes and dissolve them in 900 μL of distilled water to obtain a yam exosome solution.

[0083] 2. Preparation of spreadable hydrogel

[0084] Accurately weigh 1g of polyvinyl alcohol (PVA) powder (degree of alcoholysis 87-89%, molecular weight 67 kDa) into a beaker and add 20mL of distilled water. Place the beaker in a 90℃ water bath and stir until the PVA is completely dissolved to obtain a clear and viscous PVA solution. Cool to room temperature for later use.

[0085] Accurately weigh 0.2 g of hyaluronic acid (HA) powder (molecular weight 100 kDa) into another beaker, and add 20 mL of deionized water. Stir at room temperature until the HA is completely dissolved to obtain a clear HA solution.

[0086] PVA solution and HA solution were mixed at a volume ratio of 1:1 to obtain a homogeneous and transparent mixed solution.

[0087] Take 1 mL of the above mixed solution, add 1 mL of yam exosome solution, stir evenly, fix it through a microneedle mold, then concentrate it, and dry it at 37℃ for 48 h to obtain hydrogel microneedle patch YEVs-MN loaded with yam exosomes.

[0088] Comparative Example 4

[0089] A hydrogel microneedle patch loaded only with the clinically commonly used drug minoxidil is prepared as follows:

[0090] 1. Preparation of microneedle precursor solution

[0091] Accurately weigh 1g of polyvinyl alcohol (PVA) powder (degree of alcoholysis 87-89%, molecular weight 67 kDa) into a beaker and add 20mL of distilled water. Place the beaker in a 90℃ water bath and stir until the PVA is completely dissolved to obtain a clear and viscous PVA solution. Cool to room temperature for later use.

[0092] Accurately weigh 0.2 g of hyaluronic acid (HA) powder (molecular weight 100 kDa) into another beaker, and add 20 mL of deionized water. Stir at room temperature until the HA is completely dissolved to obtain a clear HA solution.

[0093] PVA solution and HA solution were mixed at a volume ratio of 1:1 to obtain a homogeneous and transparent mixed solution, which is the microneedle precursor solution.

[0094] 2. Preparation of hydrogel microneedle patches

[0095] Take 100 μL of minoxidil solution with a mass concentration of 50 mg / mL, add it to 1 mL of microneedle precursor solution, stir well, fix it through a microneedle mold, then concentrate it, and dry it at 37℃ for 48 h to obtain hydrogel microneedle patch Mi-MN loaded with yam exosomes.

[0096] Effect verification example

[0097] By constructing a mouse model of androgenetic alopecia (AGA), the promoting effects of different formulations prepared in the above examples and comparative examples 1-4 on hair regeneration were systematically evaluated.

[0098] 1. Laboratory animals and grouping

[0099] Fifteen male C57BL / 6 rats (Henan Skebers Biotechnology Co., Ltd.), weighing 20-25g and of similar size, were selected. After one week of acclimatization in an SPF-grade environment, all animals were randomly divided into 5 groups of 3 rats each.

[0100] Control group: The blank microneedle patch (Control-MN) prepared using Comparative Example 1.

[0101] Hydrogel exosomes (Hydrogel@YEVs): Applyable hydrogels prepared using Comparative Example 2.

[0102] Exosome microneedle group (YEVs-MN): a yam exosome microneedle patch prepared using Comparative Example 3.

[0103] Minoxidil microneedle patch (Mi-MN): Minoxidil-loaded microneedle patch prepared using Comparative Example 4.

[0104] Multifunctional microneedle patch (YEVs@Mi-MN): Multifunctional microneedle patch loaded with minoxidil-yam exosomes prepared using the examples.

[0105] 2. AGA model establishment and drug administration

[0106] a. Use an electric shaver to shave the hair off a 2 cm × 2 cm area on the back of the mouse.

[0107] b. Starting from the day of shaving, apply a 1% testosterone propionate solution (dissolved in anhydrous ethanol) to the skin surface of the shaved area daily until the end of the experiment to inhibit hair growth and simulate the AGA state.

[0108] c. Treatment intervention begins on day 0 after shaving:

[0109] Control group, YEVs-MN group, Mi-MN group, YEVs@Mi-MN group: Apply the corresponding microneedle patch base tightly to the shaved area of ​​skin, and gently press with your finger for 1 minute to ensure that the microneedles penetrate the skin and separate from the base. Administer once every 3 days.

[0110] Hydrogel@YEVs group: Apply 100 μL of the applicable hydrogel evenly to the shaved area using a pipette, gently spreading until absorbed. Administer once daily.

[0111] d. Continuously observe and record the changes in the skin on the backs of mice in each group.

[0112] 3. Observation and evaluation of hair regeneration

[0113] Eight days after hair removal, high-resolution photographs of the dorsal skin of mice in each group were taken using a digital camera under the same lighting and angles. The percentage of hair-covered area in the photographs was analyzed using ImageJ software to quantitatively assess the hair regrowth coverage rate. Results are as follows: Figure 5 As shown, no visible hair regrowth was observed in the control group, indicating that the androgenetic alopecia (AGA) model was successfully established. Compared with the control group, hair coverage was improved in all treatment groups. Among them, the Hydrogel@YEVs group alone showed limited regeneration; the hair density of the YEVs-MN group and the Mi-MN group was comparable; while the YEVs@Mi-MN group had the highest coverage and the most significant therapeutic effect.

[0114] 4. Histological and immunofluorescence analysis

[0115] a. On day 14 after administration, all mice were euthanized and intact skin tissue from the dorsal administration area was carefully excised.

[0116] b. Skin tissue was fixed in 4% paraformaldehyde, embedded in paraffin, and then cut into 3 μm thick sections.

[0117] c. H&E staining: Observe the morphology, number, and hair shaft length of the hair follicles. For example... Figure 6 As shown, no new hair follicles were observed in the control group; only a small number of sparse hair follicles were observed in the Hydrogel@YEVs group; the number and morphology of hair follicles were partially restored in both the YEVs-MN and Mi-MN groups; the YEVs@Mi-MN group had the most hair follicles, the longest hair shafts, and the most complete structure, which was significantly better than other experimental groups.

[0118] d. Immunofluorescence staining: Sections were stained with CD31 antibody (a vascular endothelial marker) and Ki67 antibody (a cell proliferation marker) to assess perifollicular angiogenesis and cell proliferation. Results are as follows: Figure 7 As shown, the fluorescence intensity of Ki67 (a cell proliferation marker) and CD31 (a vascular endothelial marker) in the YEVs@Mi-MN group was significantly higher than that in the other groups, suggesting that this microneedle system can synergistically promote the proliferation and angiogenesis of cells around hair follicles, thereby accelerating hair regeneration. In summary, the YEVs@Mi-MN microneedle array percutaneous delivery system significantly improves hair regeneration in the AGA model by enhancing cell proliferation and vascularization, demonstrating excellent synergistic therapeutic potential.

[0119] In vivo animal experiments showed that the multifunctional hydrogel microneedle patch (YEVs@Mi-MN) loaded with minoxidil-yam exosomes provided by this invention was significantly more effective than the blank control group, the group using yam exosomes alone (whether applied topically or delivered via microneedles), and the group using minoxidil microneedles alone in promoting hair regeneration in a mouse model of androgenetic alopecia. Its mechanism of action may be related to the synergistic effects of efficient transdermal delivery via microneedles, the improvement of the hair follicle microenvironment by yam exosomes, and the direct hair growth promotion by minoxidil.

[0120] The embodiments described above are merely preferred embodiments of the present invention and are not intended to limit the scope of the present invention. Various modifications and improvements made by those skilled in the art to the technical solutions of the present invention without departing from the spirit of the present invention should fall within the protection scope defined by the claims of the present invention.

Claims

1. A multifunctional hydrogel microneedle patch for promoting hair growth, characterized by, A hyaluronic acid and polyvinyl alcohol-based multifunctional hydrogel microneedle patch containing yam exosomes loaded with a drug; The mass ratio of the drug to the yam exosomes is 1:

1.

2. The multifunctional hydrogel microneedle patch of claim 1, wherein, The drug includes minoxidil or finasteride.

3. The multifunctional hydrogel microneedle patch of claim 1, wherein, The mass ratio of the hyaluronic acid to the polyvinyl alcohol is (1-3):(5-15).

4. The multifunctional hydrogel microneedle patch of claim 1, wherein, The concentration of the yam exosomes loaded with the drug in the multifunctional hydrogel microneedle patch is 5 mg / mL.

5. A method of preparing the multifunctional hydrogel microneedle patch according to any one of claims 1-4, characterized in that, The method comprises the following steps: S1. Preparing yam exosomes; S2. Mixing a drug with the yam exosomes obtained in step S1 to prepare a yam exosome solution loaded with the drug; S3. Mixing a hyaluronic acid solution with a polyvinyl alcohol solution to obtain a hydrogel matrix solution; S4. Mixing the yam exosome solution loaded with the drug obtained in step S2 with the hydrogel matrix solution obtained in step S3 to obtain a microneedle precursor mixture; S5. Injecting the microneedle precursor mixture obtained in step S4 into a microneedle mold to prepare the multifunctional hydrogel microneedle patch.

6. The preparation method according to claim 5, characterized in that, The preparation method of the yam exosomes comprises the following steps: After the yam is squeezed and filtered, it is subjected to 1000xg centrifugation for 10 min, 3000xg centrifugation for 15 min, 10000xg centrifugation for 30 min, and 20000xg centrifugation for 30 min, and the supernatant is taken; finally, the supernatant is centrifuged at 120000xg for 2 h, the precipitate is resuspended and filtered through a 0.22 μm filter membrane to obtain the yam exosomes.

7. Use of the multifunctional hydrogel microneedle patch according to any one of claims 1-4 in the preparation of a product for promoting hair growth, treating hair loss, or activating hair follicle cells.

8. Use according to claim 7, characterized in that, The product includes a drug or a medical device.

9. A product for promoting hair growth, treating hair loss or activating hair follicle cells, characterized in that, The product includes a drug or a medical device.

10. The product of claim 9, wherein, The product includes a drug or a medical device.

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