Exosome soluble microneedle based on water-soluble chitosan and manufacturing method thereof

Abstract

The invention relates to the technical field of soluble microneedles, in particular to an exosome soluble microneedle based on water-soluble chitosan and a manufacturing method thereof.The exosome soluble microneedle comprises a base plate and microneedles, the multiple microneedles are arranged at intervals, and the microneedles are fixed to the surface of the same side of the base plate; the microneedle is prepared from the following components in parts by weight: a pure chitosan substrate, crystal water, a fusion agent, a photocatalytic curing agent and exosome, the substrate comprises the following components in parts by weight: a pure chitosan substrate, crystal water and a photocatalytic curing agent; according to the exosome soluble microneedle and the manufacturing method thereof, the fusion agent can assist in rapid fusion of the exosome and the photocatalytic curing agent in the stock solution, the exosome can be distributed in all corners in the microneedle, the photocatalytic curing agent can be rapidly cured under the special illumination condition, the curing time of the product is greatly shortened, and the production efficiency is improved. The method is suitable for large-scale rapid production and is very worthy of popularization and application in the market.

Description

Technical Field

[0001] This application relates to the technical field of soluble microneedle technology, and in particular to an exosome soluble microneedle based on water-soluble chitosan and a manufacturing method thereof. Background Art

[0002] Facial anti-aging has become an increasingly popular topic in cosmetic surgery. The appearance of wrinkles and age spots is the most direct manifestation of facial aging. Therefore, wrinkle removal and freckle removal have also become topics that people pay more and more attention to. At present, both pharmaceutical beauty and surgical beauty are temporary measures that only treat the symptoms but not the root cause, and there are problems such as high risks, complications, side effects, pain, and bruising. In recent years, the soluble microneedle transdermal drug delivery technology (also known as the microcrystal technology in the industry) has been favored by the majority of beauty lovers because of its minimally invasive, painless, fast recovery, and good effect.

[0003] The skin, especially the stratum corneum, has a barrier effect on the transdermal absorption of drugs, which will hinder the absorption of drugs. Microneedles can pierce the stratum corneum barrier of the skin to generate microchannels to increase the penetration of drugs. The drugs penetrate into the capillary network of the dermis layer of the skin through the pores of the microneedles and reach the treatment target directly through the blood circulation, which can achieve the purpose of sufficient and rapid drug delivery, greatly reducing the drug dosage and improving the drug efficacy. Since the microneedles are thin and sharp, the general puncture depth is only in the stratum corneum and the upper layer of the dermis, without touching the nerve endings, reducing the degree of damage to the body tissue. At the same time, it can stimulate the dermis layer and promote the proliferation of collagen through the self-healing ability of the skin.

[0004] Mesenchymal stem cells (MSCs) are an important member of the stem cell family, originating from the mesoderm and belonging to pluripotent stem cells. MSCs can secrete a variety of growth factors (such as epidermal growth factor, vascular endothelial growth factor, collagen, and fibronectin, etc.) and inflammatory factors (interferon γ, interleukin 9, and tumor necrosis factor α, etc.), and have significant effects in many anti-aging aspects such as inhibiting skin aging, whitening the skin, assisting fat transplantation, and promoting hair regeneration.

[0005] In recent years, with the increasingly in-depth research and application of MSCs, the functions of mesenchymal stem cell exosomes have gradually become a new research hotspot. Exosomes are nano-scale lipid bilayer membrane vesicles released into the extracellular environment after the fusion of multivesicular endosomes of eukaryotic cells with the cell membrane. They can be secreted by various types of cells and contain various biologically active substances such as proteins, lipids, mRNA, microRNA, and small molecules. After fusing with the cell membrane of adjacent cells, they deliver the active substances to the recipient cells to achieve intercellular information transmission. Clinically, stem cell exosomes are mainly used to treat burns, scalds, skin ulcers, and regenerate healthy skin. In terms of skin care, they are mainly used to repair damaged, aging, and poisoned skin, comprehensively condition the skin, improve skin quality, and make the skin return to a young and healthy state. However, when stem cell exosomes are directly applied to the skin surface, most exosomes cannot enter the target cells in the inner layer of the skin due to the barrier of the stratum corneum of the skin surface. But once the skin is broken by the microneedle-mediated method, the exosomes can directly reach the basal cells along the cell channels through the pores of the microneedles and play their role in skin care and nourishment.

[0006] For example, Chinese Patent No. 202011148113.8 discloses a stem cell exosome microneedle patch for removing freckles and reducing wrinkles, which includes microneedles and a waterproof backing layer for fixing the microneedles; the microneedles are obtained by curing a tip solution and a needle body solution; the tip solution includes stem cell exosomes, astaxanthin, trehalose, chitosan, bovine serum albumin, and phosphate buffer solution; the needle body solution includes PVP K30, PEG400, squalane, and sterile water.

[0007] Regarding the above related technologies, the inventor believes that there are the following defects:

[0008] At present, most of the soluble microneedle transdermal drug delivery technologies are in the experimental research stage. It is difficult to fully incorporate stem cell exosomes into soluble microneedles to effectively prevent aging. Even if a small amount of soluble microneedles containing stem cell exosomes are manufactured through frequent and multiple pure manual experiments, it is difficult to achieve large-scale rapid production, and it is even more difficult to promote and apply them in the market. Therefore, it needs to be improved. Summary of the Invention

[0009] This application provides a stem cell exosome soluble microneedle based on water-soluble chitosan and its manufacturing method to improve the following technical problems:

[0010] At present, most of the soluble microneedle transdermal drug delivery technologies are in the experimental research stage. It is difficult to fully incorporate stem cell exosomes into soluble microneedles to effectively prevent aging. Even if a small amount of soluble microneedles containing stem cell exosomes are manufactured through frequent and multiple pure manual experiments, it is difficult to achieve large-scale rapid production, and it is even more difficult to promote and apply them in the market.

[0011] In a first aspect, the present application provides a method for fabricating exosome-soluble microneedles based on water-soluble chitosan, adopting the following technical solution:

[0012] A method for fabricating exosome-soluble microneedles based on water-soluble chitosan, comprising the following steps:

[0013] Step 1, fabricating a PDMS microneedle mold: The PDMS microneedle mold is provided with tip cavities for forming multiple microneedles and a substrate cavity for forming a substrate;

[0014] Step 2, preparing the stock solution: At 38 - 42 °C, according to the proportion of different component materials in the exosome-soluble microneedles, prepare component solutions of different concentrations for different component materials, including preparing a water-soluble chitosan solution; mix the component solutions belonging to the microneedles in corresponding proportions and stir at 25 - 30 °C for 1 - 1.5 hours; mix the component solutions belonging to the substrate in corresponding proportions and stir at 25 - 30 °C for 1 - 1.5 hours.

[0015] Step 3, pre-treating the PDMS microneedle mold: First, ultrasonically clean the PDMS microneedle mold for 15 - 25 minutes, then disinfect it with ultraviolet light for 35 - 45 minutes, and finally perform plasma treatment on the PDMS microneedle mold;

[0016] Step 4, injecting the stock solution into the mold: Take a certain amount of microneedle stock solution according to the volume of the tip cavities of the PDMS microneedle mold and inject it into the tip cavities of the PDMS microneedle mold, ensuring that the microneedle stock solution completely fills the tip cavities, then remove the excess microneedle stock solution in the substrate cavity. Then, take a certain amount of substrate stock solution according to the volume of the substrate cavity of the PDMS microneedle mold and inject it into the substrate cavity of the PDMS microneedle mold, ensuring that the substrate stock solution completely fills the substrate cavity. Then, remove the excess substrate stock solution by spreading, and place the PDMS microneedle mold in a vacuum environment of -0.08 MPa to remove air bubbles for 5 - 10 minutes;

[0017] Step 5, curing and forming: Place the PDMS microneedle mold carrying the microneedle stock solution and the substrate stock solution in the illumination environment of a UV lamp, irradiate for 3 - 5 seconds and then take it out;

[0018] Step 6, demolding: Lift the sheet-like membrane from the cavity of the PDMS microneedle mold along the opening edge of the PDMS microneedle mold to obtain the exosome-soluble microneedles;

[0019] The exosome-soluble microneedles include a substrate and microneedles. The microneedles are arranged at intervals in multiple numbers, and the microneedles are fixed on the same side surface of the substrate;

[0020] The microneedles comprise the following components in parts by weight:

[0021]

[0022] The substrate comprises the following components in parts by weight:

[0023] 69 - 80 parts of pure chitosan base

[0024] 13 - 14 parts of crystal water

[0025] 4 - 21 parts of photocatalytic curing agent;

[0026] Wherein, the crystal water is distilled water and a mixture of one or more of the following materials: medicinal ethanol, glycerol, butanediol;

[0027] Wherein, the fusion agent is a single component of the following materials or a compound of multiple components thereof: pre-cooled Thris-saturated acid, pre-cooled ammonium acetate methanol solution, ethanol solution, exosome extract;

[0028] Wherein, the photocatalytic curing agent is a single component of the following materials or a compound of multiple components thereof: porous single-crystalline nano-titanium dioxide, graphene oxide titanium dioxide, ternary complex of titanium dioxide, silicon dioxide and molybdenum oxide.

[0029] In an implementable technical solution of the present application, in step 2, the process of preparing the water-soluble chitosan solution comprises the following steps:

[0030] Step 21, dissolution of chitosan powder: Dissolve 5 parts by weight of glacial acetic acid in 499 parts by weight of deionized water to obtain an acetic acid solution with a concentration of 1%, then take 100 parts by weight of chitosan powder in a beaker, and then add 500 parts by weight of the acetic acid solution, and stir at room temperature until the chitosan is completely dissolved to obtain a chitosan solution with a solid content of 2%;

[0031] Step 22, dialysis at room temperature: Dialyze the chitosan solution at room temperature with deionized water for 48 hours, the dialysis ratio is 1:100, and deionized water is changed multiple times during dialysis;

[0032] Step 23, vacuum concentration: The chitosan solution obtained by dialysis is placed in a vacuum oven, the temperature in the vacuum oven is between 70 - 90 °C, to remove the excess water, and during drying, the oven is opened multiple times to wipe the condensed water on the inner wall of the oven until the solution concentration is between 2.8 - 3.2 wt% and there is a sign of air drying on the surface of the solution, and then gently stir to make the solution uniform, then the water-soluble chitosan solution with the required concentration can be obtained.

[0033] In an implementable technical solution of the present application, in step 22, deionized water is replaced at the 1st, 3rd, 7th, 16th, and 24th hours after the start of dialysis. After the last replacement of deionized water, dialysis is continued for 24 hours. The dialysis bag used for dialysis treatment shall not be filled to capacity, and at least half of the volume shall be reserved to prevent the dialysis bag from bursting; in step 23, the temperature inside the vacuum oven is set to 80 °C, and the inner wall of the oven is wiped with condensed water every 3 - 5 minutes.

[0034] In an implementable technical solution of the present application, the exosomes are taken from human facial serum or a dilution of serum.

[0035] In an implementable technical solution of the present application, the water of crystallization includes medicinal ethanol and distilled water. Relative to the entire exosome soluble microneedles: the weight portion of medicinal ethanol is 0.6 - 0.7 parts, and the weight portion of distilled water is 11.5 - 13.5 parts.

[0036] In an implementable technical solution of the present application, 40% of the pure chitosan substrate is the base material of the microneedles, and the remaining 60% of the pure chitosan substrate is the base material of the substrate.

[0037] In an implementable technical solution of the present application, the fusion agent is a compound of multiple components selected from the following materials: 1 volume part of pre-cooled Thris-saturated acid, 1 volume part of pre-cooled 0.1 mol / L ammonium acetate methanol solution, 5 - 10 volume parts of exosome extract, and 4 - 6 volume parts of 100% ethanol solution.

[0038] In an implementable technical solution of the present application, the photocatalytic curing agent is a compound of multiple components selected from the following materials: 1 weight part of porous single-crystalline nano-titanium dioxide, 1.5 weight parts of graphene oxide titanium dioxide, and 2.5 weight parts of a ternary composite of titanium dioxide, silicon dioxide, and molybdenum oxide.

[0039] Second, the present application provides an exosome soluble microneedle, adopting the following technical solution:

[0040] An exosome soluble microneedle is made by the above preparation method.

[0041] In an implementable technical solution of the present application, the microneedles include the following components by weight:

[0042]

[0043] The substrate includes the following components by weight:

[0044] Pure chitosan substrate 75 parts

[0045] 13.5 parts of crystal water

[0046] 12.5 parts of photocatalytic curing agent.

[0047] In summary, the present application includes at least one of the following beneficial technical effects:

[0048] The pure chitosan substrate has the function of promoting drug absorption, and can quickly dissolve and release the drug components contained therein; when the fusogen, photocatalytic curing agent, and exosome have high lipid solubility and low water solubility, the crystal water can assist their dissolution and dispersion in the stock solution to ensure the homogeneity of the product appearance. The crystal water and the pure chitosan substrate cooperate to improve the toughness of the product to avoid problems such as excessive brittleness and easy cracking.

[0049] The fusogen can assist the rapid fusion of exosomes and photocatalytic curing agent in the stock solution, which is beneficial for the exosomes to be distributed in every corner of the microneedles. The photocatalytic curing agent can be quickly cured under special light conditions, greatly reducing the curing time of the product, being suitable for large-scale rapid production, and being very worthy of promotion and application in the market. BRIEF DESCRIPTION OF THE DRAWINGS

[0050] In order to more clearly illustrate the technical solutions in the embodiments of the present application, the following will briefly introduce the drawings required for the description of the embodiments. Obviously, the drawings in the following description are only some embodiments of the present application. For those of ordinary skill in the art, other drawings can be obtained based on these drawings without creative efforts.

[0051] Figure 1 It is a schematic flowchart of the method for fabricating exosome-soluble microneedles in an embodiment of the present application. DETAILED DESCRIPTION OF THE EMBODIMENTS

[0052] In order to make the technical problems, technical solutions and beneficial effects to be solved by the present application more clearly understood, the following further details the present application in conjunction with the drawings and embodiments. It should be understood that the specific embodiments described herein are only used to explain the present application and are not used to limit the present application.

[0053] It should be noted that when an element is referred to as being "fixed to" or "disposed on" another element, it can be directly on the other element or indirectly on the other element. When an element is referred to as being "connected to" another element, it can be directly connected to the other element or indirectly connected to the other element.

[0054] It should be understood that the orientation or positional relationship indicated by terms such as "length", "width", "upper", "lower", "front", "rear", "left", "right", "vertical", "horizontal", "top", "bottom", "inner", "outer", etc. is based on the orientation or positional relationship shown in the drawings. It is only for the convenience of describing the present application and simplifying the description, rather than indicating or implying that the device or element referred to must have a specific orientation, be constructed and operated in a specific orientation, and therefore should not be construed as a limitation to the present application.

[0055] In addition, the terms "first" and "second" are only used for descriptive purposes and cannot be construed as indicating or implying relative importance or implicitly specifying the quantity of the indicated technical features. Thus, the features defined with "first" and "second" may explicitly or implicitly include one or more of such features. In the description of the present application, "a plurality of" means two or more unless otherwise specifically defined.

[0056] The following further describes the present application in detail with reference to the Figure 1 accompanying drawings.

[0057] An embodiment of the present application discloses a method for fabricating exosome-soluble microneedles based on water-soluble chitosan, including the following steps:

[0058] Step 1, fabricating a PDMS microneedle mold: The PDMS microneedle mold is provided with tip cavities for forming a plurality of microneedles and a substrate cavity for forming a substrate.

[0059] Step 2, preparing the stock solution: At 38 - 42 °C, according to the proportion of different component materials in the exosome-soluble microneedles, different component solutions with different concentrations are respectively prepared for different component materials, including preparing a water-soluble chitosan solution; mixing the component solutions belonging to the microneedles in corresponding proportions and stirring at 25 - 30 °C for 1 - 1.5 hours; mixing the component solutions belonging to the substrate in corresponding proportions and stirring at 25 - 30 °C for 1 - 1.5 hours.

[0060] Step 3, preprocessing the PDMS microneedle mold: First, ultrasonically clean the PDMS microneedle mold for 15 - 25 minutes, then disinfect the PDMS microneedle mold with ultraviolet light for 35 - 45 minutes, and finally perform plasma treatment on the PDMS microneedle mold.

[0061] Step 4, injecting the stock solution into the mold: Take a certain amount of the microneedle stock solution according to the volume of the tip cavity of the PDMS microneedle mold, and inject it into the tip cavity of the PDMS microneedle mold, ensuring that the microneedle stock solution completely fills the tip cavity. Then, remove the excess microneedle stock solution in the substrate cavity. Next, take a certain amount of the substrate stock solution according to the volume of the substrate cavity of the PDMS microneedle mold, and inject it into the substrate cavity of the PDMS microneedle mold, ensuring that the substrate stock solution completely fills the substrate cavity. Then, remove the excess substrate stock solution by spreading it flat. Place the PDMS microneedle mold in a vacuum environment of -0.08 MPa to remove air bubbles for 5 - 10 minutes;

[0062] Step 5, curing and forming: Place the PDMS microneedle mold carrying the microneedle stock solution and the substrate stock solution in the illumination environment of a UV lamp, take it out after irradiating for 3 - 5 seconds;

[0063] Step 6, demolding: Lift the sheet-like membrane from the cavity of the PDMS microneedle mold along the opening edge of the PDMS microneedle mold to obtain exosome-soluble microneedles;

[0064] The exosome-soluble microneedles include a substrate and microneedles. A plurality of microneedles are arranged at intervals, and the microneedles are fixed on the same side surface of the substrate;

[0065] The microneedles include the following components in parts by weight:

[0066]

[0067] The substrate includes the following components in parts by weight:

[0068] Pure chitosan substrate 69 - 80 parts

[0069] Crystal water 13 - 14 parts

[0070] Photocatalytic curing agent 4 - 21 parts;

[0071] Among them, the crystal water is distilled water and a mixture of one or more of the following materials: medicinal ethanol, glycerol, butanediol;

[0072] Among them, the fusion agent is a single component or a compound of multiple components among the following materials: pre-cooled Thris-saturated acid, pre-cooled ammonium acetate methanol solution, ethanol solution, exosome extract;

[0073] Among them, the photocatalytic curing agent is a single component or a compound of multiple components among the following materials: porous single-crystal nano-titanium dioxide, graphene oxide titanium dioxide, ternary complex of titanium dioxide with silicon dioxide and molybdenum oxide.

[0074] In one feasible technical solution of the present application, in step 2, the process of preparing the water-soluble chitosan solution includes the following steps:

[0075] Step 21, dissolution of chitosan powder: Dissolve 5 parts by weight of glacial acetic acid in 499 parts by weight of deionized water to obtain an acetic acid solution with a concentration of 1%. Then take 100 parts by weight of chitosan powder in a beaker, and add 500 parts by weight of the acetic acid solution. Stir at room temperature until the chitosan is completely dissolved to obtain a chitosan solution with a solid content of 2%.

[0076] Step 22, dialysis at room temperature: Dialyze the chitosan solution with deionized water at room temperature for 48 hours, with a dialysis ratio of 1:100. Replace the deionized water multiple times during the dialysis process.

[0077] Step 23, vacuum concentration: The chitosan solution obtained by dialysis is placed in a vacuum oven. The temperature in the vacuum oven is between 70 - 90°C. Remove the excess water, and wipe the condensed water on the inner wall of the oven multiple times during the drying process until the solution concentration is between 2.8 - 3.2 wt% and there is a sign of air drying on the surface of the solution. Then stir slightly to make the solution uniform to obtain the water-soluble chitosan solution with the required concentration.

[0078] In one feasible technical solution of the present application, in step 22, replace the deionized water at the 1st, 3rd, 7th, 16th, and 24th hours after the start of dialysis, and dialyze for another 24 hours after the last replacement of deionized water. The dialysis bag used for dialysis treatment should not be filled completely, and at least half of the volume should be reserved to prevent the dialysis bag from bursting. In step 23, the temperature in the vacuum oven is set to 80°C, and wipe the condensed water on the inner wall of the oven every 3 - 5 minutes.

[0079] In this embodiment, in order to make the product more compliant with the skin absorption conditions of the human face, the exosomes are taken from the serum of the human face or a dilution of the serum.

[0080] In this embodiment, the water of crystallization includes medicinal ethanol and distilled water. Relative to the entire exosome soluble microneedles: the weight portion of medicinal ethanol is 0.6 - 0.7 parts (preferably 0.65 parts), and the weight portion of distilled water is 11.5 - 13.5 parts (preferably 12.85 parts).

[0081] In this embodiment, 40% of the pure chitosan substrate is the base material of the microneedles, and the remaining 60% of the pure chitosan substrate is the base material of the substrate.

[0082] In this embodiment, the fusion agent is a compound of multiple components selected from the following materials: 1 volume part of pre-cooled Thris-saturated acid, 1 volume part of pre-cooled 0.1 mol / L ammonium acetate methanol solution, 5 - 10 volume parts of exosome extract (preferably 6 parts), and 4 - 6 volume parts of 100% ethanol solution (preferably 5 parts).

[0083] In this embodiment, the photocatalytic curing agent is a compound of multiple components selected from the following materials: 1 part by weight of porous single-crystal nano-titanium dioxide, 1.5 parts by weight of graphene oxide-titanium dioxide, and 2.5 parts by weight of a ternary composite of titanium dioxide, silicon dioxide, and molybdenum oxide.

[0084] The embodiment of the present application also provides an exosome-soluble microneedle, adopting the following technical solution:

[0085] An exosome-soluble microneedle is made by the above preparation method. Specifically, the microneedle comprises the following components in parts by weight:

[0086]

[0087] The substrate comprises the following components in parts by weight:

[0088] Pure chitosan substrate 75 parts

[0089] Water of crystallization 13.5 parts

[0090] Photocatalytic curing agent 12.5 parts.

[0091] In step four, the method for removing the excess microneedle stock solution in the concave cavity of the substrate is as follows: Place the PDMS microneedle mold carrying the microneedle stock solution on a rotating platform, and then rotate it at a speed of 100 - 200 revolutions per minute to throw out the excess microneedle stock solution in the concave cavity of the substrate.

[0092] By adopting the above technical solution, since the exosome with extremely high production cost is contained in the microneedle stock solution, after the excess microneedle stock solution in the concave cavity of the substrate is thrown out, it can be recycled to prevent the exosome, fusion agent, and photocatalytic curing agent from entering the substrate, greatly reducing the production cost of the product, and the operation is relatively convenient with high production efficiency.

[0093] In summary, the present application includes at least one of the following beneficial technical effects:

[0094] The pure chitosan substrate has the function of promoting drug absorption, and can quickly dissolve and release the drug components contained therein; when the fusogen, photocatalytic curing agent, and exosome have high lipid solubility and low water solubility, the crystal water can assist their dissolution and dispersion in the stock solution to ensure the uniformity of the product appearance. The crystal water and the pure chitosan substrate cooperate to improve the toughness of the product to avoid problems such as excessive brittleness and easy cracking.

[0095] The fusogen can assist the rapid fusion of exosomes and photocatalytic curing agents in the stock solution, which is beneficial for the exosomes to be distributed in all corners of the microneedles. The photocatalytic curing agent can be quickly cured under special light conditions, greatly reducing the curing time of the product, suitable for large-scale rapid production, and is very worthy of promotion and application in the market.

[0096] The above are only the preferred embodiments of the present application and are not intended to limit the present application. Any modifications, equivalent replacements, and improvements made within the spirit and principle of the application shall be included in the protection scope of the present application.

Claims

1. A preparation method of exosome-soluble microneedles based on water-soluble chitosan, characterized in that, It includes the following steps: Step 1, fabricate a PDMS microneedle mold: The PDMS microneedle mold is provided with tip cavities for forming multiple microneedles and a substrate cavity for forming a substrate. Step 2, prepare the stock solution: At 38 - 42 °C, according to the proportion of different component materials in the exosome-soluble microneedles, prepare component solutions of different concentrations for different component materials, including preparing a water-soluble chitosan solution. Mix the component solutions belonging to the microneedles in the corresponding proportions and stir at 25 - 30 °C for 1 - 1.5 hours; mix the component solutions belonging to the substrate in the corresponding proportions and stir at 25 - 30 °C for 1 - 1.5 hours. Step 3, pre-treat the PDMS microneedle mold: First, ultrasonically clean the PDMS microneedle mold for 15 - 25 minutes, then disinfect it with ultraviolet light for 35 - 45 minutes, and finally perform plasma treatment on the PDMS microneedle mold. Step 4, pour the stock solution into the mold: Take a certain amount of microneedle stock solution according to the volume of the tip cavities of the PDMS microneedle mold and inject it into the tip cavities of the PDMS microneedle mold, ensuring that the microneedle stock solution completely fills the tip cavities. Then remove the excess microneedle stock solution in the substrate cavity. Then take a certain amount of substrate stock solution according to the volume of the substrate cavity of the PDMS microneedle mold and inject it into the substrate cavity of the PDMS microneedle mold, ensuring that the substrate stock solution completely fills the substrate cavity. Then remove the excess substrate stock solution by spreading it flat. Place the PDMS microneedle mold in a vacuum environment of -0.08 MPa to remove air bubbles for 5 - 10 minutes. Step 5, curing and forming: Place the PDMS microneedle mold carrying the microneedle stock solution and the substrate stock solution in the illumination environment of a UV lamp, take it out after irradiating for 3 - 5 seconds. Step 6, demolding: Lift the sheet-like membrane from the cavity of the PDMS microneedle mold along the opening edge of the PDMS microneedle mold to obtain the exosome-soluble microneedles. The exosome-soluble microneedles include a substrate and microneedles. The microneedles are arranged at intervals in multiple numbers, and the microneedles are fixed on the same side surface of the substrate. The microneedles include the following components in parts by weight: The substrate includes the following components in parts by weight: Pure chitosan base 69 - 80 parts Water of crystallization 13 - 14 parts Photocatalytic curing agent 4 - 21 parts; Among them, the water of crystallization is distilled water and a mixture of one or more of the following materials: medicinal ethanol, glycerol, butanediol. Among them, the fusion agent is a single component or a compound of multiple components among the following materials: pre-cooled Thris-saturated acid, pre-cooled ammonium acetate methanol solution, ethanol solution, exosome extract. Among them, the photocatalytic curing agent is a single component or a compound of multiple components among the following materials: porous single-crystal nano-titanium dioxide, graphene oxide titanium dioxide, ternary complex of titanium dioxide, silicon dioxide and molybdenum oxide.

2. The preparation method of exosome soluble microneedles according to claim 1, wherein In step 2, the process of preparing the water-soluble chitosan solution includes the following steps: Step 21, Dissolution of chitosan powder: Take 5 parts by weight of glacial acetic acid and dissolve it in 499 parts by weight of deionized water to obtain an acetic acid solution with a concentration of 1%. Then take 100 parts by weight of chitosan powder in a beaker, and add 500 parts by weight of the acetic acid solution. Stir at room temperature until the chitosan is completely dissolved to obtain a chitosan solution with a solid content of 2%. Step 22, Dialysis at room temperature: Dialyze the chitosan solution at room temperature with deionized water for 48 hours, with a dialysis ratio of 1:

100. Replace the deionized water multiple times during dialysis. Step 23, Vacuum concentration: The chitosan solution obtained by dialysis is placed in a vacuum oven. The temperature in the vacuum oven is between 70 - 90°C. Remove the excess water. During drying, open the oven multiple times to wipe the condensed water on the inner wall of the oven until the solution concentration is between 2.8 - 3.2 wt% and there is a sign of air drying on the surface of the solution. Then gently stir to make the solution uniform to obtain the water-soluble chitosan solution with the required concentration.

3. The preparation method of exosome soluble microneedles according to claim 2, characterized in that, In Step 22, replace the deionized water at the 1st, 3rd, 7th, 16th, and 24th hours after the start of dialysis. After the last replacement of deionized water, dialyze for another 24 hours. The dialysis bag used for dialysis treatment should not be filled completely, and at least half of the volume should be reserved to prevent the dialysis bag from bursting. In Step 23, the temperature in the vacuum oven is set to 80°C, and wipe the condensed water on the inner wall of the oven every 3 - 5 minutes.

4. The preparation method of exosome soluble microneedles according to claim 1, characterized in that: The exosomes are taken from human facial serum or a dilution of serum.

5. The preparation method of exosome soluble microneedles according to claim 1, characterized in that: The crystal water includes medicinal ethanol and distilled water. Relative to the whole exosome soluble microneedles: The weight portion of medicinal ethanol is 0.6 - 0.7 parts, and the weight portion of distilled water is 11.5 - 13.5 parts.

6. The preparation method of exosome soluble microneedles according to claim 1, wherein: 40% of the pure chitosan substrate is the base material of the microneedles, and the remaining 60% of the pure chitosan substrate is the base material of the substrate.

7. The method for preparing exosome soluble microneedles according to claim 1, wherein: The fusion agent is a compound of multiple components among the following materials: 1 part by volume of pre-cooled Thris-saturated acid, 1 part by volume of pre-cooled 0.1 mol / L ammonium acetate methanol solution, 5 - 10 parts by volume of exosome extract, and 4 - 6 parts by volume of 100% ethanol solution.

8. The method for preparing exosome soluble microneedles according to claim 1, wherein: The photocatalytic curing agent is a compound of multiple components among the following materials: 1 part by weight of porous single-crystal nano-titanium dioxide, 1.5 parts by weight of graphene oxide titanium dioxide, 2.5 parts by weight of a ternary composite of titanium dioxide, silicon dioxide, and molybdenum oxide.

9. An exosome soluble microneedle, characterized in that, Prepared by the preparation method described in any one of claims 1 - 8.

10. An exosome soluble microneedle, characterized in that The microneedle comprises the following components in parts by weight: The substrate comprises the following components in parts by weight: Pure chitosan substrate 75 parts Crystal water 13.5 parts Photocatalytic curing agent 12.5 parts.

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