Microneedle patch and preparation method thereof

Abstract

The invention provides a microneedle patch and a preparation method thereof, the microneedle patch comprises a base, a microneedle and a coating layer on the surface of the microneedle, the coating layer is prepared from a coating liquid, the coating liquid is prepared from a coating material, the coating material comprises one or more of a coating matrix material, a humectant, a protein protective agent and an antibiotic, and the coating matrix material is prepared from one or more of the base material, the humectant, the protein protective agent and the antibiotic. The coating matrix material comprises at least one of high-molecular-weight hyaluronic acid and polyvinylpyrrolidone, the molecular weight of the hyaluronic acid is 250KDa-1000KDa, the concentration of the hyaluronic acid is 5-30% (w / v), the polyvinylpyrrolidone is PVP-K30, the concentration of the polyvinylpyrrolidone is 25-45% (w / v), the molecular weight of the hyaluronic acid is 250KDa-1000KDa, and the molecular weight of the polyvinylpyrrolidone is 250KDa-1000KDa. The active component comprises at least one of a small molecule compound, a vaccine, a protein drug, a peptide drug and a nucleic acid drug.

Description

Technical Field

[0001] The present invention relates to the field of microneedle patch preparations for transdermal administration, and in particular to a coated drug-carrying microneedle patch and a preparation method thereof. Background Art

[0002] The design concept of microneedles is to use micro-machining methods to make needle-forming materials into micron-level needles. When the needle body penetrates the skin and mucous membranes, it will not touch the nerve tissue, thus achieving painless drug delivery. Microneedle drug delivery has many advantages, such as painless drug delivery, which can greatly increase user compliance; microneedle drug delivery has extremely low professional technical requirements, and patients can administer the drug themselves; the inherent low humidity environment of microneedles can improve the stability of drugs; the drugs in microneedles exist in solid form, which is convenient for transportation and storage, etc.

[0003] Microneedles include soluble microneedles and insoluble microneedles (water-insoluble microneedles). The current development of soluble microneedles is limited by the difficulty in mass production, while water-insoluble microneedles are developing the fastest because they can be quickly mass-produced through many micro-processing technologies, such as injection molding, 3D printing, etc. However, due to the limitations of mass production processes and preparation materials, the active ingredients cannot be directly loaded into the needle body during the preparation of the microneedles. Therefore, there are two ways of administering water-insoluble microneedles when they are used: the first is to treat the skin with blank microneedles, apply the drug to the treated skin, and the drug freely diffuses into the skin through the pores treated with the microneedles; the second is to coat the active ingredients on the surface of the needle body after the blank microneedles are produced, that is, to coat the microneedles, and then administer the drug to the skin. Of these two methods, the first one has the defect of inaccurate drug administration, so it is basically not used in the pharmaceutical field. The second one is widely used because of the accurate drug dosage, but the coating has defects such as low drug loading.

[0004] The microneedle body is small, the surface area is small, and the coated microneedle body cannot be loaded with drugs. The coated microneedle has the limitation of low drug loading. Ordinary coating prescriptions, processes and methods have many defects. For example, in order to increase the drug loading, the number of coatings and the coating amount are increased, which will make the tip of the needle body thicker, the needle is not sharp, and the puncture effect is poor, resulting in inaccurate dosage or even drug delivery failure. For example, ordinary coating processes will cause coating drug loading failure, that is, the solution infiltrates into the base of the needle body, which will make the dosage inaccurate. Spray coating or micro-manipulation of drug loading will greatly increase manufacturing time and mass production costs, which is extremely unfavorable for industrial production. Therefore, it is urgent to develop low-cost coating prescriptions and coating methods suitable for water-insoluble microneedle coating and that meet the needs of high-dose drug loading. Summary of the invention

[0005] One of the purposes of the present invention is to provide a microneedle patch, which includes a base, microneedles and a coating layer on the surface of the microneedles.

[0006] The microneedle patch of the present invention has a spacing between the needle bodies of the microneedles of 1-5 mm, the coating layer is prepared from a coating liquid, the coating liquid is prepared by dissolving a coating material and an active ingredient in water or a buffer solution, the coating material includes a coating matrix material, a humectant, a protein protective agent, and an antibiotic, the coating matrix material includes at least one of hyaluronic acid and polyvinyl pyrrolidone, the molecular weight of the hyaluronic acid is 250KDa-1000KDa, the polyvinyl pyrrolidone is PVP-K30, the humectant includes glycerol, and the protein protective agent includes at least one of trehalose, human serum albumin, sucrose, and arginine.

[0007] Compared with common coated microneedle patches, the microneedle patch of the present invention has a higher active ingredient loading capacity and can be loaded with a variety of different active ingredients to meet different clinical needs.

[0008] The microneedle patch of the present invention has a microneedle body that is a cone or a polygonal pyramid, a needle body height of 60-900 μm, preferably 100-700 μm, more preferably 200-500 μm; a needle tip width or diameter of 5-40 μm, preferably 10-30 μm; a needle body end width or diameter of 50-300 μm, preferably 100-250 μm.

[0009] In some of the embodiments, the microneedle and the base are made of water-insoluble materials, including polymers, metals, and ceramics. The polymers include polyvinyl chloride, polycarbonate, polystyrene, polypropylene, polycaprolactone, LCP, and photosensitive resins. The metals include stainless steel, titanium, and nickel.

[0010] In some embodiments, the coating matrix material is hyaluronic acid, the molecular weight of the hyaluronic acid is 250-1000 KDa, preferably 510-950 KDa, and the concentration of the hyaluronic acid is 5-30% (w / v), preferably 11-19% (w / v).

[0011] In some embodiments, the coating matrix material is polyvinyl pyrrolidone, the polyvinyl pyrrolidone is PVP-K30, and the concentration of the polyvinyl pyrrolidone is 25-45% (w / v).

[0012] In some embodiments, the coating material also includes a moisturizer and a protein protective agent. The moisturizer includes glycerol, and the concentration of the moisturizer is 0.5-2.5%, preferably 1-2%. The protein protective agent is at least one of trehalose, sucrose, arginine, and human serum albumin, and the concentration of the protein protective agent is 1-5%, preferably 2-4%.

[0013] In some embodiments, the viscosity of the coating liquid is 370,000-1,200,000 centipoise, preferably 750,000-1,050,000 centipoise.

[0014] In some embodiments, the buffer comprises HEPES buffer, phosphate buffer, carbonate buffer, or Tris buffer.

[0015] In some embodiments, the coating solution is obtained by dissolving the coating material and the active ingredient in water or an aqueous buffer solution.

[0016] In some embodiments, the active ingredient includes at least one of a small molecule compound, a vaccine, a protein drug, a peptide drug, and a nucleic acid drug.

[0017] In some embodiments, the small molecule compound includes lidocaine, bupivacaine, ropivacaine, propranolol, zolmitriptan, levonorgestrel, minoxidil, finasteride, orlistat, and the concentration of the small molecule compound in the coating solution is 10-40%.

[0018] In some embodiments, the protein drug includes insulin, the peptide drug includes semaglutide, and the concentration of the protein drug and the peptide drug in the coating solution is 4-10%.

[0019] In some embodiments, the vaccine includes a cancer vaccine, anthrax vaccine, influenza vaccine, Lyme disease vaccine, rabies vaccine, measles vaccine, mumps vaccine, varicella vaccine, smallpox vaccine, hepatitis vaccine, hepatitis A vaccine, hepatitis B vaccine, hepatitis C vaccine, pertussis vaccine, rubella vaccine, diphtheria vaccine, encephalitis vaccine, Japanese encephalitis vaccine, respiratory syncytial virus vaccine, yellow fever vaccine, polio vaccine, herpes vaccine, human papillomavirus vaccine, rotavirus vaccine, pneumococcal vaccine, meningitis vaccine, pertussis vaccine, tetanus vaccine, typhoid vaccine, cholera vaccine, tuberculosis vaccine, severe acute respiratory syndrome (SARS) vaccine, HSV-1 vaccine, HSV-2 vaccine, HIV vaccine, and the concentration of the vaccine in the coating solution is 4-10%.

[0020] In some embodiments, the vaccine further comprises one or more adjuvants.

[0021] In some of the embodiments, the quantitative determination method of the vaccine and protein drug is the Coomassie Brilliant Blue method, the quantitative determination method of the small molecule compound and peptide drug is the high performance liquid chromatography method, and the quantitative determination method of the nucleic acid drug is the absorbance method.

[0022] In some of the embodiments, the activity detection means of the vaccine and protein drug is the Elisa method, the activity detection means of the peptides is the WB method, and the activity detection means of the plasmid is qPCR sequencing.

[0023] In some of the embodiments, the evaluation of the puncture effect is judged according to the results of the Evans blue staining method. Specifically, the microneedle patch is pressed on the ex vivo pig skin of a young Panamanian miniature pig, peeled off after 20 seconds, and then a 4% Evans blue solution is applied to the pressed area for 1 minute, and the excess dye is rinsed off with sterile water. If the microneedle puncture is successful, corresponding blue holes will appear on the skin; when the number of successful puncture holes reaches 95% of the number of needle bodies, it is an excellent puncture; if the number of successful puncture holes does not exceed 60% of the number of needle bodies, it is a poor puncture effect.

[0024] The present invention further provides a preparation method suitable for a microneedle patch, the preparation method includes a coating process, wherein the microneedle body is vertically inserted into a coating liquid, and after the needle body absorbs a layer of coating liquid, the microneedle body is pulled out, and the needle body is placed vertically downward, and then a vertical upward air flow is applied under the needle body so that the coating liquid is evenly maintained on the surface of the needle body and dries quickly, and the active ingredient is loaded on the surface of the needle body.

[0025] In some of the embodiments, the coating liquid needs to be freed of bubbles first, and the debubbling methods include decompression, pressurization, centrifugation, and standing. The coating liquid is then filled into the solution tank and filled completely. After the liquid surface is completely flat, the microneedle body is inserted into the coating liquid. The edge height of the solution tank can be 1 / 3, 1 / 2, or 3 / 4 of the height of the microneedle body, that is, the liquid level height of the coating liquid can be 1 / 3, 1 / 2, or 3 / 4 of the height of the needle body, but is not limited to a specific range, and the insertion and immersion time is 5-30S.

[0026] In some embodiments, after the solution tank is filled with the coating solution, it is required to be placed in a constant humidity environment with a humidity of 60-90% in the subsequent operations.

[0027] In some of the embodiments, the microneedle body is vertically inserted into the coating liquid, then pulled out, placed vertically downward, and then a vertical upward airflow is given under the needle body. The airflow speed is 0.5m-10m / s, preferably 0.7-4.5m / s, the airflow humidity is 1-60%, and the airflow is maintained for 1-30min, preferably 5-30min. The product is preferably obtained after drying.

[0028] In some embodiments, the wind flow also has a drying effect, and the holding time is the drying time of the coating solution on the surface of the microneedle.

[0029] In some embodiments, the microneedle patch can be coated once more after drying.

[0030] In some of the embodiments, after the microneedle patch is dried, the coating layer thickness is 2-10 μm, which does not affect the puncture performance of the microneedle itself and has a good puncture effect. The coating thickness is detected by scanning electron microscopy.

[0031] Compared with the prior art solutions, the present invention has the following beneficial effects:

[0032] 1. Compared with the common coated microneedle preparation method, the preparation method of the present invention has short time, high drug loading, small batch difference, simple operation method and low cost, and is very suitable for industrial production.

[0033] 2. Compared with ordinary coated microneedles, the microneedle patch described in the present invention, under the action of the ventilation system, the coating liquid can be evenly maintained on the surface of the needle body without displacement, and the drying speed is fast. The thickness of the drug-carrying part of the obtained microneedle body is thin, only 2-10μm thick, the needle shape is intact and sharp, the puncture performance is excellent, and the dosage is accurate.

[0034] 3. The coating liquid formulation and preparation method of the present invention are applicable to a variety of different types of active ingredients and microneedles of different materials, and have good universality. DETAILED DESCRIPTION

[0035] The following examples are further explanations of the present invention, but are by no means limiting the scope of the present invention. The present invention will be further described in detail below with reference to the examples, but it should be understood by those skilled in the art that the present invention is not limited to these examples and the preparation methods used. Moreover, those skilled in the art may carry out equivalent substitutions, combinations, improvements or modifications to the present invention based on the description of the present invention, but these will all be included within the scope of the present invention.

[0036] Example 1

[0037] This embodiment provides a microneedle patch;

[0038] Among them, the microneedles are made of polycarbonate, the spacing between the microneedles is 1mm, the microneedles are cones, the height is 500μm, the tip width is 10μm, and the diameter of the needle end is 250μm;

[0039] The coating liquid includes hyaluronic acid with a molecular weight of 300 KDa, human serum albumin, glycerol, hepatitis B vaccine and water, and the viscosity of the coating liquid is 750,000 centipoise;

[0040] The concentration of human serum albumin in the coating solution is 5%, the concentration of hyaluronic acid in the coating solution is 30%, the concentration of glycerol in the coating solution is 2.5%, and the concentration of hepatitis B vaccine in the coating solution is 4%;

[0041] The preparation method of the microneedle patch comprises the following steps:

[0042] The needle body is slowly and vertically inserted into the coating liquid from which bubbles have been removed, and soaked for 30 seconds, and then air flow is applied for 30 minutes to keep the coating liquid uniform and dry, and this step is repeated once to obtain a microneedle patch;

[0043] Specifically, the liquid level of the coating liquid is 3 / 4 of the height of the needle body;

[0044] The air flow humidity is 60% and the air flow speed is 0.7m / s;

[0045] The microneedle is placed vertically downward, with the air flow system located below the needle body, and air is blown so that the direction of the air flow is opposite to the direction of the needle tip.

[0046] Example 2

[0047] This embodiment provides a microneedle patch;

[0048] Among them, the microneedles are made of polypropylene, the spacing between the microneedles is 1mm, the microneedles are cones, the height is 500μm, the tip width is 10μm, and the diameter of the needle end is 250μm;

[0049] The coating liquid includes hyaluronic acid with a molecular weight of 300 KDa, arginine, glycerol, hepatitis B vaccine and water, and the viscosity of the coating liquid is 600,000 centipoise;

[0050] The concentration of arginine in the coating solution is 4%, the concentration of hyaluronic acid in the coating solution is 19%, the concentration of glycerol in the coating solution is 2%, and the concentration of hepatitis B vaccine in the coating solution is 10%;

[0051] The preparation method of the microneedle patch comprises the following steps:

[0052] The needle body is slowly and vertically inserted into the coating liquid from which bubbles have been removed, soaked for 15 seconds, and then air flow is applied for 20 minutes to keep the coating liquid uniform and dry, thereby obtaining a microneedle patch;

[0053] Specifically, the liquid level of the coating liquid is 3 / 4 of the height of the needle body;

[0054] The air flow humidity is 30% and the air flow speed is 2m / s;

[0055] The microneedle is placed vertically downward, with the air flow system located below the needle body, and air is blown so that the direction of the air flow is opposite to the direction of the needle tip.

[0056] Example 3

[0057] This embodiment provides a microneedle patch;

[0058] Among them, the microneedles are made of polycaprolactone, the spacing between the microneedles is 1mm, the microneedles are cones, the height is 500μm, the tip width is 10μm, and the diameter of the needle end is 250μm;

[0059] The coating liquid includes hyaluronic acid with a molecular weight of 300 KDa, sucrose, glycerol, hepatitis B vaccine and water, and the viscosity of the coating liquid is 510,000 centipoise;

[0060] The concentration of sucrose in the coating liquid is 3%, the concentration of hyaluronic acid in the coating liquid is 11%, the concentration of glycerol in the coating liquid is 1%, and the concentration of hepatitis B vaccine in the coating liquid is 4%;

[0061] The preparation method of the microneedle patch comprises the following steps:

[0062] The needle body is slowly and vertically inserted into the coating liquid from which bubbles have been removed, and soaked for 10 seconds, and then air flow is applied for 5 minutes to keep the coating liquid uniform and dry, and this step is repeated once to obtain a microneedle patch;

[0063] Specifically, the liquid level of the coating liquid is 3 / 4 of the height of the needle body;

[0064] The air flow humidity is 10% and the air flow speed is 4m / s;

[0065] The microneedle is placed vertically downward, with the air flow system located below the needle body, and air is blown so that the direction of the air flow is opposite to the direction of the needle tip.

[0066] Example 4

[0067] This embodiment provides a microneedle patch;

[0068] Among them, the microneedles are made of titanium metal, the spacing between the microneedles is 1mm, the microneedles are cones, the height is 500μm, the tip width is 10μm, and the diameter of the needle end is 250μm;

[0069] The coating liquid includes hyaluronic acid with a molecular weight of 300 KDa, trehalose, glycerol, hepatitis B vaccine and water, and the viscosity of the coating liquid is 520,000 centipoise;

[0070] The concentration of trehalose in the coating liquid is 2%, the concentration of hyaluronic acid in the coating liquid is 11%, the concentration of glycerol in the coating liquid is 1%, and the concentration of hepatitis B vaccine in the coating liquid is 10%;

[0071] The preparation method of the microneedle patch comprises the following steps:

[0072] The needle body is slowly and vertically inserted into the coating liquid from which bubbles have been removed, and soaked for 10 seconds, and then air flow is applied for 5 minutes to keep the coating liquid uniform and dry, thereby obtaining a microneedle patch;

[0073] Specifically, the liquid level of the coating liquid is 3 / 4 of the height of the needle body;

[0074] The air flow humidity is 5% and the air flow speed is 4.5m / s;

[0075] The microneedle is placed vertically downward, with the air flow system located below the needle body, and air is blown so that the direction of the air flow is opposite to the direction of the needle tip.

[0076] Example 5

[0077] This embodiment provides a microneedle patch;

[0078] Among them, the microneedles are made of polystyrene, the spacing between the microneedles is 1mm, the microneedles are cones, the height is 500μm, the tip width is 10μm, and the diameter of the needle end is 250μm;

[0079] The coating liquid includes hyaluronic acid with a molecular weight of 300 KDa, human serum albumin, glycerol, hepatitis B vaccine and water, and the viscosity of the coating liquid is 370,000 centipoise;

[0080] Wherein, the concentration of human serum albumin in the coating liquid is 1%, the concentration of hyaluronic acid in the coating liquid is 5%, the concentration of glycerol in the coating liquid is 0.5%, and the concentration of hepatitis B vaccine in the coating liquid is 4%;

[0081] The preparation method of the microneedle patch comprises the following steps:

[0082] The needle body is slowly and vertically inserted into the coating liquid from which bubbles have been removed, soaked for 5 seconds, and then air flow is applied for 1 minute to keep the coating liquid uniform and dry, and this step is repeated once to obtain a microneedle patch;

[0083] Specifically, the liquid level of the coating liquid is 3 / 4 of the height of the needle body;

[0084] The air flow humidity is 1% and the air flow speed is 10m / s;

[0085] The microneedle is placed vertically downward, with the air flow system located below the needle body, and air is blown so that the direction of the air flow is opposite to the direction of the needle tip.

[0086] Example 6

[0087] This embodiment provides a microneedle patch;

[0088] Among them, the microneedles are made of polycarbonate, the spacing between the microneedles is 1mm, the microneedles are cones, the height is 500μm, the tip width is 10μm, and the diameter of the needle end is 250μm;

[0089] The coating liquid includes hyaluronic acid with a molecular weight of 510 KDa, human serum albumin, glycerol, hepatitis B vaccine and water, and the viscosity of the coating liquid is 920,000 centipoise;

[0090] The concentration of human serum albumin in the coating solution is 5%, the concentration of hyaluronic acid in the coating solution is 30%, the concentration of glycerol in the coating solution is 2.5%, and the concentration of hepatitis B vaccine in the coating solution is 4%;

[0091] The preparation method of the microneedle patch comprises the following steps:

[0092] The needle body is slowly and vertically inserted into the coating liquid from which bubbles have been removed, and soaked for 30 seconds, and then air flow is applied for 30 minutes to keep the coating liquid uniform and dry, and this step is repeated once to obtain a microneedle patch;

[0093] Specifically, the liquid level of the coating liquid is 3 / 4 of the height of the needle body;

[0094] The air flow humidity is 60% and the air flow speed is 0.7m / s;

[0095] The microneedle is placed vertically downward, with the air flow system located below the needle body, and air is blown so that the direction of the air flow is opposite to the direction of the needle tip.

[0096] Example 7

[0097] This embodiment provides a microneedle patch;

[0098] Among them, the microneedles are made of polypropylene, the spacing between the microneedles is 1mm, the microneedles are cones, the height is 500μm, the tip width is 10μm, and the diameter of the needle end is 250μm;

[0099] The coating liquid includes hyaluronic acid with a molecular weight of 510 KDa, arginine, glycerol, hepatitis B vaccine and water, and the viscosity of the coating liquid is 850,000 centipoise;

[0100] The concentration of arginine in the coating solution is 4%, the concentration of hyaluronic acid in the coating solution is 19%, the concentration of glycerol in the coating solution is 2%, and the concentration of hepatitis B vaccine in the coating solution is 10%;

[0101] The preparation method of the microneedle patch comprises the following steps:

[0102] The needle body is slowly and vertically inserted into the coating liquid from which bubbles have been removed, soaked for 15 seconds, and then air flow is applied for 20 minutes to keep the coating liquid uniform and dry, thereby obtaining a microneedle patch;

[0103] Specifically, the liquid level of the coating liquid is 3 / 4 of the height of the needle body;

[0104] The air flow humidity is 30% and the air flow speed is 2m / s;

[0105] The microneedle is placed vertically downward, with the air flow system located below the needle body, and air is blown so that the direction of the air flow is opposite to the direction of the needle tip.

[0106] Example 8

[0107] This embodiment provides a microneedle patch;

[0108] Among them, the microneedles are made of polycaprolactone, the spacing between the microneedles is 1mm, the microneedles are cones, the height is 500μm, the tip width is 10μm, and the diameter of the needle end is 250μm;

[0109] The coating liquid includes hyaluronic acid with a molecular weight of 510 KDa, sucrose, glycerol, hepatitis B vaccine and water, and the viscosity of the coating liquid is 780,000 centipoise;

[0110] The concentration of sucrose in the coating liquid is 2%, the concentration of hyaluronic acid in the coating liquid is 11%, the concentration of glycerol in the coating liquid is 1%, and the concentration of hepatitis B vaccine in the coating liquid is 4%;

[0111] The preparation method of the microneedle patch comprises the following steps:

[0112] The needle body is slowly and vertically inserted into the coating liquid from which bubbles have been removed, and soaked for 10 seconds, and then air flow is applied for 5 minutes to keep the coating liquid uniform and dry, and this step is repeated once to obtain a microneedle patch;

[0113] Specifically, the liquid level of the coating liquid is 3 / 4 of the height of the needle body;

[0114] The air flow humidity is 10% and the air flow speed is 4m / s;

[0115] The microneedle is placed vertically downward, with the air flow system located below the needle body, and air is blown so that the direction of the air flow is opposite to the direction of the needle tip.

[0116] Example 9

[0117] This embodiment provides a microneedle patch;

[0118] Among them, the microneedles are made of titanium metal, the spacing between the microneedles is 1mm, the microneedles are cones, the height is 500μm, the tip width is 10μm, and the diameter of the needle end is 250μm;

[0119] The coating liquid includes hyaluronic acid with a molecular weight of 510 KDa, trehalose, glycerol, hepatitis B vaccine and water, and the viscosity of the coating liquid is 770,000 centipoise;

[0120] The concentration of trehalose in the coating liquid is 2%, the concentration of hyaluronic acid in the coating liquid is 11%, the concentration of glycerol in the coating liquid is 1%, and the concentration of hepatitis B vaccine in the coating liquid is 10%;

[0121] The preparation method of the microneedle patch comprises the following steps:

[0122] The needle body is slowly and vertically inserted into the coating liquid from which bubbles have been removed, and soaked for 10 seconds, and then air flow is applied for 5 minutes to keep the coating liquid uniform and dry, thereby obtaining a microneedle patch;

[0123] Specifically, the liquid level of the coating liquid is 3 / 4 of the height of the needle body;

[0124] The air flow humidity is 5% and the air flow speed is 4.5m / s;

[0125] The microneedle is placed vertically downward, with the air flow system located below the needle body, and air is blown so that the direction of the air flow is opposite to the direction of the needle tip.

[0126] Example 10

[0127] This embodiment provides a microneedle patch;

[0128] Among them, the microneedles are made of polystyrene, the spacing between the microneedles is 1mm, the microneedles are cones, the height is 500μm, the tip width is 10μm, and the diameter of the needle end is 250μm;

[0129] The coating liquid includes hyaluronic acid with a molecular weight of 510 KDa, human serum albumin, glycerol, hepatitis B vaccine and water, and the viscosity of the coating liquid is 520,000 centipoise;

[0130] Wherein, the concentration of human serum albumin in the coating liquid is 1%, the concentration of hyaluronic acid in the coating liquid is 5%, the concentration of glycerol in the coating liquid is 0.5%, and the concentration of hepatitis B vaccine in the coating liquid is 4%;

[0131] The preparation method of the microneedle patch comprises the following steps:

[0132] The needle body is slowly and vertically inserted into the coating liquid from which bubbles have been removed, soaked for 5 seconds, and then air flow is applied for 1 minute to keep the coating liquid uniform and dry, and this step is repeated once to obtain a microneedle patch;

[0133] Specifically, the liquid level of the coating liquid is 3 / 4 of the height of the needle body;

[0134] The air flow humidity is 1% and the air flow speed is 10m / s;

[0135] The microneedle is placed vertically downward, with the air flow system located below the needle body, and air is blown so that the direction of the air flow is opposite to the direction of the needle tip.

[0136] Embodiment 11

[0137] This embodiment provides a microneedle patch;

[0138] Among them, the microneedles are made of polycarbonate, the spacing between the microneedles is 1mm, the microneedles are cones, the height is 500μm, the tip width is 10μm, and the diameter of the needle end is 250μm;

[0139] The coating liquid includes hyaluronic acid with a molecular weight of 950 KDa, human serum albumin, glycerol, hepatitis B vaccine and water, and the viscosity of the coating liquid is 1,200,000 centipoise;

[0140] The concentration of human serum albumin in the coating solution is 5%, the concentration of hyaluronic acid in the coating solution is 30%, the concentration of glycerol in the coating solution is 2.5%, and the concentration of hepatitis B vaccine in the coating solution is 4%;

[0141] The preparation method of the microneedle patch comprises the following steps:

[0142] The needle body is slowly and vertically inserted into the coating liquid from which bubbles have been removed, and soaked for 30 seconds, and then air flow is applied for 30 minutes to keep the coating liquid uniform and dry, and this step is repeated once to obtain a microneedle patch;

[0143] Specifically, the liquid level of the coating liquid is 3 / 4 of the height of the needle body;

[0144] The air flow humidity is 60% and the air flow speed is 0.7m / s;

[0145] The microneedle is placed vertically downward, with the air flow system located below the needle body, and air is blown so that the direction of the air flow is opposite to the direction of the needle tip.

[0146] Example 12

[0147] This embodiment provides a microneedle patch;

[0148] Among them, the microneedles are made of polypropylene, the spacing between the microneedles is 1mm, the microneedles are cones, the height is 500μm, the tip width is 10μm, and the diameter of the needle end is 250μm;

[0149] The coating liquid includes hyaluronic acid with a molecular weight of 950 KDa, arginine, glycerol, hepatitis B vaccine and water, and the viscosity of the coating liquid is 1050000 centipoise;

[0150] The concentration of arginine in the coating solution is 4%, the concentration of hyaluronic acid in the coating solution is 19%, the concentration of glycerol in the coating solution is 2%, and the concentration of hepatitis B vaccine in the coating solution is 10%;

[0151] The preparation method of the microneedle patch comprises the following steps:

[0152] The needle body is slowly and vertically inserted into the coating liquid from which bubbles have been removed, soaked for 15 seconds, and then air flow is applied for 20 minutes to keep the coating liquid uniform and dry, thereby obtaining a microneedle patch;

[0153] Specifically, the liquid level of the coating liquid is 3 / 4 of the height of the needle body;

[0154] The air flow humidity is 30% and the air flow speed is 2m / s;

[0155] The microneedle is placed vertically downward, with the air flow system located below the needle body, and air is blown so that the direction of the air flow is opposite to the direction of the needle tip.

[0156] Embodiment 13

[0157] This embodiment provides a microneedle patch;

[0158] Among them, the microneedles are made of polycaprolactone, the spacing between the microneedles is 1mm, the microneedles are cones, the height is 500μm, the tip width is 10μm, and the diameter of the needle end is 250μm;

[0159] The coating liquid includes hyaluronic acid with a molecular weight of 950 KDa, sucrose, glycerol, hepatitis B vaccine and water, and the viscosity of the coating liquid is 880,000 centipoise;

[0160] The concentration of sucrose in the coating liquid is 3%, the concentration of hyaluronic acid in the coating liquid is 11%, the concentration of glycerol in the coating liquid is 1%, and the concentration of hepatitis B vaccine in the coating liquid is 4%;

[0161] The preparation method of the microneedle patch comprises the following steps:

[0162] The needle body is slowly and vertically inserted into the coating liquid from which bubbles have been removed, and soaked for 10 seconds, and then air flow is applied for 5 minutes to keep the coating liquid uniform and dry, and this step is repeated once to obtain a microneedle patch;

[0163] Specifically, the liquid level of the coating liquid is 3 / 4 of the height of the needle body;

[0164] The air flow humidity is 10% and the air flow speed is 4m / s;

[0165] The microneedle is placed vertically downward, with the air flow system located below the needle body, and air is blown so that the direction of the air flow is opposite to the direction of the needle tip.

[0166] Embodiment 14

[0167] This embodiment provides a microneedle patch;

[0168] Among them, the microneedles are made of titanium metal, the spacing between the microneedles is 1mm, the microneedles are cones, the height is 500μm, the tip width is 10μm, and the diameter of the needle end is 250μm;

[0169] The coating liquid includes hyaluronic acid with a molecular weight of 950 KDa, trehalose, glycerol, hepatitis B vaccine and water, and the viscosity of the coating liquid is 860,000 centipoise;

[0170] The concentration of trehalose in the coating liquid is 2%, the concentration of hyaluronic acid in the coating liquid is 11%, the concentration of glycerol in the coating liquid is 1%, and the concentration of hepatitis B vaccine in the coating liquid is 10%;

[0171] The preparation method of the microneedle patch comprises the following steps:

[0172] The needle body is slowly and vertically inserted into the coating liquid from which bubbles have been removed, and soaked for 10 seconds, and then air flow is applied for 5 minutes to keep the coating liquid uniform and dry, thereby obtaining a microneedle patch;

[0173] Specifically, the liquid level of the coating liquid is 3 / 4 of the height of the needle body;

[0174] The air flow humidity is 5% and the air flow speed is 4.5m / s;

[0175] The microneedle is placed vertically downward, with the air flow system located below the needle body, and air is blown so that the direction of the air flow is opposite to the direction of the needle tip.

[0176] Embodiment 15

[0177] This embodiment provides a microneedle patch;

[0178] Among them, the microneedles are made of polystyrene, the spacing between the microneedles is 1mm, the microneedles are cones, the height is 500μm, the tip width is 10μm, and the diameter of the needle end is 250μm;

[0179] The coating liquid includes hyaluronic acid with a molecular weight of 950 KDa, human serum albumin, glycerol, hepatitis B vaccine and water, and the viscosity of the coating liquid is 750,000 centipoise;

[0180] Wherein, the concentration of human serum albumin in the coating liquid is 1%, the concentration of hyaluronic acid in the coating liquid is 5%, the concentration of glycerol in the coating liquid is 0.5%, and the concentration of hepatitis B vaccine in the coating liquid is 4%;

[0181] The preparation method of the microneedle patch comprises the following steps:

[0182] The needle body is slowly and vertically inserted into the coating liquid from which bubbles have been removed, soaked for 5 seconds, and then air flow is applied for 1 minute to keep the coating liquid uniform and dry, and this step is repeated once to obtain a microneedle patch;

[0183] Specifically, the liquid level of the coating liquid is 3 / 4 of the height of the needle body;

[0184] The air flow humidity is 1% and the air flow speed is 10m / s;

[0185] The microneedle is placed vertically downward, with the air flow system located below the needle body, and air is blown so that the direction of the air flow is opposite to the direction of the needle tip.

[0186] Example 16

[0187] This embodiment provides a microneedle patch;

[0188] Among them, the microneedles are made of polycarbonate, the spacing between the microneedles is 1mm, the microneedles are cones, the height is 500μm, the tip width is 10μm, and the diameter of the needle end is 250μm;

[0189] The coating liquid includes PVP-K30, human serum albumin, glycerol, hepatitis B vaccine and water, and the viscosity of the coating liquid is 870,000 centipoise;

[0190] The concentration of human serum albumin in the coating solution is 4%, the concentration of PVP-K30 in the coating solution is 45%, the concentration of glycerol in the coating solution is 2%, and the concentration of hepatitis B vaccine in the coating solution is 10%;

[0191] The preparation method of the microneedle patch comprises the following steps:

[0192] The needle body is slowly and vertically inserted into the coating liquid from which bubbles have been removed, and soaked for 20 seconds, and then air flow is applied for 15 minutes to keep the coating liquid uniform and dry, thereby obtaining a microneedle patch;

[0193] Specifically, the liquid level of the coating liquid is 3 / 4 of the height of the needle body;

[0194] The air flow humidity is 30% and the air flow speed is 2m / s;

[0195] The microneedle is placed vertically downward, with the air flow system located below the needle body, and air is blown so that the direction of the air flow is opposite to the direction of the needle tip.

[0196] Embodiment 17

[0197] This embodiment provides a microneedle patch;

[0198] Among them, the microneedles are made of titanium metal, the spacing between the microneedles is 1mm, the microneedles are cones, the height is 500μm, the tip width is 10μm, and the diameter of the needle end is 250μm;

[0199] The coating liquid includes PVP-K30, trehalose, glycerol, hepatitis B vaccine and water, and the viscosity of the coating liquid is 770,000 centipoise; wherein the concentration of trehalose in the coating liquid is 2%, the concentration of PVP-K30 in the coating liquid is 25%, the concentration of glycerol in the coating liquid is 1%, and the concentration of hepatitis B vaccine in the coating liquid is 4%;

[0200] The preparation method of the microneedle patch comprises the following steps:

[0201] The needle body is slowly and vertically inserted into the coating liquid from which bubbles have been removed, and soaked for 20 seconds, and then air flow is applied for 10 minutes to keep the coating liquid uniform and dry, and this step is repeated once to obtain a microneedle patch;

[0202] Specifically, the liquid level of the coating liquid is 3 / 4 of the height of the needle body;

[0203] The air flow humidity is 10% and the air flow speed is 3m / s;

[0204] The microneedle is placed vertically downward, with the air flow system located below the needle body, and air is blown so that the direction of the air flow is opposite to the direction of the needle tip.

[0205] Embodiment 18

[0206] Compared with Example 8, this embodiment differs in that the hepatitis B vaccine is replaced by an influenza vaccine (COVID-19 vaccine-RBD protein) with a mass concentration of 4%; the other ingredients and preparation method are the same as those in Example 8.

[0207] Embodiment 19

[0208] Compared with Example 12, this embodiment differs in that the hepatitis B vaccine is replaced with an influenza vaccine (COVID-19 vaccine-RBD protein) with a mass concentration of 10%; the other ingredients and preparation method are the same as those in Example 12.

[0209] Embodiment 20

[0210] Compared with Example 16, this embodiment differs in that the hepatitis B vaccine is replaced with an influenza vaccine (COVID-19 vaccine-RBD protein) with a mass concentration of 4%; the other ingredients and preparation method are the same as those in Example 16.

[0211] Embodiment 21

[0212] The difference between this embodiment and embodiment 8 is that the hepatitis B vaccine is replaced by a tetanus vaccine with a mass concentration of 4%; the other components and preparation method are the same as those of embodiment 8.

[0213] Embodiment 22

[0214] The difference between this embodiment and embodiment 12 is that the hepatitis B vaccine is replaced by a tetanus vaccine with a mass concentration of 10%; the other ingredients and preparation method are the same as those of embodiment 12.

[0215] Embodiment 23

[0216] Compared with Example 16, this embodiment is different in that the hepatitis B vaccine is replaced by a tetanus vaccine with a mass concentration of 4%; the other ingredients and preparation method are the same as those of Example 16.

[0217] Embodiment 24

[0218] The difference between this embodiment and embodiment 8 is that the hepatitis B vaccine is replaced by insulin with a mass concentration of 4%; the other ingredients and preparation method are the same as those of embodiment 8.

[0219] Embodiment 25

[0220] The difference between this embodiment and embodiment 12 is that the hepatitis B vaccine is replaced by insulin with a mass concentration of 10%; the other ingredients and preparation method are the same as those of embodiment 12.

[0221] Embodiment 26

[0222] The difference between this embodiment and Example 16 is that the hepatitis B vaccine is replaced by insulin with a mass concentration of 4%; the other ingredients and preparation method are the same as those of Example 16.

[0223] Embodiment 27

[0224] Compared with Example 8, this example is different in that the hepatitis B vaccine is replaced by semaglutide with a mass concentration of 4%; the other ingredients and preparation method are the same as those in Example 8.

[0225] Embodiment 28

[0226] Compared with Example 12, this example is different in that the hepatitis B vaccine is replaced by semaglutide with a mass concentration of 10%; the other ingredients and preparation method are the same as those of Example 12.

[0227] Embodiment 29

[0228] Compared with Example 16, this embodiment is different in that the hepatitis B vaccine is replaced by semaglutide with a mass concentration of 4%; the other ingredients and preparation method are the same as those of Example 16.

[0229] Embodiment 30

[0230] Compared with Example 8, this embodiment differs in that the hepatitis B vaccine is replaced by a plasmid with a mass concentration of 4% (expressing COVID-19 RBD protein); the other components and preparation method are the same as those in Example 8.

[0231] Embodiment 31

[0232] Compared with Example 12, this embodiment differs in that the hepatitis B vaccine is replaced by a plasmid with a mass concentration of 10% (expressing COVID-19 RBD protein); the other components and preparation methods are the same as those in Example 12.

[0233] Embodiment 32

[0234] Compared with Example 16, this embodiment differs in that the hepatitis B vaccine is replaced by a plasmid with a mass concentration of 4% (expressing COVID-19 RBD protein); the other components and preparation method are the same as those in Example 16.

[0235] Embodiment 33

[0236] The difference between this embodiment and embodiment 8 is that the hepatitis B vaccine is replaced by lidocaine with a mass concentration of 10%; the other ingredients and preparation method are the same as those of embodiment 8.

[0237] Embodiment 34

[0238] The difference between this embodiment and embodiment 12 is that the hepatitis B vaccine is replaced by lidocaine with a mass concentration of 40%; the other ingredients and preparation method are the same as those of embodiment 12.

[0239] Embodiment 35

[0240] Compared with Example 16, this embodiment is different in that the hepatitis B vaccine is replaced by lidocaine with a mass concentration of 10%; the other ingredients and preparation method are the same as those of Example 16.

[0241] Embodiment 36

[0242] Compared with Example 8, this embodiment is different in that the hepatitis B vaccine is replaced by ropivacaine with a mass concentration of 10%; the other ingredients and preparation method are the same as those in Example 8.

[0243] Embodiment 37

[0244] Compared with Example 12, this embodiment is different in that the hepatitis B vaccine is replaced by ropivacaine with a mass concentration of 40%; the other ingredients and preparation method are the same as those of Example 12.

[0245] Embodiment 38

[0246] Compared with Example 16, this embodiment is different in that the hepatitis B vaccine is replaced by ropivacaine with a mass concentration of 10%; the other ingredients and preparation method are the same as those of Example 16.

[0247] Embodiment 39

[0248] Compared with Example 8, this embodiment is different in that the hepatitis B vaccine is replaced by zolmitriptan with a mass concentration of 10%; the other components and preparation method are the same as those in Example 8.

[0249] Embodiment 40

[0250] Compared with Example 12, this embodiment is different in that the hepatitis B vaccine is replaced by zolmitriptan with a mass concentration of 40%; the other ingredients and preparation method are the same as those of Example 12.

[0251] Embodiment 41

[0252] Compared with Example 16, this embodiment is different in that the hepatitis B vaccine is replaced by zolmitriptan with a mass concentration of 10%; other ingredients and preparation methods are the same as those of Example 16.

[0253] Embodiment 42

[0254] Compared with Example 8, this embodiment is different in that the hepatitis B vaccine is replaced by levonorgestrel with a mass concentration of 10%; the other ingredients and preparation method are the same as those in Example 8.

[0255] Embodiment 43

[0256] Compared with Example 12, this embodiment is different in that the hepatitis B vaccine is replaced by levonorgestrel with a mass concentration of 40%; the other ingredients and preparation method are the same as those of Example 12.

[0257] Embodiment 44

[0258] Compared with Example 16, this embodiment is different in that the hepatitis B vaccine is replaced by levonorgestrel with a mass concentration of 10%; the other ingredients and preparation method are the same as those in Example 16.

[0259] Embodiment 45

[0260] Compared with Example 8, this embodiment is different in that the hepatitis B vaccine is replaced by minoxidil with a mass concentration of 10%; the other ingredients and preparation method are the same as those in Example 8.

[0261] Embodiment 46

[0262] Compared with Example 12, this embodiment is different in that the hepatitis B vaccine is replaced by minoxidil with a mass concentration of 40%; the other ingredients and preparation method are the same as those of Example 12.

[0263] Embodiment 47

[0264] Compared with Example 16, this embodiment is different in that the hepatitis B vaccine is replaced by minoxidil with a mass concentration of 10%; the other ingredients and preparation method are the same as those of Example 16.

[0265] Embodiment 48

[0266] The difference between this embodiment and embodiment 8 is that the hepatitis B vaccine is replaced by orlistat with a mass concentration of 10%; the other ingredients and preparation method are the same as those in embodiment 8.

[0267] Embodiment 49

[0268] The difference between this embodiment and embodiment 12 is that the hepatitis B vaccine is replaced by orlistat with a mass concentration of 40%; the other ingredients and preparation method are the same as those of embodiment 12.

[0269] Embodiment 50

[0270] Compared with Example 16, this embodiment is different in that the hepatitis B vaccine is replaced by orlistat with a mass concentration of 10%; the other ingredients and preparation method are the same as those of Example 16.

[0271] Comparative Example 1

[0272] The difference between this comparative example and Example 8 is that the concentration of hyaluronic acid is increased to 70%, and the viscosity of the coating liquid is 1300000 centipoise; the other ingredients and preparation method are the same as those in Example 8.

[0273] Comparative Example 2

[0274] The difference between this comparative example and Example 8 is that the concentration of hyaluronic acid is reduced to 1%, and the viscosity of the coating liquid is 80,000 centipoise; the other ingredients and preparation method are the same as those of Example 8.

[0275] Comparative Example 3

[0276] The difference between this comparative example and Example 8 is that the molecular weight of hyaluronic acid is increased to 2000KDa, the concentration is 10%, the viscosity of the coating liquid is 830000 centipoise, the maximum solubility of the hepatitis B vaccine is only 0.5%, and the other ingredients and preparation method are the same as those in Example 8.

[0277] Comparative Example 4

[0278] The difference between this comparative example and Example 8 is that the molecular weight of hyaluronic acid is reduced to 100 KDa, the concentration is 70%, the viscosity of the coating liquid is 360,000 centipoise, and the other ingredients and preparation method are the same as those in Example 8.

[0279] Comparative Example 5

[0280] The difference between this comparative example and Example 8 is that the molecular weight of hyaluronic acid is reduced to 100 KDa, the concentration is 10%, the viscosity of the coating liquid is 30,000 centipoise, and the other ingredients and preparation method are the same as those of Example 8.

[0281] Comparative Example 6

[0282] This comparative example is different from Example 8 in that no air flow is introduced, and other components and preparation methods are the same as those of Example 8.

[0283] Comparative Example 7

[0284] Compared with Example 8, the present comparative example is different in that the wind direction is the same as the direction of the needle tip, that is, the needle tip is vertically upward, the wind flow system is above the needle tip and sucks air, and the other components and preparation method are the same as those of Example 8.

[0285] Comparative Example 8

[0286] The difference between this comparative example and Example 8 is that no sucrose is added, and the other ingredients and preparation method are the same as those of Example 8.

[0287] Comparative Example 9

[0288] The difference between this comparative example and Example 1 is that no human serum albumin is added, and the other components and preparation method are the same as those of Example 1.

[0289] Comparative Example 10

[0290] Compared with Example 16, this comparative example is different in that PVP-K30 is replaced by PVP-K90, the concentration is 30%, the coating liquid viscosity is 1400000 centipoise, the maximum solubility of the hepatitis B vaccine is only 1%, and the other ingredients and preparation method are the same as Example 16.

[0291] Comparative Example 11

[0292] This comparative example is different from Example 16 in that the concentration of PVP-K30 is increased to 70%, the viscosity of the coating liquid is 1,250,000 centipoise, and the other ingredients and preparation method are the same as those of Example 16.

[0293] Comparative Example 12

[0294] The difference between this comparative example and Example 16 is that PVP-K30 is replaced by PVP-K10, the concentration is 70%, the coating liquid viscosity is 340,000 centipoise, and the other ingredients and preparation method are the same as those in Example 16.

[0295] Specific test indicators and test results are shown in Table 1:

[0296] Table 1

[0297]

[0298]

[0299]

[0300]

[0301]

[0302] Among them, after drying, the microneedles of Comparative Examples 1, 4, 11, and 12 had too thick coating layers, and the needle bodies could not effectively puncture the skin.

[0303] When the microneedles of Comparative Examples 2 and 5 are soaked in the coating liquid, the coating liquid is adsorbed onto the base, and the solution coated on the needle tip further migrates to the base due to surface tension.

[0304] Among them, in the coating liquid formulations of Comparative Examples 3 and 10, the solubility of the drug therein will be greatly reduced.

[0305] Among them, after the microneedle of Comparative Example 6 was soaked in the coating liquid, no air flow was introduced. Due to the influence of gravity and the inability to dry quickly, the coating liquid gathered at the needle tip. After drying, the needle tip part appeared in a droplet shape. The rear section of the needle body of the coating layer was extremely thin, and the coating layer was displaced 60 microns toward the needle tip, resulting in poor puncture effect.

[0306] Among them, after the microneedles of comparative example 7 were coated and dried, the coating layer was still evenly coated on the needle body, but compared with the results in Example 8, the coating layer migrated 60 μm along the needle body toward the base, which made the coating height of the coating layer on the microneedle body reach 430 μm, while the coating layer in Example 8 did not migrate, and the coating height of the coating layer on the microneedle body was 370 μm. This indicator was detected by SEM. After the microneedles obtained in comparative example 7 were administered to the back skin of mice, due to skin elasticity factors, the latter half of the needle body was not completely administered, and 10% of the drug load remained on the needle body, while the microneedles in Example 8 were completely administered. The detection method of this test result is to dissolve the microneedles after administration again and quantitatively determine them by Bradford method.

[0307] Among them, the active pharmaceutical ingredients carried by the microneedles of Comparative Examples 8 and 9 were greatly reduced after drying.

[0308] According to the results of Comparative Example 1, Comparative Example 2, Comparative Example 4, Example 8, Comparative Example 10, Comparative Example 11, Comparative Example 12 and Example 16, when the coating matrix material is hyaluronic acid with a molecular weight of 250-1000KDa and polyvinylpyrrolidone K30, if the coating matrix material concentration is higher than 45%, the needle body coating layer is thick, the puncture effect is poor, and the clinical needs cannot be met. If the coating matrix material concentration is lower than 5%, the coating liquid will be adsorbed onto the needle base, resulting in coating failure; when the coating matrix material is hyaluronic acid with a molecular weight lower than 250KDa and PVP with a molecular weight lower than K30, a high concentration of the matrix material is required to be suitable for coating, otherwise it will be directly adsorbed onto the base. Under this condition, the thickness of the microneedle coating layer is thick, the puncture effect is poor, and the needs are still not met; when the coating matrix material is polyvinylpyrrolidone with a molecular weight higher than 1000KDa and a molecular weight higher than K30, due to its excessively high molecular weight, the solubility of the drug in the system drops sharply, resulting in the microneedle drug loading being too low and unable to meet the needs.

[0309] In summary, compared with ordinary coated microneedles, the microneedle patch prepared by the present invention has an intact needle body morphology and excellent puncture performance. The surface of the needle body can carry more active ingredients. The coating layer is evenly distributed on the coated part of the needle body and will not migrate. It can meet the loading requirements of a variety of different active ingredients and has good universality. The preparation method suitable for the microneedle patch of the present invention is simple and fast, has good repeatability, meets the coating and drug loading requirements of different types of water-insoluble microneedles, and is extremely suitable for industrial production.

[0310] The above is only a preferred embodiment of the present invention, and does not limit the present invention in any form. Although the present invention has been disclosed as a preferred embodiment as above, it is not used to limit the present invention. Any technician familiar with this profession can make some changes or modify the technical contents disclosed above into equivalent embodiments of equivalent changes without departing from the scope of the technical solution of the present invention. However, any simple modification, equivalent change and modification made to the above embodiments according to the technical essence of the present invention without departing from the content of the technical solution of the present invention still fall within the scope of the technical solution of the present invention.

Claims

1. A microneedle patch, characterized in that: The microneedle patch includes a base, microneedles and a coating layer on the surface of the microneedles, the coating layer is prepared from a coating liquid, the coating liquid is prepared by dissolving a coating material and an active ingredient in water or a buffer solution, the coating material includes one or more of a coating matrix material, a moisturizer, a protein protective agent, and an antibiotic, the coating matrix material includes at least one of high molecular weight hyaluronic acid and polyvinyl pyrrolidone, the moisturizer includes glycerol, the protein protective agent includes at least one of trehalose, human serum albumin, sucrose, and arginine, the molecular weight of the hyaluronic acid is 250KDa-1000KDa, the concentration of the hyaluronic acid is 5-30% (w / v), the polyvinyl pyrrolidone is PVP-K30, the concentration of the polyvinyl pyrrolidone is 25-45% (w / v), and the viscosity of the coating liquid is 370000-1200000 centipoise.

2. The microneedle patch according to claim 1, characterized in that The microneedle is a cone or a polygonal cone, the microneedle height is 60-900 μm, the tip width or diameter of the microneedle is 5-40 μm, the width or diameter of the end of the microneedle body is 50-300 μm, and the spacing between the microneedles is 1-5 mm.

3. The microneedle patch according to claim 1, characterized in that: The concentration of the moisturizer is 0.5-2.5% (w / v).

4. The microneedle patch according to claim 1, characterized in that: The concentration of the protein protectant is 1-5% (w / v).

5. The microneedle patch according to claim 1, characterized in that: The active ingredient includes at least one of small molecule compounds, vaccines, protein drugs, peptide drugs, and nucleic acid drugs.

6. A method for preparing a microneedle patch according to any one of claims 1 to 5, characterized in that: The preparation method includes a coating process, wherein the coating process is performed by inserting the microneedle body into the coating liquid for an immersion time of 5-30 seconds, pulling it out and placing it vertically downward, and then applying a vertical upward wind flow under the needle body, wherein the wind flow speed is 0.5m-10m / s, the humidity is 1-60%, and the wind flow is maintained for 1-30 minutes.

7. Use of the microneedle patch according to any one of claims 1 to 5 or the microneedle patch prepared by the preparation method according to claim 6 for encapsulating drugs, wherein the drug comprises at least one of a small molecule compound, a vaccine, a protein drug, a peptide drug, and a nucleic acid drug.

8. Use of the microneedle patch according to any one of claims 1 to 5 or the microneedle patch prepared by the preparation method according to claim 6 in preparing a disease therapeutic or disease preventive drug.

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