Cosmetic dissolvable microneedle, preparation method and application thereof

Abstract

The application discloses a kind of microneedles, the microneedle includes first component, second component and water, wherein, first component is organic acid, second component is amino acid and / or active peptide, wherein, the mass ratio of first component and second component is 0.2-2:1;The mass percentage of injectable water is 0.05-5%, and the elastic modulus of the microneedle is greater than 1Gpa.The microneedle of the application has good forming rate, high hardness of needle tip, high skin puncture rate, can effectively improve the transdermal efficacy of active ingredients such as cosmetic peptides, and the soluble microneedle can be suitable for various skin, mucosa infectious diseases and medical beauty skin care.

Description

Technical Field

[0001] This invention belongs to the field of biomaterials and relates to a cosmetic soluble microneedle, its preparation method and application. Background Technology

[0002] Microneedles consist of an array of tiny needle-like structures with a diameter of micrometers, along with a base support layer. Microneedle drug delivery is achieved by piercing the stratum corneum of the skin to create micrometer-sized channels that allow active molecules to enter the subcutaneous layer. It is a novel transdermal drug delivery method with advantages such as painlessness, good patient compliance, ease of self-administration, and efficient delivery.

[0003] Microneedling has been proven to be an effective method of drug delivery. Cosmed Pharmaceuticals of Japan has developed microneedling products using sodium hyaluronate and collagen. It has been successfully launched and is used for skin whitening and pigmentation removal applications. Some microneedle products have also entered clinical trials, such as the coated microneedles developed by Zosano Pharma. For parathyroid hormone delivery, Phase I / II study; developed by NanoPass Technologies. Hollow microneedles have been used in clinical studies to deliver insulin, influenza vaccines, and lidocaine (for local anesthesia). Literature and patents also report the use of microneedles for the delivery of various small molecule drugs, such as lidocaine, insulin, artemether, fentanyl, alendronate, levonorgestrel, huperzine A, and caffeine. Chinese patent CN111991344B discloses a microneedle patch suitable for local anesthesia, which offers advantages such as painless administration, high patient compliance, rapid onset of anesthesia, and high drug delivery efficiency.

[0004] According to the different drug release mechanisms, microneedles can be divided into solid microneedles, hollow microneedles, coated microneedles, dissolvable microneedles and hydrogel microneedles. Different microneedles have different release characteristics: 1) "poke and patch" is a two-step administration process for solid microneedles. Microneedles are applied to the skin, and then the microneedles are completely removed and the patch containing the drug preparation is applied to the microneedle application site, so that the drug diffuses into the skin through the micropores generated by the solid microneedles, and the drug dose mainly depends on the pore size and number. The advantage of this method is simple technology, without drug encapsulation or coating process, but the drug delivery efficiency is low. 2) The release mode of hollow microneedles is "poke and flow", which has the advantages of precise control of drugs by adjusting the drug delivery rate, but also has the risk of blockage of the hollow channel of the microneedle and damage to the strength of the microneedle; and the preparation of microneedles requires more complex equipment. 3) The "coated and poked" method, i.e. the release method of coated microneedles, microneedles have been coated with various drugs to form a dry coating. This method is often used for vaccine delivery. The drug is released by separating or dissolving from the surface of the microneedle. This method requires the development of an efficient coating process, and some drug coatings can reduce the sharpness and penetration ability of the microneedle. 4) "Poke and release" is generally the release mode of dissolvable microneedles and hydrogel microneedles. During preparation, the drug is encapsulated into the needle tip matrix, and after the microneedle is inserted into the skin, the needle body contacts the interstitial fluid, and the drug is released locally after dissolving. Coated microneedles or dissolvable microneedles have become a development trend due to their simple preparation process, high delivery efficiency and safety.

[0005] However, in actual application, there is a negative correlation between the loading amount of active ingredients and the strength of microneedles, which limits the increase of the drug dose of microneedles. In the preparation process of microneedles, mold casting is a common production process for microneedle preparation. However, due to the precipitation of some active ingredients in the microneedle mold, bubble aggregation and other factors, defective products are formed. In addition, the conventional application time of dissolvable microneedles is mainly 10 minutes to 8 hours (overnight) when applied to the skin, especially the skin of the face. Therefore, controlling the dissolution rate of dissolvable microneedles is also a problem to be solved. It is of great significance to optimize the microneedle formula and solve the above problems in application. SUMMARY

[0006] In view of the above background technical problems, the present application provides a carrier-free, high-dose formulation with high dry hardness and fast water-soluble. It can be used alone or very conveniently added to other product formulations, especially suitable for use as a functional coating for microneedles and a dissolvable microneedle for skin medical and beauty repair.

[0007] Active peptides as active ingredients of cosmetic products have been applied in various cosmetics, and thus the active peptides applied in the field of skin health are also called cosmetic peptides. Cosmetic peptides have many advantages, such as clear ingredients, mostly composed of 2-10 amino acids, with specific amino acid sequences; clear mechanism of action, generally acting on specific receptor genes of the skin.

[0008] To achieve the above-mentioned purpose, the first aspect of the present application provides a microneedle, the microneedle comprising a first component, a second component and water, wherein the first component is an organic acid, the second component is an amino acid and / or an active peptide, and the mass ratio of the first component to the second component is 0.2-2:1; the mass percentage of injectable water is 0.05-5%, and the elastic modulus of the microneedle is greater than 1 GPa; preferably, the microneedle is a transparent or translucent microneedle.

[0009] The active peptide is an antibacterial peptide with a net positive charge or a cosmetic peptide.

[0010] Preferably, the cosmetic peptide refers to the peptide raw materials listed in the Catalogue of Cosmetics Raw Materials (2021 Edition) issued by the National Medical Products Administration, and / or the peptide raw materials included in the International Dictionary and Handbook of Cosmetics Raw Materials, and / or the peptide raw materials included in the Official Cosmetics Ingredient Database of the European Union.

[0011] More preferably, the cosmetic peptide is selected from camosin (H-β-Ala-His-OH), decarboxycamosin, dipeptide-2, acetyl dipeptide-1, dipeptide class of snake venom peptide (H-β-Ala-Pro-Dab-NHBzl), palmitoyl dipeptide-7, copper peptide (Gly-D-His-Lys-Cu 2+Tripeptide-1, Tripeptide-4, Citrulline Tripeptide-10 (H-Lys-Asp-Ile-Cit-OH), Palmitoyl Tripeptide-1, Palmitoyl Tripeptide-5, Tetrapeptide-7, Tetrapeptide-30, Acetyl Tetrapeptide-5, Acetyl Tetrapeptide-9, Palmitoyl Tetrapeptide-3, Palmitoyl Tetrapeptide-7 (Pal-Gly-Gln-Pro-Arg-OH), Pentapeptide-3, Acetyl Pentapeptide-1, Palmitoyl Pentapeptide-3, Palmitoyl Pentapeptide-4, Palmitoyl Pentapeptide-33, Myristoyl Pentapeptide-11, Myristoyl Pentapeptide-17 (Myr-Lys-Leu-Ala-Lys-Lys-NH2), HB1518 (Ser-Leu-Tyr-Gln-Ser), Hexapeptide-2 One or more of the following: hexapeptide-5, hexapeptide-8, hexapeptide-9, hexapeptide-10, hexapeptide-11, acetyl hexapeptide-3(8)(Ac-Glu-Glu-Met-Gln-Arg-Arg-NH2), acetyl hexapeptide-38, acetyl hexapeptide-39, myristoyl hexapeptide-16, palmitoyl hexapeptide-21(Pal-FALLKL-NH2), HB1061(MGRNIRN-NH2), acetyl octapeptide-1, nonapeptide-1(Met-Pro-D-Phe-Arg-D-Trp-Phe-Lys-Lys-Pro-Val), oligopeptide-10(FAKALKALLKALKAL-NH2), and palmitoyl dipeptide-5 complex salt.

[0012] The antimicrobial peptide having a net positive charge and a separated hydrophobic and hydrophilic amphiphilic structure is selected from one or more of human LL-37, Magainin 2, human β-defensin 2 (HBD2), human α-defensin 5 (HD5), CATH-2, SGX942 (H-Arg-Ile-Val-Pro-Ala-NH2), silk peptide, Brilacidin, and derivatives of taurine.

[0013] To address the issue of a negative correlation between the loading of active ingredients and the strength of microneedles, which limits the dosage of microneedle administration, this invention achieves a formulation entirely composed of active ingredients suitable for microneedle preparation through phase modulation. By controlling intermolecular interactions, a ternary supramolecular network system of organic acid, active peptide, and water is proposed. This lowers the lattice energy of the active peptide, causing the ternary system to form a new liquid phase under heating conditions. This new liquid phase has high viscosity and solidifies upon cooling. The solidified system possesses both hardness and toughness, making it suitable for microneedle preparation.

[0014] Secondly, a method for preparing the aforementioned microneedles is provided, which mainly includes the following steps:

[0015] 1) Prepare the first component solution, add the second component of the formula to the first component solution, and mix well;

[0016] 2) The mixed solution in step 1 is subjected to a system dehydration solidification treatment;

[0017] 3) When the water content in the system in step 2 is reduced to a certain value, the system is placed at room temperature to obtain the preparation.

[0018] Specifically, the dehydration solidification treatment includes one or a combination of several of heating drying, reduced pressure drying, air blowing, hot air blowing, nitrogen blowing, and supercritical drying.

[0019] The heating drying temperature is 40-100°C, preferably 40-80°C.

[0020] The water content is in the range of 0.05%-5%.

[0021] In the preparation, the combined water in the system regulates the multiple non-covalent interactions, especially the hydrogen bond interactions, between the organic acid and the active peptide, forming a supramolecular hydrogen bond network, which strengthens the mechanical strength of the material, thereby enhancing the mechanical strength of the microneedle in the subsequent microprocessing, and enabling the microneedle to successfully penetrate the skin. In addition, the relatively stable combined water network in the preparation significantly improves the stability of the active peptide reservoir, thereby making it more suitable for the application of peptide active molecules.

[0022] The preparation provided by the present application can also load other skin valuable substances, including but not limited to antioxidants, moisturizers, whitening agents, anti-inflammatory agents, freckle-removing agents, wrinkle-removing agents, hair growth-promoting agents, sunscreen agents, and other functional ingredients. The content of the skin valuable substance is not more than 5% of the total mass of the preparation.

[0023] In a third aspect, the preparation of the present application can be used as a needle tip coating layer for preparing coated microneedles.

[0024] Specifically, the preparation of the present application can be coated onto a solid microneedle by heating flow-cooling solidification (fusion method) to obtain a coated microneedle. The solid microneedle can be selected from solid or porous microneedles prepared from silicon-based, glass, ceramic, metal, polymer, and sugar.

[0025] Preparation of microneedle array

[0026] In a fourth aspect, the preparation of the present application can be used as a pre-prepared liquid to prepare a microneedle array by casting, stretching, atomization spraying, microfluidics, or 3D printing.

[0027] In a fifth aspect, the present application also provides a method for preparing a microneedle array by casting using the above-mentioned preparation as a pre-prepared liquid, which comprises the following steps:

[0028] 1) Heat the preparation of the first aspect to obtain a flowable pre-prepared liquid, and preheat a microneedle negative mold;

[0029] 2) Pouring an appropriate amount of the pre-prepared liquid in step 1 into the preheated microneedle negative mold, filling the needle tip matrix liquid into the microneedle mold cavity through defoaming treatment, and removing air bubbles;

[0030] 3) Cooling the mold, and stripping the microneedles after the microneedle body is solidified, to obtain the microneedle array.

[0031] Alternatively, the preparation method of the microneedle array can also be combined with the preparation of the formulation and the pouring of the pre-prepared liquid, and prepared by the following steps:

[0032] 1) Preparing organic acid solution and active peptide solution respectively;

[0033] 2) Pouring the mixture of the organic acid solution and the active peptide solution in step 1 into the microneedle mold after mixing uniformly according to a certain proportion, and performing system dehydration and solidification treatment;

[0034] 3) When the water content in the system in step 2 is reduced to a certain value, performing defoaming treatment;

[0035] 4) After the microneedles are solidified, stripping the microneedles to obtain the microneedle array.

[0036] The water content is in the range of 0.05% to 5%.

[0037] Preferably, the pouring includes high-pressure spraying, centrifugation, vacuum adsorption or self-leveling.

[0038] In some embodiments, centrifugation is used to remove air in the needle tip matrix liquid and / or in the microneedle mold cavity.

[0039] In some embodiments, pressurization is used to remove air in the needle tip matrix liquid and / or in the microneedle mold cavity.

[0040] In some embodiments, reduced pressure (such as vacuum) is used to remove air in the needle tip matrix liquid and / or in the microneedle mold cavity.

[0041] In the sixth aspect, the method according to the fourth and fifth aspects can also be combined with other conventional and well-known preparation processes to prepare bubble microneedles, porous microneedles, layered microneedles, segmented microneedles, sustained-release microneedles, etc.

[0042] Specifically, in some embodiments, the prepared multi-layer microneedle array includes a microneedle base layer and a microneedle body, the microneedle body includes a microneedle root and a microneedle tip, and the microneedle root is a part connecting the microneedle base and the microneedle tip.

[0043] The microneedle root and / or the microneedle base are made of a hydrophilic polymer.

[0044] The hydrophilic polymer includes, but is not limited to, at least one of hyaluronic acid, chitosan, polyvinyl alcohol, chondroitin sulfate, polyvinylpyrrolidone, trehalose, dextran, maltose, sucrose, and carboxymethyl cellulose, and the like water-soluble polymer.

[0045] The needle tip is prepared from the formulation of the first aspect.

[0046] Specifically, in some embodiments, the multi-cavity microneedle can be prepared by adding a pore-forming agent to the pre-prepared liquid.

[0047] The pore-forming agent includes, but is not limited to, one or more of sodium chloride, sodium carbonate, sodium bicarbonate, ammonium bicarbonate, trehalose, maltose, polyethylene glycol, cyclodextrin and its derivatives, polyvinylpyrrolidone (PVP), low molecular weight hyaluronic acid and its sodium salt (molecular weight 5-100 kDa), low molecular weight cellulose derivatives (molecular weight 5-100 kDa).

[0048] Microneedle patch

[0049] In the seventh aspect, the microneedle array of the present application can be used as a soluble microneedle for buccal administration alone, or, in order to maintain the integrity of the needle tip, it can also be made into a microneedle patch. The microneedle patch refers to a substrate layer including the microneedle array and the back of the matrix of the microneedle array. The back refers to the matrix surface on the side opposite to the protruding surface of the microneedle. The substrate layer is not an essential component, and is mainly to help the microneedle application to conduct the pressing force more uniformly, so that the microneedle penetrates the stratum corneum of the skin to a consistent depth.

[0050] In order to stably apply the microneedle patch to the skin and keep it on the skin, it is not necessary to provide an adhesive support on the back of the patch, but it is more preferable. Here, the "back" refers to the side of the microneedle opposite to the side where the microneedles are densely arranged. The adhesive support is a support film having an adhesive layer on one side.

[0051] As the adhesive layer in the present application, an adhesive sheet formed of a commercially available adhesive can be used. Rubber-based adhesives, silicone-based adhesives, acrylic-based adhesives, and the like can be used.

[0052] As the support film, a film formed of a synthetic polymer is preferable, and it is required to have excellent adhesion to the adhesive, to be able to maintain strength, and to be able to be easily formed into a thin film. Specifically, it is selected from polyethylene, PET (polyethylene terephthalate), polyvinylpyrrolidone, polyvinyl alcohol, and an acrylic resin. In the acrylic resin, the hardness is preferably 3 N or more. The value of the hardness is more preferably 4 or more and 50 or less. If the hardness is less than 3, sometimes the support film produces adhesion, and use becomes inconvenient. Non-woven fabric, woven fabric, and the like can also be preferable supports.

[0053] In an eighth aspect, the present application provides a use of the dissolvable microneedle product in transdermal administration of skin diseases and / or medical and cosmetic repair projects. The skin diseases include, but are not limited to, treatment of acne, skin infection, anti-inflammatory repair, wound healing, etc. The medical and cosmetic repair projects include, but are not limited to, anti-aging projects for promoting collagen regeneration, wrinkle-removing projects, anti-free radical oxidation and anti-carbonylation, skin whitening and freckle-removing projects, slimming and body slimming projects, projects for promoting eyelash (hair) growth, breast augmentation, and other projects for improving the appearance or health status of the skin.

[0054] As used herein, the term "peptide", "active peptide" refers to a molecule having at least two amino acids connected by a peptide bond, the number of amino acids being less than or equal to 50. The term also includes peptides and derivatives thereof (e.g., glycosylated derivatives and pegylated derivatives).

[0055] Compared with the prior art, the present application has the following beneficial effects:

[0056] 1) The present application effectively solves the hardness and toughness problems of the microneedle body by forming a supramolecular hydrogen bond dynamic network among the organic acid, the active peptide and water, thereby improving the formability of the microneedle and the skin puncture ability.

[0057] 2) The present application effectively improves the poor storage stability of the active peptide by forming a supramolecular hydrogen bond dynamic network among the organic acid, the active peptide and water, so that it can be stored at room temperature for a long time.

[0058] 3) The present application improves the release rate of the microneedle by forming a supramolecular hydrogen bond dynamic network among the organic acid, the active peptide and water, so that it can be completely released within one hour. BRIEF DESCRIPTION OF DRAWINGS

[0059] Figure 1 Physical photos of the formulation obtained in Example 1;

[0060] Figure 2 Photos of PDMS negative film molds 1 and 2 used for preparing microneedles by casting method;

[0061] Figure 3 Photos showing the microneedles before (left) and after (right) defoaming in Example 13;

[0062] Figure 4 Photos showing the microneedles before (left) and after (right) defoaming in Example 15;

[0063] Figure 5 Photos of microneedle arrays prepared in Examples 9-12;

[0064] Figure 6 Photos of microneedle arrays prepared in Example 16;

[0065] Figure 7 Photograph of microneedle array prepared in Example 14;

[0066] Figure 8 Photograph of microneedle array prepared in Example 14 simulating puncture of a sealing film. DETAILED DESCRIPTION

[0067] The present application will be further described with reference to the following examples and drawings, but the embodiments of the application are not limited to the examples. In the examples, unless otherwise specified, the techniques or conditions are performed according to the techniques or conditions described in the literature in the art or according to the product manual.

[0068] The present application will be further described with reference to the following examples and drawings, but the embodiments of the application are not limited to the examples. In the examples, unless otherwise specified, the techniques or conditions are performed according to the techniques or conditions described in the literature in the art or according to the product manual.

[0069] Formulation Preparation

[0070] The formulations described in Examples 1-8 were prepared using the formulations in Table 1 according to the following procedure:

[0071] 1) Prepare a solution of the first component and add the second component in the amount of the formulation to the solution of the first component and mix well;

[0072] 2) Subject the mixture from step 1 to system heating and drying;

[0073] 3) When the water content of the system from step 2 is reduced to a certain value, place it at room temperature to obtain the formulation.

[0074] The modulus of elasticity of the resulting formulation material was measured and the results are shown in Table 1.

[0075]

[0076]

[0077] Figure 1The physical picture of the formula preparation obtained in Example 1 shows that the obtained formula preparation material has good plasticity and hardness, which lays a foundation for subsequent preparation of microneedles.

[0078] PDMS microneedle negative mold

[0079] The PDMS microneedle negative mold in the present application is purchased from Taizhou Microchip Pharmaceutical Technology Co., Ltd.

[0080] The specific parameters are shown in Table 2 as follows:

[0081]

[0082] Figure 2 The photos of mold 1 (left) and mold 2 (right) are shown.

[0083] Preparation of microneedle array in Examples 9-12

[0084] The formula preparation in the above examples is used as a pre-liquid, and microneedles are prepared by the following steps.

[0085] 1) The formula preparation described in Examples 1-4 is heated to obtain a flowable pre-liquid, and the microneedle negative mold 1 is preheated;

[0086] 2) A proper amount of the pre-liquid in step 1 is poured into the preheated microneedle negative mold, and the needle tip matrix liquid is filled into the microneedle mold cavity and the air bubbles are removed by centrifugal defoaming treatment;

[0087] 3) The mold is cooled, and after the microneedle body is solidified, the microneedles are stripped and demolded to obtain a microneedle array.

[0088] Preparation of microneedle array in Example 13

[0089] The formula preparation in the above examples is used as a pre-liquid, and microneedles are prepared by the following steps.

[0090] 1) The formula preparation described in Example 5 is heated to obtain a flowable pre-liquid, and the microneedle negative mold 2 is preheated;

[0091] 2) A proper amount of the pre-liquid in step 1 is poured into the preheated microneedle negative mold, and the needle tip matrix liquid is filled into the microneedle mold cavity and the air bubbles are removed by centrifugal defoaming treatment;

[0092] 3) The mold is cooled, and after the microneedle body is solidified, the microneedles are stripped and demolded to obtain a microneedle array.

[0093] Figure 3 The photos of the pre-liquid after being poured into the mold in Example 13, step 2, before defoaming (left) and after defoaming (right) are shown.

[0094] Preparation of microneedle array in Example 14

[0095] The formulation in the above examples is prepared as a pre-liquid, and the microneedle is prepared by the following steps.

[0096] 1) The formulation described in Example 6 is heated to obtain a flowable pre-liquid, and the microneedle negative mold 1 is preheated;

[0097] 2) A suitable amount of the pre-liquid in step 1 is poured into the preheated microneedle negative mold, and the needle tip matrix liquid is filled into the microneedle mold cavity and the air bubbles are removed by vacuum degassing treatment;

[0098] 3) Cool the mold, and after the microneedle body is solidified, the microneedle is stripped and demolded to obtain a microneedle array.

[0099] Preparation of a microneedle array in Example 15

[0100] 1) According to the formulation of Example 7, organic acid solution and active peptide solution are prepared respectively;

[0101] 2) The organic acid solution and the active peptide solution in step 1 are mixed in a certain proportion and then poured into the microneedle mold 1, and the system is subjected to heating, drying and dehydration treatment;

[0102] 3) When the water content in the system of step 2 is reduced to 5%, centrifugal degassing treatment is performed;

[0103] 4) After the mold is cooled, the microneedle is solidified, and the microneedle is stripped and demolded to obtain a microneedle array.

[0104] Figure 4 The photos show the pre-liquid in Example 15, step 2, before (left) and after (right) degassing after being added to the mold.

[0105] Preparation of a microneedle array in Example 16

[0106] 1) According to the formulation of Example 8, organic acid solution and active peptide solution are prepared respectively;

[0107] 2) The organic acid solution and the active peptide solution in step 1 are mixed in a certain proportion and then poured into the microneedle mold 3, and the system is subjected to heating, drying and dehydration treatment;

[0108] 3) When the water content in the system of step 2 is reduced to 0.05%, centrifugal degassing treatment is performed;

[0109] 4) After the mold is cooled, the microneedle is solidified, and the microneedle is stripped and demolded to obtain a microneedle array.

[0110] Figure 5 Photos of microneedle arrays prepared in Examples 9-12.

[0111] Figure 6 Photograph of microneedle array prepared in Example 16.

[0112] Figure 7 Photograph of microneedle array prepared in Example 14.

[0113] Method for measuring mechanical properties and piercing experiment of microneedle

[0114] The piercing ability of microneedle array was measured by TA.newplus texture analyzer (ISENSO, USA). According to the literature, the penetration force required for microneedle to pierce the skin should be greater than 0.05 N, so the trigger force was set to 0.05 N, the pre-measurement rate was 0.5 mm / s, the measurement rate was 0.5 mm / s, and the post-measurement rate was 15 mm / s. The relationship between the stress and the displacement of the probe during the compression of the microneedle tip was measured by the texture analyzer to determine the breaking force. The stress of the microneedle tip increased slowly with the increase of the deformation variable of the tip. The results showed that no obvious breaking point was observed in the tested range (deformation variable 0.5 mm). When the deformation variable of the microneedle tip in each example was 0.2 mm, the pressure on the tip was greater than 1 N (Table 3), indicating that the tip could easily pierce the skin. The elastic modulus and hardness of the microneedle were measured by G200 nanoindenter (Agilent). The measurement method was to press the microneedle material with a constant strain rate (0.05 s -1 ) using a triangular pyramid diamond indenter, and the average elastic modulus and hardness data were obtained by plotting the load force against the displacement.

[0115] In order to visually measure the depth of the microneedle piercing the skin, the piercing performance of the microneedle was further evaluated by the Parafilm membrane insertion test. The specific method was as follows: after the prepared microneedle array was fixed on the microneedle needle insertion device, 8 layers of sealing film (Parafilm M Laboratory Film sealing film) were stacked together (thickness about 1 mm) to simulate the stratum corneum of the skin, and were placed on the foam board. The microneedle array was vertically pressed on the 8 layers of sealing film, and the pressing force was applied for 2 min, then the sealing film was peeled off layer by layer, and the piercing condition of the sealing film and the integrity of the needle body were observed. The results, as shown in Figure 8 , showed that the sealing film was completely pierced, and the tip was not broken.

[0116] Table 3: Evaluation of mechanical property parameters of microneedle

[0117]

[0118]

[0119] The above results show that the microneedles prepared from the formulation of the present application have high hardness and toughness. The soluble microneedles prepared from the formulation have good forming rate, high hardness of the needle tip and good puncture performance while maintaining high active substance loading.

[0120] Evaluation of the rapid dissolution of the microneedles after puncturing the skin

[0121] Wistar ST rats were taken and the back was shaved to form a 2cm x 2cm hairless area. After 24h, the microneedle array was used to act on the site with a force of about 15N for 3min, and the dissolution of the microneedles was observed at 15min and 60min after the action, respectively.

[0122] The percentage of the height of the remaining microneedle tip to the height of the original microneedle tip was calculated to reflect the dissolution of the microneedles.

[0123] Table 4: Evaluation of the rapid dissolution of the microneedles after puncturing the skin

[0124]

[0125] As can be seen from the data in the table, the microneedles improved by the present application can complete more than 80% of the needle body dissolution within one hour, and can quickly release active molecules.

[0126] The applicant states that the above examples illustrate the detailed method of the present application, but the present application is not limited to the above detailed method, i.e. it does not mean that the present application must rely on the above detailed method to be implemented. It should be understood by those skilled in the art that any improvement of the present application, equivalent replacement of each raw material of the product of the present application, addition of auxiliary ingredients, selection of specific methods, etc. fall within the protection scope and disclosure scope of the present application.

Claims

1. A microneedle comprising a first component, a second component, and water, wherein, The first component is an organic acid, the second component is an amino acid and / or an active peptide, wherein the mass ratio of the first component to the second component is 0.2-2:1; the mass percentage of injectable water is 0.05-5%, the modulus of elasticity of the microneedle is greater than 1 GPa; the organic acid is selected from one or more of salicylic acid, citric acid, malic acid, chlorogenic acid and acetic acid; the active peptide is one or more of an antibacterial peptide with a net positive charge, a cosmetic peptide selected from the group consisting of camosin with the sequence H-β-Ala-His-OH, palmitoyl tripeptide-1, palmitoyl tetrapeptide-7 with the sequence Pal-Gly-Gln-Pro-Arg-OH, myristoyl pentapeptide-11, acetyl hexapeptide-3 with the sequence Ac-Glu-Glu-Met-Gln-Arg-Arg-NH2, oligopeptide-10 with the sequence FAKALKALLKALKAL-NH2; the antibacterial peptide is one or more of human LL-37, Magainin 2, human beta defensin 2, SGX942 with the sequence H-Arg-Ile-Val-Pro-Ala-NH2; and the amino acid is arginine.

2. The microneedle of claim 1, wherein, The microneedle is a transparent or translucent microneedle.

3. The microneedle of claim 1, wherein, The microneedle is obtained by dehydrating and curing a system containing the first component, the second component and water; the dehydrating and curing process includes one or a combination of several of heating drying, reduced pressure drying, air blowing, hot air blowing, nitrogen blowing, supercritical drying.

4. The microneedle of claim 1, which is a coated microneedle, a bubble microneedle, a porous microneedle, a layered microneedle, a segmented microneedle or a sustained release microneedle.

5. A microneedle array, characterized by, At least a portion of the microneedles in the microneedle array are the microneedles of any one of claims 1-4.

6. The microneedle array of claim 5, wherein, The microneedle array is obtained by one or a combination of several of fusion, casting, stretching, atomization spraying, microfluidic method or 3D printing method.

7. The microneedle array of claim 5 or 6, wherein, The microneedle array does not load other active ingredients or further loads delivery of antioxidants, moisturizers, whitening agents, anti-inflammatory agents, depigmentation agents, wrinkle-removing agents, hair growth-promoting agents, sunscreens and / or other cosmetic active ingredients.

8. Use of a microneedle array according to any one of claims 5-7, said use comprising: Use in the preparation of a medicament for treating various skin and mucosal infectious diseases or use in the preparation of a skin care preparation.

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