A dissolvable microneedle patch and a preparation method thereof

Abstract

The present application provides a soluble microneedle patch. The needle body of the soluble microneedle patch of the present application can directly act on the epidermal basement layer through the stratum corneum, accelerating the transdermal absorption of effective components. Moreover, the active ingredients in the central layer and the outer layer of the microneedle can synergistically enhance the absorption and utilization effect of multiple components. In addition, unlike the liquid environment of traditional emulsions, the microneedle is in solid form, which can minimize the reactivity of active ingredients. The optimized soluble microneedle patch surface spraying scheme in the present application can spray and solidify the substances that are unstable in contact in a very short time on the surface of the microneedle and the patch base, thereby forming a formula form that flexibly matches the central layer and the outer layer of the soluble microneedle needle body, and realizing the improvement in function.

Description

TECHNICAL FIELD

[0001] The present application belongs to the technical field of skin care products, and particularly relates to a soluble microneedle patch and a preparation method thereof. BACKGROUND

[0002] Traditional skin care products are often designed as emulsion state for easy application. In the processing process, the oil phase raw materials and the water phase raw materials are fully dissolved and mixed, and a surfactant is added to form a water-oil mixed emulsion structure. Special attention should be paid to the stability of the complex of various raw materials. Improper collocation may cause the inactivation of active ingredients or cause the system to be unstable due to emulsion breaking. The liquid environment and the complex system are prone to produce redox systems, which also bring great challenges to the full play of some precious raw materials. SUMMARY

[0003] Therefore, the present application aims to solve the technical problem and provides a soluble microneedle patch and a preparation method thereof. The present application provides a soluble microneedle, which utilizes an outer active material layer to protect the active ingredients in the center layer of the microneedle to play a stable role, and is flexibly collocated with the outer layer (i.e. the spraying layer). The active ingredients can directly act on the epidermal basal layer through the stratum corneum of the skin, realizing stable and efficient absorption of the active ingredients.

[0004] The present application provides a soluble microneedle patch, which comprises a needle body and a base, wherein the needle body comprises a center layer and an outer layer covering the center layer.

[0005] The center layer comprises a shaped polymer and GHK-Cu.

[0006] The outer layer is an active material layer, and the active material is selected from active materials that are prone to react with GHK-Cu in a liquid environment.

[0007] Preferably, the active material comprises Sophora flavescens root extract, fullerene, grape seed extract, witch hazel extract, calendula extract, nicotinamide, and preferably Sophora flavescens root extract.

[0008] Preferably, in the center layer, the shaped polymer is selected from polymers with good water solubility but poor alcohol solubility, and preferably one or more of hyaluronic acid, chitosan, starch and polycarboxymethyl cellulose.

[0009] Preferably, in the center layer, the mass ratio of the shaped polymer to blue copper peptide is 3-100:1.

[0010] Preferably, the mass ratio of GHK-Cu to the active material of the outer layer is 350-1:1.

[0011] Preferably, the needle body is a frustum, the diameter of the bottom end of the needle body is 100-400 μm, and the height of the needle body is 10-550 μm.

[0012] Preferably, the needle body top end diameter is less than 80 μm, and the needle body is arranged in an array on the base, with an array density of 1-400 needles per square centimeter.

[0013] The application also provides a preparation method of the microneedle patch, comprising the following steps:

[0014] A) mixing the molding polymer, the blue copper peptide and water to obtain a gel solution;

[0015] B) dissolving the active substance in an alcohol solvent to obtain an alcohol solution of the active substance;

[0016] B) dissolving the active substance in an alcohol solvent to obtain an alcohol solution of the active substance;

[0017] B) dissolving the active substance in an alcohol solvent to obtain an alcohol solution of the active substance;

[0018] The application also provides application of the microneedle patch in skin care products with oil control, convergence and repair anti-inflammatory effects.

[0019] Preferably, the microneedle patch has the effects of inhibiting skin inflammation and long-term anti-aging.

[0020] Compared with the prior art, the application provides a soluble microneedle patch, comprising a needle body and a base, wherein the needle body is composed of a center layer and an outer layer coated on the center layer; the center layer is composed of a molding polymer and a blue copper peptide; and the outer layer is an active substance layer, and the active substance is selected from active substances that are prone to react with the blue copper peptide in a liquid environment. The needle body of the soluble microneedle patch of the application can directly act on the epidermal basal layer through the stratum corneum of the skin, accelerating transdermal absorption of effective components. Moreover, the center layer of the microneedle and the active components of the outer layer can synergistically enhance the absorption and utilization effect of multiple components. In addition, unlike the liquid environment of traditional emulsions, the microneedle is in a solid form, which can minimize the reactivity of active components. The optimized surface spraying scheme of the soluble microneedle patch in the application can spray and solidify substances that are unstable in contact in a very short time on the surface of the microneedle and the patch base, thereby forming a formula form that flexibly matches the center layer and the outer layer of the soluble microneedle needle body, and realizing improvement in function. BRIEF DESCRIPTION OF DRAWINGS

[0021] Figure 1 Structure diagram of a blue copper peptide active component microneedle patch prepared for application;

[0022] Figure 2 Microscope diagram of a blue copper peptide active component microneedle patch prepared for application;

[0023] Figure 3 Structure diagram of the microneedle patch provided by the present application, which is coated with the (GHK-Cu active ingredient) center layer and the (Sophora flavescens root extract) outer layer;

[0024] Figure 4 Structure diagram of the hyaluronic acid microneedle;

[0025] Figure 5 Microscope diagram of the hyaluronic acid microneedle;

[0026] Figure 6 Axial force test results of the microneedle;

[0027] Figure 7 Scanning electron microscope picture of the regular microneedle patch coated with Sophora flavescens root extract;

[0028] Figure 8 Scanning electron microscope picture of the deformed microneedle patch coated with Sophora flavescens root extract. DETAILED DESCRIPTION

[0029] The present application provides a soluble microneedle patch, which comprises a needle body and a base, wherein the needle body is composed of a center layer and an outer layer coated on the center layer.

[0030] The center layer is composed of a shaped polymer and GHK-Cu.

[0031] The outer layer is an active substance layer, and the active substance is selected from active substances that are prone to react with GHK-Cu in a liquid environment.

[0032] The microneedle patch provided by the present application comprises a needle body, wherein the needle body comprises a center layer composed of a shaped polymer and GHK-Cu.

[0033] In the present application, the shaped polymer is selected from polymers that are well soluble in water but less soluble in alcohol, preferably one or more of hyaluronic acid, chitosan, starch, and polycarboxymethyl cellulose, and further preferably hyaluronic acid with a molecular weight of 300,000-1,500,000.

[0034] In the center layer, the mass ratio of the shaped polymer to GHK-Cu is 3-100:1, preferably 3:1, 6:1, 10:1, 20:1, 30:1, 40:1, 50:1, 60:1, 70:1, 80:1, 90:1, 100:1, or any value between 3-100:1, and further preferably any value between 20-80:1.

[0035] In the present application, the microneedle patch further comprises an outer layer covering the central layer. The outer layer is an active substance layer, and the active substance is selected from active substances that are prone to react with GHK-Cu in a liquid environment. The GHK-Cu is a glycine-histidine-lysine-copper complex that can induce fibroblasts to produce collagen, promote collagen production, stimulate glucose polyamine synthesis, help keratinocyte production, and has strong and effective anti-free radical function by blocking the formation of active oxygen, and has excellent ability in skin anti-aging. However, GHK-Cu is a water-soluble component, and in an aqueous environment, the complex structure of amino acids and copper ions is easily destroyed by some common reducing, acidic or strong ionic skin care ingredients, so there are many taboos in use.

[0036] In the present application, the active substance is selected from one or more of sophora root extract, fullerene, grape seed extract, witch hazel extract, calendula extract, and nicotinamide, preferably sophora root extract.

[0037] In the present application, the design of the central layer and the outer layer can isolate the two reactive substances, avoid dissolving together and reacting in the same layer structure, and reduce the efficacy.

[0038] The present application separates the active substance layer and the central layer containing GHK-Cu, which not only ensures that the structure of GHK-Cu is not destroyed, but also realizes the gradual release of active ingredients in stages, so that the active ingredients in the central layer and the outer layer of the microneedle can synergistically enhance the synergistic effect of the soluble microneedle body and the multiple components in the skin basal layer.

[0039] The mass ratio of the GHK-Cu to the active substance of the outer layer is 350-1:1, preferably 350:1, 300:1, 250:1, 200:1, 150:1, 100:1, 50:1, 25:1, 10:1, 5:1, 2.5:1, 1:1, or any value between 350-1:1, and further preferably any value between 100-2.5:1.

[0040] In the present application, the needle body is frustum-shaped, the needle body bottom end diameter is 100-400 μm, preferably 100, 200, 300, 400, or any value between 100-400 μm; the needle body height is 10-550 μm, preferably 10, 50, 80, 100, 150, 200, 250, 300, 350, 400, 450, 500, 550, or any value between 10-550 μm; the needle body top end diameter is less than 80 μm, which is arranged on the base in an array form by the needle body, the array density is 1-400 needles per square centimeter, preferably 1, 50, 100, 150, 200, 250, 300, 350, 400, or any value between 1-400 needles per square centimeter.

[0041] The present application also provides a preparation method of the above-mentioned microneedle patch, comprising the following steps:

[0042] A) mixing the molding polymer, GHK-Cu and water to obtain a gel solution;

[0043] adding the gel solution to the mold, drying and demolding to obtain the microneedle patch with the center layer;

[0044] B) dissolving the active substance in an alcohol solvent to obtain an alcohol solution of the active substance;

[0045] solidifying the alcohol solution of the active substance on the surface of the microneedle patch with the center layer of active substance by using the ultrasonic spray atomization technology, and obtaining the microneedle patch with the composite outer layer and the center layer after spray drying.

[0046] The present application first mixes the molding polymer, GHK-Cu and water to obtain a gel solution.

[0047] Specifically, the present application first dissolves GHK-Cu in water, then adds the molding polymer to dissolve to a uniform and clear state to obtain a gel solution for preparing the needle body center layer.

[0048] Then, the gel solution is added to the mold, ensuring that the gel solution completely covers the mold cavity, and then transferred to a vacuum oven, vacuumed to remove bubbles, and then dried and demolded to obtain the microneedle patch with the center layer. See Figure 1 , Figure 1 The structure diagram of the microneedle patch with the center layer of active substance.

[0049] In the present application, the base can be a base containing GHK-Cu or a base not containing GHK-Cu.

[0050] Then, the active substance of the outer layer is mixed with an alcohol solvent to obtain an alcohol solution thereof. The alcohol solvent is selected from volatile alcohol solvents such as methanol and ethanol, and is preferably ethanol. The concentration of the solvent is 0.5% to 10%, and is preferably saturated with respect to the ethanol solution of the Sophora flavescens root extract to reduce the number of spraying times.

[0051] A Siansonic ultrasonic precision spraying machine is used, which is configured with a full-digital ultrasonic controller and a precision ultrasonic nozzle. After the alcohol solution is transferred to the syringe, the syringe pushes the solution to the ultrasonic device at a certain rate, and the solution is determined to drop in the form of small droplets at the ultrasonic nozzle. The ultrasonic device is turned on, and the droplets are atomized. The injection rate of the device and the ultrasonic power are adjusted to atomize the solution uniformly, and the dissolved substances are dried during the atomization process.

[0052] The patch after spraying can be completely dried by standing in place.

[0053] The soluble microneedle patch prepared above is placed on the sample table of the spraying device, the number of spraying back and forth is set, the distance between the nozzle and the sample is set to 8 cm, the ultrasonic atomization column can completely cover the surface of the sprayed patch, and the dissolved substances are coated on the patch in a nearly dry state. After standing, the solvent is completely volatilized, the product is dried, and the microneedle patch is obtained. See Figure 2 , Figure 2 The structure of the microneedle patch provided by the present application is shown in the schematic diagram.

[0054] In the present application, the forming polymer has good water solubility and poor alcohol solubility. The outer layer is preferably an alcohol-soluble raw material, which can further avoid dissolution and reaction of the two. At the same time, the forming polymer has good water solubility and poor alcohol solubility, which is also the key to ensure the stability of the patch structure. If the center layer material is an alcohol-soluble polymer, a small amount of un-volatilized solvent will swell it, causing the needle tip to deform or the patch base to deform, thereby the patch shape retention effect is not good, affecting the subsequent use.

[0055] In some specific embodiments of the present application, the spraying solvent is ethanol, and the mixture is an ethanol solution of Sophora flavescens root extract. In the spraying process, the spraying volume per unit time of the solution, the power of ultrasonic atomization (the power of the spraying device) can be set to control the volatilization degree of the solvent ethanol. The Sophora flavescens root extract coated on the microneedle surface should be in a dry state, or it can be volatilized in a short time to form a coating layer on the surface of the microneedle. The dry state is more helpful to the shape stability of the microneedle; the dry state of the substance is helpful to avoid the reaction of the center layer and the outer layer.

[0056] The atomization rate is related to the flow rate setting, the diameter of the atomization port, and the distance between the atomization port and the sample.

[0057] The application also provides the application in skin care products with oil control, anti-inflammatory and anti-aging effects.

[0058] The application can manufacture channels on the cuticle layer of the skin by using the soluble microneedle technology, and directly deliver the solid active substances to the epidermis and below, thereby greatly improving the absorption efficiency of the active substances on the skin relative to the smearing emulsion cosmetics. Meanwhile, the soluble microneedle patch processing is to use soluble polymers as carriers, mix various active ingredients in a liquid environment first, and then solidify and form. Thus, the soluble microneedle patch processing has great advantages in the stable storage of the active substances, so that the trace ingredients can also play a high-efficiency function. In addition, the soluble microneedle technology can also realize the gradual release of the ingredients on the skin surface, thereby providing more possibilities for the compounding of raw materials.

[0059] The application utilizes the soluble microneedle body to directly act on the epidermal basal layer through the cuticle layer of the skin, thereby accelerating the absorption of the active ingredients by the skin. Moreover, the active ingredients in the central layer and the outer layer of the microneedle can synergistically enhance the synergistic effect of the multiple ingredients in the skin basal layer based on the soluble microneedle body. In addition, in the preparation method provided by the application, the solidification and forming characteristics of the soluble microneedle can protect the stability of the loaded active ingredients, and the surface spraying technology of the soluble microneedle can protect the stability of the coating ingredients from reacting with the pre-loaded substances.

[0060] In order to further understand the application, the soluble microneedle patch and the preparation method thereof provided by the application are described below in combination with examples, and the protection scope of the application is not limited by the following examples.

[0061] Example 1 GHK-Cu soluble microneedle

[0062] S0 configuration microneedle patch solution: 0.5 parts of GHK-Cu is dissolved in 96.5 parts of water, and after being dissolved uniformly, 3 parts of compounded hyaluronic acid is added and dissolved to a uniform and clear state to obtain a gel solution for preparing the needle body. In this formula, the compounded hyaluronic acid is 2% hyaluronic acid with a molecular weight of 3w-5w and 1% hyaluronic acid with a molecular weight of less than 1w.

[0063] S1 a small amount of the gel solution configured in S0 is added to the mold, so as to ensure that the gel solution completely covers the mold cavity, and then the gel solution is transferred to a vacuum oven, vacuumized for 6 minutes to remove bubbles, and dried at room temperature for 12 hours. After demolding, an integrally formed GHK-Cu soluble microneedle body and base are obtained. See Figure 1 . The needle body is conical, the bottom diameter is 150 μm, and the needle body height is 230 μm. See Figure 2 .

[0064] Example 2-8 GHK-Cu soluble microneedle

[0065] Based on Example 1, for the addition of hyaluronic acid in S0, the optional molecular weight of sodium hyaluronate also includes less than 1w, 3w-5w, 20w-40w, 80-100w and 130w-150w and cross-linked sodium hyaluronate with uncertain molecular weight, the weight ratio range can be 1%-10%, preferably the average molecular weight of the used sodium hyaluronate is 2w-10w.

[0066] Based on Example 1, for the use of blue copper peptide in S0, the weight ratio range of active GHK-Cu in the soluble microneedle body can be 0.01-5%, preferably 0.1%-1%.

[0067] Taking the typical proportion of sodium hyaluronate and GHK-Cu as an example, the mass of the prepared soluble microneedle patch and the mass of the active GHK-Cu are shown in the following table. In Table 1, the mass of the soluble microneedle refers to the total mass of the weighed microneedle and base; the mass of GHK-Cu is calculated according to the proportion in the stock solution in the solidified ingredient.

[0068] Table 1 Mass of soluble microneedle patch with different formula proportions and corresponding mass of GHK-Cu active substance

[0069]

[0070] The above-mentioned Examples 2-8 prepare the pre-spraying patch of the soluble microneedle patch, and the microneedle patch product with a composite coating and a central layer is obtained after the following S2 and S3 steps.

[0071] S2: 2g of Sophora flavescens extract is dissolved in 20mL of ethanol, after complete dissolution, it is transferred to the spraying device injector, and air is exhausted after standing for 10min. The device injection speed is set to 0.1mL / min, and the air flow speed is adjusted to uniformly atomize the solution.

[0072] S3: The soluble microneedle patch prepared in S1 is placed on the sample table of the spraying equipment, and the spraying stroke is set to 10 times back and forth, and is uniformly sprayed on the surface of the patch. The patch is taken out after standing for 3min, and is used after drying.

[0073] Example 9 GHK-Cu active soluble microneedle + Sophora flavescens extract compound coating

[0074] S0: Prepare a soluble microneedle solution: dissolve 0.5 parts of GHK-Cu in 96.5 parts of water, after uniform dissolution, add 3 parts of the compound hyaluronic acid prepared in Example 5 to it, and dissolve to a uniform and clear state to obtain a gel solution for preparing the needle body.

[0075] S1 drop a small amount of gel solution prepared by S0 on the mold, make sure the gel solution completely covers the mold cavity, transfer to the vacuum oven, vacuum for 6 min to remove bubbles, dry at room temperature for 12 h. After demolding, the one-piece GHK-Cu soluble microneedle body and base are obtained. See Figure 1 . Wherein the needle body is conical, the bottom end diameter is 150 μm, and the needle body height is 230 μm. See Figure 2 .

[0076] S2 dissolve 2 g of Sophora flavescens extract in 20 mL of ethanol, and after complete dissolution, transfer to a spray device injector, and stand for 10 min to exhaust air. Set the device injection speed to 0.1 mL / min, and adjust the airflow speed to uniformly atomize the solution.

[0077] S3 place the soluble microneedle patch prepared by S1 on the sample table of the spraying equipment, set the spraying stroke to 10 times back and forth, and uniformly spray on the surface of the patch. After the patch is dried, it is taken out. See Figure 3 .

[0078] Comparative Example 1 Pure matrix soluble microneedle + Sophora flavescens extract compound coating

[0079] S0 Prepare a soluble microneedle solution: prepare a 3% concentration of hyaluronic acid solution, stir and dissolve until uniform and clear, and obtain a gel solution for preparing the needle body.

[0080] S1 drop a small amount of solution on the mold, make sure the mixed solution completely covers the mold cavity, transfer to the vacuum oven, vacuum for 6 min to remove bubbles, dry at room temperature for 12 h. After demolding, the soluble microneedle containing only the hyaluronic acid matrix is obtained. See Figure 4 , Figure 5 .

[0081] S2 dissolve 2 g of Sophora flavescens extract in 20 mL of ethanol, and after complete dissolution, transfer to a spray device injector, and stand for 10 min to exhaust air. Set the device injection speed to 0.1 mL / min, and adjust the airflow speed to uniformly atomize the solution.

[0082] S3 place the soluble microneedle patch prepared by S1 on the sample table of the spraying equipment, set the spraying stroke to 10 times back and forth, and uniformly spray on the surface of the patch. After the patch is dried, it is taken out. See

[0083] Comparative Example 2 GHK-Cu + Sophora flavescens extract mixed soluble microneedle

[0084] S0 Configuration of soluble microneedle solution: 0.5 parts of GHK-Cu was dissolved in water to get a blue clear solution, then 0.1 parts of Sophora root extract was added, the color of the solution changed to light gray blue. Then 3 parts of compounded hyaluronic acid was added, stirred to dissolve until uniform and clear, to get the gel solution for preparing the needle body.

[0085] S1 A small amount of gel solution prepared in S0 was added to the mold to ensure that the gel solution completely covers the mold cavity, and then transferred to a vacuum oven, vacuumed for 6 min to remove bubbles, and dried at room temperature for 12 h. After demolding, the soluble microneedle mixed with GHK-Cu and Sophora root extract was obtained.

[0086] Example 10

[0087] The Instron 34TM-5 tensile machine mold was used to place the soluble microneedle patch on the stainless steel cylindrical probe in a room environment with 60 ± 15% R.H. and a temperature of 30°C. The probe was moved vertically downward at a speed of 0.5 mm / min, and the contact with the highest point of the soluble microneedle patch triggered the test. Then the axial pressure was applied vertically to the soluble microneedle patch. The axial strength of the microneedle was recorded by the change of pressure and displacement curve. Three patches of each type of sample were tested three times to obtain the average data. See Figure 6 Compared with Example 1, 10 times of active ingredient spraying on the soluble microneedle was added in Example 9, and the results showed that the axial force of the microneedle did not change significantly. Compared with Example 9, the central layer of the soluble microneedle did not contain the active ingredient GHK-Cu in Comparative Example 1, and the axial force of the microneedle also did not change significantly. In Comparative Example 2, the soluble microneedle mixed with GHK-Cu and Sophora root extract maintained the same level as the Sophora root coated soluble microneedle and the GHK-Cu soluble microneedle. The type and form of active ingredient had no effect on the strength of the soluble microneedle.

[0088] Example 11

[0089] After spraying, the weight gain of the patch was considered as the mass of the Sophora root extract coated. This data was directly related to the concentration of the coating solution and the number of spraying times. We counted the data of spraying Sophora root extract solution for 1 time, 3 times, 10 times, 20 times, 40 times, 60 times, and 100 times.

[0090] Table 2. Microneedle spraying times and changes

[0091]

[0092] As can be seen from the table, the longer the number of repeated spraying, the higher the risk of deformation of the microneedle, and the corresponding increase in the cost of spraying time. After spraying for 10 times, see Figure 7 , and after spraying for 100 times, seeFigure 8 As can be observed from the figures, the needle shape of microneedles, the bending of the needle tip, and the deformation of the needle body, which is no longer a regular cone shape. This is due to the fact that the swelling deformation strength of the needle tip is affected by the fact that a large amount of solvent volatilizes too slowly during the repeated spraying process of ultrasonic atomization, which in turn affects the transdermal effect of the microneedles and affects the use of the soluble microneedle patch.

[0093] The mass of active GHK-Cu in Example 1 was calculated according to the mass of the patch and the addition ratio. The ratio of Sophora root extract to GHK-Cu was determined by the experimental conditions. The ratio of each formula and condition is shown in Table 3 below. For example, the addition amount of GHK-Cu is 0.1%, which corresponds to Example 2 in Table 1, and the spraying mass of Sophora root extract is 0.04, 0.15, 0.30, 0.45, and 0.6 mg for 3, 10, 20, 40, and 60 times of spraying, respectively, and the mass ratio of blue copper peptide to Sophora root is 74:1, 20:1, 10:1, 7:1, and 2.5:1, respectively.

[0094] Table 3. Mass and ratio of GHK-Cu and Sophora root extract

[0095]

[0096]

[0097] According to the above table, the mass ratio of GHK-Cu to Sophora root extract varies in the range of 350:1 to 1:1 under different formulas and spraying settings. In this method, Sophora root extract is quickly solidified by spraying, and the probability of mutual reaction between GHK-Cu and Sophora root extract is minimized, and the efficacy is fully exerted. Preferably, the number of microneedle sprays is 10-20 times, and the solid ratio of GHK-Cu is 0.05-0.5%, and under this condition, the mass ratio of GHK-Cu to Sophora root extract is in the range of 100:2.5:1.

[0098] Example 12

[0099] Fifteen subjects with oily and acne skin, aged between 18 and 45 years, were selected for clinical evaluation. The indoor environment temperature was 20±1℃, and the humidity was 50±10% R.H. The Sebumeter SM 815 was used to test the oil content of the subjects using the product. Specifically, for each batch of product of the examples or the comparative examples, each subject could not use any cosmetic or external medicine on the test site for 2-3 days before the test, and could not touch any water and oil substances for 1 h-3 h; the middle position of the forehead was selected as the test area, and if there were acne, it was not necessary to avoid it, and the test was performed in the afternoon from 13:00 to 16:00 when the sebum secretion was more vigorous; clean tissue paper was used to clean and wipe the test site before the test, and the skin oil content was tested after 30 min; then a one-time soluble microneedle patch was used, and each use lasted for 2 h, and after use, clean tissue paper was used for cleaning, and the oil content of the area was tested after 30 min. As can be seen from Table 4, the average decrease in oil content of the subjects after using the product of Example 9 was 56.3%, the average decrease in oil content of the subjects after using the product of Example 1 was 19.1%, the average decrease in oil content of the subjects after using the product of Comparative Example 1 was 15.2%, and the average decrease in oil content of the subjects after using the product of Comparative Example 2 was 12.7%. For people with oily and acne skin, the decrease in oil content helps to maintain the unobstructed condition of the oil in the skin pores, thereby reducing the outbreak of acne or the formation of large-area acne.

[0100] After continuous use for 1 week, a questionnaire survey was conducted on the subjects' feelings about the oil control effect of the soluble microneedle patch after use. As can be seen from Table 3, the number of people satisfied with the use of the product of Example 9 was 11, the number of people satisfied with the use of the product of Example 1 was 7, the number of people satisfied with the use of the product of Comparative Example 1 was 5, and the number of people satisfied with the use of the product of Comparative Example 2 was 4.

[0101] Table 4 Effect of using different microneedle patches and satisfaction survey

[0102]

[0103] GHK-Cu is a complex of glycine-histidine-lysine-copper, which has anti-inflammatory repair and anti-aging effects. Specifically, it can induce fibroblasts to produce collagen, stimulate glucose polyamine synthesis, and help restore the barrier function of keratinocytes; and it can block the formation of active oxygen and has good anti-free radical function. However, GHK-Cu is a water-soluble ingredient, and in an aqueous environment, the amino acid and copper ion complex structure is easily destroyed by some common reducing, acidic or strong ionic skin care ingredients, so there are many taboos for use. Sophora root extract is an effective skin astringent containing a large amount of polyphenol compounds, and its natural astringent properties can help inhibit the secretion of sebum from sebaceous glands and help oily and acne-prone skin control the growth of propionibacterium acnes (which feeds on oil). However, due to its strong coordination and reactivity, mixing with GHK-Cu can cause significant instability, resulting in loss of ingredient efficacy. In the process of Comparative Example 2, it can be clearly seen that GHK-Cu and Sophora root extract have changed in color due to the reaction.

[0104] In Example 9, by using a coating to match the active ingredients, the astringent and oil-controlling Sophora root extract in the coating layer and the repair and anti-inflammatory GHK-Cu in the center layer are released step by step in the skin basal layer, and the efficacy is not compromised. Moreover, it has potential synergistic improvement ability for acne and inflammatory aging induced by oily skin.

[0105] The above only describes the preferred embodiments of the present application, and it should be noted that for those skilled in the art, without departing from the principles of the present application, several improvements and refinements can be made, and these improvements and refinements should also be considered within the scope of protection of the present application.

Claims

1. A dissolvable microneedle patch, characterized by, The needle body comprises a center layer and an outer layer covering the center layer; The center layer comprises a molding polymer and GHK-Cu, and the molding polymer is selected from polymers with good water solubility but poor alcohol solubility; The outer layer is an active substance layer, and the active substance is selected from active substances that are easy to react with GHK-Cu in a liquid environment, and the active substance comprises one or more of Sophora root extract, fullerene, grape seed extract, witch hazel extract, marigold extract, and nicotinamide.

2. The microneedle patch of claim 1, wherein, The active substance is Sophora root extract.

3. The microneedle patch of claim 1, wherein, In the center layer, the molding polymer is one or more of hyaluronic acid, chitosan, starch, and polycarboxymethyl cellulose.

4. The microneedle patch of claim 1, wherein, In the center layer, the mass ratio of the molding polymer to GHK-Cu is 3-100:

1.

5. The microneedle patch of claim 1, wherein, The mass ratio of GHK-Cu to the active substance of the outer layer is 350-1:

1.

6. The microneedle patch of claim 1, wherein, The needle body is a frustum, the bottom diameter of the needle body is 100-400 μm, and the height of the needle body is 10-550 μm.

7. The microneedle patch of claim 1, wherein, The top diameter of the needle body is less than 80 μm, the needle body is arranged in an array on the base, and the array density is 1-400 needles per square centimeter.

8. A method of manufacturing the microneedle patch according to any one of claims 1 to 7, characterized by, The method comprises the following steps: A) mixing the molding polymer, GHK-Cu, and water to obtain a gel solution; The gel solution is added dropwise into a mold, dried, and demolded to obtain a microneedle patch with a center layer; B) dissolving the active substance in an alcohol solvent to obtain an alcohol solution of the active substance; The alcohol solution of the active substance is sprayed on the surface of the microneedle patch with the center layer, and dried to obtain a microneedle patch.

9. Use of the microneedle patch according to any one of claims 1-7 in the preparation of skin care products with oil control, astringency, repair, and anti-inflammatory effects.

10. Use according to claim 9, characterized in that, The microneedle patch has the effects of inhibiting skin inflammation and long-term anti-aging.

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