A two-dimensional conductive material, its preparation method and application, and a microneedle patch, its preparation method and application

Abstract

The present invention belongs to the technical field of microneedle patches, and provides a two-dimensional conductive material, a preparation method and application thereof, a microneedle patch, and a preparation method and application thereof. The method comprises the following steps: sequentially stretching and laser engraving a mold to obtain a processed mold; adding a two-dimensional conductive material to the surface of the processed mold, and demolding after curing to obtain an inverse structure microneedle template with a stacked conductive material; dropping a microneedle body material on the surface of the inverse structure microneedle template, and demolding after curing to obtain the microneedle patch. The present invention effectively solves the problem of crack propagation of the two-dimensional conductive material by using the reversible retraction of the silicone rubber material, and prepares an inverse structure microneedle array template with high precision and adjustable specifications at a low cost; the present invention uses a mixed solution of silk fibroin and waterborne polyurethane as the microneedle body material, and the finally obtained microneedle patch has good biocompatibility and mechanical strength and can adapt to human skin.

Description

Technical Field

[0001] The present invention relates to the technical field of microneedle patches, and particularly to a two-dimensional conductive material, a preparation method and application thereof, a microneedle patch, and a preparation method and application thereof. Background Art

[0002] In recent years, microneedle patches composed of micro needles have broad application prospects in the field of piercing the stratum corneum and delivering drugs to the dermis in a minimally invasive manner. Since the length of these micron-sized protrusions is usually only 100 to 1000 microns, they can pierce the stratum corneum, and their interaction with nerve endings in the dermis is limited. Compared with traditional needles, they cause less pain, tissue damage and skin inflammation to patients, and the usage method is simple, and users do not need professional training. In order to mass-produce polymer microneedles with ideal functions and meet demand characteristics, the commonly used, reusable and high-precision method today is the template replication method. That is, a master structure with the same structure as the microneedle is obtained through microfabrication and other means, and then a negative mold is obtained by casting a curable material on the master structure and peeling it off. Finally, a prepolymer or other microneedle materials are added to fill the negative mold, and the microneedle patch is obtained after separation. Therefore, the processing of the master structure is crucial in the production process of the microneedle patch. The current main methods are etching, laser ablation of metals and 3D printing, etc. However, these methods inevitably have the problems of long time consumption and high cost. Therefore, it is of great significance to provide a low-cost, simple and efficient preparation process for microneedle patches. Summary of the Invention

[0003] The purpose of the present invention is to overcome the problems existing in the prior art, and provide a two-dimensional conductive material, a preparation method and application thereof, a microneedle patch, and a preparation method and application thereof.

[0004] In order to achieve the above-mentioned invention purpose, the present invention provides the following technical solutions:

[0005] The present invention provides a preparation method of a two-dimensional conductive material, comprising the following steps:

[0006] (1) Mix 2-methylimidazole, zinc acetate and water to obtain a MOF product;

[0007] (2) Mix lithium fluoride, hydrochloric acid solution and titanium aluminum carbide to obtain a Ti 3 AlC 2 MXene supernatant;

[0008] (3) Mix the MOF solution and the Ti 3 AlC 2 MXene supernatant to obtain the two-dimensional conductive material.

[0009] Preferably, the mass-volume ratio of 2-methylimidazole, zinc acetate and water in step (1) is 950-1000 mg: 35-40 mg: 4.5-5.5 mL.

[0010] Preferably, the concentration of the hydrochloric acid solution in step (2) is 8-10 mol / L; the mass-volume ratio of lithium fluoride, hydrochloric acid solution and titanium aluminum carbide is 4.5-5 g: 55-65 mL: 2.5-3.5 g;

[0011] The MOF solution in step (3) contains MOF product and water, and the mass-volume ratio of the MOF product to water is 4-6 mg: 180-220 mL; the mass concentration of the Ti 3 AlC 2 MXene supernatant is 1.5-2.5 mg / mL;

[0012] The volume ratio of the MOF solution and Ti 3 AlC 2 MXene supernatant in step (3) is 1:6-8.

[0013] The present invention also provides the two-dimensional conductive material obtained by the preparation method.

[0014] The present invention also provides the application of the two-dimensional conductive material in the preparation of microneedle patches.

[0015] The present invention also provides a preparation method of a microneedle patch, comprising the following steps:

[0016] (1) Stretching and laser engraving the mold sequentially to obtain a processed mold;

[0017] (2) Adding a two-dimensional conductive material to the surface of the processed mold, and demolding after curing to obtain an inverse structure microneedle template with a stacked conductive material;

[0018] (3) Dropping a microneedle body material on the surface of the inverse structure microneedle template, and demolding after curing to obtain the microneedle patch.

[0019] Preferably, the material of the mold in step (1) is methyl vinyl silicone rubber, nitrile silicone rubber or fluorosilicone rubber;

[0020] The stretching is performed in equal proportion along the X-axis and Y-axis, and the stretching ratio is 85-100%;

[0021] The laser intensity of the laser engraving is 8-12%.

[0022] Preferably, the dosage of the two-dimensional conductive material in step (2) is 0.2-0.4 mL / cm 2, the curing temperature in step (2) is 60-70°C and the time is 1-3 h;

[0023] The volume ratio of the microneedle body material in step (3) to the two-dimensional conductive material in step (2) is 1.5-2.5:2.5-3.5; the microneedle body material in step (3) comprises silk fibroin and aqueous polyurethane, and the volume ratio of the silk fibroin to the aqueous polyurethane is 2.5-3.5:6.5-7.5;

[0024] The curing temperature in step (3) is 60-70°C and the time is 1-3 h.

[0025] The present invention also provides a microneedle patch obtained by the preparation method.

[0026] The present invention also provides the application of the microneedle patch in motion sensing monitoring.

[0027] The beneficial effects of the present invention are:

[0028] (1) The present invention provides a preparation method of a two-dimensional conductive material, which method comprises the following steps: mixing 2-methylimidazole, zinc acetate and water to obtain a MOF product; mixing lithium fluoride, hydrochloric acid solution and titanium aluminum carbide to obtain a Ti 3 AlC 2 MXene supernatant; mixing the MOF solution and the Ti 3 AlC 2 MXene supernatant to obtain a two-dimensional conductive material. The preparation process of the present invention is simple, and the obtained two-dimensional conductive material has excellent electrical conductivity.

[0029] (2) The present invention provides a preparation method of a microneedle patch, which method comprises the following steps: sequentially stretching and laser engraving a mold to obtain a processed mold; adding a two-dimensional conductive material on the surface of the processed mold, and demolding after curing to obtain an inverse structure microneedle template with a stacked conductive material; dropping a microneedle body material on the surface of the inverse structure microneedle template, and demolding after curing to obtain a microneedle patch. The preparation method is simple, the material price is low, and the obtained microneedle patch has good mechanical strength, good conductivity and high precision, and can be applied to fields such as motion sensing.

[0030] (3) The present invention provides a new technology for the preparation of a conductive microneedle patch, which is fast, simple and low-cost. This technology utilizes the reversible retraction of a silicone rubber material to effectively solve the problem of crack propagation of the two-dimensional conductive material, and prepares an inverse structure microneedle array template with high precision and adjustable specifications at a low cost; the present invention uses a mixed solution of silk fibroin and aqueous polyurethane as the microneedle body material, and the finally obtained microneedle patch has good biocompatibility and mechanical strength and can adapt to human skin. Description of the Drawings

[0031] Figure 1 Schematic diagram of the process for preparing the microneedle patch in Example 1;

[0032] Figure 2 Characterization diagrams of the microneedle patch obtained in Example 1 with a stretching ratio of 0 before and after the stretching test;

[0033] Figure 3 Characterization diagrams of the microneedle patch obtained in Example 1 with a stretching ratio of 80% before and after the stretching test;

[0034] Figure 4 Characterization diagrams of the microneedle patch obtained in Example 1 with a stretching ratio of 100% before and after the stretching test;

[0035] Figure 5 Schematic diagram of the microneedle patch in Example 2 for motion sensing monitoring (Time - time). Detailed implementation manners

[0036] The present invention provides a method for preparing a two - dimensional conductive material, comprising the following steps:

[0037] (1) Mix 2 - methylimidazole, zinc acetate and water to obtain a MOF product;

[0038] (2) Mix lithium fluoride, hydrochloric acid solution and titanium aluminum carbide to obtain a Ti 3 AlC 2 MXene supernatant;

[0039] (3) Mix the MOF solution and the Ti 3 AlC 2 MXene supernatant to obtain the described two - dimensional conductive material.

[0040] In the present invention, the mass - volume ratio of the 2 - methylimidazole, zinc acetate and water in step (1) is preferably 950 - 1000 mg: 35 - 40 mg: 4.5 - 5.5 mL, more preferably 960 - 990 mg: 36 - 39 mg: 4.7 - 5.3 mL, and still more preferably 970 - 980 mg: 37 - 38 mg: 4.9 - 5.1 mL.

[0041] In the present invention, in step (1), the mixing is carried out by first adding 2-methylimidazole to water, and then adding zinc acetate, followed by stirring and centrifugation in sequence; the temperature of the stirring is preferably 20-30 °C, more preferably 22-28 °C, and even more preferably 24-26 °C; the rotation speed is preferably 200-600 r / min, more preferably 300-500 r / min, and even more preferably 350-450 r / min; the time is preferably 5-15 min, more preferably 7-13 min, and even more preferably 9-11 min; the temperature of the centrifugation is preferably 20-30 °C, more preferably 22-28 °C, and even more preferably 24-26 °C; the rotation speed is preferably 17000-19000 r / min, more preferably 17500-18500 r / min, and even more preferably 17700-18300 r / min; the time is preferably 5-15 min, more preferably 7-13 min, and even more preferably 9-11 min.

[0042] In the present invention, after the centrifugation in step (1) is completed, the obtained precipitate is collected and washed with water and dried in sequence to obtain the MOF product; the number of times of washing with water is preferably ≥2 times, more preferably ≥3 times, and even more preferably ≥4 times; the drying temperature is preferably 50-70 °C, more preferably 55-65 °C, and even more preferably 57-63 °C; the drying time is preferably 3-5 h, more preferably 3.5-4.5 h, and even more preferably 3.7-4.3 h.

[0043] In the present invention, in step (2), the concentration of the hydrochloric acid solution is preferably 8-10 mol / L, more preferably 8.5-9.5 mol / L, and even more preferably 8.8-9.3 mol / L; the mass-to-volume ratio of lithium fluoride, the hydrochloric acid solution and titanium aluminum carbide is preferably 4.5-5 g: 55-65 mL: 2.5-3.5 g, more preferably 4.6-4.9 g: 57-63 mL: 2.7-3.3 g, and even more preferably 4.7-4.8 g: 59-61 mL: 2.9-3.1 g.

[0044] In the present invention, in step (2), the mixing is carried out by first dissolving lithium fluoride in a hydrochloric acid solution to obtain a lithium fluoride solution, and then slowly adding titanium aluminum carbide to the lithium fluoride solution, followed by stirring and centrifugation in sequence; the temperature of the stirring is preferably 30 - 40 °C, more preferably 32 - 38 °C, and still more preferably 33 - 37 °C; the rotation speed is preferably 500 - 800 r / min, more preferably 600 - 700 r / min, and still more preferably 630 - 670 r / min; the time is preferably 44 - 52 h, more preferably 46 - 50 h, and still more preferably 47 - 49 h; the temperature of the centrifugation is preferably 20 - 30 °C, more preferably 22 - 28 °C, and still more preferably 24 - 26 °C; the rotation speed is preferably 3000 - 4000 r / min, more preferably 3200 - 3800 r / min, and still more preferably 3300 - 3700 r / min; the time is preferably 3 - 7 min, more preferably 4 - 6 min, and still more preferably 4.5 - 5.5 min.

[0045] In the present invention, after the centrifugation in step (2) is completed, the obtained precipitate is washed with water, and then the steps of centrifugation and washing are repeated. Centrifugation is stopped after reaching the target pH value to obtain a Ti 3 AlC 2 MXene suspension, wherein the pH value is preferably 6.5 - 7, more preferably 6.6 - 6.9, and still more preferably 6.7 - 6.8.

[0046] In the present invention, the obtained Ti 3 AlC 2 MXene suspension is subjected to ultrasonic treatment and centrifugation in sequence. After completion, the dark supernatant is collected and diluted with water to obtain a Ti 3 AlC 2 MXene supernatant; the temperature of the ultrasonic treatment is preferably 20 - 30 °C, more preferably 22 - 28 °C, and still more preferably 24 - 26 °C; the frequency is preferably 30 - 50 kHz, more preferably 35 - 45 kHz, and still more preferably 37 - 43 kHz; the time is preferably 55 - 65 min, more preferably 57 - 63 min, and still more preferably 59 - 61 min; the temperature of the centrifugation is preferably 20 - 30 °C, more preferably 22 - 28 °C, and still more preferably 24 - 26 °C; the rotation speed is preferably 3000 - 4000 r / min, more preferably 3200 - 3800 r / min, and still more preferably 3300 - 3700 r / min; the time is preferably 25 - 35 min, more preferably 27 - 33 min, and still more preferably 29 - 31 min; after dilution, the Ti 3 AlC 2The mass concentration of the MXene supernatant is preferably 1.5 - 2.5 mg / mL, more preferably 1.7 - 2.3 mg / mL, and even more preferably 1.9 - 2.1 mg / mL.

[0047] In the present invention, the MOF solution in step (3) contains the MOF product and water. The mass - to - volume ratio of the MOF product to water is preferably 4 - 6 mg: 180 - 220 mL, more preferably 4.5 - 5.5 mg: 185 - 215 mL, and even more preferably 4.7 - 5.3 mg: 190 - 210 mL. The specific preparation process of the MOF solution includes the following steps: ultrasonic - dispersing the MOF product in water to obtain the MOF solution. The temperature of the ultrasonic dispersion is preferably 20 - 30 °C, more preferably 22 - 28 °C, and even more preferably 24 - 26 °C; the frequency is preferably 4 - 6 W, more preferably 4.5 - 5.5 W, and even more preferably 4.7 - 5.3 W; the time is preferably 25 - 35 min, more preferably 27 - 33 min, and even more preferably 29 - 31 min.

[0048] In the present invention, the MOF solution in step (3) and Ti 3 AlC 2 The volume ratio of the MXene supernatant is preferably 1:6 - 8, more preferably 1:6.5 - 7.5, and even more preferably 1:6.8 - 7.3.

[0049] In the present invention, after mixing the MOF solution with Ti 3 AlC 2 MXene supernatant, stirring and centrifugation are carried out in sequence to obtain the two - dimensional conductive material. The temperature of the stirring is preferably 20 - 30 °C, more preferably 22 - 28 °C, and even more preferably 24 - 26 °C; the rotation speed is preferably 200 - 600 r / min, more preferably 300 - 500 r / min, and even more preferably 350 - 450 r / min; the time is preferably 15 - 25 min, more preferably 17 - 23 min, and even more preferably 19 - 21 min; the temperature of the centrifugation is preferably 20 - 30 °C, more preferably 22 - 28 °C, and even more preferably 24 - 26 °C; the rotation speed is preferably 3000 - 4000 r / min, more preferably 3200 - 3800 r / min, and even more preferably 3300 - 3700 r / min; the time is preferably 5 - 15 min, more preferably 7 - 13 min, and even more preferably 9 - 11 min.

[0050] The present invention also provides the two - dimensional conductive material obtained by the above - mentioned preparation method.

[0051] The present invention also provides the application of the two - dimensional conductive material in the preparation of microneedle patches.

[0052] The present invention also provides a method for preparing a microneedle patch, comprising the following steps:

[0053] (1) Stretch and laser engrave a mold sequentially to obtain a processed mold;

[0054] (2) Add a two-dimensional conductive material to the surface of the processed mold, and after curing, demold an inverse structure microneedle template with a stacked conductive material;

[0055] (3) Drop microneedle body material on the surface of the inverse structure microneedle template, and after curing, demold to obtain the microneedle patch.

[0056] In the present invention, before step (1), a desired pattern is designed in advance on a computer. The diameter of the conical bottom of the microneedle structure in the pattern is preferably 0.1 - 3 mm, more preferably 0.2 - 2 mm, and even more preferably 0.3 - 1 mm.

[0057] In the present invention, the material of the mold in step (1) is methyl vinyl silicone rubber, nitrile silicone rubber or fluorosilicone rubber.

[0058] In the present invention, the stretching in step (1) is an equal-proportion stretching along the X-axis and Y-axis. The stretching ratio is preferably 85 - 100%, more preferably 90 - 99%, and even more preferably 95 - 98%. After stretching, fix the template on a solid plate made by 3D printing and perform laser engraving.

[0059] In the present invention, the laser engraving in step (1) is performed using a common commercial laser engraving machine to engrave the pattern designed in advance on the computer on the stretched template. The laser intensity of the laser engraving is preferably 8 - 12%, more preferably 8.5 - 11.5%, and even more preferably 9 - 11%.

[0060] In the present invention, after adding the two-dimensional conductive material in step (2), evacuate the mold in a vacuum drying oven to remove the residual bubbles in the mold, and then perform curing. The dosage of the two-dimensional conductive material is preferably 0.2 - 0.4 mL / cm 2 , more preferably 0.25 - 0.35 mL / cm 2 , even more preferably 0.27 - 0.33 mL / cm 2 ; the evacuation time is preferably 25 - 35 s, more preferably 27 - 33 s, and even more preferably 29 - 31 s; the curing temperature is preferably 60 - 70 °C, more preferably 62 - 68 °C, and even more preferably 63 - 67 °C; the time is preferably 1 - 3 h, more preferably 1.5 - 2.5 h, and even more preferably 1.7 - 2.3 h.

[0061] In the present invention, after the curing in step (2) is completed, the mold is peeled off from the solid state plate, and it shrinks back to its initial size. At the same time, the crack-like shape of the two-dimensional conductive material is converted into a stacked shape, the pattern size on the mold is reduced accordingly, and the diameter of the conical bottom of the microneedle structure is also reduced accordingly, thus obtaining the anti-structured microneedle template described above.

[0062] In the present invention, the volume ratio of the microneedle body material in step (3) to the two-dimensional conductive material in step (2) is preferably 1.5 - 2.5:2.5 - 3.5, more preferably 1.7 - 2.3:2.7 - 3.3, and even more preferably 1.9 - 2.1:2.9 - 3.1; the microneedle body material in step (3) comprises silk fibroin and aqueous polyurethane, and the volume ratio of the silk fibroin to the aqueous polyurethane is preferably 2.5 - 3.5:6.5 - 7.5, more preferably 2.7 - 3.3:6.7 - 7.3, and even more preferably 2.9 - 3.1:6.9 - 7.1; after the dropping is completed, the template is evacuated in a vacuum drying oven, and the operation is repeated once to further remove the residual bubbles in the mold, and then curing is carried out; the time for a single evacuation is preferably 5 - 15 s, more preferably 7 - 13 s, and even more preferably 9 - 11 s.

[0063] In the present invention, the temperature for curing in step (3) is preferably 60 - 70 °C, more preferably 62 - 68 °C, and even more preferably 63 - 67 °C; the time is preferably 1 - 3 h, more preferably 1.5 - 2.5 h, and even more preferably 1.7 - 2.3 h.

[0064] The present invention also provides a microneedle patch obtained by the above preparation method.

[0065] The present invention also provides the application of the microneedle patch in motion sensing monitoring.

[0066] The technical solutions provided by the present invention will be described in detail below with reference to the embodiments, but they should not be construed as limiting the protection scope of the present invention.

[0067] Example 1

[0068] 970 mg of 2-methylimidazole was added to 5 mL of water, and then 38 mg of zinc acetate was added. The mixture was stirred for 10 min at a temperature of 25 °C and a rotation speed of 400 r / min, and then centrifuged for 10 min at a temperature of 25 °C and a rotation speed of 18,000 r / min. The obtained precipitate was collected, washed with water three times, and dried at 60 °C for 4 h to obtain the MOF product; 4.8 g of lithium fluoride was dissolved in 60 mL of a hydrochloric acid solution with a concentration of 9 mol / L to obtain a lithium fluoride solution, and then 3 g of titanium aluminum carbide was slowly added to the lithium fluoride solution. The mixture was stirred for 48 h at a temperature of 35 °C and a rotation speed of 600 r / min, and then centrifuged for 5 min at a temperature of 25 °C and a rotation speed of 3,500 r / min. After centrifugation, the obtained precipitate was washed with water, and then the steps of centrifugation and washing were repeated until the pH value of the solution was 7, and centrifugation was stopped to obtain Ti 3 AlC 2 MXene suspension; the obtained suspension was ultrasonicated for 60 min at a temperature of 25 °C and a frequency of 40 kHz, and then centrifuged for 30 min at a temperature of 25 °C and a rotation speed of 3,500 r / min. After completion, the dark supernatant was collected and diluted with water to obtain a Ti 3 AlC 2 MXene supernatant with a mass concentration of 2 mg / mL; 5 mg of the MOF product was ultrasonically dispersed in 200 mL of water at a temperature of 25 °C and a frequency of 5 W, and the ultrasonic dispersion time was set to 30 min to obtain a MOF solution; 10 mL of the MOF solution and 70 mL of Ti 3 AlC 2 MXene supernatant were mixed and stirred for 20 min at a temperature of 25 °C and a rotation speed of 400 r / min, and then centrifuged for 10 min at a temperature of 25 °C and a rotation speed of 3,500 r / min to obtain the two-dimensional conductive material;

[0069] Design the required pattern on a computer in advance. The diameter of the conical bottom of the microneedle structure in the pattern is 0.6 mm. Select methyl vinyl silicone rubber as the mold, and the mold size is 3×3 cm. Stretch the mold in equal proportion in both the X-axis and Y-axis directions, and the stretching ratio is 100%. Stretch the mold from 3×3 cm to 6×6 cm. After the stretching is completed, fix the template on a solid plate made by 3D printing, and use a common commercial laser engraving machine for laser engraving (engrave the pattern designed on the computer in advance on the stretched template). Set the laser intensity to 10.5% to obtain the processed mold. Add 3 mL of two-dimensional conductive material to the surface of the processed mold. After the addition is completed, evacuate the mold in a vacuum drying oven for 30 s, and then cure it at 65 °C for 2 h. After the curing is completed, peel off the methyl vinyl silicone rubber mold from the fixing plate to make it retract to the initial size of 3×3 cm. At the same time, the crack-like shape of the two-dimensional conductive material is converted into a stacked shape, and the pattern size on the mold is reduced by 1 time, and the diameter of the conical bottom of the microneedle structure is also reduced to 0.3 mm to obtain an inverse structure microneedle template. Drop 2 mL of microneedle body material (the microneedle body material contains silk fibroin and waterborne polyurethane, and the volume ratio of silk fibroin to waterborne polyurethane is 3:7) on the surface of the inverse structure microneedle template. After the dropping is completed, evacuate the template in a vacuum drying oven for 10 s, repeat the evacuation operation once, and then cure it at 70 °C for 1 h. Demold to obtain the microneedle patch (the microneedle patch obtained when the stretching ratio is 100%).

[0070] The flow chart of preparing the microneedle patch in this embodiment is as follows Figure 1 shown

[0071] Under the condition that other conditions in this embodiment remain unchanged, replace the stretching ratio with 0 and 80% respectively to obtain the microneedle patch obtained when the stretching ratio is 0 and the microneedle patch obtained when the stretching ratio is 80%.

[0072] Characterize and test the stretching ability of the microneedle patch obtained when the stretching ratio is 0, the microneedle patch obtained when the stretching ratio is 80%, and the microneedle patch obtained when the stretching ratio is 100% respectively, and obtain the characterization diagram of the microneedle patch obtained when the stretching ratio is 0 before and after the stretching test, as follows Figure 2 shown; (where the morphology characterization diagram of the microneedle patch obtained when the stretching ratio is 0 is as follows Figure 2 (i); the morphology characterization diagram of the microneedle patch obtained when the stretching ratio is 0 after being stretched by 50% is as follows Figure 2 (ii); the enlarged morphology characterization diagram of the microneedle patch obtained when the stretching ratio is 0 after being stretched by 50% with the conductive path schematic diagram is as follows Figure 2 (iii)); the characterization diagram of the microneedle patch obtained when the stretching ratio is 80% before and after the stretching test, as follows Figure 3As shown; (wherein, the morphological characterization diagram of the microneedle patch obtained when the stretching ratio is 80% is as Figure 3 (i); the morphological characterization diagram of the microneedle patch obtained when the stretching ratio is 80% after stretching by 50% is as Figure 3 (ii); the enlarged morphological characterization diagram of the microneedle patch obtained when the stretching ratio is 80% after stretching by 50% as a conductive path schematic diagram is as Figure 3 (iii)); the characterization diagrams of the microneedle patch obtained when the stretching ratio is 100% before and after the stretching test are as Figure 4 shown; (wherein, the morphological characterization diagram of the microneedle patch obtained when the stretching ratio is 100% is as Figure 4 (i); the morphological characterization diagram of the microneedle patch obtained when the stretching ratio is 100% after stretching by 50% is as Figure 4 (ii); the enlarged morphological characterization diagram of the microneedle patch obtained when the stretching ratio is 100% after stretching by 50% as a conductive path schematic diagram is as Figure 4 (iii)). It can be obtained from Figures 2 to 4 that: the surface of the microneedle patch obtained when the stretching ratio is 0% has more cracks, and the conductive path is restricted; the surface cracks of the microneedle patch obtained when the stretching ratio is 80% are significantly reduced, but its conductive path is still restricted to a certain extent; while the surface of the microneedle patch obtained when the stretching ratio is 100% is uniform, the crack expansion phenomenon is eliminated, and the conductive path increases, improving the electrical conductivity.

[0073] Example 2

[0074] 980 mg of 2-methylimidazole was added to 5.2 mL of water, and then 37 mg of zinc acetate was added. It was stirred at a temperature of 23 °C and a rotation speed of 500 r / min for 12 min, and then centrifuged at a temperature of 23 °C and a rotation speed of 18500 r / min for 12 min. The obtained precipitate was collected, washed 4 times with water, and dried at 55 °C for 4.5 h to obtain the MOF product; 4.7 g of lithium fluoride was dissolved in 63 mL of a hydrochloric acid solution with a concentration of 9.2 mol / L to obtain a lithium fluoride solution, and then 3.5 g of titanium aluminum carbide was slowly added to the lithium fluoride solution. It was stirred at a temperature of 37 °C and a rotation speed of 700 r / min for 50 h, and then centrifuged at a temperature of 23 °C and a rotation speed of 3700 r / min for 6.5 min. After centrifugation, the obtained precipitate was washed with water, and then the steps of centrifugation and washing were repeated until the pH value of the solution was 6.8, and centrifugation was stopped to obtain Ti 3 AlC 2MXene suspension; The obtained suspension was ultrasonically treated for 62 min at a temperature of 23 °C and a frequency of 50 kHz, and then centrifuged for 28 min at a temperature of 23 °C and a rotation speed of 3700 r / min. After that, the dark supernatant was collected and diluted with water to obtain a Ti with a mass concentration of 2.2 mg / mL 3 AlC 2 MXene supernatant; 5.5 mg of the MOF product was ultrasonically dispersed in 210 mL of water at a temperature of 23 °C and a frequency of 6 W. The ultrasonic dispersion time was set to 32 min to obtain a MOF solution; 10 mL of the MOF solution and 75 mL of Ti 3 AlC 2 MXene supernatant were mixed and stirred at a temperature of 23 °C and a rotation speed of 500 r / min for 18 min, and then centrifuged at a temperature of 23 °C and a rotation speed of 3700 r / min for 8 min to obtain the two-dimensional conductive material;

[0075] Design the required pattern on a computer in advance. The diameter of the conical bottom of the microneedle structure in the pattern is 0.8 mm; Fluorosilicone rubber was selected as the mold, and the mold size was 3.5×3.5 cm; The mold was stretched bidirectionally in equal proportion along the X-axis and Y-axis, and the stretching ratio was 100%. The mold was stretched from 3.5×3.5 cm to 7×7 cm. After the stretching was completed, the template was fixed on a solid plate made by 3D printing, and a common commercial laser engraver was used for laser engraving (engraving the pattern designed on the computer in advance on the stretched template), and the laser intensity was set to 11% to obtain the processed mold; 3.6 mL of the two-dimensional conductive material was added to the surface of the processed mold. After the addition, the mold was evacuated in a vacuum drying oven for 32 s, and then cured at 67 °C for 2.3 h. After the curing was completed, the fluorosilicone rubber mold was peeled off from the fixing plate, and it shrank back to the initial size of 3.5×3.5 cm. At the same time, the crack shape of the two-dimensional conductive material was converted into a stacked shape, and the pattern size on the mold was reduced by 1 times, and the diameter of the conical bottom of the microneedle structure was also reduced to 0.4 mm to obtain an inverse structure microneedle template; 2.2 mL of the microneedle body material (the microneedle body material contains silk fibroin and aqueous polyurethane, and the volume ratio of silk fibroin to aqueous polyurethane is 3.2:7) was dropped on the surface of the inverse structure microneedle template. After the dropping was completed, the template was evacuated in a vacuum drying oven for 8 s, and the evacuation operation was repeated once, and then cured at 68 °C for 1.5 h; Demolding to obtain the microneedle patch.

[0076] The microneedle patches prepared in this example were respectively attached to different parts of the body, and the point signals were recorded by connecting an RMS multimeter to obtain a schematic diagram of the microneedle patch for motion sensing monitoring in this example, as Figure 5 shown (where Figure 5(a), (b), and (c) respectively correspond to the monitoring schematic diagrams of different bending angles of the fingers, wrists, and elbows. Figure 5 (d) and (e) are respectively the monitoring schematic diagrams during nodding and swallowing movements. Figure 5 (f) is the monitoring schematic diagram during the finger bending - recovery cycle). As can be seen from Figure 5 this, when the body part bends at different angles, the corresponding resistance gradually increases, and it can be converted into easily recognizable electrical signals through external movement, thereby realizing the movement monitoring of the human body.

[0077] Example 3

[0078] Add 955 mg of 2 - methylimidazole to 4.5 mL of water, then add 36 mg of zinc acetate, stir at a temperature of 27 °C and a rotation speed of 350 r / min for 8 min, then centrifuge at a temperature of 27 °C and a rotation speed of 17000 r / min for 9 min, collect the obtained precipitate, wash it 3 times with water, and dry it at 57 °C for 3 h to obtain the MOF product; dissolve 4.5 g of lithium fluoride in 55 mL of hydrochloric acid solution with a concentration of 8.5 mol / L to obtain a lithium fluoride solution, then slowly add 2.7 g of titanium aluminum carbide to the lithium fluoride solution, stir at a temperature of 32 °C and a rotation speed of 800 r / min for 46 h, then centrifuge at a temperature of 27 °C and a rotation speed of 3300 r / min for 3 min. After centrifugation, wash the obtained precipitate with water, and then repeat the steps of centrifugation and washing until the pH value of the solution is 6.7, stop centrifugation, and obtain Ti 3 AlC 2 MXene suspension; ultrasonicate the obtained suspension at a temperature of 27 °C and a frequency of 35 kHz for 55 min, then centrifuge at a temperature of 27 °C and a rotation speed of 3300 r / min for 28 min. After completion, collect the dark supernatant, add water for dilution, and obtain a Ti 3 AlC 2 MXene supernatant with a mass concentration of 1.8 mg / mL; ultrasonically disperse 4.5 mg of the MOF product in 190 mL of water at a temperature of 27 °C and a frequency of 4 W, and set the ultrasonication time to 25 min to obtain a MOF solution; mix 10 mL of the MOF solution and 66 mL of Ti 3 AlC 2 MXene supernatant, stir at a temperature of 27 °C and a rotation speed of 350 r / min for 27 min, then centrifuge at a temperature of 27 °C and a rotation speed of 3000 r / min for 13 min to obtain the described two - dimensional conductive material.

[0079] Design the required pattern on a computer in advance. The diameter of the conical bottom of the microneedle structure in the pattern is 0.7 mm. Select nitrile silicone rubber as the mold, and the mold size is 3×3 cm. Stretch the mold in equal proportion in both the X-axis and Y-axis directions, and the stretching ratio is 95%. Stretch the mold from 3×3 cm to 5.85×5.85 cm. After the stretching is completed, fix the template on a solid plate made by 3D printing, and use a common commercial laser engraving machine for laser engraving (engrave the pattern designed on the computer in advance on the stretched template), set the laser intensity to 10%, and obtain the processed mold. Add 3.5 mL of two-dimensional conductive material to the surface of the processed mold. After the addition is completed, evacuate the mold in a vacuum drying oven for 25 s, and then cure it at 60 °C for 2.5 h. After the curing is completed, peel off the nitrile silicone rubber mold from the fixed plate to make it retract to the initial size of 3×3 cm. At the same time, the crack-like shape of the two-dimensional conductive material is converted into a stacked shape, and the pattern size on the mold is reduced by 1 times, and the diameter of the conical bottom of the microneedle structure is also reduced to about 0.36 mm, obtaining an inverse structure microneedle template. Drop 2.2 mL of microneedle body material (the microneedle body material contains silk fibroin and waterborne polyurethane, and the volume ratio of silk fibroin to waterborne polyurethane is 2.5:6.7) on the surface of the inverse structure microneedle template. After the dropping is completed, evacuate the template in a vacuum drying oven for 11 s, repeat the evacuation operation once, and then cure it at 68 °C for 1.5 h. Demold to obtain the microneedle patch.

[0080] As can be seen from the above embodiments, the present invention provides a preparation method of a microneedle patch, which effectively solves the problem of crack propagation of two-dimensional conductive materials by using the reversible retraction of silicone rubber materials, and prepares an inverse structure microneedle array template with high precision and adjustable specifications at a low cost; the present invention uses a mixed solution of silk fibroin and waterborne polyurethane as the microneedle body material, and the finally obtained microneedle patch has good biocompatibility and mechanical strength and can adapt to the human skin.

[0081] This preparation method is simple, the materials are inexpensive, and the prepared microneedle patch has good mechanical strength, good conductivity and high precision, and can be applied to fields such as motion sensing.

[0082] The above are only the preferred embodiments of the present invention. It should be pointed out that for those of ordinary skill in the art, without departing from the principle of the present invention, several improvements and retouches can be made, and these improvements and retouches should also be regarded as the protection scope of the present invention.

Claims

1. Application of a two-dimensional conductive material in the preparation of a microneedle patch, Characterized in that, The preparation method of the two-dimensional conductive material comprises the following steps: (1) Mix 2-methylimidazole, zinc acetate and water to obtain a MOF product; (2) Mix lithium fluoride, hydrochloric acid solution and titanium aluminum carbide to obtain Ti 3 AlC 2 MXene supernatant; (3) Mix the MOF solution and the Ti 3 AlC 2 MXene supernatant to obtain the two-dimensional conductive material described above.

2. The application according to claim 1, Characterized in that, The mass-volume ratio of 2-methylimidazole, zinc acetate and water in step (1) is 950-1000 mg: 35-40 mg: 4.5-5.5 mL.

3. The application according to claim 1 or 2, Characterized in that, The concentration of the hydrochloric acid solution in step (2) is 8-10 mol / L; the mass-volume ratio of lithium fluoride, hydrochloric acid solution and titanium aluminum carbide is 4.5-5 g: 55-65 mL: 2.5-3.5 g; The MOF solution described in step (3) contains a MOF product and water, and the mass-volume ratio of the MOF product to water is 4-6 mg: 180-220 mL; the Ti 3 AlC 2 mass concentration of the MXene supernatant is 1.5-2.5 mg / mL; The MOF solution and Ti described in step (3) 3 AlC 2 The volume ratio of the MXene supernatant is 1:6 to 8.

4. A preparation method of a microneedle patch, Characterized in that, Comprises the following steps: (1) Stretch and laser engrave the mold in sequence to obtain a processed mold; (2) Add the two-dimensional conductive material described in claim 1 to the surface of the processed mold, and demold after curing to obtain an inverse structure microneedle template with a stacked conductive material; (3) Drop the microneedle body material on the surface of the inverse structure microneedle template, and demold after curing to obtain the microneedle patch.

5. The preparation method according to claim 4, Characterized in that, The material of the mold in step (1) is methyl vinyl silicone rubber, nitrile silicone rubber or fluorosilicone rubber; The stretching is equi-proportionally stretched along the X-axis and Y-axis, and the stretching ratio is 85-100%; The laser intensity of the laser engraving is 8-12%.

6. The preparation method according to claim 4 or 5, Characterized in that, The dosage of the two-dimensional conductive material described in step (2) is 0.2 to 0.4 mL / cm 2 , the curing temperature described in step (2) is 60 to 70 °C, and the time is 1 to 3 h; The volume ratio of the microneedle body material in step (3) to the two-dimensional conductive material in step (2) is 1.5-2.5: 2.5-3.5; the microneedle body material in step (3) comprises silk fibroin and waterborne polyurethane, and the volume ratio of silk fibroin and waterborne polyurethane is 2.5-3.5: 6.5-7.5; The temperature of the curing in step (3) is 60-70 °C, and the time is 1-3 h.

7. A microneedle patch obtained by the preparation method according to any one of claims 4-6.

8. Application of the microneedle patch according to claim 7 in motion sensing monitoring.

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