A microneedle patch and its preparation method and application

Abstract

The present application provides a microneedle patch, a preparation method, and an application thereof. The microneedle patch comprises a microneedle layer and an adhesive hydrogel layer. The microneedle layer comprises a substrate and microneedles disposed on the substrate surface. The microneedles are all embedded in the adhesive hydrogel layer, and the thickness of the adhesive hydrogel layer is greater than the length of the microneedles in the thickness direction of the adhesive hydrogel layer. The microneedle patch not only effectively reduces the breakage rate of microneedles, but also has a simple method of use. During use, the microneedles can be inserted into the skin to achieve simultaneous drug delivery, greatly simplifying the use of microneedles and reducing the difficulty of operation, which is conducive to the promotion and use of microneedle technology.

Description

Technical Field

[0001] The present application relates to the technical field of skin care products, and in particular to a microneedle patch and a preparation method and application thereof. Background Art

[0002] Microneedle technology uses microneedle patches to deliver drugs through the skin. When used, the active ingredients are injected into the dermis of the skin through the microneedles, allowing the active ingredients to be completely absorbed and dissolved by the skin, thereby improving various skin problems. Microneedle technology has good application prospects due to its outstanding features such as painless penetration, low cost, good efficacy, and relative safety. Currently, there are solid microneedles, coated microneedles, hollow microneedles, and soluble microneedles. Among them, hollow microneedles and soluble microneedles are prone to breakage during use, so they have high operational requirements, and special packaging boxes are also required for material transportation, resulting in high production and use costs; coated microneedles have a small drug loading capacity and the coating is easy to fall off; although solid microneedles have high structural strength, their use method is to first puncture the skin to form a drug delivery channel and then apply a drug delivery patch. This method has complicated steps and limits the application scenarios of microneedles. Therefore, it is necessary to provide a new microneedle patch to simplify the use of microneedles and promote the application of microneedle technology. Summary of the Invention

[0003] To solve the above problems, the present application provides a microneedle patch, which can not only effectively reduce the breakage rate of microneedles, but also is easy to use. During use, the microneedles can be inserted into the skin to achieve synchronous drug delivery, which greatly simplifies the use of microneedles and reduces the difficulty of operation, which is conducive to the promotion and use of microneedle technology.

[0004] Specifically, the first aspect of the present application provides a microneedle patch, which includes a microneedle layer and a sticky hydrogel layer. The microneedle layer includes a substrate and microneedles arranged on the surface of the substrate. The microneedles are all embedded in the sticky hydrogel layer, and the thickness of the sticky hydrogel layer is greater than the length of the microneedles in the thickness direction of the sticky hydrogel layer.

[0005] In the microneedle patch of the present application, the adhesive hydrogel layer not only has a certain degree of stickiness, which can fix the microneedle patch on the skin surface, but also the thicker adhesive hydrogel layer can fully wrap the microneedles, provide effective support and protection for the microneedles, and reduce the breakage rate of the microneedles during transportation and use; during the use of the microneedle patch, after the microneedle patch is pressed, the microneedles will pass through the adhesive hydrogel layer and penetrate the skin to form microchannels. The active components in the adhesive hydrogel layer can penetrate into the skin through the microchannels, thereby achieving synchronous drug delivery, which greatly simplifies the use steps of the microneedle patch; in addition, the adhesive hydrogel layer can also disperse the stress of pressing, so that the microneedles can penetrate the skin evenly, thereby promoting drug delivery.

[0006] Optionally, the substrate is entirely embedded in the adhesive hydrogel layer.

[0007] Optionally, the distance between the surface of the viscous hydrogel layer close to the microneedle tip and the microneedle tip is 0.5 mm to 2 mm.

[0008] Optionally, the length of the microneedle in the thickness direction of the viscous hydrogel layer is 1 mm to 3 mm.

[0009] Optionally, the material of the microneedle includes one or more of silicon, metal, ceramic and polymer material; and the polymer material is insoluble in water.

[0010] Optionally, the polymer material includes one or more of PVC (polyvinyl chloride), PP (polypropylene), PCL (polycaprolactone), PTFE (polytetrafluoroethylene), PC (polycarbonate), and PE (polyethylene).

[0011] Optionally, the microneedle includes at least one of a hollow microneedle and a solid microneedle.

[0012] Optionally, the adhesive hydrogel layer includes a first polymer compound, and the first polymer compound includes one or more of polyacrylic acid, sodium alginate, gum arabic or konjac gum.

[0013] Optionally, the adhesive hydrogel layer comprises the following components in percentage by weight: 2% to 20% of the first polymer compound, 30% to 50% of water, 20% to 40% of the first polyol, and 2% to 20% of the first auxiliary agent.

[0014] Optionally, the first polyol includes one or more of methylpropylene glycol, pentanediol or hexanediol.

[0015] Optionally, the first auxiliary agent includes one or more of a cross-linking agent, a pH regulator, an antibacterial agent, a preservative, a colorant or a flavoring agent.

[0016] Optionally, the cross-linking agent includes a metal salt, and the metal salt includes one or more of an iron salt and an aluminum salt.

[0017] Optionally, the antibacterial agent includes one or more of chitosan, chlorphenesin, caprylyl glycol, sodium benzoate and potassium sorbate.

[0018] Optionally, the pH adjuster includes sodium citrate.

[0019] Optionally, the thickness of the viscous hydrogel layer is 2 mm to 9 mm.

[0020] Optionally, the adhesive force of the adhesive hydrogel layer is 0.1N to 20N.

[0021] Optionally, the elongation at break of the viscous hydrogel layer is 10% to 25%; and the elastic modulus of the viscous hydrogel layer is 0.1 MPa to 5 MPa.

[0022] Optionally, the ratio of the length of the microneedle in the thickness direction of the viscous hydrogel layer to the thickness of the viscous hydrogel layer is 0.5 to 0.75.

[0023] Optionally, the microneedle patch further comprises a slippery hydrogel layer disposed on a surface of the adhesive hydrogel layer away from the microneedle tips, and the water content of the slippery hydrogel layer is greater than the water content of the adhesive hydrogel layer.

[0024] Optionally, the water content of the viscous hydrogel layer is 30% to 50%, and the water content of the slippery hydrogel layer is 50% to 60%.

[0025] Optionally, the slippery hydrogel layer includes a second polymer compound, and the second polymer compound includes one or more of carrageenan, xanthan gum, gelatin or cellulose gum.

[0026] Optionally, the slippery hydrogel layer comprises the following components in percentage by weight: 1% to 15% of the second high molecular compound, 50% to 60% of water, 20% to 40% of the second polyol, and 1% to 6% of the second auxiliary agent.

[0027] Optionally, the second polyol includes one or more of dipropylene glycol, sorbitol or butylene glycol.

[0028] Optionally, the second auxiliary agent includes one or more of an antibacterial agent, a preservative, a colorant or a flavoring agent.

[0029] Optionally, the surface roughness of the slippery hydrogel layer is 1.6 μm to 3.2 μm.

[0030] Optionally, the slippery hydrogel layer has a thickness of 1 mm to 5 mm.

[0031] Optionally, the thickness of the microneedle patch is 4 mm to 15 mm.

[0032] Optionally, the conductivity of the microneedle patch is 150 μS / cm to 250 μS / cm.

[0033] Optionally, the shape of the microneedle patch includes any one of a crescent shape, a horseshoe shape, a glasses shape, and a comma shape.

[0034] Optionally, the microneedle patch further includes a protective layer, which is disposed on the surface of the adhesive hydrogel layer.

[0035] Optionally, the protective layer is arranged on the surface of the slippery hydrogel layer.

[0036] Optionally, the protective layer is provided on the substrate surface of the microneedle layer.

[0037] Optionally, the protective layer includes any one of a hydrophilic non-woven fabric and a pearlescent film.

[0038] The second aspect of the present application provides a method for preparing a microneedle patch, comprising:

[0039] The microneedle layer is placed in a viscous hydrogel solution, and the viscous hydrogel solution is cross-linked and subjected to water dehydration treatment to obtain a microneedle patch; the microneedle patch includes a microneedle layer and a viscous hydrogel layer, the microneedle layer includes a substrate and microneedles arranged on the surface of the substrate, and the microneedles are all embedded in the viscous hydrogel layer, and the thickness of the viscous hydrogel layer is greater than the length of the microneedles in the thickness direction of the viscous hydrogel layer.

[0040] Optionally, the temperature of the dehydration treatment is 55° C. to 65° C., and the time of the dehydration treatment is 2 h to 3 h.

[0041] Optionally, the viscous hydrogel solution includes the following components in percentage by weight: 1% to 6% of the first polymer compound, 60% to 70% of water, 20% to 30% of the first polyol, and 0.1% to 6% of the first auxiliary agent.

[0042] Optionally, the preparation method of the viscous hydrogel solution includes: dispersing a first polymer compound in a first polyol, adding water, heating to 70° C. to 85° C., adding a first auxiliary agent (excluding a cross-linking agent), and mixing to obtain a viscous hydrogel solution.

[0043] Optionally, the cross-linking molding includes: adding a cross-linking agent to the viscous hydrogel solution.

[0044] Optionally, the preparation method further comprises: subjecting the slippery hydrogel base layer to a second water dehydration treatment to obtain a slippery hydrogel layer, and covering the slippery hydrogel layer on a side of the sticky hydrogel layer away from the microneedle tip to obtain a microneedle patch.

[0045] Optionally, the slippery hydrogel base layer comprises the following components in percentage by weight: 1% to 4.5% of the second high molecular compound, 60% to 80% of water, 20% to 30% of the second polyol, and 0.1% to 6% of the second auxiliary agent.

[0046] Optionally, the method for preparing the slippery hydrogel base layer includes: dispersing a second polymer compound in a second polyol, adding water, heating to 70° C. to 85° C., adding a second auxiliary agent, introducing the mixed solution into a mold, and cooling it to obtain a slippery gel layer.

[0047] Optionally, the temperature of the second dehydration treatment is 40° C. to 45° C., and the time of the second dehydration treatment is 3 hours to 4 hours;

[0048] The third aspect of the present application provides a method for using a microneedle patch, comprising: fixing the microneedle patch described in the first aspect on the skin surface, and pressing the microneedle patch to allow the active components in the adhesive hydrogel layer to penetrate into the skin.

[0049] Optionally, the pressing is performed using an instrument, and the instrument includes at least one of a radio frequency instrument or an ultrasonic instrument.

[0050] Optionally, the instrument is pressed on the surface of the slippery hydrogel layer of the microneedle patch.

[0051] Optionally, the power of the radio frequency instrument is 6W to 10W, the frequency of the radio frequency instrument is 1MHz to 1.2MHz, the action time of the radio frequency instrument is 5min to 10min; and the action depth of the radio frequency instrument is 1mm to 5mm.

[0052] Optionally, the power of the ultrasonic instrument is 50W to 80W, the frequency of the ultrasonic instrument is 40kHz to 50kHz, the action time of the ultrasonic instrument is 5min to 10min; and the action depth of the ultrasonic instrument is 5mm to 8mm. BRIEF DESCRIPTION OF THE DRAWINGS

[0053] Figure 1 A schematic structural diagram of a microneedle patch provided in one embodiment of the present application;

[0054] Figure 2 A schematic structural diagram of a microneedle patch provided in one embodiment of the present application;

[0055] Figure 3 A diagram illustrating the use of a microneedle patch according to an embodiment of the present application;

[0056] Figure 4 A diagram illustrating the use of a microneedle patch according to an embodiment of the present application;

[0057] Figure 5 A schematic structural diagram of a microneedle layer provided in one embodiment of the present application;

[0058] Figure 6 A schematic structural diagram of a microneedle patch provided in one embodiment of the present application;

[0059] Figure 7 A schematic structural diagram of a microneedle patch provided in one embodiment of the present application;

[0060] Figure 8 A diagram illustrating the use of a microneedle patch according to an embodiment of the present application;

[0061] Figure 9 A schematic structural diagram of a microneedle patch provided in one embodiment of the present application;

[0062] Figure 10 A schematic structural diagram of a microneedle patch provided in one embodiment of the present application;

[0063] Figure 11 This is a flow chart of a method for preparing a microneedle patch according to one embodiment of the present application. DETAILED DESCRIPTION

[0064] The following will be combined with the drawings in the embodiments of this application to clearly and completely describe the technical solutions in the embodiments of this application. Obviously, the embodiments described are only part of the embodiments of this application, not all of the embodiments. Based on the embodiments in this application, all other embodiments obtained by ordinary technicians in this field without making creative efforts are within the scope of protection of this application.

[0065] Currently, microneedle patches on the market suffer from high breakage rates and cumbersome usage procedures. To reduce the breakage rate, promote effective absorption of the active ingredients in the microneedle patch by the human body, and simplify the use of the microneedle patch, this application provides a microneedle patch with a low breakage rate and simple usage, which is conducive to expanding the application scenarios of the microneedle patch.

[0066] See also Figure 1 , Figure 1 This is a structural schematic diagram of a microneedle patch provided in one embodiment of the present application. The microneedle patch 100 includes a stacked microneedle layer 10 and a viscous hydrogel layer 20. The microneedle layer includes a substrate 11 and microneedles 12 arranged on the surface of the substrate. The microneedles 12 are all embedded in the viscous hydrogel layer 20, and the length of the microneedles 12 in the first direction is less than the thickness of the viscous hydrogel layer 20 in the first direction, wherein the first direction refers to the thickness direction of the viscous hydrogel layer.

[0067] See also Figure 2 , Figure 2 This is a schematic diagram of the structure of a microneedle patch provided in one embodiment of the present application. The microneedle patch 100 includes a microneedle layer 10 and an adhesive hydrogel layer 20. The microneedle layer 12 is completely embedded in the adhesive hydrogel layer 20, and the distance h from the surface of the adhesive hydrogel layer 20 on the side close to the microneedle 12 tip to the microneedle 12 tip is greater than 0. In some embodiments of the present application, the distance h from the surface of the adhesive hydrogel layer 20 on the side close to the microneedle tip to the microneedle 12 tip is 0.5 mm to 2 mm. The distance from the surface of the adhesive hydrogel layer on the side close to the microneedle tip to the microneedle tip can be, but is not limited to, 0.5 mm, 0.7 mm, 1 mm, 1.5 mm, or 2 mm.

[0068] See also Figure 3 and Figure 4 , Figure 3 and Figure 4 This is a diagram of the use process of the microneedle patch provided in one embodiment of the present application. Figure 3 When the microneedle patch is pressed, the sticky hydrogel layer is deformed, and the microneedles pass through the sticky hydrogel layer to reach the surface of the skin. As the pressing depth increases, the microneedles penetrate the epidermis. By controlling the pressing force, the depth of microneedle penetration can be adjusted so that the microneedles can reach the target depth or the pain point that the human body can tolerate. Figure 4 When the external pressure is removed, the viscous hydrogel layer rebounds and returns to its original shape, and the microneedles leave the skin surface, leaving micropores on the skin surface. The active components in the viscous hydrogel layer penetrate into the dermis of the skin through the micropores and are then absorbed and dissolved by the skin. In the embodiments of the present application, the microneedle patch can be pressed manually, such as by applying pressure with the fingertips, or by an instrument, such as an ultrasound instrument probe or a radiofrequency instrument probe.

[0069] In the embodiment of the present application, the adhesive hydrogel layer not only has a strong adhesive force that can adhere to the skin surface to fix the microneedle patch, but also has a certain structural strength. On the one hand, the adhesive hydrogel layer can effectively protect the microneedles and reduce the risk of microneedles breaking during transportation, thereby simplifying the packaging of the microneedle iron sheet and reducing transportation costs. On the other hand, in the process of pressing the microneedles into the skin, the adhesive hydrogel layer can improve the force distribution of the microneedle patch during pressing, so that the microneedles can penetrate the skin vertically and reduce the breakage rate of the microneedles. When the length of the microneedles is less than the thickness of the adhesive hydrogel layer, the adhesive hydrogel layer can not only effectively protect the microneedles, but also because the adhesive hydrogel layer has a certain rebound performance, when the external pressure is removed, the microneedles will detach from the skin surface again, thereby effectively controlling the depth of microneedle penetration and simplifying the use conditions of the microneedle patch.

[0070] In the embodiments of the present application, the viscous hydrogel layer contains active ingredients, which may be ingredients for wrinkle removal, anti-aging, repair, whitening, hair growth stimulation, blood microcirculation promotion, and capillary constriction. The microneedle patch of the present application injects the active ingredients into the viscous hydrogel layer. When the microneedles are inserted into the skin to form microchannels, the active ingredients in the viscous hydrogel layer also enter the skin and are absorbed by the body. This method achieves microneedle insertion and drug delivery with a single press, greatly simplifying the use steps of the microneedle patch.

[0071] In some embodiments of the present application, the adhesive hydrogel layer comprises the following components in percentage by weight: 2% to 20% of a first polymer compound, 30% to 50% of water, 20% to 40% of a first polyol, and 2% to 20% of a first auxiliary agent. In some embodiments of the present application, the first polymer compound comprises one or more of polyacrylic acid, sodium alginate, gum arabic, or konjac gum. The first polymer compound selected in the present application has good self-adhesive properties, which facilitates securely attaching the microneedle patch to the skin surface. Furthermore, the first polymer compound has excellent mechanical properties, resulting in good molding effect and high stability, effectively protecting the microneedles and reducing the breakage rate of the microneedles. In some embodiments of the present application, the first polyol includes one or more of methylpropanediol, pentanediol or hexanediol. The above polyols can not only disperse the first polymer compound well and inhibit the agglomeration of the first polymer compound, but also the first polyol has good moisturizing and permeability. When the viscous hydrogel layer adheres to the skin, the first polyol can penetrate into the skin, increase the skin's moisturizing ability, and work together with the active ingredients to improve skin problems; in addition, the first polyol has a certain antibacterial ability, which makes the viscous hydrogel layer have a certain antiseptic ability.

[0072] In some embodiments of the present application, the first auxiliary agent includes one or more of a cross-linking agent, a pH regulator, an antibacterial agent, a preservative, a colorant or a flavoring agent. In some embodiments of the present application, the cross-linking agent includes a metal salt. Using a metal salt as a cross-linking agent is beneficial to improving the mechanical properties of the adhesive hydrogel layer, thereby effectively fixing the microneedles. In some embodiments, the metal salt includes a trivalent metal salt, and the trivalent metal salt includes one or more of an iron salt and an aluminum salt. In some embodiments of the present application, the pH regulator includes sodium citrate. Adding a pH regulator to the hydrogel layer can adjust the pH value of the adhesive hydrogel layer. On the one hand, it can make the pH value of the adhesive hydrogel layer closer to that of human skin and improve the affinity of the adhesive hydrogel layer. On the other hand, it can improve the adhesion of the adhesive hydrogel layer, making it more firmly attached to the skin surface. In some embodiments of the present application, the antibacterial agent includes one or more of chitosan, chlorphenesin, caprylyl glycol, sodium benzoate and potassium sorbate.

[0073] In some embodiments of the present application, the thickness of the viscous hydrogel layer is 2 mm to 9 mm, and the thickness of the viscous hydrogel layer can be, but is not limited to, 2 mm, 3 mm, 4 mm, 5 mm, 6 mm, 7 mm, or 9 mm. When the thickness of the viscous hydrogel layer is controlled to be 4 mm to 9 mm, the viscous hydrogel layer has good rebound properties, which is beneficial for controlling the depth of microneedle penetration. Moreover, a hydrogel layer of this size is easy to prepare, which is beneficial for reducing process costs. In addition, the viscous hydrogel layer can also disperse the stress of pressing, allowing the microneedles to penetrate the skin evenly, thereby promoting drug delivery. In some embodiments of the present application, the elongation at break of the viscous hydrogel layer is 10% to 25%, and the elongation at break of the viscous hydrogel layer can be, but is not limited to, 10%, 15%, 20%, or 25%. The viscous hydrogel layer of the present application has moderate structural strength, which not only ensures that the microneedles can penetrate the skin through the viscous hydrogel layer, but also effectively buffers the impact of external forces on the microneedles, reducing the breakage rate of the microneedles. In some embodiments of the present application, the elastic modulus of the viscous hydrogel layer is 0.1MPa to 5MPa, and the elastic modulus of the viscous hydrogel layer can be, but is not limited to, 0.1MPa, 0.5MPa, 1MPa, 3MPa, or 5MPa. Controlling the elastic modulus of the viscous hydrogel layer can ensure that the microneedles can rebound again after deformation, allowing the microneedles to detach from the skin surface. In some embodiments of the present application, the adhesive force of the viscous hydrogel layer is 0.1N to 20N, and the adhesive force of the viscous hydrogel layer can be, but is not limited to, 0.1N, 0.5N, 1N, 3N, 5N, 10N, 15N, or 20N. In the present application, the viscous hydrogel layer can be transparent or opaque. In some embodiments, the viscous hydrogel layer is colored. In some embodiments, the viscous hydrogel layer has suspended particles inside.

[0074] In some embodiments of the present application, the shape of the microneedle can be either conical or pyramidal. When the microneedle is vertebral, the length of the microneedle is the height of the vertebral body. Figure 5 , Figure 5 This is a schematic structural diagram of a microneedle layer provided in one embodiment of the present application. Figure 5In the embodiment, the microneedle layer includes a substrate 11 and microneedles 12 disposed on the surface of the substrate. The microneedles 12 are arranged in an array on the surface of the substrate 11. The length d of the microneedles is the distance from the base of the microneedles to the tips, wherein the bases of the microneedles are closer to the substrate and the tips of the microneedles are farther away from the substrate. In some embodiments of the present application, the length of the microneedles is 1 mm to 3 mm. The length of the microneedles can be, but is not limited to, 1 mm, 1.5 mm, 2 mm, 2.5 mm, or 3 mm. A microneedle length of 1 mm to 3 mm facilitates better control of the depth of microneedle penetration into the skin, ensuring that the microneedles can pass through the viscous hydrogel layer and penetrate the skin. In some embodiments, the depth of microneedle penetration into the skin is 1 μm to 1500 μm. In some embodiments of the present application, the ratio of the length of the microneedles to the thickness of the viscous hydrogel layer is 0.5 to 0.75. The ratio of the length of the microneedles to the thickness of the viscous hydrogel layer can be, but is not limited to, 0.5, 0.6, 0.7, or 0.75.

[0075] In the embodiment of the present application, the material of the microneedle includes one or more of silicon, metal, ceramic and polymer materials, wherein the polymer material is insoluble in water, and the polymer material can be one or more of PVC, PP or PCL. In the present application, the microneedle can be a hollow microneedle or a solid microneedle. In some embodiments, the microneedles in the microneedle layer are solid microneedles, and solid microneedles have a higher structural strength, which is beneficial to reducing the breakage rate of the microneedles. In some embodiments, the microneedles in the microneedle layer are hollow microneedles, and the substrate in the microneedle layer can be built with active components. During the process of pressing the microneedle patch, the active components in the substrate enter the viscous hydrogel layer through the microneedles and then penetrate into the skin. In some embodiments of the present application, the microneedles in the microneedle layer are hollow microneedles. The substrate in the microneedle layer contains a first active ingredient, and the adhesive hydrogel layer contains a second active ingredient. When the microneedle patch is pressed, the first active ingredient is directly injected into the skin, while the second active ingredient acts on the skin surface, thereby achieving drug delivery to multiple layers and varying depths of the skin. This structure also prevents the first and second active ingredients from deteriorating and becoming ineffective due to a slow chemical reaction caused by prolonged mixing, thereby extending the shelf life of the product and achieving better therapeutic or cosmetic effects. In some embodiments, the first active ingredient is coenzyme Q10 for whitening, and the second active ingredient is asiaticoside for repair.

[0076] In some embodiments of the present application, the microneedle patch further comprises a slippery hydrogel layer. Figure 6 , Figure 6 A schematic structural diagram of a microneedle patch provided in one embodiment of the present application. Figure 6 In the embodiment, the microneedle patch includes a microneedle layer 10, an adhesive hydrogel layer 20, and a slippery hydrogel layer 30, wherein the microneedle layer 10 is located between the slippery hydrogel layer 30 and the adhesive hydrogel layer 20. Figure 7 , Figure 7A schematic structural diagram of a microneedle patch provided in one embodiment of the present application. Figure 7 In the present invention, the microneedle patch includes a microneedle layer 10, a viscous hydrogel layer 20, and a slippery hydrogel layer 30. The microneedle layer 10 is completely embedded in the viscous hydrogel layer 20, and the slippery hydrogel layer 30 covers the side of the viscous hydrogel layer 20 away from the microneedle tips. In this application, the provision of a slippery hydrogel layer facilitates the use of the microneedle patch with an instrument, thereby accelerating the penetration of the active ingredients in the microneedle patch and promoting absorption by the human body. Please refer to Figure 8 , Figure 8 This is a diagram of the use process of the microneedle patch provided in one embodiment of the present application. Figure 8 In the invention, the instrument can be an ultrasonic instrument or a radio frequency instrument. The ultrasonic instrument can generate ultrasonic waves. The mechanical energy generated by the ultrasonic cavitation effect can not only act on different depths of the skin and improve the firmness of the skin, but more importantly, it can also accelerate the diffusion and absorption of active components. The higher smoothness of the slippery hydrogel layer can reduce the air resistance and reduce the energy loss of ultrasound, thereby improving the efficiency of the instrument. The radio frequency instrument can generate heat energy, accelerate the diffusion of active components in the microneedle patch, thereby shortening the use time of the product. The hydrogel patch of the present application can reduce the sliding resistance of the radio frequency instrument on the skin and improve the experience of using the instrument.

[0077] In some embodiments of the present application, an ultrasonic instrument is used in conjunction with a microneedle patch. The power of the ultrasonic instrument is 50W to 80W, the frequency of the ultrasonic instrument is 40kHz to 50kHz, the action time of the ultrasonic instrument is 5min to 10min, and the action depth of the ultrasonic instrument is 5mm to 8mm. When the parameters of the ultrasonic instrument are controlled within the above ranges, the penetration of the active ingredient into the skin can be accelerated. In some embodiments of the present application, a radio frequency instrument is used in conjunction with a microneedle patch. The power of the radio frequency instrument is 6W to 10W, the frequency of the radio frequency instrument is 1MHz to 1.2MHz, the action time of the radio frequency instrument is 5min to 10min, and the action depth of the radio frequency instrument is 1mm to 5mm. When the parameters of the radio frequency instrument are controlled within the above ranges, the penetration of the active ingredient into the skin can be accelerated.

[0078] In the embodiments of the present application, the conductivity of the microneedle patch is 150 μS / cm to 250 μS / cm. The conductivity of the microneedle patch can be, but is not limited to, 150 μS / cm, 170 μS / cm, 200 μS / cm, 230 μS / cm, or 250 μS / cm. A microneedle patch with a certain conductivity can ensure that the patch can be used with the instrument.

[0079] In some embodiments of the present application, the slippery hydrogel layer comprises the following components in percentage by weight: 1% to 15% of a second polymer compound, 50% to 60% of water, 20% to 40% of a second polyol, and 1% to 6% of a second auxiliary agent. In some embodiments of the present application, the second polymer compound comprises one or more of carrageenan, xanthan gum, gelatin, or cellulose gum. The second polymer compound of the present application has excellent water-retention properties, ensuring the slippery hydrogel layer has high smoothness. During instrument operation, the surface of the microneedle patch maintains low surface roughness, thereby reducing instrument sliding resistance. In some embodiments of the present application, the second polyol comprises one or more of dipropylene glycol, sorbitol, or butylene glycol. These second polyols can effectively disperse the second polymer compound and inhibit its aggregation. Furthermore, during the interaction between the instrument probe and the slippery hydrogel layer, the second polyol's water absorption capacity prevents volatilization, thereby ensuring good stability of the slippery hydrogel layer. Furthermore, the second polyol's antibacterial properties provide the slippery hydrogel layer with a certain degree of corrosion resistance. In some embodiments of the present application, the second auxiliary agent includes one or more of an antimicrobial agent, a preservative, a colorant, or a flavoring agent. In some embodiments of the present application, the surface roughness of the slippery hydrogel layer is 1.6 μm to 3.2 μm. The surface roughness of the slippery hydrogel layer can be, but is not limited to, 1.6 μm, 2 μm, 2.2 μm, 2.5 μm, 2.7 μm, 3 μm, or 3.2 μm.

[0080] In the embodiments of the present application, the viscous hydrogel layer and the slippery hydrogel layer are bonded via hydrogen bonds and van der Waals forces, i.e., they are directly connected and in contact. The polymer compounds in both the viscous and slippery hydrogel layers contain a large number of hydroxyl and carboxyl groups, which facilitate interaction and bonding between the polymer compounds in the viscous and slippery hydrogel layers. This bonding ensures that the entire microneedle patch is conductive. During instrumentation, the instrument's energy is evenly distributed, promoting absorption of the active ingredient by the human body.

[0081] In some embodiments of the present application, the thickness of the slippery hydrogel layer is 1 mm to 5 mm. The thickness of the slippery hydrogel layer can be, but is not limited to, 1 mm, 2 mm, 3 mm, or 5 mm. In some embodiments, the thickness of the viscous hydrogel layer is greater than the thickness of the slippery hydrogel layer. The thicker viscous hydrogel layer facilitates sufficient fixation of the microneedles in the microneedle patch. In some embodiments of the present application, the thickness of the microneedle patch is 4 mm to 15 mm.

[0082] In some embodiments of the present application, the shape of the microneedle patch includes any one of a crescent shape, a horseshoe shape, a glasses shape, and a comma shape, and the shape of the microneedle patch can be cut according to needs. In some embodiments, the microneedle patch is applied to the eye, that is, used as an eye patch.

[0083] In some embodiments of the present application, the microneedle patch further includes a protective layer. Figure 9 , Figure 9 This is a schematic diagram of the structure of a microneedle patch provided in one embodiment of the present application. The microneedle patch includes a first protective layer 40, a microneedle layer 10, an adhesive hydrogel layer 20, and a second protective layer 50 arranged in sequence. The first protective layer can be a cloth-based non-woven fabric, and the second protective layer can be a pearlescent film. Figure 10 , Figure 10 This is a schematic structural diagram of a microneedle patch provided in one embodiment of the present application. The microneedle patch includes a third protective layer 60, a slippery hydrogel layer 30, a microneedle layer 10, a sticky hydrogel layer 20 and a fourth protective layer 70 arranged in sequence, wherein the third protective layer can be a pearlescent film and the fourth protective layer can be a pearlescent film.

[0084] The present application also provides a method for preparing a microneedle patch, comprising:

[0085] The microneedle layer is placed in a viscous hydrogel solution, and the viscous hydrogel solution is cross-linked and subjected to water loss treatment to obtain a microneedle patch;

[0086] In the present application, the preparation method of the viscous hydrogel solution includes: dispersing a first polymer compound in a first polyol, adding water, heating to 70°C to 85°C, adding a first auxiliary agent (excluding a crosslinking agent), and mixing to obtain a viscous hydrogel solution. The viscous hydrogel solution includes the following components in percentage by weight: 1% to 6% of the first polymer compound, 60% to 70% of water, 20% to 30% of the first polyol, and 0.1% to 6% of the first auxiliary agent. In an embodiment of the present application, after placing the microneedle layer in the viscous hydrogel solution, the viscous hydrogel solution is cross-linked and formed. The cross-linking forming includes: adding a crosslinking agent to the viscous hydrogel solution.

[0087] In some embodiments of the present application, the dehydration treatment temperature is 55° C. to 65° C., and the dehydration treatment time is 2 h to 3 h. The dehydration treatment can adjust the water content of the viscous hydrogel layer to ensure that the viscous hydrogel layer has moderate viscosity and structural strength.

[0088] In some embodiments of the present application, the preparation method of the microneedle patch is as follows Figure 11 As shown, Figure 11 This is a flow chart of a method for preparing a microneedle patch according to one embodiment of the present application.

[0089] In some embodiments of the present application, the method for preparing a microneedle patch includes:

[0090] Step 100: placing the microneedle layer in a viscous hydrogel solution, and obtaining a microneedle patch precursor after cross-linking and dehydration treatment of the viscous hydrogel solution. The microneedle patch precursor includes the microneedle layer and the viscous hydrogel layer;

[0091] Step 200: The slippery hydrogel base layer is subjected to a dehydration treatment to obtain a slippery hydrogel layer, and the slippery hydrogel layer is covered on the surface of the sticky hydrogel layer of the microneedle patch precursor away from the microneedle tips to obtain a microneedle patch.

[0092] In one embodiment of the present application, a method for preparing a slippery hydrogel base layer comprises: dispersing a second polymer compound in a second polyol, adding water, heating to 70°C to 85°C, adding a second additive, pouring the mixture into a mold, and cooling it to obtain the slippery hydrogel base layer. The slippery hydrogel base layer comprises the following components in percentage by weight: 1% to 4.5% of the second polymer compound, 60% to 80% of water, 20% to 30% of the second polyol, and 0.1% to 6% of the second additive.

[0093] In step 200 of the present application, when the slippery hydrogel layer is covered on the surface of the sticky hydrogel layer, since the sticky hydrogel layer has a certain adhesive force, the polymer compounds in the slippery hydrogel layer and the sticky hydrogel layer can be chemically bonded to form a composite structure.

[0094] The preparation method of the hydrogel patch provided in the present application is simple to operate, has a controllable process, and is suitable for industrial production.

[0095] The present application also provides a method for using the microneedle patch, comprising:

[0096] Step 100: Attaching the adhesive hydrogel layer of the microneedle patch to the skin surface;

[0097] Step 200: Press the microneedle patch, causing the adhesive hydrogel layer to deform and the microneedles to penetrate the skin to the target depth.

[0098] Step 300: The pressure is released, the viscous hydrogel layer returns to its original shape, leaving micropores in the skin, and the active ingredients in the viscous hydrogel layer penetrate the skin to the target depth.

[0099] In some embodiments, the method of using the microneedle patch includes:

[0100] Step 100: Attaching the adhesive hydrogel layer of the microneedle patch to the skin surface;

[0101] Step 200: Press the microneedle patch, causing the adhesive hydrogel layer to deform and the microneedles to penetrate the skin to the target depth.

[0102] Step 300: The pressure is released, the viscous hydrogel layer returns to its original shape, leaving micropores in the skin, and the active ingredients in the viscous hydrogel layer penetrate the skin to the target depth.

[0103] Step 400: Using an instrument to act on the slippery hydrogel layer to further accelerate the penetration rate of the active ingredient in the viscous hydrogel layer and shorten the time it takes for the active ingredient to penetrate into the target depth.

[0104] The following is a further description of the implementation of the present application with reference to a number of examples.

[0105] Example 1

[0106] 1. A method for preparing a microneedle patch, comprising:

[0107] Sodium polyacrylate and konjac gum were dispersed in methylpropylene glycol, water was added, heated to 75°C, and stirred at 2000 rpm for 15 minutes. After vacuuming, a uniform, bubble-free thick liquid was obtained. Sodium citrate was added to the liquid to adjust the pH to 6. A portion of the mixture was poured into a mold, and a microneedle layer was placed on the surface of the mixture. The mold was then filled with the mixture. Ferric sulfate was added to cross-link and form a viscous hydrogel solution. The viscous hydrogel solution included the following components by weight percentage: 1.5% sodium polyacrylate, 1% konjac gum, 30% methylpropylene glycol, 64.5% water, 2% ferric sulfate, and 1% sodium citrate. The viscous hydrogel solution was placed at 60°C for 2 hours and dehydrated to obtain a microneedle patch. The resulting microneedle patch had a microneedle length of 2 mm and a viscous hydrogel layer thickness of 3 mm.

[0108] 2. Application of the microneedle patch: Place one side of the sticky hydrogel layer of the microneedle patch on the skin surface and press firmly to allow the microneedles to penetrate the skin surface. Remove the pressing pressure and keep the microneedle patch attached. After 30 minutes, the content of the remaining active ingredient in the sticky hydrogel layer is 53.4% ​​of the initial content.

[0109] Example 2

[0110] 1. A method for preparing a microneedle patch, comprising:

[0111] Sodium polyacrylate and sodium alginate were dispersed in hexylene glycol, water was added, and the mixture was heated to 70°C. Stirring was carried out at 2000 rpm for 15 minutes. Vacuuming was performed to obtain a uniform, bubble-free, thick liquid. Sodium citrate was added to the liquid to adjust the pH to 6.5. A portion of the mixture was poured into a mold, and a microneedle layer was placed on the surface of the mixture. The mold was then filled with the mixture. Ferric sulfate was added to crosslink the viscous hydrogel solution to form the viscous hydrogel. The viscous hydrogel solution contained the following components in the following weight percentages: 2% sodium polyacrylate, 1% sodium alginate, 25% hexylene glycol, 69% water, 2% aluminum chloride, and 1% sodium citrate. The viscous hydrogel solution was then stored at 60°C for 2 hours and dehydrated to obtain the microneedle patch precursor.

[0112] Carrageenan, gum arabic, and konjac gum are dispersed in butylene glycol, water is added, and the mixture is heated to 80°C and stirred at 1000 rpm for 10 minutes. After vacuuming, a uniform, bubble-free, thick liquid is obtained. The mixture comprises the following components in percentage by weight: 2% carrageenan, 0.5% gum arabic, 0.5% konjac gum, 25% butylene glycol, and 72% water. The mixture is poured into a mold and cooled at 40°C to form a slippery hydrogel base layer. The slippery hydrogel base layer is then allowed to stand at 40°C for 4 hours to form a slippery hydrogel layer.

[0113] The viscous hydrogel layer and the slippery hydrogel layer were laminated to form a microneedle patch. The microneedle length of the obtained microneedle patch was 1.5 mm, the thickness of the viscous hydrogel layer was 3 mm, and the thickness of the slippery hydrogel layer was 3 mm.

[0114] 2. Application of the microneedle patch: Place one side of the sticky hydrogel layer in the microneedle patch on the skin surface, press hard to make the microneedles penetrate the skin surface, remove the pressing pressure, keep the microneedle patch attached, and use an ultrasonic instrument to continuously slide on the surface of the slippery hydrogel layer. The ultrasonic instrument has an operating power of 60W, an operating frequency of 45kHz, an operating depth of 6mm, and an operating time of 8 minutes. After 30 minutes, the content of the remaining active components in the sticky hydrogel layer is 48.2% of the initial content.

[0115] Example 3

[0116] 1. A method for preparing a microneedle patch, comprising:

[0117] Sodium polyacrylate, gum arabic, and konjac gum were dispersed in pentanediol, water was added, and the mixture was heated to 85°C. Stirring was carried out at 2000 rpm for 15 minutes, and vacuuming was performed to obtain a uniform, bubble-free, thick liquid. Sodium citrate was added to the liquid to adjust the pH to 6.8. A portion of the mixture was poured into a mold, and a microneedle layer was placed on the surface of the mixture. The mold was then filled with the mixture. Iron sulfate was added to cross-link and form a viscous hydrogel solution containing the following components by weight: 3% sodium polyacrylate, 0.5% gum arabic, 0.5% konjac gum, 22% pentanediol, 69% water, 3% aluminum sulfate, and 2% sodium citrate. The viscous hydrogel solution was then placed at 60°C for 2 hours and dehydrated to obtain a microneedle patch precursor.

[0118] Carrageenan and xanthan gum were dispersed in butanediol, water was added, and the mixture was heated to 70°C. Stirring was carried out at 1000 rpm for 10 minutes. Vacuuming was performed to obtain a uniform, bubble-free, thick liquid. The mixture comprised the following components by weight: 3% carrageenan, 0.5% xanthan gum, 20% butanediol, and 76.5% water. The mixture was poured into a mold and cooled at 40°C to form a slippery hydrogel base layer. The slippery hydrogel base layer was then allowed to stand at 40°C for 3 hours to obtain a slippery hydrogel layer.

[0119] The viscous hydrogel layer and the slippery hydrogel layer were laminated to form a microneedle patch. The microneedle length of the obtained microneedle patch was 1 mm, the thickness of the viscous hydrogel layer was 2 mm, and the thickness of the slippery hydrogel layer was 2 mm.

[0120] 2. Application of the microneedle patch: Attach one side of the sticky hydrogel layer in the microneedle patch to the skin surface, press hard to make the microneedles penetrate the skin surface, remove the pressing pressure, keep the microneedle patch attached, and use an ultrasonic instrument to continuously slide on the surface of the slippery hydrogel layer. The ultrasonic instrument has an action power of 55W, an action frequency of 40kHz, an action depth of 5mm, and an action time of 5 minutes. Use a radio frequency instrument to continuously slide on the surface of the slippery hydrogel layer. The radio frequency instrument has an action power of 6W, an action frequency of 1MHz, an action depth of 3mm, and an action time of 5 minutes. After 30 minutes, the content of the remaining active components in the sticky hydrogel layer is 45.7% of the initial content.

[0121] Example 4

[0122] 1. A method for preparing a microneedle patch, comprising:

[0123] Sodium polyacrylate, sodium alginate, gum arabic, and konjac gum were dispersed in pentanediol, water was added, and the mixture was heated to 85°C. Stirring was carried out at 2000 rpm for 15 minutes, and vacuumization was performed to obtain a uniform, bubble-free, thick liquid. Sodium citrate was added to the liquid to adjust the pH to 6.3. A portion of the mixture was poured into a mold, and a microneedle layer was placed on the surface of the mixture. The mold was then filled with the mixture. Iron sulfate was added to cross-link and form a viscous hydrogel solution. The viscous hydrogel solution contained the following components by weight: 2.5% sodium polyacrylate, 0.8% gum arabic, 0.5% sodium alginate, 0.3% konjac gum, 28% pentanediol, 63.4% water, 3% aluminum sulfate, and 1.5% sodium citrate. The viscous hydrogel solution was then placed at 60°C for 2 hours and dehydrated to obtain a microneedle patch precursor.

[0124] Carrageenan, xanthan gum, gum arabic, and konjac gum are dispersed in dipropylene glycol, water is added, and the mixture is heated to 70°C and stirred at 1000 rpm for 10 minutes. After vacuuming, a uniform, bubble-free, thick liquid is obtained. The mixture comprises the following components in percentage by weight: 2.5% carrageenan, 0.1% xanthan gum, 0.2% gum arabic, 0.1% konjac gum, 23% dipropylene glycol, and 74.1% water. The mixture is poured into a mold and cooled at 40°C to form a slippery hydrogel base layer. The slippery hydrogel base layer is then allowed to stand at 40°C for 3.5 hours to form a slippery hydrogel layer.

[0125] The viscous hydrogel layer and the slippery hydrogel layer were laminated to form a microneedle patch. The resulting microneedle patch had a microneedle length of 2.5 mm, a viscous hydrogel layer thickness of 4.5 mm, and a slippery hydrogel layer thickness of 4 mm.

[0126] 2. Application of the microneedle patch: Stick one side of the sticky hydrogel layer in the microneedle patch on the skin surface, press hard to make the microneedles penetrate the skin surface, remove the pressing pressure, keep the microneedle patch attached, and use a radio frequency instrument to continuously slide on the surface of the slippery hydrogel layer. The radio frequency instrument has an action power of 8W, an action frequency of 1.2MHz, an action depth of 4mm, and an action time of 8min; use an ultrasonic instrument to continuously slide on the surface of the slippery hydrogel layer. The ultrasonic instrument has an action power of 55W, an action frequency of 40kHz, an action depth of 5mm, and an action time of 5min. After 30min, the content of the remaining active components in the sticky hydrogel layer is 50.3% of the initial content.

[0127] Effect embodiment

[0128] In order to verify the performance of the microneedle patch prepared in this application, this application also provides an effect example.

[0129] 1) The water content of each hydrogel layer in the microneedle patches of Examples 1-4 was tested. The test conditions were as follows: the wet weight of the viscous hydrogel layer was measured as W1. The viscous hydrogel layer was then baked in an oven at 110°C for 24 hours to remove moisture. The dry weight of the viscous hydrogel layer was measured as W2. The difference between W1 and W2 was the water content of the viscous hydrogel layer. The water content of the slippery hydrogel layer was measured using the same method. For relevant test results, please refer to Table 1.

[0130] Table 1 Parameters of microneedle patches of Examples 1-4

[0131]

[0132] 2) The adhesion of the viscous hydrogel layer in the microneedle patches of Examples 1-4 was tested under the following test conditions: testing was performed on pig skin in accordance with GB / T 2792-2014 "Test Method for Peel Strength of Adhesive Tapes"; the smoothness of the slippery hydrogel layer was tested by roughness level comparison; and the conductivity of the microneedle patches of Examples 1-4 was tested using a conductivity meter. The relevant test results are shown in Table 2.

[0133] Table 2 Parameters of microneedle patches of Examples 1-4

[0134] Experimental group Adhesion force N Surface roughness (μm) Conductivity (μS / cm) Example 1 7.2 1.6 192.3 Example 2 5.4 3.2 172.8 Example 3 10.8 3.2 210.6 Example 4 17.7 1.6 228.8

[0135] 3) The elongation at break and elastic modulus of the viscous hydrogel layer in the microneedle patches of Examples 1-4 were tested. The elongation at break of the viscous hydrogel layer was measured using a Dongzhiri computerized double-arm tensile testing machine, and the elastic modulus of the viscous hydrogel layer was measured using a static GTM elastic modulus tester. For relevant test results, please refer to Table 3.

[0136] Table 3 Parameters of microneedle patches of Examples 1-4

[0137]

[0138]

[0139] The above-described embodiments merely illustrate several implementations of the present invention, and while their descriptions are relatively specific and detailed, they should not be construed as limiting the scope of the present invention. It should be noted that a person skilled in the art would be able to make numerous variations and improvements without departing from the spirit of the present invention, all of which fall within the scope of protection of the present invention. Therefore, the scope of protection of the present invention shall be determined by the appended claims.

Claims

1. A microneedle patch, characterized in that: The microneedle patch includes a microneedle layer and a sticky hydrogel layer, the microneedle layer includes a substrate and microneedles arranged on the surface of the substrate, the microneedles are all embedded in the sticky hydrogel layer, the thickness of the sticky hydrogel layer is greater than the length of the microneedles in the thickness direction of the sticky hydrogel layer; the thickness of the sticky hydrogel layer is 4mm~9mm; the microneedle patch also includes a slippery hydrogel layer arranged on the surface of the sticky hydrogel layer away from the microneedle needle tip, the water content of the slippery hydrogel layer is greater than the water content of the sticky hydrogel layer, and the instrument acts on the slippery hydrogel layer; the conductivity of the microneedle patch is 150μS / cm~250μS / cm.

2. The microneedle patch according to claim 1, wherein The ratio of the length of the microneedle in the thickness direction of the viscous hydrogel layer to the thickness of the viscous hydrogel layer is 0.5-0.

75.

3. The microneedle patch according to claim 1, wherein The length of the microneedle in the thickness direction of the viscous hydrogel layer is 1 mm to 3 mm.

4. The microneedle patch according to claim 1, wherein The elongation at break of the viscous hydrogel layer is 10% to 25%; and the elastic modulus of the viscous hydrogel layer is 0.1 MPa to 5 MPa.

5. The microneedle patch according to claim 1, wherein The microneedles include at least one of hollow microneedles and solid microneedles.

6. A method for preparing the microneedle patch according to any one of claims 1 to 5, characterized in that: include: placing the microneedle layer in a viscous hydrogel solution, and subjecting the viscous hydrogel solution to cross-linking, molding, and water-dehydration treatment to obtain a microneedle patch precursor; The microneedle patch precursor includes a microneedle layer and an adhesive hydrogel layer; The slippery hydrogel base layer is subjected to a dehydration treatment to obtain a slippery hydrogel layer, and the slippery hydrogel layer is covered on the surface of the adhesive hydrogel layer of the microneedle patch precursor away from the microneedle tip to obtain a microneedle patch; The microneedle layer includes a substrate and microneedles arranged on the surface of the substrate. The microneedles are all embedded in the viscous hydrogel layer. The thickness of the viscous hydrogel layer is greater than the length of the microneedles in the thickness direction of the viscous hydrogel layer.

7. The preparation method according to claim 6, wherein The temperature of the dehydration treatment is 55° C. to 65° C., and the time of the dehydration treatment is 2 h to 3 h.

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