Composite micro-current permeation-promoting skin patch and preparation method thereof

Abstract

The invention belongs to the technical field of skin care, and particularly relates to a composite micro-current permeation promoting skin patch and a preparation method thereof. The composite micro-current permeation-promoting skin patch comprises a controller and a permeation-promoting patch, and the controller is used for generating and outputting a direct-current micro-current signal used for achieving electric ion permeation and an alternating-current micro-current signal used for achieving EMS muscle electrical stimulation; the permeation promoting patch is detachably connected with the controller through a magnetic attraction buckle structure; the permeation promoting patch is of a flexible integral structure and comprises an elastic adhesive tape layer, an electrode slice layer, a sponge cloth layer, an adhesive layer and a release film which are sequentially stacked from top to bottom; the controller can stably output direct current and alternating current, the direct current is used for forming a directional stable electric field to drive the charged biological agent to realize electric ion permeation, and the charged biological agent directionally moves into the corium layer of the skin through directional release of the electrode slice layer and the sponge cloth layer; the alternating current is used for outputting a stimulation waveform matched with the EMS function, and the infiltration promotion efficiency is further improved by stimulating muscle movement.

Description

TECHNICAL FIELD

[0001] The present application belongs to the technical field of skin care, and particularly relates to a composite micro-current penetration-promoting skin patch and a preparation method thereof. BACKGROUND

[0002] As a natural barrier, the stratum corneum of the skin severely limits the transdermal penetration efficiency of cosmetic liquids, active ingredients and other biological agents, resulting in that most of the external biological agents are difficult to achieve the ideal effect. In order to break through this barrier, various penetration-promoting schemes have appeared in the prior art, but all have significant defects: manual application + massage: only relying on mechanical friction to assist penetration, which cannot break through the fundamental barrier of the stratum corneum, and the penetration-promoting effect is extremely limited; ultrasonic introduction, iontophoresis, and radiofrequency introduction equipment: although they can improve the penetration rate to a certain extent, such equipment is generally bulky, heavy, and high in manufacturing cost, and is difficult to achieve portable use; traditional patch-type hydrogel face patch + micro-current scheme: has the problems of poor adhesion and easy falling off, and is highly dependent on conductive media, and can only adapt to specific formulations of hydrogel; existing micro-current penetration-promoting equipment: most are in the form of large instruments, poor in portability, and also have the problem of poor biological agent adaptability, and the patch structure is mostly fixed and not replaceable, poor in hygiene, and not convenient for consumable promotion.

[0003] Micro-current does not damage the integrity of the skin tissue when acting on the skin, and can regulate the skin state through electrochemical action; and the composite micro-current refers to a dual-mode current combining direct current micro-current and alternating current micro-current. The technology realizes ion penetration through outputting direct current micro-current, and realizes EMS (electrical muscle stimulation) through alternating current micro-current, and the synergistic effect of the two can effectively widen the skin penetration channel, drive the directional migration of charged biological agents, and further improve the transdermal efficiency. However, the existing transdermal penetration-promoting scheme based on composite micro-current still has many significant defects, and cannot meet the actual use requirements. Therefore, it is a technical requirement to be solved in the current field to develop a transdermal patch which is simple in structure, strong in portability, can freely adapt to various biological agents, and has high penetration-promoting effect. SUMMARY

[0004] In view of the deficiencies of the prior art, the present application proposes a composite micro-current penetration promoting skin patch and a preparation method thereof; the present application adopts a multi-layer composite structure design, and through the synergistic compounding of the elastic adhesive tape layer, the electrode sheet layer, the sponge cloth liquid storage layer, the adhesive layer and the release film, an external magnetic attraction detachable micro-current controller is matched to form an integrated penetration promoting system.The preparation method covers the composite formation of the multi-layer structure of the patch and the preparation, debugging and pairing of the software and hardware of the controller, and the process is simple and controllable;The use method is convenient and easy to operate, can be adapted to various target biological agents, realizes one-time use of consumables, ensures hygiene, and solves the technical problems of poor adaptability, inconvenience, insufficient hygiene and limited penetration efficiency of the existing transdermal penetration promoting products.The present application effectively improves the transdermal penetration effect of biological agents through the AC and DC electricity output by the controller, and takes into account the adaptability, convenience and safety, solves the pain points of the limitations of the fixed formula of traditional products, the hygiene hazards of repeated use and the insufficient portability, is suitable for daily health care scenes, and has significant practical value.

[0005] In view of the deficiencies of the prior art, the technical solutions adopted by the present application are as follows: The present application provides a composite micro-current penetration promoting skin patch, which comprises a controller and a penetration promoting patch, the controller is used for generating and outputting a composite micro-current electric stimulation signal, the micro-current is a direct current micro-current signal for realizing ionic penetration and an alternating current micro-current signal for realizing EMS muscle electric stimulation, the output parameters of the two electric stimulation signals can be accurately controlled to realize double-mode independent work or synergistic penetration promotion;The penetration promoting patch is detachably connected with the controller through a magnetic attraction buckle structure; The penetration promoting patch is a flexible whole structure, and the elastic adhesive tape layer, the electrode sheet layer, the sponge cloth layer, the adhesive layer and the release film are sequentially stacked from top to bottom to form an integrated structure; The electrode sheet layer comprises the following raw materials in a mass ratio: TPU (thermoplastic polyurethane elastomer): [EMIM][TFSI] (1-ethyl-3-methylimidazolium bis(trifluoromethylsulfonyl) imide ionic liquid): graphene quantum dot: chitosan: graphene oxide dispersion = 100: 15-30: 1: 10: 1; The preparation method of the electrode sheet layer comprises the following steps: A1, take TPU, add N,N-dimethylformamide (DMF), the dosage ratio of TPU and DMF is 1g:10-15mL, stir in a 60℃ water bath until completely dissolved, then add [EMIM][TFSI], graphene quantum dots and mixed salt solution to it in sequence, the dosage ratio of mixed salt solution and graphene quantum dots is 10mL:1g, then place it in an ultrasonic cleaning instrument, ultrasonic dispersion for 60 minutes to obtain conductive slurry; A2, the conductive paste is cast on a clean glass substrate, the wet film thickness is controlled to be 200-300 μm by an automatic film doctor, then non-solvent induced phase separation is carried out, after soaking for 120 minutes, the conductive film is taken out and placed in flowing deionized water for continuous washing for 72 hours; A3, the conductive film is cut, taken as a working electrode, placed in an electrochemical cell containing 0.5 mol / L sodium chloride solution, a platinum sheet is taken as a counter electrode, a saturated calomel electrode is taken as a reference electrode, a direct current voltage of +5.0 V is applied for 30 minutes, after treatment, the surface is washed with deionized water, and naturally dried at room temperature to obtain a smart electrode layer pre-loaded with sodium ions; A4, chitosan is taken, 1% by mass fraction of glacial acetic acid solution is added, the use amount ratio of chitosan to glacial acetic acid solution is 1 g:100 mL, magnetic stirring is carried out in a 40℃ water bath until completely dissolved to obtain a chitosan solution with a mass concentration of 1%, the chitosan solution is mixed with a graphene oxide dispersion solution with a mass concentration of 2 mg / mL to form a mixed solution, the mixed solution is placed in an ice water bath, and ultrasonic treatment is carried out for 30 minutes to obtain a uniform composite sol; A5, the composite sol is injected into a specially-made polytetrafluoroethylene mold, a one-way freezing gradient of 10℃ / min is set, freezing is carried out from the bottom to the top, the freezing process lasts for 120 minutes, after the sol is completely frozen, the sample is quickly transferred to a freeze dryer together with the mold, and drying is carried out for 48 hours to obtain a porous scaffold; A6, the porous scaffold is immersed in anhydrous ethanol solution containing 1% by mass fraction of glutaraldehyde, crosslinking treatment is carried out in a 50℃ water bath for 6 hours, after the crosslinking is completed, washing is carried out with deionized water until the pH value of the washing liquid is neutral, then the scaffold is transferred to an ascorbic acid solution with a mass concentration of 0.1 mol / L, reduction is carried out in a 90℃ water bath for 12 hours, the hydrogel scaffold after reduction is immersed in an ethanol solution containing 3% by volume fraction of 3-aminopropyltriethoxysilane, reaction is carried out at room temperature for 24 hours, after taking out, washing is carried out with ethanol for 3 times, then the scaffold is immersed in a N,N-dimethylformamide solution of succinic anhydride with a mass concentration of 5%, reaction is carried out at 60℃ for 6 hours to obtain a bridging layer; A7, a layer of medical-grade silicone gel adhesive is uniformly coated on the ion preloading surface of the smart electrode layer, the coating thickness is controlled to be 10-15 μm, the bridging layer is aligned with the adhesive surface with the inlet face of the vertical pore facing downward, high-precision lamination equipment is used for precise alignment and lamination, after lamination, pressure bonding is carried out under the condition of 0.2 MPa pressure and room temperature for 60 seconds, then the sample is transferred to a 60℃ oven for curing for 120 minutes to form an electrode sheet layer.

[0006] Further, the mixed salt solution is prepared by mixing 0.1 mol / L sodium chloride solution and 0.1 mol / L potassium chloride solution, and the volume ratio of the two is 1:1.

[0007] The sponge cloth layer is prepared from high water absorption sponge and functional composite microspheres, and the temperature-sensitive drug-loaded microspheres comprise the following raw materials in a mass ratio: N-isopropyl acrylamide:N,N'-methylene bisacrylamide: ammonium persulfate: CTAB (hexadecyl trimethyl ammonium bromide) = 2-3:0.1:0.1:2. Preferably, the high water absorption sponge is one of polyurethane sponge, polyether sponge and polyester sponge. The preparation method of the sponge cloth layer comprises the following steps: Y1, N-isopropyl acrylamide and N,N'-methylene bisacrylamide are dissolved in deionized water, the dosage ratio of N-isopropyl acrylamide to deionized water is 1g:100mL, high-purity nitrogen is bubbled to remove oxygen for 30 minutes, ammonium persulfate is added, the temperature is raised to 70℃, and the reaction is carried out under nitrogen protection for 6 hours; after the reaction is completed, the obtained emulsion is centrifuged and separated, the precipitate is collected, washed and dried for 24 hours to obtain temperature-sensitive microspheres; Y2, CTAB is dissolved in deionized water, 28% ammonia water solution is added, and stirred uniformly, tetraethyl orthosilicate is added dropwise under vigorous stirring, the dosage ratio of CTAB, tetraethyl orthosilicate, ammonia water solution and deionized water is 2g:5mL:10mL:200mL, and the stirring is continued at room temperature for 24 hours; the precipitate is collected by centrifugation, washed, placed in a muffle furnace, heated to 550℃ at a rate of 2℃ / min at room temperature, and calcined for 6 hours to remove the template agent to obtain mesoporous silica microspheres; Y3, the high water absorption sponge is cut into a preset size, the temperature-sensitive microspheres and the mesoporous silica microspheres are mixed according to a mass ratio of 2:1 to form functional composite microspheres, which are ultrasonically dispersed in anhydrous ethanol to prepare a suspension with a solid content of 15%, the sponge sheet is immersed in the suspension, and dried to constant weight to obtain the sponge cloth layer.

[0008] Further, the shell of the controller is made of PC (polycarbonate) / ABS (acrylonitrile-butadiene-styrene copolymer) material, has a light, thin and small structure, and is internally integrated with a micro-current waveform output module, an MCU (microcontroller) control chip, a power module (battery), functional buttons and indicator lights. The micro-current waveform output module is internally provided with a full-bridge inverter circuit, which can invert the direct current provided by the power module into an alternating micro-current suitable for the EMS function; the MCU control chip serves as a main control unit and independently regulates and controls the output voltage, frequency, waveform and working time sequence of the direct micro-current and the alternating micro-current, so as to realize independent working or collaborative penetration switching of the ion permeation and EMS penetration promotion modes and adapt to the transdermal penetration requirements of different biological agents. The biological agent added in the transdermal patch, i.e. the substance component with charged ions, is stably carried with a specified single charge through pH value adjustment technology, thereby providing a basic condition for ion permeation and penetration promotion.

[0009] The controller precisely connects to the electrode layer of the penetration-enhancing patch via a magnetic electrode interface, ensuring distortion-free transmission of DC and AC microcurrents. The controller can stably output adjustable 3-100V DC and AC power. The DC power is used to create a directional, stable electric field, driving charged biological agents to achieve ion penetration. Under the Coulomb force of the directional electric field, the charged biological agents are directionally released through the electrode layer and sponge layer, smoothly passing through the tiny gaps in the stratum corneum, hair follicles, and sweat gland channels, moving directionally into the dermis to achieve precise transdermal delivery of active ingredients. The AC power is used to output stimulation waveforms adapted to EMS functionality, further enhancing penetration efficiency and the absorption and diffusion of active ingredients in the dermis by stimulating muscle movement. The two work synergistically to achieve highly efficient transdermal penetration.

[0010] The elastic adhesive tape layer is made of elastic fabric, selected from PE (polyethylene) elastic fabric, spandex elastic fabric, and non-woven composite elastic fabric; the elastic adhesive tape layer has good extensibility and skin-fit, can adapt to the contours of different parts of the skin, improve the overall adhesion stability of the patch, and at the same time protect the internal structure. The electrode sheet is provided with at least two magnetic conductive contacts, which are matched with the magnetic electrode interface of the external controller to realize automatic alignment, electrical connection and mechanical fixation with the external controller. The adhesive layer is attached to the lower surface of the sponge fabric layer and is made of medical-grade skin-friendly hydrogel or pressure-sensitive adhesive. The adhesive layer has good biocompatibility and adhesion, which can stably fix the patch to the skin surface without causing skin irritation. The release film is attached to the lower surface of the adhesive layer as a packaging protective layer. It is made of non-stick material and can be peeled off before use. It can effectively protect the adhesiveness of the adhesive layer and avoid contamination during transportation and storage.

[0011] The method for preparing the controller includes the following steps: i. Housing preparation: Take PC / ABS composite material and injection mold the controller housing, reserve the component assembly position, function button mounting hole, indicator light mounting hole and magnetic electrode interface mounting position, design PCB circuit board, and solder the micro current waveform output module, MCU control chip, power module and full bridge inverter circuit components to the PCB circuit board. ii. Program the microcurrent control program into the MCU control chip, adjust the microcurrent output parameters, and enable the controller to programmatically output a composite microcurrent signal of electro-ionization mode and EMS ionization mode. Assemble the PCB circuit board, lithium battery, function buttons, indicator lights, and magnetic electrode interface into the shell in sequence, seal and close it, and then power on to test to ensure that the controller works stably and the microcurrent transmission is normal, thus obtaining the controller.

[0012] This invention also provides a method for preparing a composite microcurrent-enhanced skin patch, specifically including the following steps: S1, Take the elastic fabric and cut it to obtain the elastic adhesive tape layer; S2, take the electrode sheet, set magnetic conductive contacts on the electrode sheet, then attach the electrode sheet to the lower surface of the elastic adhesive tape layer, and press it together to form the first composite. S3, take the sponge cloth layer, perform hydrophilic treatment on the sponge cloth layer, soak it in deionized water for 2-3 hours, then take it out and dry it, apply medical grade adhesive to the lower surface of the electrode sheet layer, align and attach the treated sponge cloth layer to the lower surface of the first composite, and perform constant temperature curing treatment after attachment to form the second composite. S4. Select medical-grade skin-friendly hydrogel or pressure-sensitive adhesive as the adhesive material, coat the adhesive material evenly on the upper surface of the release film, cure it to form an adhesive layer, then align the composite structure of the adhesive layer and the release film and attach it to the lower surface of the second composite. After attachment, perform a pressing process to form the third composite. S5. Cut the third composite material into whole pieces, inspect the appearance of the cut patches, package them to obtain the penetration-enhancing patches, magnetically connect the controller to the penetration-enhancing patches, inspect and package them to obtain composite microcurrent penetration-enhancing skin patches.

[0013] The method of using the composite microcurrent-enhanced skin patch prepared by this invention includes the following steps: (1) The user takes out the composite microcurrent-promoting skin patch of the present invention and peels off the release film; (2) The target biological agent is dripped onto the sponge cloth layer to ensure that the biological agent is fully adsorbed by the sponge cloth layer; (3) Attach the patch to the target skin area through the adhesive layer and press gently to make the patch adhere tightly to the skin; (4) Align the controller with the magnetic conductive contacts of the patch electrode layer by magnetic attraction to achieve the fixation and electrical connection between the controller and the patch; (5) Start the device by pressing the function button on the controller. The controller outputs a preset output waveform, which is transmitted to the skin surface through the electrode sheet and the sponge cloth layer. (6) After use, turn off the controller, separate the controller from the patch, peel off the patch and discard it to achieve one-time use of consumables.

[0014] Compared with the prior art, the beneficial effects achieved by the present invention are as follows: 1. Wide compatibility with biological agents: Through the independent sponge layer design, it can hold various liquid biological agents, improving the flexibility of use. At the same time, the composite microcurrent controller can independently adjust the AC and DC microcurrent output parameters, and the built-in full-bridge inverter circuit can invert DC power into AC power adapted to EMS function, which can be adapted to biological agents with different charge characteristics and different concentrations. 2. High transdermal penetration efficiency: The electrode sheet design enables the constant charge adaptation and directional driving of biological agents. The intelligent electrode layer is preloaded with balanced ions, and the pH-responsive modification of the biomimetic ion bridging layer helps maintain the charge stability of biological agents. Combined with the directional electric field generated by the controller output, the biological agents can penetrate into the dermis through the tiny gaps in the stratum corneum, hair follicles, and sweat gland channels under the action of the electric field, greatly improving the directionality and efficiency of penetration. The AC microcurrent output by the controller can realize EMS muscle electrical stimulation. By stimulating the rhythmic contraction and relaxation of muscles, it further widens the skin penetration channels and promotes the absorption and diffusion of the agent in the dermis. It forms a synergistic effect with the electrode sheet and the sponge cloth layer. After modification, the sponge cloth layer has dual liquid-locking and anti-leakage and micro-thermal response active drug release characteristics. It can work synergistically with the microcurrent of the controller to improve the penetration efficiency, adapt to a variety of biological agents, and significantly improve the transdermal penetration efficiency of biological agents. 3. Convenient and hygienic to use: The controller is miniaturized and portable, and the magnetic connection makes it easy to operate. At the same time, the magnetic interface ensures distortion-free transmission of microcurrents, ensuring that the core penetration-promoting principle of the controller's AC and DC dual microcurrents is fully utilized. The patch adopts a replaceable consumable design, which is disposable and avoids hygiene risks such as bacterial growth caused by repeated use. In addition, the patch achieves stable adhesion through the adhesive layer, and with the extensibility of the elastic adhesive tape layer, it can be adapted to the skin of different parts such as the face, neck, and limbs, making it suitable for a wide range of applications. 4. Reasonable structural design: It adopts a multi-layer composite flexible structure with each layer tightly bonded. The liquid storage layer and the electrode sheet layer are tightly bonded, which can effectively prevent leakage of biological agents. At the same time, the permeation-enhancing patch and the controller are connected by magnetic detachment to achieve automatic alignment, which is simple to operate and not easy to misconnect. 5. Advantages of the preparation process: The preparation method is simple and highly controllable, with reasonable process parameters for each step, enabling large-scale production and lower production costs, which is conducive to the market promotion of the product. Attached Figure Description

[0015] Figure 1 This is a schematic diagram of the overall structure of the composite microcurrent-enhanced skin patch prepared according to the present invention; Figure 2 This is a schematic diagram of the installation structure of the composite microcurrent-enhanced skin patch prepared according to the present invention; Figure 3 This is a schematic diagram of the structure of the penetration-enhancing patch prepared according to the present invention; The following are the symbols and their meanings: 1. Controller; 2. Permeation-enhancing patch; 3. Magnetic conductive contact; 4. Elastic adhesive tape layer; 5. Electrode sheet layer; 6. Sponge cloth layer; 7. Adhesive layer; 8. Release film. Detailed Implementation

[0016] To enable those skilled in the art to better understand the technical solutions of the present invention and to make the above-mentioned features, objectives, and advantages of the present invention clearer and easier to understand, the present invention will be further described below with reference to embodiments. These embodiments are for illustrative purposes only and are not intended to limit the scope of the present invention.

[0017] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as those familiar to those skilled in the art. Furthermore, any methods and materials similar to or equivalent to those described herein may be applied to this invention. The preferred embodiments and materials described herein are for illustrative purposes only and do not limit the scope of this application.

[0018] Unless otherwise specified, all methods described in the following embodiments are conventional. Unless otherwise specified, all materials used in the following embodiments are new materials purchased from the market.

[0019] Example 1: This example provides a composite microcurrent permeation-enhancing skin patch, which includes a controller and a permeation-enhancing patch. The controller is used to generate and output an electrical stimulation signal, and the permeation-enhancing patch is detachably connected to the controller via a magnetic snap-fit ​​structure. The penetration-enhancing patch is a flexible integral structure, which includes, from top to bottom, an elastic adhesive layer, an electrode sheet layer, a sponge cloth layer, an adhesive layer, and a release film, with each layer tightly bonded together to form an integrated structure. The elastic adhesive tape layer is made of PE elastic fabric; The electrode sheet is provided with two magnetic conductive contacts, which are matched with the magnetic electrode interface of the external controller, enabling automatic alignment, electrical connection and mechanical fixation with the external controller; The adhesive layer is bonded to the lower surface of the sponge fabric layer and is made of hyaluronic acid hydrogel. The release film is adhered to the lower surface of the adhesive layer as a packaging protective layer; the release film is a PET film coated with a silicone anti-stick coating, which can be peeled off before use; The electrode sheet comprises raw materials in the following mass ratio: TPU:[EMIM][TFSI]:graphene quantum dots:chitosan:graphene oxide dispersion = 100:15:1:10:1; The method for preparing the electrode sheet includes the following steps: A1. Take TPU and add it to DMF. The ratio of TPU to DMF is 1g:10mL. Stir in a 60℃ water bath until completely dissolved. Add [EMIM], [TFSI], graphene quantum dots and mixed salt solution in sequence. The mixed salt solution is prepared by mixing 0.1mol / L sodium chloride solution and 0.1mol / L potassium chloride solution in a volume ratio of 1:1. The ratio of mixed salt solution to graphene quantum dots is 10mL:1g. Then place the mixture in an ultrasonic cleaner and ultrasonically disperse it at 500W for 60 minutes to obtain a uniform black conductive slurry. A2. The conductive paste is poured onto a clean glass substrate. The wet film thickness is controlled to be 200μm using an automatic film coating machine. The entire glass plate coated with the paste is immediately immersed in a 25°C deionized water coagulation bath for non-solvent-induced phase separation. After soaking for 120 minutes, it is taken out and placed in flowing deionized water for continuous washing for 72 hours. The washing water is changed every 24 hours to completely remove residual solvent and form a conductive film. A3. The conductive film was cut into a 10cm×10cm square sheet and used as the working electrode. It was placed in an electrochemical cell containing a 0.5mol / L sodium chloride solution, with a platinum sheet as the counter electrode and a saturated calomel electrode as the reference electrode. A +5.0V DC voltage was applied for 30 minutes. After treatment, the film was removed, the surface was rinsed with deionized water, and it was air-dried at room temperature to obtain a smart electrode layer preloaded with sodium ions. A4. Take chitosan and add it to a 1% (w / w) glacial acetic acid solution. The ratio of chitosan to glacial acetic acid solution is 1g:100mL. Stir magnetically in a 40℃ water bath until completely dissolved to obtain a 1% (w / w) chitosan solution. Mix the chitosan solution with a 2mg / mL (w / w) graphene oxide dispersion. Place the mixture in an ice-water bath and sonicate at 400W for 30 minutes to obtain a uniform composite sol. A5. The composite sol was injected into a specially made polytetrafluoroethylene mold. The bottom of the mold was a copper heat-conducting plate, and the side walls were made of polyurethane insulation material. The bottom of the mold was placed on a copper cold finger cooled by liquid nitrogen. A unidirectional freezing gradient of 10℃ / min was set, and freezing was carried out from the bottom up. The freezing process lasted for 120 minutes. After the composite sol was completely frozen, the sample and the mold were quickly transferred to a freeze dryer and dried at -50℃ and 0.1Pa for 48 hours to obtain a porous scaffold. A6. The porous scaffold was immersed in an anhydrous ethanol solution containing 1% glutaraldehyde and crosslinked in a 50°C water bath for 6 hours. After crosslinking, it was repeatedly rinsed with deionized water until the pH of the washing solution was neutral. Then, the scaffold was transferred to a 0.1 mol / L ascorbic acid solution and reduced in a 90°C water bath for 12 hours. The reduced hydrogel scaffold was immersed in an ethanol solution containing 3% 3-aminopropyltriethoxysilane and reacted at room temperature for 24 hours. After removal, it was washed three times with ethanol. Then, the scaffold was immersed in a 5% N,N-dimethylformamide solution of succinic anhydride and reacted at 60°C for 6 hours. Finally, pH-responsive carboxyl groups were modified on the inner wall of the nanochannel to obtain a bridging layer. A7. A layer of medical-grade silicone gel adhesive is uniformly coated on the ion preload surface of the smart electrode layer, with the coating thickness controlled at 10μm. The bridging layer is aligned with the adhesive coating surface with the entrance face of its vertical channel, and precise alignment and bonding are performed using a high-precision bonding device. After bonding, it is pressed for 60 seconds under a pressure of 0.2MPa and room temperature, and then transferred to a 60℃ oven for curing for 120 minutes to form an electrode sheet.

[0020] The sponge fabric layer is made of superabsorbent sponge and functional composite microspheres. The functional composite microspheres include raw materials in the following mass ratio: N-isopropylacrylamide: N,N'-methylenebisacrylamide: ammonium persulfate: CTAB = 2:0.1:0.1:2. The method for preparing the sponge fabric layer includes the following steps: Y1, N-isopropylacrylamide and N,N'-methylenebisacrylamide were dissolved in deionized water at a ratio of 1g:100mL. High-purity nitrogen gas was bubbled through the solution to remove oxygen for 30 minutes. Ammonium persulfate was added, and the temperature was raised to 70℃. The reaction was carried out under nitrogen protection for 6 hours. After the reaction was completed, the resulting emulsion was centrifuged, the precipitate was collected, washed three times with anhydrous ethanol, and dried in a freeze dryer for 24 hours to obtain temperature-sensitive microspheres. Y2, CTAB was dissolved in deionized water, and 28% ammonia solution was added. The mixture was stirred until homogeneous, and tetraethyl orthosilicate was added dropwise under vigorous stirring. The ratio of CTAB, tetraethyl orthosilicate, ammonia solution and deionized water was 2g:5mL:10mL:200mL. The mixture was stirred at room temperature for 24 hours. The precipitate was collected by centrifugation and washed three times alternately with deionized water and ethanol. The precipitate was placed in a muffle furnace and heated to 550℃ at a rate of 2℃ / min at room temperature. The temperature was maintained for calcination for 6 hours to remove the template agent and obtain mesoporous silica microspheres. Y3. Take polyurethane sponge and cut it into 6cm×3cm sizes. Mix temperature-sensitive microspheres and mesoporous silica microspheres at a mass ratio of 2:1 to form functional composite microspheres. Disperse the mixture ultrasonically in anhydrous ethanol to prepare a suspension with a solid content of 15%. Immerse the cut polyurethane sponge in the suspension and place it in a vacuum dryer. Evacuate the vacuum to -0.1MPa and maintain it for 30 minutes to allow the suspension to fully penetrate the pores of the sponge. Remove the sponge and dry it in a 60℃ oven to constant weight to obtain the sponge cloth layer.

[0021] The method for preparing the controller includes the following steps: i. Housing preparation: Take PC / ABS composite material and injection mold the controller housing, reserve the component assembly position, function button mounting hole, indicator light mounting hole and magnetic electrode interface mounting position, design PCB circuit board, and solder the micro current waveform output module, MCU control chip, power module and full bridge inverter circuit components to the PCB circuit board. ii. Program the microcurrent control program into the MCU control chip, adjust the microcurrent output parameters, and enable the controller to programmatically output a composite microcurrent signal of electro-ionization mode and EMS ionization mode. Assemble the PCB circuit board, lithium battery, function buttons, indicator lights, and magnetic electrode interface into the shell in sequence, seal and close it, and then power on to test to ensure that the controller works stably and the microcurrent transmission is normal, thus obtaining the controller.

[0022] This embodiment also provides a method for preparing a composite microcurrent-enhanced skin patch, which specifically includes the following steps: S1. Select a PE elastic cloth with a thickness of 0.1mm, set the patch size to 6cm×3cm, cut it to obtain the elastic adhesive cloth layer, and after cutting, grind the edges of the elastic adhesive cloth layer to remove burrs. S2, set magnetic conductive contacts on the electrode sheet to ensure that the position of the magnetic conductive contacts corresponds to the magnetic electrode interface of the external controller. Then, use medical acrylic pressure-sensitive adhesive to attach the electrode sheet to the lower surface of the elastic adhesive tape layer, and then press it together. The pressing pressure is 0.3MPa, the pressing temperature is 40℃, and the pressing time is 10s to form the first composite. S3. The sponge cloth layer is hydrophilicized by immersing it in deionized water for 2 hours, then it is taken out and dried to constant weight. Medical acrylic pressure-sensitive adhesive is evenly applied to the lower surface of the electrode sheet. The treated sponge cloth layer is aligned and attached to the lower surface of the first composite. The second composite is formed by constant temperature curing for 30 minutes at a curing temperature of 50°C. S4. Select hyaluronic acid hydrogel, uniformly coat the hyaluronic acid hydrogel on the upper surface of the release film with a coating thickness of 0.1 mm, cure for 20 min at a curing temperature of 60℃ to form an adhesive layer. Then, align the adhesive layer and the composite structure of the release film and attach them to the lower surface of the second composite. Press them together with a pressure of 0.2 MPa for 5 s to ensure that the adhesive layer and the sponge cloth layer are tightly bonded together to form the third composite. S5, Cutting and Packaging: Cut the third composite into 6cm×3cm patches, individually aseptically package the qualified patches to obtain penetration-enhancing patches, magnetically connect the controller to the penetration-enhancing patches, test, and package to obtain composite microcurrent penetration-enhancing skin patches.

[0023] Example 2: This example provides a composite microcurrent permeation-enhancing skin patch, which includes a controller and a permeation-enhancing patch. The controller is used to generate and output an electrical stimulation signal, and the permeation-enhancing patch is detachably connected to the controller via a magnetic snap-fit ​​structure. The penetration-enhancing patch is a flexible integral structure, which includes, from top to bottom, an elastic adhesive layer, an electrode sheet layer, a sponge cloth layer, an adhesive layer, and a release film, with each layer tightly bonded together to form an integrated structure. The elastic adhesive layer is made of a lightweight film and is made of spandex elastic fabric; The electrode sheet is provided with two magnetic conductive contacts, which are matched with the magnetic electrode interface of the external controller, enabling automatic alignment, electrical connection and mechanical fixation with the external controller; The adhesive layer is bonded to the lower surface of the sponge fabric layer and is made of sodium alginate hydrogel. The release film is adhered to the lower surface of the adhesive layer as a packaging protective layer; the release film is made of an anti-stick material and can be peeled off before use.

[0024] The method for preparing the controller is the same as in Example 1.

[0025] The electrode sheet comprises raw materials in the following mass ratio: TPU:[EMIM][TFSI]:graphene quantum dots:chitosan:graphene oxide dispersion = 100:20:1:10:1; The method for preparing the electrode sheet includes the following steps: A1. Take TPU and add it to DMF. The ratio of TPU to DMF is 1g:12mL. Stir in a 60℃ water bath until completely dissolved. Add [EMIM], [TFSI], graphene quantum dots and mixed salt solution in sequence. The mixed salt solution is prepared by mixing 0.1mol / L sodium chloride solution and 0.1mol / L potassium chloride solution in a volume ratio of 1:1. The ratio of mixed salt solution to graphene quantum dots is 10mL:1g. Then place the mixture in an ultrasonic cleaner and ultrasonically disperse it at 500W for 60 minutes to obtain a uniform black conductive slurry. A2. The conductive paste is poured onto a clean glass substrate. The wet film thickness is controlled to be 250μm using an automatic film coating machine. The entire glass plate coated with the paste is immediately immersed in a 25°C deionized water coagulation bath for non-solvent-induced phase separation. After soaking for 120 minutes, it is taken out and placed in flowing deionized water for continuous washing for 72 hours. The washing water is changed every 24 hours to completely remove residual solvent and form a conductive film. A3. The conductive film was cut into a 10cm×10cm square sheet and used as the working electrode. It was placed in an electrochemical cell containing a 0.5mol / L sodium chloride solution, with a platinum sheet as the counter electrode and a saturated calomel electrode as the reference electrode. A +5.0V DC voltage was applied for 30 minutes. After treatment, the film was removed, the surface was rinsed with deionized water, and it was air-dried at room temperature to obtain a smart electrode layer preloaded with sodium ions. A4. Take chitosan and add it to a 1% (w / w) glacial acetic acid solution. The ratio of chitosan to glacial acetic acid solution is 1g:100mL. Stir magnetically in a 40℃ water bath until completely dissolved to obtain a 1% (w / w) chitosan solution. Mix the chitosan solution with a 2mg / mL (w / w) graphene oxide dispersion. Place the mixture in an ice-water bath and sonicate at 400W for 30 minutes to obtain a uniform composite sol. A5. The composite sol was injected into a specially made polytetrafluoroethylene mold. The bottom of the mold was a copper heat-conducting plate, and the side walls were made of polyurethane insulation material. The bottom of the mold was placed on a copper cold finger cooled by liquid nitrogen. A unidirectional freezing gradient of 10℃ / min was set, and freezing was carried out from the bottom up. The freezing process lasted for 120 minutes. After the sol was completely frozen, the sample and the mold were quickly transferred to a freeze dryer and dried at -50℃ and 0.1Pa for 48 hours to obtain a porous scaffold. A6. The porous scaffold was immersed in an anhydrous ethanol solution containing 1% glutaraldehyde and crosslinked in a 50°C water bath for 6 hours. After crosslinking, it was repeatedly rinsed with deionized water until the pH of the washing solution was neutral. Then, the scaffold was transferred to a 0.1 mol / L ascorbic acid solution and reduced in a 90°C water bath for 12 hours. The reduced hydrogel scaffold was immersed in an ethanol solution containing 3% 3-aminopropyltriethoxysilane and reacted at room temperature for 24 hours. After removal, it was washed three times with ethanol. Then, the scaffold was immersed in a 5% N,N-dimethylformamide solution of succinic anhydride and reacted at 60°C for 6 hours. Finally, pH-responsive carboxyl groups were modified on the inner wall of the nanochannel to obtain a bridging layer. A7. A layer of medical-grade silicone gel adhesive is uniformly coated on the ion preload surface of the smart electrode layer, with the coating thickness controlled at 15μm. The bridging layer is aligned with the adhesive coating surface with the entrance face of its vertical channel, and precise alignment and bonding are performed using a high-precision bonding device. After bonding, it is pressed for 60 seconds under 0.2MPa pressure and room temperature, and then transferred to a 60℃ oven for curing for 120 minutes to form an electrode sheet.

[0026] The sponge fabric layer is made of super absorbent sponge and functional composite microspheres. The functional composite microspheres include raw materials in the following mass ratio: N-isopropylacrylamide: N,N'-methylenebisacrylamide: ammonium persulfate: CTAB = 2.5: 0.1: 0.1: 2. The method for preparing the sponge fabric layer includes the following steps: Y1, N-isopropylacrylamide and N,N'-methylenebisacrylamide were dissolved in deionized water at a ratio of 1g:100mL. High-purity nitrogen gas was bubbled through the solution to remove oxygen for 30 minutes. Ammonium persulfate was added, and the temperature was raised to 70℃. The reaction was carried out under nitrogen protection for 6 hours. After the reaction was completed, the resulting emulsion was centrifuged, the precipitate was collected, washed three times with anhydrous ethanol, and dried in a freeze dryer for 24 hours to obtain temperature-sensitive microspheres. Y2, CTAB was dissolved in deionized water, and 28% ammonia solution was added. The mixture was stirred until homogeneous, and tetraethyl orthosilicate was added dropwise under vigorous stirring. The ratio of CTAB, tetraethyl orthosilicate, ammonia solution and deionized water was 2g:5mL:10mL:200mL. The mixture was stirred at room temperature for 24 hours. The precipitate was collected by centrifugation and washed three times alternately with deionized water and ethanol. The precipitate was placed in a muffle furnace and heated to 550℃ at a rate of 2℃ / min at room temperature. The temperature was maintained for calcination for 6 hours to remove the template agent and obtain mesoporous silica microspheres. Y3. Take polyether sponge and cut it into 8cm×4cm sizes. Mix temperature-sensitive microspheres and mesoporous silica microspheres at a mass ratio of 2:1 to form functional composite microspheres. Disperse the mixture ultrasonically in anhydrous ethanol to prepare a suspension with a solid content of 15%. Immerse the cut polyether sponge in the suspension and place it in a vacuum dryer. Evacuate the vacuum to -0.1MPa and maintain it for 30 minutes to allow the suspension to fully penetrate the pores of the sponge. Remove the sponge and dry it in a 60℃ oven to constant weight to obtain the sponge fabric layer.

[0027] This embodiment also provides a method for preparing a composite microcurrent-enhanced skin patch, which specifically includes the following steps: S1. Select 0.1mm spandex elastic fabric with a size of 8cm×4cm. Cut the elastic fabric layer using a cutting device. After cutting, grind the edges of the elastic fabric layer to remove burrs. S2, set magnetic conductive contacts on the electrode sheet to ensure that the position of the magnetic conductive contacts corresponds to the magnetic electrode interface of the external controller. Then, use medical silicone pressure-sensitive adhesive to attach the electrode sheet to the lower surface of the elastic adhesive tape layer. After attachment, press the electrode sheet to form the first composite by pressing at a pressure of 0.4 MPa, a temperature of 45°C and a time of 15 seconds. S3. The sponge cloth layer is hydrophilicized by immersing it in deionized water for 2.5 hours. Then, it is taken out and dried to constant weight. Medical silicone pressure-sensitive adhesive is evenly applied to the lower surface of the electrode sheet. The treated sponge cloth layer is aligned and attached to the lower surface of the first composite. After attachment, it is cured at a constant temperature of 55°C for 35 minutes to form the second composite. S4. Select sodium alginate hydrogel and coat it evenly on the upper surface of the release film using a coating process. The coating thickness is 0.2 mm. Then, cure it at a curing temperature of 65℃ for 25 min to form an adhesive layer. Subsequently, align the composite structure of the adhesive layer and the release film and attach it to the lower surface of the second composite. After bonding, perform a pressing process with a pressing pressure of 0.3 MPa and a pressing time of 8 s to form the third composite. S5, Cutting and Packaging: Cut the third composite into 8cm×4cm patches, inspect them, and individually aseptically package the qualified patches to obtain penetration-enhancing patches. Connect the controller and the penetration-enhancing patches magnetically, inspect them, and package them to obtain composite microcurrent penetration-enhancing skin patches.

[0028] Example 3: This example provides a composite microcurrent permeation-enhancing skin patch, which includes a controller and a permeation-enhancing patch. The controller is used to generate and output an electrical stimulation signal, and the permeation-enhancing patch is detachably connected to the controller via a magnetic snap-fit ​​structure. The penetration-enhancing patch is a flexible integral structure, which includes, from top to bottom, an elastic adhesive layer, an electrode sheet layer, a sponge cloth layer, an adhesive layer, and a release film, with each layer tightly bonded together to form an integrated structure. The elastic adhesive layer is made of a lightweight film and is made of non-woven fabric composite elastic fabric; The electrode sheet is provided with 4 magnetic conductive contacts, which are matched with the magnetic electrode interface of the external controller, so as to realize automatic alignment, electrical connection and mechanical fixation with the external controller. The adhesive layer is bonded to the lower surface of the sponge fabric layer and is made of medical-grade skin-friendly hydrogel or pressure-sensitive adhesive; The release film is adhered to the lower surface of the adhesive layer as a packaging protective layer; the release film is made of an anti-stick material and can be peeled off before use. The method for preparing the controller is the same as in Example 1.

[0029] The electrode sheet comprises raw materials in the following mass ratio: TPU:[EMIM][TFSI]:graphene quantum dots:chitosan:graphene oxide dispersion = 100:30:1:10:1; The method for preparing the electrode sheet includes the following steps: A1. Take TPU and add it to DMF. The ratio of TPU to DMF is 1g:15mL. Stir in a 60℃ water bath until completely dissolved. Add [EMIM], [TFSI], graphene quantum dots and mixed salt solution in sequence. The mixed salt solution is prepared by mixing 0.1mol / L sodium chloride solution and 0.1mol / L potassium chloride solution in a volume ratio of 1:1. The ratio of mixed salt solution to graphene quantum dots is 10mL:1g. Then place the mixture in an ultrasonic cleaner and ultrasonically disperse it at 500W for 60 minutes to obtain a uniform black conductive slurry. A2. The conductive paste is poured onto a clean glass substrate. The wet film thickness is controlled to be 300μm using an automatic film coating machine. The entire glass plate coated with the paste is immediately immersed in a 25°C deionized water coagulation bath for non-solvent-induced phase separation. After soaking for 120 minutes, it is taken out and placed in flowing deionized water for continuous washing for 72 hours. The washing water is changed every 24 hours to completely remove residual solvent and form a conductive film. A3. The conductive film was cut into a 10cm×10cm square sheet and used as the working electrode. It was placed in an electrochemical cell containing a 0.5mol / L sodium chloride solution, with a platinum sheet as the counter electrode and a saturated calomel electrode as the reference electrode. A +5.0V DC voltage was applied for 30 minutes. After treatment, the film was removed, the surface was rinsed with deionized water, and it was air-dried at room temperature to obtain a smart electrode layer preloaded with sodium ions. A4. Take chitosan and add it to a 1% (w / w) glacial acetic acid solution. The ratio of chitosan to glacial acetic acid solution is 1g:100mL. Stir magnetically in a 40℃ water bath until completely dissolved to obtain a 1% (w / w) chitosan solution. Mix the chitosan solution with a 2mg / mL (w / w) graphene oxide dispersion. Place the mixture in an ice-water bath and sonicate at 400W for 30 minutes to obtain a uniform composite sol. A5. The composite sol was injected into a specially made polytetrafluoroethylene mold. The bottom of the mold was a copper heat-conducting plate, and the side walls were made of polyurethane insulation material. The bottom of the mold was placed on a copper cold finger cooled by liquid nitrogen. A unidirectional freezing gradient of 10℃ / min was set, and freezing was carried out from the bottom up. The freezing process lasted for 120 minutes. After the sol was completely frozen, the sample and the mold were quickly transferred to a freeze dryer and dried at -50℃ and 0.1Pa for 48 hours to obtain a porous scaffold. A6. The porous scaffold was immersed in an anhydrous ethanol solution containing 1% glutaraldehyde and crosslinked in a 50°C water bath for 6 hours. After crosslinking, it was repeatedly rinsed with deionized water until the pH of the washing solution was neutral. Then, the scaffold was transferred to a 0.1 mol / L ascorbic acid solution and reduced in a 90°C water bath for 12 hours. The reduced hydrogel scaffold was immersed in an ethanol solution containing 3% 3-aminopropyltriethoxysilane and reacted at room temperature for 24 hours. After removal, it was washed three times with ethanol. Then, the scaffold was immersed in a 5% N,N-dimethylformamide solution of succinic anhydride and reacted at 60°C for 6 hours. Finally, pH-responsive carboxyl groups were modified on the inner wall of the nanochannel to obtain a bridging layer. A7. A layer of medical-grade silicone gel adhesive is uniformly coated on the ion preload surface of the smart electrode layer, with the coating thickness controlled at 15μm. The bridging layer is aligned with the adhesive coating surface with the entrance face of its vertical channel, and precise alignment and bonding are performed using a high-precision bonding device. After bonding, it is pressed for 60 seconds under 0.2MPa pressure and room temperature, and then transferred to a 60℃ oven for curing for 120 minutes to form an electrode sheet.

[0030] The sponge fabric layer is made of super absorbent sponge and functional composite microspheres. The functional composite microspheres include raw materials in the following mass ratio: N-isopropylacrylamide: N,N'-methylenebisacrylamide: ammonium persulfate: CTAB = 3:0.1:0.1:2. The method for preparing the sponge fabric layer includes the following steps: Y1, N-isopropylacrylamide and N,N'-methylenebisacrylamide were dissolved in deionized water at a ratio of 1g:100mL. High-purity nitrogen gas was bubbled through the solution to remove oxygen for 30 minutes. Ammonium persulfate was added, and the temperature was raised to 70℃. The reaction was carried out under nitrogen protection for 6 hours. After the reaction was completed, the resulting emulsion was centrifuged, the precipitate was collected, washed three times with anhydrous ethanol, and dried in a freeze dryer for 24 hours to obtain temperature-sensitive microspheres. Y2, CTAB was dissolved in deionized water, and 28% ammonia solution was added. The mixture was stirred until homogeneous, and tetraethyl orthosilicate was added dropwise under vigorous stirring. The ratio of CTAB, tetraethyl orthosilicate, ammonia solution and deionized water was 2g:5mL:10mL:200mL. The mixture was stirred at room temperature for 24 hours. The precipitate was collected by centrifugation and washed three times alternately with deionized water and ethanol. The precipitate was placed in a muffle furnace and heated to 550℃ at a rate of 2℃ / min at room temperature. The temperature was maintained for calcination for 6 hours to remove the template agent and obtain mesoporous silica microspheres. Y3. Take a polyester sponge and cut it into 10cm×5cm pieces. Mix the temperature-sensitive microspheres and mesoporous silica microspheres at a mass ratio of 2:1 to form functional composite microspheres. Disperse the mixture ultrasonically in anhydrous ethanol to prepare a suspension with a solid content of 15%. Immerse the cut polyester sponge in the suspension and place it in a vacuum dryer. Evacuate the vacuum to -0.1MPa and maintain it for 30 minutes to allow the suspension to fully penetrate the pores of the sponge. Remove the sponge and dry it in a 60℃ oven to constant weight to obtain the sponge fabric layer.

[0031] This embodiment also provides a method for preparing a composite microcurrent-enhanced skin patch, which specifically includes the following steps: S1. Select viscose nonwoven fabric and spandex fiber composite fabric with a size of 10cm×5cm, cut to obtain elastic adhesive tape layer, and after cutting, grind the edges of the elastic adhesive tape layer to remove burrs. S2 sets magnetic conductive contacts on the electrode sheet to ensure that the position of the magnetic conductive contacts corresponds to the magnetic electrode interface of the external controller. Then, medical-grade environmentally friendly adhesive is used to attach the electrode sheet to the lower surface of the elastic adhesive layer, and the pressing process is carried out. The pressing pressure is 0.5MPa, the pressing temperature is 50℃, and the pressing time is 20s to form the first composite. S3. The sponge cloth layer is hydrophilicized by immersing it in deionized water for 3 hours, then it is taken out and dried to constant weight. Medical-grade adhesive is evenly applied to the lower surface of the electrode sheet layer. The treated sponge cloth layer is aligned and attached to the lower surface of the first composite. After attachment, it is cured at a constant temperature for 40 minutes at a curing temperature of 60°C to form the second composite. S4. Select medical silicone pressure-sensitive adhesive as the adhesive material. Apply the medical silicone pressure-sensitive adhesive evenly to the upper surface of the release film with a coating thickness of 0.2 mm. Curing treatment is performed at a curing temperature of 70℃ and a curing time of 30 min to form an adhesive layer. Subsequently, the composite structure of the adhesive layer and the release film is aligned and bonded to the lower surface of the second composite. After bonding, a pressing treatment is performed with a pressing pressure of 0.4 MPa and a pressing time of 10 s to form the third composite. S5, Cutting and Packaging: Cut the third composite into patches with a size of 10cm×5cm. Pack the qualified patches individually and aseptically to obtain penetration-enhancing patches. Connect the controller and the penetration-enhancing patches magnetically, test, and package to obtain composite microcurrent penetration-enhancing skin patches.

[0032] The difference between Comparative Example 1 and Example 2 is that the controller is removed; otherwise, they are exactly the same as Example 2.

[0033] The difference between Comparative Example 2 and Example 2 is that a commercially available conventional microcurrent hydrogel patch was used; the rest of the parts are exactly the same as in Example 2.

[0034] The difference between Comparative Example 3 and Example 2 is that no electrode sheet is added; the rest is exactly the same as Example 2.

[0035] Experimental example: 1. Permeation Enhancement Efficiency: Isolated pigskin was fixed between the supply and receiving cells of a Franz diffusion cell. The supply cell side consisted of the pigskin epidermis, while the receiving cell contained sterile saline solution as the receiving medium. The temperature was maintained for 30 minutes until it stabilized. Composite microcurrent permeation enhancement skin patches prepared in Examples 1-3 and Comparative Examples 1-3 were used as test samples. 0.5 ml of NAD+ essence was added to each test sample, and the patch was attached to the pigskin surface on the supply cell side. An external controller was connected, and the patch was started and operated for 10 minutes. At 0.5 h, 1 h, 2 h, and 4 h after the start of the test, 1 mL of the receiving medium was extracted from the receiving cell, and 1 mL of sterile saline solution was added simultaneously to maintain a constant volume. The concentration of NAD+ in the extracted sample was detected by HPLC, and the cumulative permeation amount (μg / cm³) at each time point was calculated. 2 ), plot the permeability curve; use the cumulative permeation over 2 hours as the core evaluation index, the higher the value, the better the permeation efficiency; simultaneously calculate the permeation rate (μg / cm). 2 (·h), and the results are recorded in Table 1.

[0036] 2. Compatibility with biological agents: The composite microcurrent-enhanced transdermal patches prepared in Examples 1-3 and Comparative Examples 1-3 of this invention were used as test patches. NAD+ essence, ergothioneine solution, and vitamin C essence were selected respectively, with 10 experimental patches corresponding to each preparation. 0.5 mL of the corresponding preparation was added to each patch, and the adsorption rate of the sponge layer (≤30s is qualified) and whether there was liquid accumulation or leakage were observed. The cumulative permeation of the three preparations over 2 hours was tested according to the transdermal permeation efficiency test method described above, and the results are recorded in Table 1.

[0037] 3. Skin compatibility: The composite microcurrent-enhanced skin patches prepared in Examples 1-3 and Comparative Examples 1-3 of this invention were used as test samples. Three healthy rabbits were selected, and their backs were shaved (area 5cm × 5cm / side). They were divided into an experimental group and a blank control group (no patch was applied). The experimental group was fitted with the test sample of this invention (with physiological saline added, no biological agents) for 24 hours. Skin reactions were observed at 24h, 48h, and 72h after the patch was removed. No irritation reactions such as erythema, edema, or itching were considered acceptable. Mild erythema that subsided within 48 hours was considered basically acceptable. Obvious erythema and edema were considered unacceptable. The results are recorded in Table 1.

[0038] 4. Stability: The composite microcurrent-enhanced skin patches prepared in Examples 1-3 and Comparative Examples 1-3 of this invention were used as test patches; 1) Adhesion stability test: The test patch is attached to a simulated facial curved surface model to simulate human facial movements and is observed continuously for 4 hours; Evaluation criteria: Record the time when the edge of the patch lifts up and whether it completely falls off. No lifting or falling off within 4 hours is excellent, slight lifting (≤1mm) is qualified, and complete falling off is unqualified.

[0039] 2) Leakage prevention performance test: Take a test patch, add 0.5mL of NAD+ essence, attach it to the surface of the detached pigskin, activate the corresponding electrical signal, and work continuously for 10 minutes. After the test, observe whether there is any liquid leakage on the back and around the pigskin.

[0040] 3) Conductivity stability test: After attaching the test patch to the detached pigskin, the resistance value at both ends of the electrode layer was measured using a resistance meter. The test was conducted continuously for 10 minutes, with the resistance value recorded every minute. Evaluation criteria: A stable resistance value within the range of 1-10Ω and a fluctuation range ≤10% indicates stable conductivity; a resistance value >20Ω or a fluctuation range >20% indicates unstable conductivity. The results are recorded in Table 2.

[0041] Table 1: Performance test results of the composite microcurrent-enhanced skin patch prepared in this invention

[0042] Table 1 shows the results. Comparative Example 1, due to the removal of the controller, relied solely on natural skin absorption and sponge layer penetration, resulting in significantly lower efficiency than Examples 1-3. Comparative Example 2, using a conventional microcurrent hydrogel, achieved an efficiency only about 50% of the examples. Comparative Example 3, by eliminating the electrode sheet layer, significantly reduced its penetration efficiency. Comparative Examples 1 and 3 have the same structure as Example 2, allowing for free formulation combinations, thus exhibiting excellent compatibility. Comparative Example 2, limited by its fixed hydrogel formulation, could not change external formulations, resulting in poor compatibility. Examples 1-3 and Comparative Examples 1 and 3 all contain an elastic adhesive layer and a ring-shaped anti-overflow adhesive layer, exhibiting excellent adhesion and leak-proof performance. Comparative Example 2 lacks an elastic adhesive layer for support, resulting in generally poor hydrogel adhesion, easy lifting, and slight leakage. The commercially available hydrogel in Comparative Example 2 contains fixed conductive components, some of which can cause mild skin reactions.

[0043] Table 2: Stability Test Table of the Composite Microcurrent-Enhanced Skin Patch Prepared in This Invention

[0044] As shown in Table 2, Examples 1-3 and Comparative Example 3 have the same electrical signal transmission structure, small resistance fluctuations, and stable conductivity; Comparative Example 2 has weaker conductivity of microcurrent hydrogel and slightly higher fluctuation amplitude.

[0045] Figure 1 The positional relationship between controller 1 and penetration-enhancing patch 2 is shown; Figure 2 The magnetic conductive contact 3 can be clearly seen, which confirms that the controller 1 and the penetration-enhancing patch 2 are connected through the magnetic conductive contact 3 to form an integral composite microcurrent penetration-enhancing skin patch. Figure 3 The diagram shows the structure of the penetration-enhancing patch prepared by the present invention, clarifying the bonding position relationship of the elastic adhesive layer 4, electrode sheet layer 5, sponge cloth layer 6, adhesive layer 7 and release film 8, as well as the position of the magnetic conductive contact 3, and intuitively presenting the structural synergy of each layer.

[0046] In summary, this invention presents a microcurrent-based skin patch designed to enhance skin penetration, achieved through a multi-layered composite structure combined with a magnetically detachable controller. The composite microcurrent-based skin patch prepared by this invention exhibits significantly higher penetration efficiency than electroporation-free controllers and commercially available conventional microcurrent hydrogel patches. It also demonstrates excellent compatibility with biological agents, adhesion stability, and leak-proof performance. Skin irritation testing showed no abnormalities, and conductivity stability was good, fully meeting the needs of daily health care scenarios. Compared to a comparative invention with an integrated controller, while the core performance is essentially equivalent, the magnetically detachable design allows for one-time patch replacement, ensuring hygiene, reducing user consumable costs, and adapting to patches of different locations and sizes. This effectively solves the pain points of poor hygiene, limited applicability, and high cost associated with integrated structures, demonstrating significant advancements and practical value.

[0047] The above description is only a preferred embodiment of the present invention, but the scope of protection of the present invention is not limited thereto. Any equivalent substitutions or modifications made by those skilled in the art within the scope of the technology disclosed in the present invention, based on the technical solution and inventive concept of the present invention, should be covered within the scope of protection of the present invention.

Claims

1. A composite microcurrent-enhanced skin patch, characterized in that, The composite microcurrent iontophoresis-enhancing skin patch includes a controller and an iontophoresis-enhancing patch. The controller is used to generate and output a composite microcurrent, which includes a DC microcurrent for achieving electro-iontophoresis and an AC microcurrent for achieving EMS. The iontophoresis-enhancing patch and the controller are detachably connected by a magnetic snap-fit ​​structure. The penetration-enhancing patch has a flexible integral structure, which includes, from top to bottom, an elastic adhesive layer, an electrode sheet layer, a sponge cloth layer, an adhesive layer, and a release film. The electrode sheet comprises raw materials in the following mass ratio: TPU:[EMIM][TFSI]:graphene quantum dots:chitosan:graphene oxide dispersion = 100:15-30:1:10:1; The method for preparing the electrode sheet includes the following steps: A1. Take TPU, add it to DMF, stir in a water bath, add [EMIM][TFSI], graphene quantum dots and mixed salt solution in sequence, and disperse by ultrasonication to obtain conductive slurry; A2, the conductive paste is cast into a film, then non-solvent-induced phase separation is performed, followed by washing to form a conductive film; A3. Cut the conductive film and perform ion preloading treatment to obtain the smart electrode layer; A4. Take chitosan, add it to glacial acetic acid solution, stir magnetically to obtain chitosan solution, mix chitosan solution with graphene oxide dispersion, and sonicate under ice bath to obtain composite sol; A5, freeze-dry the composite sol to obtain a porous scaffold; A6. The porous scaffold was immersed in an anhydrous ethanol solution containing glutaraldehyde for cross-linking treatment, rinsed, and then reduced in ascorbic acid solution to obtain a hydrogel scaffold. Then, the surface was functionalized to obtain a bridging layer. A7 involves bonding and curing the smart electrode layer and the bridging layer together to form an electrode sheet layer.

2. The composite microcurrent-enhanced skin patch according to claim 1, characterized in that, In step A1, the ratio of TPU to DMF is 1g:10-15mL; the ratio of mixed salt solution to graphene quantum dots is 10mL:1g.

3. The composite microcurrent-enhanced skin patch according to claim 1, characterized in that, In step A6, the surface functionalization modification process is as follows: the hydrogel scaffold is immersed in an ethanol solution containing 3-aminopropyltriethoxysilane for reaction, washed, and then immersed in an N,N-dimethylformamide solution containing succinic anhydride for reaction.

4. The composite microcurrent-enhanced skin patch according to claim 1, characterized in that, The sponge fabric layer is made of superabsorbent sponge and functional composite microspheres. The functional composite microspheres include raw materials in the following mass ratio: N-isopropylacrylamide: N,N'-methylenebisacrylamide: ammonium persulfate: CTAB = 2-3: 0.1: 0.1:

2. The method for preparing the sponge fabric layer includes the following steps: Y1, N-isopropylacrylamide and N,N'-methylenebisacrylamide were dissolved in deionized water, deoxygenated, ammonium persulfate was added, separated, washed, and freeze-dried to obtain temperature-sensitive microspheres; Y2, CTAB is dissolved in deionized water, ammonia solution is added, the mixture is stirred evenly, then tetraethyl orthosilicate is added dropwise, stirred, centrifuged, washed, and calcined to obtain mesoporous silica microspheres; Y3. Take a super absorbent sponge, cut it, mix the temperature-sensitive microspheres with mesoporous silica microspheres to form functional composite microspheres, then ultrasonically disperse them in anhydrous ethanol, immerse the cut super absorbent sponge in it, and dry it to constant weight to obtain a sponge cloth layer.

5. The composite microcurrent-enhanced skin patch according to claim 1, characterized in that, The controller's housing is made of PC / ABS material and integrates an EMS / EPT waveform output module, an MCU control chip, a power module, function buttons, and indicator lights. The controller can stably output 3-100V adjustable DC and AC power. The controller is magnetically connected to the electrode layer of the penetration-enhancing patch through a magnetic electrode interface.

6. The composite microcurrent-enhanced skin patch according to claim 4, characterized in that, In step Y2, the ratio of CTAB, tetraethyl orthosilicate, ammonia solution and deionized water is 2g:5mL:10mL:200mL. In step Y3, the mass ratio of the temperature-sensitive microspheres to the mesoporous silica microspheres is 2:

1.

7. The composite microcurrent-enhanced skin patch according to claim 4, characterized in that, The super absorbent sponge is made of one of the following: polyurethane sponge, polyether sponge, or polyester sponge.

8. A method for preparing a composite microcurrent-enhanced skin patch according to any one of claims 1-7, characterized in that, Specifically, the following steps are included: S1. Select elastic fabric, cut and polish it to obtain an elastic adhesive tape layer; S2, the electrode sheet is attached to the lower surface of the elastic adhesive tape layer and pressed together to form the first composite; S3, apply adhesive to the lower surface of the first composite, adhere it to the sponge cloth layer, and cure it at a constant temperature to form the second composite; S4. Take medical-grade skin-friendly hydrogel or pressure-sensitive adhesive as the adhesive material, coat it on the upper surface of the release film, cure it to form an adhesive layer, and then attach the composite structure of the adhesive layer and the release film to the lower surface of the second composite to form the third composite. S5. Cut, inspect, and package the third composite to obtain a permeation-enhancing patch. Magnetically connect the controller to the permeation-enhancing patch, debug, inspect, and package to obtain a composite microcurrent permeation-enhancing skin patch.

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