Flexible intelligent drug delivery device based on moisture power generation

Abstract

The invention provides a flexible intelligent drug delivery device based on moisture power generation, which comprises a moisture power generation unit, the moisture power generation unit comprises an anode and a cathode, one side of the anode facing the cathode is provided with a polycation layer, one side of the cathode facing the anode is provided with a polyanion layer, and the polycation layer and the polyanion layer are attached to each other; the polycation layer is formed by printing a poly (diallyldimethylammonium chloride) aqueous solution on a corresponding position and then drying to form a film; the polyanion layer is formed by printing a mixed aqueous solution of polystyrolsulfon acid and polyvinyl alcohol at a corresponding position and then drying to form a film; one side of the drug-loaded hydrogel is used for being attached to the skin of a drug administration object; the iontophoresis electrode is used for applying an electric field to the drug-loaded hydrogel, so that the drug permeates into the skin of a drug administration object from the drug-loaded hydrogel. The polycation layer and the polyanion layer are formed through printing, the operation is simple, and the flexible intelligent drug delivery device is easy to produce in batches.

Description

TECHNICAL FIELD

[0001] The present application relates to the technical field of intelligent drug delivery, and in particular to a flexible intelligent drug delivery device based on moisture power generation. BACKGROUND

[0002] Skin health is closely related to the quality of life, and facial skin diseases such as acne are major global public health problems. Acne skin disease patients will experience pain, itching or numbness, and even permanent damage to the skin to leave scars. Traditional skin disease treatment methods mainly apply medicine to the disease site, and common drug delivery methods are to deliver antibacterial drugs or anti-inflammatory drugs through ointments and other products. However, due to the existence of the skin barrier, only a small part of the drugs can passively diffuse through the skin, and the diffusion speed is slow, making it challenging to maintain an effective transdermal drug delivery level.

[0003] Existing iontophoresis transdermal drug delivery devices are mainly desktop devices and handheld devices, which have the disadvantages of complex operation, poor comfort, and difficulty in completely adhering to the skin. So far, people lack in-situ and efficient drug delivery strategies through the surface skin for the care of skin diseases such as acne, and there is also a lack of shape design personalization and drug delivery effect customization strategies for skin disease care of different populations and different disease sites.

[0004] For example, patent application No. CN111888641A discloses an iontophoresis drug delivery device. The iontophoresis drug delivery device includes: a power supply for generating electricity required for penetrating a drug to be penetrated into a drug administration area of a living body; an integrated medium layer for covering the drug administration area, the integrated medium layer including: a gel body, and a drug to be penetrated in a free state with a polarity; and a plurality of electrodes for electrically connecting the power supply and the integrated medium layer, respectively, so that the electricity generated by the power supply flows through the drug administration area and at least part of the integrated medium layer, and at least part of the integrated medium layer has a predetermined resistance value.

[0005] For example, patent application No. CN102202728A discloses an iontophoresis drug delivery system for pre-assembly, which includes an iontophoresis skin patch assembly containing a power supply, electronic equipment, electrodes, and a drug package assembly with a therapeutic agent as a separate sealed component.

[0006] For example, patent application CN118576883A discloses a kind of integrated wearable transdermal iontophoresis patch powered by humidity generator and its preparation method, it includes flexible circuit board and two electrode sheets, the flexible circuit board is provided with power generation module, the positive and negative two levels of power generation module are connected with two electrode sheets respectively, the power generation module includes humidity generator array, the humidity generator array includes a plurality of humidity generator groups arranged side by side in parallel, the humidity generator group includes a plurality of humidity generator devices arranged in series, the humidity generator device includes active material, steel mesh electrode and graphite paper electrode.The active material of humidity generator device in the scheme is made into film and pasted, the operation is more complex, cannot realize disposable mass production.

[0007] Therefore, it is of great significance to develop a flexible intelligent drug delivery device based on humidity power generation for personalized skin disease treatment and skin health, and it is also of great significance to mass-produce the drug delivery device. SUMMARY

[0008] To solve the above technical problems in the prior art, the present application provides a flexible intelligent drug delivery device based on humidity power generation.

[0009] The present application provides a flexible intelligent drug delivery device based on humidity power generation, comprising: a humidity power generation unit for generating power using humidity, the humidity power generation unit comprising an anode and a cathode, the anode having a polycation layer on the side facing the cathode, the cathode having a polyanion layer on the side facing the anode, the polycation layer and the polyanion layer being in contact with each other; the polycation layer is formed by printing a polydiallyldimethylammonium chloride aqueous solution at the corresponding position and then drying to form a film; the polyanion layer is formed by printing a mixed aqueous solution of polystyrene sulfonic acid and polyvinyl alcohol at the corresponding position and then drying to form a film, the mass ratio of polystyrene sulfonic acid to polyvinyl alcohol being 1-5:1; a drug-loaded hydrogel, one side of which is used to adhere to the skin of a drug administration subject, the drug-loaded hydrogel containing a drug; an iontophoresis electrode powered by the humidity power generation unit, for applying an electric field to the drug-loaded hydrogel to cause the drug to penetrate from the drug-loaded hydrogel to the skin of the drug administration subject.

[0010] Preferably, the mass ratio of polystyrene sulfonic acid to polyvinyl alcohol is 3:2, and the output performance of the humidity power generation unit prepared is better.

[0011] Preferably, the anode is below and the cathode is above, the polycation layer is formed on the anode by printing first, and then the polyanion layer is formed on the polycation layer by printing; or, the cathode is below and the anode is above, the polyanion layer is formed on the cathode by printing first, and then the polycation layer is formed on the polyanion layer by printing.

[0012] Further preferably, the anode is a metal anode, the cathode is a metal cathode, the humidity power generation unit further comprises a metal conductive layer; the metal anode and the metal conductive layer are respectively connected with a wire; the metal anode, the metal conductive layer and the wire are formed on a flexible substrate by a flexible printed circuit process; the metal cathode is a conductive metal sheet; when the anode is below and the cathode is above, one end of the metal cathode is electrically connected with the polyanion layer and the other end is electrically connected with the metal conductive layer; when the cathode is below and the anode is above, one end of the metal anode is electrically connected with the polycation layer and the other end is electrically connected with the metal conductive layer.

[0013] Further preferably, the flexible substrate is a flexible polyimide.

[0014] Further preferably, the metal cathode is an aluminum sheet, a magnesium sheet or a zinc sheet; when the anode is below and the cathode is above, one end of the metal cathode is overlaid on the polyanion layer and the other end is overlaid on the metal conductive layer; when the cathode is below and the anode is above, one end of the metal anode is overlaid on the polycation layer and the other end is overlaid on the metal conductive layer.

[0015] Further preferably, when the anode is below and the cathode is above, the metal cathode covers part of the surface of the polyanion layer, and when the cathode is below and the anode is above, the metal anode covers part of the surface of the polycation layer; the covering ratio is preferably 30% to 70%, so that the polyanion layer or the polycation layer is partially exposed, ensuring that the humidity enters the polyanion layer and the polycation layer more smoothly, and that the polyanion layer and the polycation layer partially hydrolyze after absorbing water molecules in the air to generate freely movable ions, which are directionally aggregated according to the concentration difference and the electric field driving, thereby generating electric energy.

[0016] Preferably, a plurality of humidity power generation units are included, and the humidity power generation units are connected in series to form a humidity power generation array.

[0017] Preferably, when preparing the polycation layer, the mass concentration of the polydiallyldimethylammonium chloride aqueous solution is 20% to 50%.

[0018] Further preferably, when preparing the polycation layer, the mass concentration of the polydiallyldimethylammonium chloride aqueous solution is 30% to 40%, the solution has moderate viscosity, and the printing effect is better.

[0019] Preferably, when preparing the polyanion layer, the mass concentration of polystyrene sulfonic acid in the mixed aqueous solution of polystyrene sulfonic acid and polyvinyl alcohol is 23.07%-28.30%, and the mass concentration of polyvinyl alcohol is 5.66%-23.07%.

[0020] Preferably, the iontophoresis electrode comprises a permeation cathode and a permeation anode; the permeation cathode and the permeation anode are connected to the pins through electrode connecting wires, respectively. The permeation cathode is in a serpentine bending structure and forms an annular shape with a notch, and each end of the annular shape is connected to an electrode connecting wire; the permeation anode is located in the middle of the annular shape formed by the permeation cathode.

[0021] Further preferably, a 3-5 μm gold plating layer is formed on the surface of the metal anode by a gold plating process, so as to prevent the polycation layer and the polyanion layer from corroding the metal; and a 3-5 μm gold plating layer is formed on the surface of the permeation cathode and the permeation anode by a gold plating process, so as to protect the permeation cathode and the permeation anode from being oxidized and corroded by the environment solution.

[0022] Preferably, the drug loaded in the drug-loaded hydrogel is an aqueous solution of sodium salicylate, acetaminophen, ibuprofen or loxoprofen sodium.

[0023] Preferably, the packaging layer further comprises a skin packaging layer having a drug-loaded hydrogel positioning hole, so as to fix the drug-loaded hydrogel and enable the drug-loaded hydrogel to be in close contact with the skin. The moisture upper packaging layer covers the moisture power generation unit and is used to isolate moisture before use, and the moisture upper packaging layer needs to be torn off when in use.

[0024] Preferably, the moisture lower packaging layer is arranged between the moisture power generation array and the iontophoresis electrode, and is used to isolate the influence of the iontophoresis electrode on the moisture power generation array.

[0025] Preferably, the radius of the permeation anode is 2-3 mm, and the drug permeation efficiency is relatively high.

[0026] Compared with the prior art, the present application has the following beneficial effects: (1) The polycation layer and the polyanion layer are formed by printing, and the operation is simple, and a large number of printing can be performed at one time, so that the flexible intelligent drug delivery device is easy to be mass-produced. (2) The upper and lower stacked series structure of the moisture power generation unit can enhance the output performance. The structure can increase the contact area of the polyanion layer and the polycation layer while keeping the cathode and the anode on the two sides, so as to facilitate the series connection between the units.

[0027] (3) Through the array design between the modules, the flexible intelligent drug delivery device can be personalized in shape and iontophoresis effect, and can be applied to different drug delivery scenes such as masks and plasters in an array, so as to meet the multidirectional drug delivery needs of different groups and scenes, and has the advantages of convenient operation, convenient use, wide application, and no limitation of users and use places. BRIEF DESCRIPTION OF DRAWINGS

[0028] Figure 1 is a planar schematic diagram of a flexible intelligent drug delivery device array unit based on moisture power generation provided by an embodiment of the application; Figure 2 is an exploded structural schematic diagram of a flexible intelligent drug delivery device based on moisture power generation provided by an embodiment of the application; Figure 3 is a front view structural schematic diagram of a moisture power generation unit in an embodiment of the application; Figure 4 is an exploded structural schematic diagram of a moisture power generation unit in an embodiment of the application; Figure 5 is a relationship diagram of the mass ratio of polystyrene sulfonic acid and polyvinyl alcohol in the polyanion layer of the moisture power generation unit in an embodiment of the application and the output voltage and current; Figure 6 is a relationship diagram of the mass fraction of polydimethyl diallyl ammonium chloride in the polycation layer of the moisture power generation unit in an embodiment of the application and the output voltage and current; Figure 7 is an external output current and power diagram of a moisture power generation array in an embodiment of the application; Figure 8 is a planar structural schematic diagram of an iontophoresis electrode of a flexible intelligent drug delivery device based on moisture power generation provided by an embodiment of the application; Figure 9 is a linear relationship diagram of the absorbance of a sodium salicylate aqueous solution at 292 nm and the concentration of the sodium salicylate aqueous solution; Figure 10 is a relationship diagram of the radius of a permeation anode and the content of a permeated drug of a flexible intelligent drug delivery device based on moisture power generation provided by an embodiment of the application; Figure 11 is a relationship diagram of the permeation voltage and the content of a permeated drug of a flexible intelligent drug delivery device based on moisture power generation provided by an embodiment of the application; Figure 12 is a planar schematic diagram of a flexible intelligent drug delivery device based on moisture power generation provided by an embodiment of the application, which is used for a mask through personalized combination.

[0029] Figure numerals: upper moisture encapsulation layer 1, moisture power generation array 2, lower moisture encapsulation layer 3, iontophoresis electrode 4, drug-loaded hydrogel 5, skin encapsulation layer 6, metal anode 21, metal conductive layer 22, polycation layer 23, polyanion layer 24, metal cathode 25, serpentine wire 26, permeation cathode 31, permeation anode 32, serpentine electrode connecting line 33, upper mask encapsulation layer 41, moisture power generation array 42, electroosmosis electrode array layer 43, drug-loaded gel array 44, lower mask encapsulation layer 45. DETAILED DESCRIPTION

[0030] like Figure 1 As shown in the figure, the embodiment of the present invention provides a flexible intelligent drug delivery device based on moisture power generation, which comprises, in the direction pointing to the skin, an upper moisture encapsulation layer 1, a moisture power generation array 2, a lower moisture encapsulation layer 3, an iontophoresis electrode 4, a drug-loaded hydrogel 5, and a skin-attaching encapsulation layer 6. Figure 2 As shown, the upper moisture encapsulation layer 1 covers the moisture power generation array 2 to isolate moisture before use; the lower moisture encapsulation layer 3 is used to isolate the influence of the iontophoresis electrode 4 on the moisture power generation array 2; the moisture power generation array 2 is used to generate electricity using moisture, and the moisture power generation array 2 and the iontophoresis electrode 4 are electrically connected via a serpentine electrode connecting wire; the iontophoresis electrode 4 is in contact with the drug-loaded hydrogel 5; the skin encapsulation layer 6 has a drug-loaded hydrogel positioning hole for fixing the drug-loaded hydrogel and allowing the drug-loaded hydrogel to be in close contact with the skin. The iontophoresis electrode 4 is provided with electrical energy by the moisture power generation array 2 and is used to apply an electric field to the drug-loaded hydrogel 5 so that the drug penetrates from the drug-loaded hydrogel 5 into the skin of the subject. The drug contained in the drug-loaded hydrogel 5 can be an aqueous solution of sodium salicylate, acetaminophen, ibuprofen, or loxoprofen sodium.

[0031] The wet gas power generation array 2 is composed of a plurality of wet gas power generation units connected in series, and each wet gas power generation unit is connected by a serpentine wire 26, which is stretchable. Figures 3-4As shown, the humidity power generation unit is composed of a metal anode 21, a metal conductive layer 22, a polycation layer 23, a polyanion layer 24, a metal cathode 25 and a serpentine wire 26. The bottom layer of the humidity power generation unit is the metal anode 21 and the metal conductive layer 22 which are not in contact with each other; the polycation layer 23 and the polyanion layer 24 are printed on the metal anode 21 layer by layer, the metal cathode 25 is covered on the top of the metal conductive layer 22, the metal cathode 25 extends to the top of the polyanion layer 24 and is in contact with the polyanion layer 24; the metal conductive layer 22 and the metal anode 21 are respectively connected with the serpentine wire 26. The metal anode 21, the metal conductive layer 22 and the serpentine wire 26 are printed on a flexible substrate by a flexible printed circuit process, and the flexible substrate is preferably a flexible polyimide (PI); the upper surface of the metal anode 21 is plated with a 3-5 μm gold layer by a gold plating process for electrode oxidation resistance. In order to make the humidity enter the polycation layer 23 and the polyanion layer 24 smoothly, the metal cathode 25 does not completely cover the polyanion layer 24, and the polyanion layer 24 is exposed to air by 50% area. The metal anode, the metal conductive layer and the serpentine wire are made of copper material and are packaged in a flexible polyimide (PI) material by a flexible printed circuit board process, wherein the part of the upper surface of the metal anode in contact with the polycation layer, the part of the upper surface of the metal conductive layer in contact with the metal cathode, and the rest of the serpentine wire are not covered by the PI material by the way of opening window of the PI, and the rest are all wrapped by the PI flexible substrate.

[0032] The structure of the humidity power generation unit can also be: on the basis of the above, the positions of the metal anode and the metal cathode are interchanged, the positions of the polyanion layer and the polycation layer are interchanged, and the metal anode does not completely cover the polycation layer, so that the polycation layer is exposed to air by 50% area. The printing sequence is changed to: first, the polyanion layer is formed on the cathode by printing, and then the polycation layer is formed on the polyanion layer by printing.

[0033] The excess material is removed according to the structure of the serpentine line through a laser cutting process, ensuring electrical connection between the moisture power generation units, while having good stretchability; the ink-like PDDA solution (polydiallyldimethylammonium chloride aqueous solution) is printed on the metal anode of each moisture power generation unit through a screen printing process and dried in an oven at 60 ℃ for 1 h to form a dry PDDA polycation layer; after the above step, the ink-like PSSA solution (mixed aqueous solution of polystyrene sulfonic acid and polyvinyl alcohol) is printed on the dry PDDA polyanion layer of each moisture power generation unit through a screen printing process, and dried in an oven at 60 ℃ for 1 h to form a dry PSSA polyanion layer, which can effectively ensure the relative consistency of the electrolyte layer thickness of each unit and improve the working stability of the moisture power generation array; the metal cathode is composed of an aluminum sheet, one end of the metal cathode is covered on the PSSA polyanion layer, half of the polyanion layer is exposed to ensure that the moisture enters the electrolyte layer smoothly, and the other end is in contact with the metal conductive layer for current conduction; the serpentine wire ensures the electrical connection between the moisture power generation units, while improving the stretchability and ductility of the entire array.

[0034] To meet the screen printing process, the ratio of PSS (polystyrene sulfonic acid) and PVA (polyvinyl alcohol) in the polyanion layer and the concentration of PDDA in the polycation layer need to be changed. Changing the mass ratio of PSS and PVA will change the skeleton structure of the PSSA mixed solution, thereby affecting the viscosity and output performance of the electrolyte solution. With the increase of the mass ratio of PVA, the viscosity of the electrolyte solution will gradually increase. By changing the mass ratio of PSS and PVA to control the viscosity of the PSSA solution to meet the requirements of the screen printing process, the relationship between different mass ratios of PSS and PVA and the energy output efficiency of the power generation unit is tested. The polyanion layer with PSS:PVA (mass ratio) of 5:1, 4:1, 3:1, 2:1, 3:2, 4:3 and 1:1, and 30wt% PDDA aqueous solution as the polyanion layer of the moisture power generation unit are used to test the open-circuit voltage and short-circuit current of the moisture power generation unit, wherein the amount of each component of the polyanion layer is: PVA is weighed according to the mass ratio and dissolved in 10 g of 30wt% PSS aqueous solution. As shown in Figure 5 different PSS:PVA (mass ratio) printed PSSA ink can be used as a polyanion layer, and the output performance of the moisture power generation unit prepared under the mass ratio of 3:2 is the best, and meets the viscous state of the solution ink that can be printed. The PSSA solution of the polyanion layer can be configured according to the requirements to form polyanion layers with different characteristics to adjust the output of the moisture power generation unit, and the output voltage of a single power generation unit can be adjusted within 0.4-0.5 V.

[0035] The viscosity of the PDDA aqueous solution can be changed by changing the concentration of the PDDA aqueous solution, and the relationship between the energy output efficiency of the power generation unit and the PDDA aqueous solution with different mass fractions is tested. The open-circuit voltage and short-circuit current of the moisture power generation unit made of the PDDA aqueous solution with a mass fraction of 20wt%, 30wt%, 40wt%, and 50wt% as the polycation layer and the PSSA aqueous solution with a PSS:PVA mass ratio of 3:2 as the polyanion layer are tested. The PSSA aqueous solution is prepared by weighing PVA according to the mass ratio and dissolving it in 10 g of PSS aqueous solution with a concentration of 30wt%. As shown in Figure 6 , the PDDA solutions with different mass fractions have no significant difference in output efficiency of the power generation unit, but the viscosity of the PDDA aqueous solution affects the printing effect. If the solution is too dilute, the printing effect is poor, and if the solution is too thick, it cannot be printed. The PDDA aqueous solution with a mass fraction of 30wt%-40wt% has moderate viscosity and good printing effect. The moisture power generation unit made by screen printing technology using the PSSA ink (PSS:PVA mass ratio of 3:2) polyanion layer and the PDDA aqueous solution with a mass fraction of 40wt% as the polycation layer is made again. Four moisture power generation units are made to form a moisture power generation array to make a flexible intelligent drug delivery device. The output power curve is shown in Figure 7 , and the maximum output power density is 271 μW·cm -2 , which meets the energy supply of the designed iontophoresis system and also shows that the moisture power generation array can achieve energy supply by connecting multiple moisture power generation units in series.

[0036] As shown in Figure 8 , the iontophoresis electrode 4 includes a permeation cathode 31, a permeation anode 32, and a serpentine electrode connecting line 33. The permeation cathode 31 has a serpentine bending structure and forms an annular shape with a notch, and each end of the annular shape is connected to a serpentine electrode connecting line 33. The permeation anode 32 is located in the middle of the annular shape formed by the permeation cathode, and the permeation anode 32 is circular. The permeation anode 32 is connected to a serpentine electrode connecting line 33. The permeation cathode 31 and the permeation anode 32 are connected to the pins through the serpentine electrode connecting line 33. The permeation cathode 31 and the permeation anode 32 are electrically connected to the moisture power generation array 2 through the serpentine electrode connecting line 33.

[0037] The width of the serpentine conductive material is 100-150 μm; the inner circle radius of the annular structure of the permeation cathode 31 is 8-10 mm, and the outer circle radius is 11-15 mm, which can perfectly fit the curvature of the facial skin to tightly fit the drug-loaded hydrogel.

[0038] The iontophoresis electrode is encapsulated in a flexible polyimide (PI) material by a flexible printed circuit board (FPCB) process, the snake-shaped stretchable permeable cathode and the permeable anode are exposed and covered with a 3-5 μm gold plating layer by a gold plating process to prevent oxidation of the permeable cathode and the permeable anode; the surface of the snake-shaped electrode connecting wire is covered with a polyimide (PI) material for insulation to prevent damage to the electrode electric field structure; finally, the PI encapsulation is removed by laser cutting technology to realize the production of the entire electrode.

[0039] The working principle of the flexible intelligent drug delivery device based on moisture power generation is as follows: when in use, the moisture power generation array contacts water molecules in the air, the electrolyte layer (polyanion layer and polycation layer) has a certain hygroscopicity, the water molecules are converted from gaseous state in the air to liquid state in the electrolyte layer, and part of the electrolyte layer is dissociated to generate free moving charged ions in the polyanion layer and the polycation layer. Under the superimposed action of concentration difference and electric field force, movement and power generation are generated. The generated voltage can form an electric field between the permeable anode, the drug-loaded hydrogel, the skin and the permeable cathode, and the drug ions (such as salicylate ions, negatively charged) diffuse from the drug-loaded hydrogel to the facial skin under the action of the electric field, thereby realizing efficient drug delivery.

[0040] The Franz diffusion cell is used to simulate the drug penetration of the skin in the transdermal drug delivery experiment. Pigskin is placed in the middle of the diffusion cell for fixation, the flexible intelligent drug delivery device based on moisture power generation is placed in the upper clamp to apply iontophoresis, and phosphate buffer solution (PBS) is added to the lower diffusion cell to contact the pigskin below, and the drug above penetrates through the pigskin to the below by passive diffusion and iontophoresis electric field effect. The transdermal drug delivery efficiency can be evaluated by measuring the content of sodium salicylate in the PBS in the diffusion cell.

[0041] The concentration of sodium salicylate in the solution is measured by testing the absorbance of the solution at 292 nm by ultraviolet spectrophotometry. The standard sodium salicylate solution is linearly calibrated by ultraviolet spectrophotometry to obtain the linear relationship between the concentration of the sodium salicylate solution and the absorbance of the spectrophotometer at 292 nm. As shown in Figure 9 , it is shown that the absorbance of sodium salicylate at 292 nm and the solution concentration have a good linear relationship.

[0042] The iontophoresis electrode affects the drug penetration efficiency by changing the area of the permeable anode. In the experiment, 1wt% sodium salicylate aqueous solution is used to prepare drug-loaded hydrogel, the radius of the permeable anode is changed to explore the effect of the electrode area on the transdermal drug delivery efficiency, and the permeable anode with a radius of 1 mm, 2 mm, 3 mm and 4 mm is used to apply the same voltage to the fresh pigskin for transdermal drug delivery test. As shown in Figure 10As shown, when the area of the permeation anode increases, the amount of transdermal drug first increases and then decreases. The results show that in this device, different drug delivery effects can be obtained by changing the area of the permeation anode. When the radius of the permeation anode is 2-3 mm, the drug permeation efficiency is higher.

[0043] A drug-loaded hydrogel was prepared with a 1wt% aqueous solution of sodium salicylate, and the influence of the electro-osmotic electric field strength on the transdermal drug delivery efficiency was explored by changing the voltage applied to the iontophoresis electrode. Fresh pig skin was tested for transdermal drug delivery at voltages of 1 V, 2 V, 3 V, and 4 V, respectively. As shown, Figure 11 As the electro-osmotic voltage gradually increases, the amount of transdermal drug gradually increases, and when the permeation voltage reaches 3 V, the amount of permeated drug slightly decreases. The results show that in this device, different drug delivery effects can be obtained by changing the applied permeation voltage according to the needs.

[0044] The preparation method of the drug-loaded hydrogel is as follows: 1wt% sodium salicylate solution is added to 8wt% acrylamide, N,N-methylenebisacrylamide is used as the crosslinking agent, 2M ammonium persulfate and 0.8M tetramethyl ethylenediamine are used as the initiator and accelerator, the gel solution is poured into a mold after mixing for 10-15 min, and the acrylamide drug-loaded hydrogel containing sodium salicylate is obtained after gelation. The surface residual monomers are removed by rapid cleaning in water to complete the preparation of the drug-loaded hydrogel.

[0045] The flexible intelligent drug delivery device can be customized by changing the number of moisture power generation units, the number and distribution position of the iontophoresis electrode, and the number of drug-loaded hydrogels. As shown, Figure 12 As shown, the customized intelligent drug delivery mask can be customized according to the area and position of the facial drug administration site, the moisture power generation array 42 is customized and assembled as needed, the distribution of the iontophoresis electrode is customized according to the position of the facial disease pain point, the iontophoresis electrode array layer 43 is formed, the drug-loaded hydrogel array 44 is distributed below the iontophoresis electrode array layer 43 to realize drug delivery, the moisture power generation array 42, the iontophoresis electrode array layer 43, and the drug-loaded hydrogel array 44 are encapsulated between the upper encapsulation layer 41 of the mask and the lower encapsulation layer 45 of the mask, the upper encapsulation layer 41 of the mask is removed to activate the moisture power generation film power supply when in use, the lower encapsulation layer 45 of the mask is attached to the facial skin, and the drug delivery is targeted to the desired position.

[0046] The present application realizes efficient delivery of skin disease drugs based on the flexible intelligent drug delivery device of moisture power generation. Combined with moisture power generation, the device realizes self-energy supply by starting the moisture power generation array with water vapor in the air, without relying on external energy. The flexible drug delivery device array can be customized to cope with various drug delivery scenarios, realizing flexible treatment scenarios. The flexible intelligent drug delivery device is convenient to operate and use, and is not limited by the user and the use place. The present application can realize efficient penetration of skin disease drugs and whitening drugs, and has great attraction and important application value for patients in need of treatment.

Claims

1. A flexible intelligent drug delivery device based on moisture power generation, characterized in that: include: A wet gas power generation unit for generating electricity using wet gas, comprising an anode and a cathode, wherein the anode has a polycation layer on its side facing the cathode, and the cathode has a polyanion layer on its side facing the anode, wherein the polycation layer and the polyanion layer are bonded to each other; the polycation layer is formed by printing an aqueous solution of polydiallyldimethylammonium chloride at corresponding locations and then drying it to form a film; the polyanion layer is formed by printing an aqueous solution of a mixture of polystyrene sulfonic acid and polyvinyl alcohol at corresponding locations and then drying it to form a film, wherein the mass ratio of polystyrene sulfonic acid to polyvinyl alcohol is 1 to 5:1; A drug-loaded hydrogel, one surface of which is adapted to adhere to the skin of a subject, wherein the drug-loaded hydrogel is loaded with a drug; The iontophoresis electrode is powered by the moisture power generation unit and is used to apply an electric field to the drug-loaded hydrogel so that the drug penetrates from the drug-loaded hydrogel into the skin of the subject.

2. The flexible intelligent drug delivery device based on moisture power generation according to claim 1, characterized in that: The anode is at the bottom and the cathode is at the top, the polycation layer is first formed on the anode by printing, and then the polyanion layer is formed on the polycation layer by printing; Alternatively, the cathode is at the bottom and the anode is at the top, the polyanion layer is first formed on the cathode by printing, and then the polycation layer is formed on the polyanion layer by printing.

3. The flexible intelligent drug delivery device based on moisture power generation according to claim 2, characterized in that: The anode is a metal anode, the cathode is a metal cathode, and the moisture power generation unit further includes a metal conductive layer; the metal anode and the metal conductive layer are respectively connected to wires; The metal anode, metal conductive layer and wire are formed by printing on a flexible substrate through a flexible printed circuit process; the metal cathode is a conductive metal sheet; When the anode is at the bottom and the cathode is at the top, one end of the metal cathode is conductively connected to the polyanion layer, and the other end is conductively connected to the metal conductive layer; when the cathode is at the bottom and the anode is at the top, one end of the metal anode is conductively connected to the polycation layer, and the other end is conductively connected to the metal conductive layer.

4. The flexible intelligent drug delivery device based on moisture power generation according to claim 3, characterized in that: The metal cathode is an aluminum sheet, a magnesium sheet or a zinc sheet; When the anode is at the bottom and the cathode is at the top, one end of the metal cathode is pressed on the polyanion layer and the other end is pressed on the metal conductive layer; when the cathode is at the bottom and the anode is at the top, one end of the metal anode is pressed on the polycation layer and the other end is pressed on the metal conductive layer.

5. The flexible intelligent drug delivery device based on moisture power generation according to claim 4, characterized in that: When the anode is at the bottom and the cathode is at the top, the metal cathode covers part of the surface of the polyanion layer; When the cathode is at the bottom and the anode is at the top, the metal anode covers part of the surface of the polycationic layer.

6. The flexible intelligent drug delivery device based on moisture power generation according to claim 1, characterized in that: It comprises a plurality of wet gas power generation units, and the wet gas power generation units are connected in series to form a wet gas power generation array.

7. The flexible intelligent drug delivery device based on moisture power generation according to claim 1, characterized in that: When preparing the polycationic layer, the mass concentration of the polydiallyldimethylammonium chloride aqueous solution is 20% to 50%; When preparing the polyanion layer, in the mixed aqueous solution of polystyrene sulfonic acid and polyvinyl alcohol, the mass concentration of polystyrene sulfonic acid is 23.07% to 28.30%, and the mass concentration of polyvinyl alcohol is 5.66% to 23.07%.

8. The flexible intelligent drug delivery device based on moisture power generation according to claim 1, characterized in that: The iontophoresis electrode includes a permeation cathode and a permeation anode; the permeation cathode and the permeation anode are connected to the pins respectively through electrode connecting wires; The permeation cathode is a serpentine bending structure and forms a ring with a gap. Both ends of the ring are connected to an electrode connection line. The permeation anode is located in the middle of the ring formed by the permeation cathode.

9. The flexible intelligent drug delivery device based on moisture power generation according to claim 1, characterized in that: The drug loaded in the drug-loaded hydrogel is an aqueous solution of sodium salicylate, acetaminophen, ibuprofen or loxoprofen sodium.

10. The flexible intelligent drug delivery device based on moisture power generation according to claim 1, characterized in that: The skin-mounted encapsulation layer is provided with a drug-loaded hydrogel positioning hole for fixing the drug-loaded hydrogel and allowing the drug-loaded hydrogel to be in close contact with the skin. It also includes a moisture encapsulation layer covering the moisture power generation unit and used to isolate moisture before use.

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