An integrated wearable transdermal iontophoresis patch powered by a moisture generator and a preparation method thereof

Abstract

The application provides an integrated wearable transdermal iontophoresis patch powered by a moisture generator and a preparation method thereof, and belongs to the technical field of medical devices and biomedical materials. The problems of high distance requirement, large energy loss in the transmission process, inability to provide stable power supply, long-term use, complex device structure and operation of the existing iontophoresis transdermal drug delivery equipment are solved. It comprises a flexible circuit board and two electrode sheets, the flexible circuit board is provided with a power generation module, the positive and negative levels of the power generation module are connected with the two electrode sheets respectively, the power generation module comprises a moisture generator array, the moisture generator array comprises a plurality of moisture generator groups arranged side by side in parallel, the moisture generator group comprises a plurality of moisture generator devices arranged in series, and the moisture generator device comprises an active material, a steel mesh electrode and a graphite paper electrode. It is mainly used for transdermal drug delivery.

Description

TECHNICAL FIELD

[0001] The present application belongs to the technical field of medical devices and biomedical materials, in particular to an integrated wearable transdermal iontophoresis patch powered by a moisture generator and a preparation method thereof. BACKGROUND

[0002] Compared with traditional oral administration and subcutaneous injection, transdermal administration is a mild and non-invasive method of drug delivery, which can reduce the first-pass metabolism of the liver, drug side effects and patient discomfort. Due to the shielding effect of the stratum corneum of human skin, it is difficult for drugs to penetrate the human skin by natural diffusion. Therefore, researchers have assisted drugs into the skin through external actions such as iontophoresis, electroporation, microneedles, ultrasound, and thermal ablation. Among them, iontophoresis is widely used in clinical drug transdermal delivery due to its non-invasive, controllable and low-cost advantages.

[0003] Iontophoresis transdermal drug delivery drives ionized drugs to move in the electroosmotic flow in the skin by applying an external electric field. For a long time, people have used external power conversion equipment to achieve appropriate driving voltage and current. However, the complex external power supply equipment and line connection limits the patient's free movement and causes certain psychological burden. Although small portable power sources such as lithium batteries or button batteries can be used to power the device to achieve wearable devices. However, complex power management modules require tedious operation and cause discomfort during the patient wearing process. Fortunately, the development of self-powered power supplies provides a new energy supply strategy for iontophoresis devices. Friction nanogenerators can collect energy from human motion and show certain potential in iontophoresis transdermal drug delivery. Since energy needs to be generated during movement, the power supply needs to be installed in the body movement part, which requires wires to introduce electrical energy to the patient part. In addition, the alternating current pulse electrical signal generated by the nanogenerator needs to be converted into direct current by the power supply, increasing the complexity of the device. Another self-powered strategy is to use glucose, lactic acid and other substances in sweat to convert energy into device power supply through enzymatic biofuel cells. Limited by the activity of enzymes and the supply of biofuels, biofuel cells cannot provide stable power supply and long-term use. In recent years, the use of NFC wireless transmission of electrical energy requires a high distance, energy loss during transmission and the complexity of operation, which limits the application scenarios. Therefore, it is necessary to seek a stable, uninterrupted and simple power supply to provide long-term and effective power supply for iontophoresis devices. SUMMARY

[0004] Therefore, the application aims to provide an integrated wearable transdermal iontophoresis patch powered by a moisture generator and a preparation method thereof to solve the problems of high distance requirement, large energy loss in transmission process, inability to provide stable power supply and long-term use, and complex device structure and operation of the existing iontophoresis transdermal drug delivery device.

[0005] To achieve the above-mentioned purpose, the application adopts the following technical scheme: an integrated wearable transdermal iontophoresis patch powered by a moisture generator, comprising a flexible circuit board and two electrode sheets, wherein the flexible circuit board is provided with a power generation module, the positive and negative levels of the power generation module are respectively connected with the two electrode sheets, the power generation module comprises a moisture generator array, the moisture generator array comprises a plurality of moisture generator groups arranged in parallel, each moisture generator group comprises a plurality of moisture generator devices arranged in series, the flexible circuit board is provided with a plurality of metal pads corresponding to the moisture generator devices, the moisture generator device comprises an active material, a steel mesh electrode and a graphite paper electrode, the steel mesh electrode and the graphite paper electrode are respectively connected with the top end and the bottom end of the active material, the active material is arranged on the metal pad, and the steel mesh electrode and the graphite paper electrode are connected with the metal pad.

[0006] Further, the steel mesh electrode is provided with a porous structure arranged at the connection between the steel mesh electrode and the active material.

[0007] Further, the flexible circuit board is provided with a control module connected in series with the power generation module, the control module comprises a four-gear switch and a control circuit, the four-gear switch is connected with the power generation module through the control circuit, the control circuit comprises a first gear branch, a second gear branch, a third gear branch and a fourth gear branch connected in parallel, the first gear branch, the second gear branch and the third gear branch are all passageways, the fourth gear branch is a disconnection, the first gear branch and the second gear branch are respectively provided with a first resistor and a second resistor, and the first resistor and the second resistor have different resistance values.

[0008] Further, the bottom of the flexible circuit board is connected with a PDMS bottom layer, the PDMS bottom layer is provided with a water vapor collection channel and a water vapor leading-out channel, the water vapor collection channel and the water vapor leading-out channel are communicated, two hydrogel chambers are symmetrically arranged in the middle of the PDMS bottom layer, a hydrogel layer is arranged in the hydrogel chamber, and the hydrogel layer is connected with the electrode sheet.

[0009] Further, a plurality of gas channels are arranged on the flexible circuit board, the plurality of gas channels are arranged around the moisture generator device, and the gas channels are communicated with the water vapor leading-out channel.

[0010] Further, the top of the flexible circuit board is connected with a PDMS cover layer.

[0011] Further, the material of the flexible circuit board is polyimide.

[0012] Further, the graphite paper electrode is pasted on the metal pad through conductive graphite glue, and the steel mesh electrode is connected with the metal pad through soldering.

[0013] Further, the active material is a hybrid membrane formed by combining polystyrene sulfonic acid and polyvinyl alcohol.

[0014] The application also provides a preparation method of an integrated wearable transdermal iontophoresis patch powered by a moisture generator, which comprises the following steps:

[0015] Step 1: a PDMS bottom layer required convex mold is prepared by using a photosensitive resin 3D printing mold;

[0016] Step 2: then, the PDMS prepolymer and the curing agent are thoroughly mixed in a ratio of 10:1 and poured on the convex mold, and the vacuum degassed device is placed in a 80℃ drying box for curing for 2h;

[0017] Step 3: the flexible circuit board is placed on the cured PDMS bottom layer;

[0018] Step 4: the flexible circuit board pad area is covered with a mask;

[0019] Step 5: a layer of PDMS is continuously poured to form a PDMS cover layer, and after the PDMS cover layer is cured, the mask in the pad area is removed;

[0020] Step 6: the moisture generator array is installed in the pad area;

[0021] Step 7: the PDMS cover layer is subjected to oxygen plasma treatment, then the device is pressed together in the order of top and bottom and placed on a 80℃ hot plate for bonding for 2h;

[0022] Step 8: the hydrogel layer containing the drug is installed in the hydrogel chamber of the PDMS bottom layer.

[0023] Compared with the prior art, the application has the beneficial effects that:

[0024] 1. The application provides an integrated wearable transdermal iontophoresis patch powered by a moisture generator, air or skin water vapor enters the active material through the porous structure on the steel mesh electrode, the moisture generator generates electric energy under the action of moisture, and the current is applied on the hydrogel patch through the circuit, so as to promote the release and transdermal delivery of the drug in the hydrogel, realize the collection of humidity energy in the environment and the application of the iontophoresis transdermal drug delivery.

[0025] 2、The active material upper layer of the steel mesh electrode in the application is provided with a porous structure, water vapor in the air can enter the active material through the holes, the lower layer of graphite paper electrode cannot permeate water molecules, the active material can continuously absorb water molecules, produce hydrogen ion dissociation and concentration gradient, therefore, constant ion diffusion can produce continuous current output. The device can realize continuous self-powered transdermal drug delivery without complex power management module and moving parts, the application provides a non-invasive treatment scheme for transdermal drug delivery, and provides an effective method for deep drug delivery and skin disease treatment.

[0026] 3、The application provides an integrated wearable transdermal iontophoresis patch powered by a humidity generator, which has the characteristics of small volume, low cost and simple operation. BRIEF DESCRIPTION OF DRAWINGS

[0027] The accompanying drawings, which form a part of the disclosure, are intended to provide further understanding of the application and are incorporated herein for explanatory purposes. The schematic embodiments of the application and their descriptions are used to explain the application and do not constitute an improper limitation on the application. In the drawings:

[0028] Figure 1 An exploded view of the overall structure of the integrated wearable transdermal iontophoresis patch powered by a humidity generator according to the application;

[0029] Figure 2 A structure schematic view of the humidity generator device in the integrated wearable transdermal iontophoresis patch powered by a humidity generator according to the application;

[0030] Figure 3 A structure schematic view of the flexible circuit board in the integrated wearable transdermal iontophoresis patch powered by a humidity generator according to the application;

[0031] Figure 4 A structure schematic view of the PDMS bottom layer in the integrated wearable transdermal iontophoresis patch powered by a humidity generator according to the application;

[0032] Figure 5 A circuit principle view of the integrated wearable transdermal iontophoresis patch powered by a humidity generator according to the application;

[0033] Figure 6 A schematic view of the integrated wearable transdermal iontophoresis patch powered by a humidity generator according to the application applied to the skin.

[0034] 1-PDMS cover layer, 2-humidity generator array, 21-steel mesh electrode, 211-porous structure, 22-active material, 23-graphite paper electrode, 3-flexible circuit board, 31-gas channel, 32-metal pad, 33-four-position switch, 34-first resistor, 35-second resistor, 4-PDMS bottom layer, 41-water vapor collection channel, 42-hydrogel chamber, 43-water vapor leading channel, 5-hydrogel layer. DETAILED DESCRIPTION

[0035] The technical solutions in the embodiments of the present application will be clearly and completely described below with reference to the drawings in the embodiments of the present application. It should be noted that the embodiments in the present application and the features in the embodiments can be combined with each other without conflict, and the described embodiments are only some of the embodiments of the present application, not all the embodiments.

[0036] Reference is made to Figures 1-6 In the present embodiment, an integrated wearable transdermal iontophoresis patch powered by a humidity generator includes a flexible circuit board 3 and two electrode sheets, the flexible circuit board 3 is provided with a power generation module, the positive and negative levels of the power generation module are connected with the two electrode sheets respectively, the power generation module includes a humidity generator array 2, the humidity generator array 2 includes a plurality of humidity generator groups arranged side by side in parallel, each humidity generator group includes a plurality of humidity generator devices arranged in series, the flexible circuit board 3 is provided with a plurality of metal pads 32 corresponding to the humidity generator devices one by one, the humidity generator device includes an active material 22, a steel mesh electrode 21 and a graphite paper electrode 23, the steel mesh electrode 21 and the graphite paper electrode 23 are connected with the top end and the bottom end of the active material 22 respectively, the active material 22 is arranged on the metal pad 32, and the steel mesh electrode 21 and the graphite paper electrode 23 are connected with the metal pad 32. In the present embodiment, the humidity generator array 2 is mainly used to collect humidity in the air and convert the humidity into electric energy to provide power for the entire patch, and the flexible circuit board 3 is mainly used to array connect and integrate a plurality of humidity generator devices to amplify voltage and current, the steel mesh electrode 21 is provided with a porous structure 211, the porous structure 211 is arranged at the connection between the steel mesh electrode 21 and the active material 22, and the porous structure 211 ensures that water vapor can effectively enter the active material 22.

[0037] In the present embodiment, the humidity generator array 2 includes six humidity generator groups arranged side by side in parallel, and each humidity generator group includes five humidity generator devices arranged in series.

[0038] In the present embodiment, the steel mesh electrode 21 is used as an upper electrode to realize circuit connection, the active material 22 is used to convert water vapor energy into electric energy, and the graphite paper electrode 23 is used as a bottom electrode of the humidity generator device.

[0039] The water vapor in the air or around the skin enters the active material 22 through the porous structure 211 on the steel mesh electrode 21, the wetness power generator generates electricity under the action of the water vapor, and the current is applied to the hydrogel layer 5 through the circuit and the electrode sheet, which promotes the release and transdermal delivery of the drug in the hydrogel layer 5, realizes the collection of humidity energy in the environment and application to iontophoretic transdermal drug delivery. Since the upper electrode of the active material 22 is the steel mesh electrode 21, the water vapor in the air can enter the active material 22 through the porous structure 211 of the steel mesh electrode 21, and the lower graphite paper electrode 23 cannot permeate water molecules, thus forming a water gradient along the thickness direction. The water molecules entering the active material 22 induce the dissociation of the positively charged hydrogen ions in the upper active material 22, and due to the difference in water molecule concentration, an ion concentration gradient along the thickness direction is naturally formed. The positively charged hydrogen ions move and diffuse towards the bottom graphite paper electrode 23 driven by the concentration difference, while the carboxyl groups on the polymer backbone cannot move, thereby generating a potential difference and a current. Due to the air impermeability of the graphite paper electrode 23, the active material 22 can continuously absorb water molecules, generate hydrogen ion dissociation and concentration gradient, and thus constant ion diffusion can produce continuous current output. Considering that there is no need for complex power management modules and moving parts, and water vapor energy is available everywhere, the integrated wearable transdermal iontophoresis patch powered by the wetness power generator in this embodiment provides a non-invasive treatment scheme for transdermal drug delivery, and provides an effective method for deep drug delivery and treatment of skin diseases.

[0040] As shown in Figure 6 The integrated wearable transdermal iontophoresis patch powered by the wetness power generator in this embodiment is attached to the skin, and the electrical energy generated by the wetness power generator is transmitted to the two hydrogel layers 5 at the bottom through the traces on the flexible circuit board 3, and the electric field formed by the hydrogel layer 5 on the skin is used to drive the drug ions in the drug-loaded hydrogel to penetrate into the skin. The drug-loaded hydrogel containing negative ion drugs is installed at the cathode, and the conductive hydrogel containing 0.9% NaCl is installed at the anode to form a conductive loop. The drug ions move towards the deep skin under the action of electric migration and diffusion, and move towards the other electrode under the action of electroosmosis.

[0041] The flexible circuit board 3 in the embodiment is provided with a control module connected in series with the power generation module, the control module includes a four-gear switch 33 and a control circuit, the four-gear switch 33 is connected with the power generation module through the control circuit, the control circuit includes a first gear branch, a second gear branch, a third gear branch and a fourth gear branch connected in parallel, the first gear branch, the second gear branch and the third gear branch are all passways, and the fourth gear branch is a break. The first gear branch and the second gear branch are respectively provided with a first resistor 34 and a second resistor 35, the first resistor 34 and the second resistor 35 have different resistance values, the four-gear switch 33 in the embodiment is divided into four gears, each gear realizes the control of the on-off of the circuit and the size of the current by connecting different gear branches, the first gear branch, the second gear branch and the third gear branch are passways, and the size of the current is adjusted by adjusting the resistance value of the branch, which is used to control the speed of the drug penetrating the skin, and the fourth gear branch is a break, which is used to realize the control of the on-off of the circuit.

[0042] The embodiment effectively promotes the transdermal transport of ionic drugs in skin tissue. The chemical potential energy of water molecules in the air is converted into electrical energy by the moisture power generation device. In an 80% RH environment humidity condition, a single moisture power generation device can generate an open-circuit voltage of 0.80V and a short-circuit current of 11.65μA, and a plurality of moisture power generation devices are connected in series and parallel to form a moisture power generation array 2, so as to realize the amplification of the output of the circuit and realize power supply. The continuous and stable electrical energy output by the moisture power generation device supplies the iontophoresis patch, and the delivery depth of the drug is controlled by adjusting the four-gear switch 33. In the in-vitro pig skin transdermal experiment of the sodium fluorescein model drug, the iontophoresis patch designed by the embodiment can increase the transdermal depth of the drug by 3 times compared with the natural diffusion of the drug. The iontophoresis patch device does not need complex circuit management and moving parts to realize continuous self-powered transdermal drug delivery. The wearable iontophoresis patch powered by the moisture power generation device provides a self-powered strategy for iontophoresis, and provides a basic platform for future skin disease treatment and personalized drug delivery.

[0043] The bottom of the flexible circuit board 3 in this embodiment is connected with a PDMS bottom layer 4, which is provided with a water vapor collection channel 41 and a water vapor outlet channel 43, and the water vapor collection channel 41 and the water vapor outlet channel 43 are communicated. The middle part of the PDMS bottom layer 4 is symmetrically provided with two hydrogel chambers 42, and the hydrogel chambers 42 are provided with a hydrogel layer 5. The hydrogel layer 5 is connected with an electrode sheet. The hydrogel layer 5 is an acrylamide hydrogel, and the hydrogel layer 5 is mixed with a drug. The hydrogel layer 5 is mainly used for storing and iontophoretic releasing the drug. A plurality of gas channels 31 are formed in the flexible circuit board 3, and the plurality of gas channels 31 are arranged around the wet gas power generation device. The gas channels 31 are communicated with the water vapor outlet channel 43. The PDMS bottom layer 4 is mainly used for collecting the water vapor around the skin and introducing the water vapor into the wet gas power generation device array 2. The water vapor around the skin flows into the water vapor outlet channel 43 through the water vapor collection channel 41, and the water vapor around the skin is guided out of the wet gas power generation device array 2 on the flexible circuit board 3 through the water vapor outlet channel 43 and the gas channel 31 and is converted into electric energy.

[0044] The top of the flexible circuit board 3 in this embodiment is connected with a PDMS cover layer 1. The PDMS cover layer 1 mainly realizes covering other components, and realizes the connection and integration of a plurality of components.

[0045] The material of the flexible circuit board 3 in this embodiment is polyimide.

[0046] The graphite paper electrode 23 in this embodiment is pasted on the metal pad 32 by conductive graphite glue, and the steel mesh electrode 21 is connected with the metal pad 32 by means of soldering.

[0047] The active material 22 in this embodiment is a hybrid film formed by combining polystyrene sulfonic acid and polyvinyl alcohol, and lithium chloride is doped to enhance the hygroscopicity of the active material 22. The introduction of the polyvinyl alcohol component enhances the flexibility of the active material 22. The active material 22 in this embodiment can spontaneously absorb water vapor in the air and form an internal ion concentration difference, thereby generating a potential difference.

[0048] This embodiment also provides a preparation method of an integrated wearable transdermal iontophoresis patch powered by a wet gas power generator, which comprises the following steps:

[0049] Step 1: using a photosensitive resin 3D printing mold to prepare a male mold mold required for the PDMS bottom layer 4;

[0050] Step 2: then the PDMS prepolymer and the curing agent are thoroughly mixed in a ratio of 10:1 and poured on the male mold mold. The vacuum degassed device is placed in a 80℃ drying box for curing for 2h;

[0051] Step 3: Place the flexible circuit board 3 on the cured PDMS bottom layer 4;

[0052] Step 4: Cover the area of the metal pads 32 of the flexible circuit board 3 with a mask;

[0053] Step 5: Continue to pour a layer of PDMS to form the PDMS cover layer 1. After the PDMS cover layer 1 is cured, remove the mask in the area of the pads;

[0054] Step 6: Install the array of moisture power generators 2 in the area of the metal pads 32;

[0055] Step 7: Subject the PDMS cover layer 1 to oxygen plasma treatment, then place the device in the order of bottom, middle and top, and bond them together on a hot plate at 80°C for 2h;

[0056] Step 8: Install the hydrogel layer 5 containing the drug in the hydrogel chamber 42 of the PDMS bottom layer 4, and ensure that the hydrogel layer 5 is in contact with the electrode sheet.

[0057] The components of the curing agent described in Step 2 of the present embodiment are prior art, and are not described here.

[0058] The above disclosed embodiments of the present application are only used to help explain the present application. The embodiments do not describe all the details, nor limit the present application to the specific embodiments described. Based on the content of the present specification, many modifications and variations can be made. The present specification selects and specifically describes these embodiments in order to better explain the principles and practical applications of the present application, so that those skilled in the art can well understand and utilize the present application.

Claims

1. An integrated wearable transdermal iontophoresis patch powered by a moisture generator, characterized in that: It includes a flexible circuit board (3) and two electrode plates. A power generation module is provided on the flexible circuit board (3). The positive and negative terminals of the power generation module are respectively connected to the two electrode plates. The power generation module includes a moisture generator array (2). The moisture generator array (2) includes multiple moisture generator groups arranged in parallel. The moisture generator groups include multiple moisture generator devices arranged in series. The flexible circuit board (3) is provided with multiple metal pads (32) that correspond one-to-one with the moisture generator devices. The moisture generator devices include active materials (22), steel mesh electrodes (21), and graphite paper electrodes (23). The steel mesh electrodes (21) and graphite paper electrodes (23) are respectively The active material (22) is connected to the top and bottom of the active material (22), which is placed on the metal pad (32). The steel mesh electrode (21) and the graphite paper electrode (23) are both connected to the metal pad (32). The bottom of the flexible circuit board (3) is connected to the PDMS bottom layer (4). The PDMS bottom layer (4) has a water vapor collection channel (41) and a water vapor outlet channel (43). The water vapor collection channel (41) and the water vapor outlet channel (43) are connected. Two hydrogel chambers (42) are symmetrically opened in the middle of the PDMS bottom layer (4). A hydrogel layer (5) is provided in the hydrogel chamber (42). The hydrogel layer (5) is connected to the electrode sheet.

2. The integrated wearable transdermal iontophoresis patch powered by a moisture generator according to claim 1, characterized in that: The steel mesh electrode (21) is provided with a porous structure (211), which is located at the connection between the steel mesh electrode (21) and the active material (22).

3. The integrated wearable transdermal iontophoresis patch powered by a moisture generator according to claim 1, characterized in that: The flexible circuit board (3) is provided with a control module connected in series with the power generation module. The control module includes a four-position switch (33) and a control circuit. The four-position switch (33) is connected to the power generation module through the control circuit. The control circuit includes a first-position branch, a second-position branch, a third-position branch and a fourth-position branch connected in parallel. The first-position branch, the second-position branch and the third-position branch are all closed circuits. The fourth-position branch is an open circuit. A first resistor (34) and a second resistor (35) are respectively provided on the first-position branch and the second-position branch. The resistance values ​​of the first resistor (34) and the second resistor (35) are different.

4. The integrated wearable transdermal iontophoresis patch powered by a moisture generator according to claim 1, characterized in that: The flexible circuit board (3) has multiple gas channels (31) which surround the moisture generator and are connected to the water vapor outlet channel (43).

5. An integrated wearable transdermal iontophoresis patch powered by a moisture generator according to claim 1, characterized in that: The top of the flexible circuit board (3) is connected to a PDMS cover layer (1).

6. The integrated wearable transdermal iontophoresis patch powered by a moisture generator according to claim 1, characterized in that: The flexible circuit board (3) is made of polyimide.

7. An integrated wearable transdermal iontophoresis patch powered by a moisture generator according to claim 2, characterized in that: The graphite paper electrode (23) is attached to the metal pad (32) by conductive graphite adhesive, and the stencil electrode (21) is connected to the metal pad (32) by soldering.

8. An integrated wearable transdermal iontophoresis patch powered by a moisture generator according to claim 1, characterized in that: The active material (22) is a hybrid membrane formed by combining polystyrene sulfonic acid and polyvinyl alcohol.

9. A method for preparing an integrated wearable transdermal iontophoresis patch powered by a moisture generator as described in any one of claims 1-8, characterized in that: It includes the following steps: Step 1: Prepare the punch mold required for the PDMS bottom layer (4) using a photosensitive resin 3D printing mold; Step 2: Then, thoroughly mix the PDMS prepolymer and curing agent in a 10:1 ratio and pour the mixture onto the punch mold. Place the vacuum-degassed device in an 80°C drying oven for 2 hours to cure. Step 3: Place the flexible circuit board (3) on the cured PDMS substrate (4); Step 4: Cover the metal pad (32) area of ​​the flexible circuit board (3) with a mask; Step 5: Continue to pour another layer of PDMS to form a PDMS cover layer (1). After the PDMS cover layer (1) has cured, remove the mask in the pad area. Step 6: Install the moisture generator array (2) in the area of ​​the metal pad (32); Step 7: The PDMS capping layer (1) is treated with oxygen plasma, and then the devices are pressed together in the order of top and bottom and bonded on an 80°C hot plate for 2 hours. Step 8: Install the drug-containing hydrogel layer (5) into the hydrogel chamber (42) of the PDMS bottom layer (4).

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