Device and method for scalp deep electricity delivery

Abstract

The invention relates to the technical field of transdermal drug delivery, in particular to a device and method for scalp deep electric delivery. The device comprises an electric signal generator used for generating pulse voltage, a main control module electrically connected with the electric signal generator and a comb-shaped shell, and the electric signal generator and the main control module are integrated in the comb-shaped shell. The device further comprises a plurality of first electrodes, a plurality of second electrodes and a medicine supply module, wherein the first electrodes and the second electrodes are electrically connected with the electric signal generator and used for forming a directional electric field. The multiple first electrodes and the multiple second electrodes are arranged on the comb-shaped shell according to a preset arrangement rule, and the length of the first electrodes is larger than that of the second electrodes. The comb-shaped shell comprises a comb handle and a comb body connected to one end of the comb handle. Wherein the main control module is configured to control the electric signal generator to generate corresponding pulse voltage when receiving a trigger signal, so that a directional electric field is applied to a target area through the first electrode and the second electrode, and medicine is conveyed to the deep position of hair follicles of the head.

Description

Technical Field

[0001] This invention relates to the field of transdermal drug delivery technology, and more specifically to a device and method for deep electrodelivery to the scalp. Background Technology

[0002] Androgenetic alopecia (AGA) is a common, chronic, progressive hair loss disease. Its pathological mechanism is mainly related to genetic susceptibility and the toxic effects of androgens (especially dihydrotestosterone) on hair follicles, leading to gradual miniaturization of hair follicles, shortened growth phases, and ultimately, thinning hair or even baldness. Effective AGA treatment relies on the precise delivery of active drugs or biological factors to the deep layers of the hair follicle, especially key targets such as dermal papilla cells, to inhibit androgen signaling pathways, reverse follicle atrophy, and promote hair growth. Therefore, the ability of drugs to efficiently penetrate the scalp barrier and accumulate in the deep tissues of the hair follicle is a core factor determining the success or failure of treatment.

[0003] Currently, the mainstream clinical treatments for AGA mainly include oral medications and topical preparations. Oral 5α-reductase inhibitors (such as finasteride) exert their effects by systemically reducing dihydrotestosterone levels in the body. However, due to their lack of local targeting, they are often accompanied by systemic adverse reactions such as decreased libido and erectile dysfunction. Some patients refuse long-term use due to concerns about side effects, and rebound effects are common after discontinuation. In contrast, topical vasodilators (such as minoxidil) are widely used due to their convenience and relatively high safety. However, they rely on passive diffusion mechanisms, which are limited by the natural barrier effect of the scalp stratum corneum and the physical obstruction of drug distribution by dense hair, making it difficult for the drug to effectively penetrate deep into the hair follicle. A large amount of drug remains on the skin surface or adheres to the hair shaft, resulting in low bioavailability, large individual differences in efficacy, and slow onset of action, making it difficult to meet the needs for stable and effective treatment.

[0004] To overcome these limitations, various novel transdermal delivery technologies have emerged in recent years, with microneedle devices being a prime example. Microneedles create micron-sized channels in the stratum corneum, significantly improving drug penetration efficiency and demonstrating promising follicle-targeting potential under laboratory conditions. However, this technology is inherently a minimally invasive or intrusive method, with significant drawbacks in practical applications: firstly, repeated punctures can cause pain, redness, swelling, bleeding, and even secondary infections, leading to poor patient tolerance; secondly, in hair-covered areas, microneedle patches are difficult to adhere tightly to the scalp, resulting in insufficient sealing and drug leakage or uneven distribution, severely impacting delivery efficiency. More importantly, AGA, as a chronic disease requiring long-term management, demands highly practical and comfortable treatment plans, while existing microneedle devices are generally cumbersome to operate and uncomfortable, making them unsuitable for daily, large-area, and long-term home use.

[0005] Based on this, some studies have attempted to use physical permeation enhancement techniques (such as iontophoresis and magnetic therapy) for local drug delivery.

[0006] For example, patent application CN116764090A discloses a physiotherapy method and system using a drug iontophoresis absorption scalp membrane, comprising the following steps: Step 1, applying an absorbent scalp membrane to the scalp; Step 2, ionization treatment, ionizing the drug through a drug ionization module; Step 3, introducing drug ions into the scalp membrane; Step 4, promoting drug absorption in the scalp through iontophoresis. While this method utilizes ionization for drug delivery, it requires covering the scalp with a separate scalp membrane, i.e., a drug carrier. However, to cover the scalp with the scalp membrane, hair needs to be removed beforehand to eliminate physical interference from the scalp. This can lead to significant psychological resistance from users, thus reducing the user experience and resulting in low compliance.

[0007] For example, invention patent CN1178103A discloses a multifunctional massage comb that integrates magnetotherapy, pulse electrotherapy, drug therapy, far-infrared therapy, and vibration massage. This comb has a built-in battery and electronic circuitry to generate electrical pulses, a drug capsule and conduit for magnetizing medication, and a volatile structure similar to a medicated pillow at the front of the comb teeth to release the medication. Simultaneously, far-infrared radiation material is covered at the contact points, and magnets are embedded in the comb teeth or massage heads to enhance the therapeutic effect. This design aims to improve hair quality and prevent hair loss through long-term use, and claims to have an adjunctive therapeutic effect on various head and systemic diseases. This patent application utilizes magnetization technology to magnetize the medicinal liquid, increasing its osmotic pressure and enhancing its oxygen-dissolving capacity, thus making it easier for the scalp to absorb and thereby enhancing its efficacy.

[0008] It is evident that existing technologies offer two different non-invasive drug delivery methods, but the drug absorption efficiency under these two methods needs further improvement. Summary of the Invention

[0009] The purpose of this invention is to provide an apparatus and method for deep scalp electrodelivery, which partially solves or alleviates the above-mentioned deficiencies in the prior art and can promote drug absorption.

[0010] To solve the aforementioned technical problems, the present invention specifically adopts the following technical solution: A first aspect of the present invention is to provide an apparatus for deep scalp electrodelivery, comprising an electrical signal generator for generating pulse voltages, a main control module electrically connected to the electrical signal generator, and a comb-shaped housing, wherein the electrical signal generator and the main control module are integrated within the comb-shaped housing; The device further includes: a plurality of first electrodes and a plurality of second electrodes electrically connected to the electrical signal generator for forming a directional electric field, and a drug delivery module; the plurality of first electrodes and the plurality of second electrodes are arranged on the comb-shaped housing according to a preset arrangement rule, wherein the length L1 of the first electrode is greater than the length L2 of the second electrode; the comb-shaped housing includes: a comb handle, and a comb body connected to one end of the comb handle; wherein, The main control module is configured to, upon receiving a trigger signal, control the electrical signal generator to generate a corresponding pulse voltage, so as to apply a directional electric field to the target area through the first electrode and the second electrode, so as to deliver the drug to the depth of the hair follicles on the head.

[0011] Furthermore, the preset layout rules include: two-dimensional planar layout rules and three-dimensional layout rules; wherein, The two-dimensional planar layout rule includes: multiple first electrodes and multiple second electrodes are alternately arranged along the length direction of the comb body, serving as a row of comb teeth connected to the comb body; The three-dimensional layout rules include: The plurality of first electrodes and the plurality of second electrodes are respectively located on at least two mutually parallel planes, serving as at least two rows of comb teeth connected to the comb body; Alternatively, at least two rows of comb teeth are connected to the comb body, and multiple first electrodes and multiple second electrodes in each row of comb teeth are alternately arranged along the length direction of the comb body; Alternatively, multiple first electrodes and multiple second electrodes are respectively located on multiple mounting surfaces spaced apart around the comb body, thereby serving as multiple rows of comb teeth spaced apart circumferentially around the comb body, and multiple first electrodes and multiple second electrodes are respectively mounted on two adjacent mounting surfaces; Alternatively, multiple first electrodes and multiple second electrodes are respectively located on multiple mounting surfaces spaced apart around the comb body, thereby serving as multiple rows of comb teeth spaced apart circumferentially around the comb body, with multiple first electrodes and multiple second electrodes alternately arranged on each mounting surface.

[0012] Furthermore, the second electrode includes a second conductive element extending along the axial direction of the comb teeth, and correspondingly, the drug supply module includes a drug storage chamber built into the second electrode; The second conductive element is built into the drug storage chamber and can reciprocate along the axial direction of the drug storage chamber; the end of the second conductive element is provided with a conductive sealing element and an elastic reset element. When there is no external force, under the action of the elastic reset member, the sealing member at the end of the second conductive element will seal the outlet of the drug storage chamber; When the end of the first electrode and the sealing member of the second electrode act on the head, under the squeezing action of the head, the sealing member disengages from the outlet of the drug storage chamber, thereby allowing the drug liquid to flow out from the outlet and permeate under the action of the directional electric field formed between the first electrode and the second electrode.

[0013] Furthermore, the drug delivery module includes a drug coating applied to the contact surface of the second electrode end that comes into contact with the skin.

[0014] Furthermore, the difference between the length L1 of the first electrode and the length L2 of the second electrode is greater than 0 mm and less than 2 mm.

[0015] Furthermore, the distance L3 between the first electrode and the second electrode is greater than 0 mm and less than 14 mm.

[0016] Furthermore, a first limiting member is fixedly installed inside the drug storage chamber, and a second limiting member is detachably installed at the outlet of the drug storage chamber. The two ends of the elastic reset member abut against the first limiting member and the second limiting member respectively, and the second conductive element passes through the first limiting member and can reciprocate relative to the first limiting member along the axial direction of the drug storage chamber. The second limiting member is provided with a through hole that cooperates with the sealing member.

[0017] Furthermore, the second limiting member is funnel-shaped.

[0018] A second aspect of the present invention is to provide a method for deep scalp electrodelivery, implemented based on the aforementioned apparatus for deep scalp electrodelivery, comprising the following steps: S1. Configure device parameters; the device parameters include: pulse voltage value; S2. When a trigger signal is received, the electrical signal generator in the device is controlled to generate and send a corresponding pulse voltage to the first and second electrodes in the device according to the preset pulse voltage value. A directional electric field is formed on the head through the first and second electrodes to open the channel and deliver the drug to the depth of the hair follicles on the head.

[0019] A third aspect of the present invention is to provide a method for deep scalp electrodelivery, implemented based on the aforementioned apparatus for deep scalp electrodelivery, comprising the following steps: S1. Configure device parameters; the device parameters include: working mode, wherein the working mode includes: electrical stimulation mode, drug electrical delivery mode and hybrid mode; S2. When a trigger signal is received, identify the current working mode. If it is the electrical stimulation mode, execute step S3; if it is the drug electrical delivery mode, execute step S4; if it is the mixed mode, execute step S5. S3, according to the first preset pulse voltage value, the electrical signal generator in the device generates and sends a corresponding pulse voltage to the first electrode and the second electrode in the device, and forms a directional electric field on the head through the first electrode and the second electrode to perform electrical stimulation; S4, according to the second preset pulse voltage value, the electrical signal generator in the device generates and sends a corresponding pulse voltage to the first electrode and the second electrode in the device, and forms a directional electric field on the head through the first electrode and the second electrode, so as to open the channel and deliver the drug to the depth of the hair follicle of the head. S5, according to the preset interval time T, the electrical stimulation mode and the drug electrical delivery mode are activated sequentially, so that the channel is opened first by the electrical stimulation mode, and then the drug is efficiently delivered through the opened channel by the drug electrical delivery mode.

[0020] Beneficial technical effects of the present invention: The comb-shaped device proposed in this invention differs fundamentally from current treatments for androgenetic alopecia in its technical principle, mode of action, and applicability, thus offering significant advantages. The advantages of this invention are as follows: 1. It has overcome a long-standing core challenge in existing technologies: successfully solving the industry-wide problem of how to achieve non-invasive, efficient, and deep targeted drug delivery in hair-covered scalp areas. It unifies the seemingly contradictory concepts of "non-invasive" and "efficient," overcoming the shortcomings of insufficient penetration of traditional topical formulations and the invasiveness and unsuitability of microneedle devices.

[0021] 2. Achieved higher treatment efficiency and efficacy potential: Enhanced targeting: Directed electric field force drives the drug to move in a directional manner to the hair follicle, reducing drug waste in non-target tissues; Penetration depth and intracellular delivery: Not only can the drug be delivered to the deep layers of the hair follicle, but also the efficiency of cell uptake of the drug can be greatly improved through reversible electroporation; Synergistic effect: Combining the dual efficacy of electrical stimulation for hair growth and drug action, it is expected to produce effects superior to single therapy.

[0022] 3. Significantly improves patient compliance and treatment accessibility: Painless and non-invasive: eliminates the fear and discomfort associated with using microneedles and other devices; Convenient and easy to use: The comb-like operation seamlessly integrates into daily life, is simple and quick, and suitable for long-term adherence. Suitable for large-area treatment: The comb-shaped design facilitates even and rapid coverage of the entire hair loss area.

[0023] 4. Opens up new technological avenues and application prospects: This solution innovatively combines electrodynamic delivery technology with ergonomic comb-shaped devices, providing a completely new paradigm for transdermal drug delivery in dermatology and aesthetic medicine. It can not only be used for AGA (Advanced Gastrointestinal Sclerosis), but its principles may also be extended to other indications requiring deep local drug delivery to the scalp or skin in the future.

[0024] 5. This invention, by setting up a comb-shaped device and configuring a first electrode and a second electrode with a height difference, upgrades the symmetrical two-dimensional planar electric field to a three-dimensional electric field compared to the method of using electrodes of equal height / aligned electrodes. Compared to the method of a uniform electric field without a height difference, it utilizes positive and negative electrodes (such as a first electrode as the positive electrode and a second electrode as the negative electrode) to form a directional penetrating electric field in the tissue (i.e., a directional electric field, for example, the first electrode as the positive electrode points to the second electrode as the negative electrode; or the second electrode as the positive electrode points to the first electrode as the negative electrode). The height difference design allows the current to flow through a deeper tissue area to reach the other electrode, thereby increasing the penetration depth of the electric field. While providing deep electrical stimulation, it guides drug molecules to be delivered deep along a specific path. In addition, since there is no need to add a scalp membrane as a drug-carrying layer, and the electrode directly contacts the scalp for drug delivery, the physical obstruction of the scalp membrane is avoided, which helps to achieve deep targeted delivery and thus improves drug delivery efficiency.

[0025] By coupling the mechanical on / off switch (i.e. the sealing element at the end of the second conductive element) with the fluid passage control on the same movable part, "conduction upon contact and administration upon pressure" is achieved, eliminating the need for additional electrically controlled valves and complex control circuits, greatly reducing costs and improving the user experience.

[0026] 6. The present invention can provide not only a single electrical stimulation mode or a single delivery mode, but also a hybrid mode in which the electrical stimulation mode and the delivery mode work together (for example, electrical stimulation is performed first at preset time intervals, and then drug delivery is performed).

[0027] In summary, this invention is not a simple improvement on existing technologies, but rather a systematic solution to the deep delivery bottleneck and patient compliance problem in AGA treatment through principle innovation (active electrodynamic drive), design innovation (comb-shaped structure adapted to hairy environments), and mode innovation (non-invasive synergistic treatment), providing a more efficient, user-friendly, and promising next-generation solution. Attached Figure Description

[0028] To more clearly illustrate the technical solutions in the embodiments of the present invention or the prior art, the drawings used in the description of the embodiments or the prior art will be briefly introduced below. In all the drawings, similar elements or parts are generally identified by similar reference numerals. The elements or parts in the drawings are not necessarily drawn to scale. Obviously, the drawings described below are some embodiments of the present invention, and those skilled in the art can obtain other drawings based on these drawings without any creative effort.

[0029] Figure 1A This is a schematic diagram of the device for deep scalp electrodelivery provided in an embodiment of the present invention; Figure 1B A partial structural schematic diagram of a device for deep scalp electrodelivery provided in an embodiment of the invention; Figure 1C A schematic diagram showing the disassembly of the cover portion in the device for deep scalp electrodelivery provided in the embodiments of the invention; Figure 2 The present invention provides a schematic diagram of a device for deep electroscalp delivery that delivers therapeutic molecules deep into hair follicle cells to promote hair regeneration. A is a schematic diagram of the delivery of regulatory molecules SRD5A2 siRNA and VEGF-A (SRD5A2 siRNA can reduce androgen levels and promote hair growth; VEGF-A promotes angiogenesis and hair growth). B is a schematic diagram of the mechanism by which the delivery device achieves deep delivery of SRD5A2 siRNA and VEGF-A plasmids. C is a schematic diagram of the internal circuitry of the delivery device. D is a schematic diagram of the pulse signal applied to the head when the electrodes in the delivery device contact the scalp. Figure 3 This is a comparative schematic diagram of the simulation results of the electric field formed by the device for deep scalp electrodelivery provided in the embodiments of the present invention and the delivery device with aligned comb teeth; A is a schematic diagram of the symmetrical electric field formed by the delivery device with aligned comb teeth (i.e., equal height electrodes); B is a schematic diagram of the directional electric field of the delivery device in the embodiments of the present invention; C is a comparative bar chart of the two electric field intensities formed between adjacent comb teeth in A and adjacent comb teeth in B under the condition of applying the same pulse voltage (e.g., 30V). Figure 4To verify the delivery effect of the device for deep scalp electrodelivery provided in this embodiment of the invention; wherein, A is a two-photon microscopy (TPM) image of the head of four groups of experimental animals, which reflects the efficiency of molecular delivery in the skin of the four groups; B is a tissue section image of the molecular delivery depth (red signal indicates delivery depth) in the skin of the head of four groups of experimental animals (AB propidium iodide is used as the verification molecule for delivery); C is a schematic diagram of the quantitative analysis results of fluorescence intensity PI in the four groups of skin shown in A; D is a schematic diagram of the quantitative analysis results of molecular delivery depth in the four groups of skin shown in B; E is the transmembrane potential of deep hair follicle cells under a simulated electric field; F is a schematic diagram of the principle of deep molecular delivery using the delivery device of the present invention; G and H are the analysis results obtained by qPCR analysis of the content of delivered molecules: VEGFA plasmid and SRD5A2 siRNA in the four groups of skin tissue; Figure 5 To verify the effect of the device for deep scalp electrodelivery provided in this embodiment of the invention on promoting hair regeneration: A is a schematic diagram of the treatment regimens of six AGA mouse models using different methods; B is the expression level of VEGFA mRNA after molecular delivery using the device of this embodiment of the invention; C is the expression level of SRD5A2 after molecular delivery using the device of this embodiment of the invention. mRNA expression level; D represents Western blot analysis of VEGFA and SRD5A2 protein expression levels; E represents quantitative analysis of VEGFA and SRD5A2 protein expression levels; F represents representative photographs showing hair growth in each group from day 1 to day 28; G represents representative H&E stained longitudinal sections of skin tissue on day 28; H represents immunofluorescence staining images of hair follicle activation markers CD31 (red) and CD34 (green) in skin tissue; I and J represent comparative quantitative results of hair recovery area and hair growth cycle score on day 28 after treatment; K represents statistical analysis results of hair follicle count in skin tissue on day 28; L and M represent quantitative analysis results of CD31 FI intensity and CD34 FI intensity on day 28.

[0030] Summary of attached labeling and identification: 1. Comb-shaped outer shell; 2. Comb handle; 3. First electrode; 4. Second electrode; 5. Comb body; 401. Elastic reset component; 402. Drug storage chamber; 403. Sealing component; 404. Second conductive element; 405. First limiting component; 406. Second limiting component. Detailed Implementation

[0031] To make the objectives, technical solutions, and advantages of the embodiments of the present invention clearer, the technical solutions of the embodiments of the present invention will be clearly and completely described below with reference to the accompanying drawings. Obviously, the described embodiments are only some, not all, of the embodiments of the present invention. All other embodiments obtained by those skilled in the art based on the embodiments of the present invention without creative effort are within the scope of protection of the present invention.

[0032] In this document, suffixes such as "module," "part," or "unit" used to denote elements are used only for the purpose of illustrative purposes and have no specific meaning in themselves. Therefore, "module," "part," or "unit" may be used interchangeably.

[0033] In this document, the terms "upper," "lower," "inner," "outer," "front," "rear," "one end," and "the other end," etc., indicate the orientation or positional relationship based on the orientation or positional relationship shown in the accompanying drawings. They are used only for the convenience of describing the present invention and for simplifying the description, and do not indicate or imply that the device or element referred to must have a specific orientation, or be constructed and operated in a specific orientation. Therefore, they should not be construed as limitations on the present invention. Furthermore, the terms "first" and "second" are used for descriptive purposes only and should not be construed as indicating or implying relative importance.

[0034] In this document, unless otherwise explicitly specified and limited, the terms "installed," "equipped with," "connected," etc., should be interpreted broadly. For example, "connection" can be a fixed connection, a detachable connection, or an integral connection; it can be a mechanical connection, a direct connection, or an indirect connection through an intermediate medium; it can be a connection within two components. Those skilled in the art can understand the specific meaning of the above terms in this invention based on the specific circumstances.

[0035] In this document, "and / or" includes any and all combinations of one or more of the listed related items.

[0036] In this article, "several" and "multiple" refer to two or more, that is, including two, three, four, five, etc.

[0037] As used in this specification, the term "about" typically means + / -5% of the value, more typically + / -4% of the value, more typically + / -3% of the value, more typically + / -2% of the value, even more typically + / -1% of the value, and even more typically + / -0.5% of the value.

[0038] In this specification, certain embodiments may be disclosed in a range-bound format. It should be understood that this "range-bound" description is merely for convenience and brevity and should not be construed as a rigid limitation on the disclosed range. Therefore, the description of a range should be considered as having specifically disclosed all possible subranges and the individual numerical values ​​within those ranges. For example, a description of the range 1-6 should be considered as having specifically disclosed subranges such as from 1 to 3, from 1 to 4, from 1 to 5, from 2 to 4, from 2 to 6, from 3 to 6, etc., and the individual numbers within those ranges, such as 1, 2, 3, 4, 5, and 6. This rule applies regardless of the breadth of the range.

[0039] In this article, "deep transdermal layer" refers to the area between the epidermis and the hair follicle.

[0040] Example 1: like Figure 1A and Figure 1B As shown, this embodiment provides a device for deep scalp electro-delivery, including an electrical signal generator for generating pulse voltages, a main control module electrically connected to the electrical signal generator, and a comb-shaped housing 1. The electrical signal generator and the main control module are integrated within the comb-shaped housing 1. The comb-shaped housing 1 includes: a comb handle 2 and a comb body 5 connected to one end of the comb handle 2.

[0041] Specifically, the comb-shaped outer shell refers to a common comb-like shape, such as the handheld part and the comb body with teeth. Specifically, this includes combs with a single row of teeth, combs with multiple rows of parallel teeth, fan-shaped combs with teeth at a certain angle, or combs with a cylindrical body and multiple rows of teeth evenly distributed around the circumference. This device is designed in a comb shape externally, with a hollow internal structure for housing various electronic devices, such as the main control module, electrical signal generator, and other components (such as the first and second electrodes) connected to the main control module via wiring. In use, the comb-shaped structure allows the hair to be parted, avoiding physical interference from the hair and allowing direct contact with the scalp, ensuring effective contact between the directional electric field and the electrodes with the targeted skin area.

[0042] The device further includes: a plurality of first electrodes 3 and a plurality of second electrodes 4 electrically connected to the electrical signal generator for forming a directional electric field, and a drug supply module; the plurality of first electrodes 3 and the plurality of second electrodes 4 are arranged on the comb-shaped housing 1 according to a preset arrangement rule, wherein the length L1 of the first electrode 3 is greater than the length L2 of the second electrode 4.

[0043] Specifically, in this embodiment, the first electrode 3 and the second electrode 4 are disposed in the hollow structure of the comb teeth, or their structure itself can serve as comb teeth. Preferably, the electrical signal generator is disposed in the hollow interior of the comb body, and the main control module is disposed in the hollow interior of the comb handle. Alternatively, the electrical signal generator and the main control module are integrated together and disposed in the comb handle (comb-shaped outer shell). This device ingeniously assembles its functional components (such as the electrical signal generator, main control module, etc.) into one unit within a limited space.

[0044] In some embodiments, the preset arrangement rule includes a two-dimensional planar arrangement rule, which includes: a plurality of first electrodes 3 and a plurality of second electrodes 4 are alternately arranged along the length direction of the comb body 5, as a row of comb teeth connected to the comb body 5, such as... Figure 1A and Figure 1B As shown.

[0045] In this embodiment, the arrangement of the first electrode 3 and the second electrode 4 is required to form a directional electric field, thereby delivering drugs to the deep layers of the scalp. For example, the first electrode 3 and the second electrode 4, which have a height difference, are arranged alternately. This structural design will cause local skin deformation when in contact with the scalp, forming microprotrusions and circuits. When combined with an electrical signal generator, it can achieve effective deep electrical stimulation of the scalp tissue under a pulse voltage input of about 20V-33V (preferably 30V), thereby achieving reversible electroporation to form microchannels for delivering drug molecules.

[0046] In this embodiment, the plurality of first electrodes 3 and second electrodes 4 are designed in an alternating comb-like shape to form a directional electric field. Specifically, the length L1 of the first electrode is greater than the length L2 of the second electrode.

[0047] In this design, the longer first electrode 3 serves as the positive electrode, while the shorter second electrode 4 serves as the negative electrode, and the shorter second electrode 4 is integrated with the drug delivery module. Of course, if it is necessary to utilize the negative electrode to deliver the drug, the drug delivery module is integrated onto the electrode serving as the negative electrode.

[0048] Of course, in other embodiments, if it is necessary to use the positive electrode to deliver drugs, the drug delivery module is integrated on the electrode that serves as the positive electrode. Accordingly, the shorter second electrode 4 serves as the positive electrode, while the longer first electrode serves as the negative electrode.

[0049] In some embodiments, the second electrode 4 includes a second conductive element 404 extending along the axial direction of the comb teeth. Correspondingly, the drug supply module includes a drug storage chamber 402 extending along the axial direction of the comb teeth (for example, the comb-shaped outer shell also includes hollow comb teeth, and the drug storage chamber 402 is the cavity inside the hollow comb teeth). The second conductive element 404 is built into the drug storage chamber 402 and can reciprocate along the axial direction of the drug storage chamber 402. A conductive sealing member 403 is provided at the end of the second conductive element 404, and an elastic reset member 401 is provided at the end of the second conductive element 404.

[0050] In some embodiments, a first limiting member 405 is fixedly disposed inside the drug storage chamber 402, and a second limiting member 406 is detachably disposed (e.g., by threaded connection) at the outlet of the drug storage chamber 402. The two ends of the elastic reset member 401 abut against the first limiting member 405 and the second limiting member 406 respectively, and the second conductive element 404 passes through the first limiting member 405 and can reciprocate relative to the first limiting member 405 along the axial direction of the drug storage chamber 402. The first limiting member 405 is provided with at least one liquid flow channel to connect the spaces on the upper and lower sides of the first limiting member 405; the second limiting member 406 is provided with a through hole that cooperates with the sealing member 403. Preferably, the second limiting member 406 is funnel-shaped.

[0051] When there is no external force, under the action of the elastic reset member 401, the sealing member 403 at the end of the second conductive element 404 seals the outlet of the drug storage chamber 402; when the end of the first electrode 3 acts on the head, under the squeezing action of the head, the sealing member 403 disengages from the outlet of the drug storage chamber 402, thereby allowing the liquid medicine to flow out from the outlet.

[0052] Preferably, the drug in the drug reservoir 402 employs a ball-bearing release mechanism, functioning similarly to a ballpoint pen. Specifically, the sealing member 403 at the end of the second electrode 4 acts as a valve switch for the drug reservoir 402. Once the sealing member 403 contacts the head and is compressed, a gap is formed between the sealing member 403 and the through hole of the second limiting member 406, thus opening the outlet of the drug reservoir 402 and allowing the drug to flow out. Furthermore, during operation (e.g., during combing), the height difference between adjacent comb teeth (first electrode 3 and second electrode 4) generates a directional electric field from the comb teeth acting as the positive electrode to the comb teeth acting as the negative electrode. This directional electric field drives the released therapeutic molecules to undergo active transdermal transport, guiding them to the deep region of the hair follicle. In addition, the applied electric field induces reversible electroporation on the hair follicle cell membrane, momentarily enhancing membrane permeability to accelerate intracellular molecule uptake. After the device is removed and the electric field dissipates, the membrane integrity can spontaneously recover, ensuring the safety and effectiveness of the delivery process.

[0053] In this application, when the elastic reset member 401 comes into contact with the scalp and is squeezed, the second conductive element of the second electrode 4 moves along its axial direction, further increasing the height difference between the second electrode and the first electrode.

[0054] The working principle of this device is as follows: When a trigger signal is received (for example, a trigger signal generated by the user through a pre-set trigger button), the electrical signal generator generates a corresponding pulse voltage (the amplitude of the pulse voltage is pre-stored). At this time, since no circuit is formed between the first electrode 3 and the second electrode 4, no directional electric field is formed.

[0055] When a user combs their hair using this device, the end of the first electrode 3 and the sealing member 403 of the second electrode 4 act on the head. Under the pressure of the head, the second conductive element 404 moves axially towards the comb body, causing the sealing member 403 to disengage from the outlet of the drug storage chamber 402 (here, disengagement means that there is a gap between the surface of the sealing member 403 and the outlet of the drug storage chamber 402, such as the through hole of the second limiting member, for the drug to flow out), allowing the drug to flow out. However, the sealing member 403 of the second electrode 4 is still in contact with the head, thereby forming a circuit between the first electrode 3 and the second electrode 4, and further forming a directional electric field between the first electrode and the second electrode, driving the drug to be delivered deep into the hair follicles of the head.

[0056] This application, by setting up a comb-shaped device and electrodes with height differences, upgrades two-dimensional planar electrical stimulation to three-dimensional stereoscopic stimulation compared to using electrodes of equal height / aligned electrodes. That is, it transforms a uniform, symmetrical planar electric field into a directional electric field from positive to negative with higher penetration, thereby opening the skin surface barrier and forming a channel for drug delivery. See [link to relevant documentation]. Figure 2 Furthermore, since there is no need to add a scalp membrane as a drug-carrying layer, and the electrode directly contacts the scalp to administer the drug, the physical obstruction of the scalp membrane is avoided, which is more conducive to achieving deep targeted delivery and thus improving drug delivery efficiency.

[0057] Furthermore, by coupling the mechanical on / off switch (i.e. the sealing element at the end of the second conductive element) with the fluid passage control on the same movable part, "conduction upon contact and administration upon pressure" is achieved, eliminating the need for additional electrically controlled valves and complex control circuits, greatly reducing costs and improving the user experience.

[0058] In other embodiments, the drug delivery module may be a drug coating directly applied to the entire second electrode 4, or applied to the contact surface of the end of the second electrode 4 that comes into contact with the skin (such as the local area where the sealing member comes into contact with the skin).

[0059] In some embodiments, the end of the first electrode 3 may be a conductive spherical structure that is in direct contact with the scalp and has a shape similar to the sealing element of the second electrode.

[0060] See Figure 3 It is known that, under the premise of applying the same voltage between the positive and negative electrodes, the electric field strength formed between the positive and negative electrodes using an electrode array with a height difference is greater than that of the aligned comb array. For example, when a voltage of 30V is applied, the electric field strength formed between the positive and negative electrodes in the electrode array with a height difference is more than three times greater than that in the aligned comb array.

[0061] In some embodiments, the difference between the length L1 of the first electrode 3 and the length L2 of the second electrode 4 is greater than 0 mm and less than 2 mm (preferably, the difference between the two electrode lengths is 1 mm to 2 mm, more preferably, 1.5 mm); the distance L3 between the first electrode 3 and the second electrode 4 is greater than 0 mm and less than 14 mm (preferably, the distance between the two electrodes is 7 mm to 14 mm), where the distance L3 between the two electrodes refers to the distance between the edges of two adjacent electrodes (comb teeth), see [reference]. Figure 1C .

[0062] In this embodiment, the device is shaped like a comb, with the second electrode and the first electrode forming the shape of the comb teeth. The appropriate tooth spacing is used to part the hair.

[0063] To accommodate everyday grooming habits, the device is designed in a comb-like configuration. Unlike traditional combs, this device uses two metal-tipped combs with alternating height differences. This design causes localized skin deformation upon contact with the scalp, creating micro-protrusions. When used in conjunction with an integrated electrical signal generator, it can provide effective deep electrical stimulation to the scalp tissue with a pulsed voltage input of approximately 30V. Figure 2 ).

[0064] To achieve efficient delivery of therapeutic molecules, deep tissue molecule delivery functionality is integrated into the device. Specifically, drug-loading modules are integrated into the lower comb teeth for pre-loading therapeutic molecules; the tips employ a ball-based release mechanism, functioning similarly to a ballpoint pen, enabling contact-triggered drug delivery.

[0065] Furthermore, during operation, adjacent first and second electrodes in the electrode array with a height difference generate a directional electric field from positive to negative. This electric field drives the released therapeutic molecules to undergo active transdermal transport, directing them to the deep regions of the hair follicle. In addition, the applied electric field induces reversible electroporation on the hair follicle cell membrane, transiently enhancing membrane permeability to accelerate intracellular molecule uptake. After the device is removed and the electric field dissipates, the membrane integrity can spontaneously recover, ensuring the safety and effectiveness of the delivery process.

[0066] In some embodiments, see Figure 2 The circuitry of the device includes a trigger button, a main control module (e.g., an MCU), and a voltage modulator electrically connected to the main control module. A voltage signal generator (which can be an existing voltage signal generator to generate the corresponding pulse voltage; however, in some embodiments, the voltage signal generator may not be integrated into the main control module) is integrated within the main control module. Specifically, once the user presses the trigger button, the main control module receives the corresponding trigger signal, i.e., outputs a small pulse voltage (e.g., a 3.3V pulse voltage) through the voltage signal generator, and the modulator modulates this pulse voltage to a preset amplitude (e.g., 30V). The modulator includes a linear regulator (LDO) (preferably 3.3V), a DC-DC boost converter, a MOSFET as an electronic switch, and the LDO (preferably 30V). This modulator is prior art, and its internal structure and operating principle will not be described in detail here.

[0067] In some embodiments, the comb body 5 includes a main body connected to the comb teeth of each hollow structure, and a cover portion detachably mounted on the main body. When the cover portion is removed, the desired medication can be directly injected into the medication storage compartment through the injection ports on the main body that communicate with the medication storage compartment. Specifically, the cover portion and the main body portion can be detachably connected by means of snap-fit ​​connection or other methods. In some embodiments, a circuit board is integrated inside the cover portion and a circuit board is integrated inside the comb handle. The two circuit boards are electrically connected by a pluggable and conductive connecting wire. Preferably, the circuit board in the comb handle integrates a main control module, a trigger button (or switch button), and an electrical signal generator, etc.; while the circuit board in the comb body mainly integrates a power supply interface that can output the pulse voltage output by the circuit board in the comb handle to each pluggable electrode. Specifically, a conductive terminal that can be plugged into and connected to the power supply interface is provided on the top of the first electrode near the cover; a conductive terminal that can be plugged into and connected to the power supply interface is provided on the top of the second electrode near the cover, and the conductive terminal is electrically connected to the top of the second electrode through a wire. By setting the wire and the conductive terminal, the second electrode can move up and down along its axis in the drug storage compartment without affecting its electrical connection with the main control module.

[0068] Example 2: This embodiment provides another device for deep scalp electrodelivery, which has the same structure as the device in Embodiment 1 above, except for the preset arrangement of the first electrode and the second electrode.

[0069] In this embodiment, the preset arrangement of the first electrode and the second electrode adopts a three-dimensional arrangement rule. Specifically, at least two rows of comb teeth are connected to the comb body 5, and multiple first electrodes 3 and multiple second electrodes 4 in each row of comb teeth are alternately arranged along the length direction of the comb body 5.

[0070] In this embodiment, the height difference between the first electrode and the second electrode and the principle of drug delivery are the same as in the above embodiment, that is, they act as a comb structure to part the scalp area covered by hair.

[0071] Example 3: This third embodiment provides another device for deep scalp electrodelivery, which has the same structure as the device in the first embodiment, except that the preset arrangement of the first electrode and the second electrode adopts a different three-dimensional arrangement rule.

[0072] Specifically, the plurality of first electrodes 3 and the plurality of second electrodes 4 are respectively located on at least two parallel planes, serving as at least two rows of comb teeth connected to the comb body 5. The distance between the two planes is the distance between the first electrodes and the second electrodes.

[0073] Example 4: This embodiment provides another device for deep scalp electro-delivery, which has the same structure as the device in Embodiment 1 above. The difference is that the preset arrangement of the first electrode and the second electrode adopts a different three-dimensional arrangement rule. Specifically, multiple first electrodes 3 and multiple second electrodes 4 are respectively located on multiple mounting surfaces spaced around the comb body, thus serving as multiple rows of comb teeth spaced around the comb body 5, and multiple first electrodes 3 and multiple second electrodes 4 are respectively mounted on two adjacent mounting surfaces.

[0074] Preferably, in this embodiment, the comb body has a certain width, and multiple mounting surfaces (i.e., the plane where the same row of comb teeth is located) are spaced apart along the width direction of the comb body. Preferably, the multiple mounting surfaces can be parallel to each other or at a certain angle.

[0075] Of course, the comb body can also be cylindrical, with multiple mounting surfaces evenly spaced along the circumference of the comb body.

[0076] Example 5: This fifth embodiment provides another device for deep scalp electrodelivery, which has the same structure as the device in the first embodiment, except that the preset arrangement of the first electrode and the second electrode adopts a different three-dimensional arrangement rule; specifically, multiple first electrodes 3 and multiple second electrodes 4 are respectively located on multiple mounting surfaces spaced around the comb body 5, thus serving as multiple rows of comb teeth spaced around the comb body 5, and multiple first electrodes 3 and multiple second electrodes 4 are alternately arranged on each mounting surface.

[0077] Preferably, in this embodiment, the comb body has a certain width, and multiple mounting surfaces (i.e., the plane containing the same row of comb teeth) are spaced apart along the width direction of the comb body. Preferably, the multiple mounting surfaces can be parallel to each other or at a certain angle. Of course, the comb body can also be cylindrical, with multiple mounting surfaces evenly spaced along the circumference of the comb body.

[0078] Example 6: This embodiment provides a method for deep scalp electrodelivery, implemented based on a device for deep scalp electrodelivery described in any of the above embodiments, and includes the following steps: S1. Configure device parameters; the device parameters include: pulse voltage value.

[0079] In some embodiments, the pulse voltage value may be pre-stored in the device, for example, a factory default value. In other embodiments, the user can set device parameters such as the pulse voltage value via adjustment / setting buttons electrically connected to the main control module.

[0080] In some embodiments, the pulse voltage value is 20-33V; preferably, 30V.

[0081] S2. When a trigger signal is received, the electrical signal generator in the device is controlled to generate and send a corresponding pulse voltage to the first electrode 3 and the second electrode 4 in the device according to the preset pulse voltage value. A directional electric field is formed on the head through the first electrode 3 and the second electrode 4 to deliver the drug to the depth of the hair follicles of the head while opening the channel.

[0082] In some embodiments, the user can generate a corresponding trigger signal via a trigger button (such as a power switch) electrically connected to the main control module. This triggers the main control module to control an electrical signal generator to generate a corresponding pulse voltage, which forms a circuit with the user's head through the first and second electrodes, thereby creating a directional electric field for drug delivery. The specific working principle can be found in Embodiment 1 above, and will not be repeated here.

[0083] Example 7: This embodiment also provides another method for deep scalp electrodelivery, implemented based on a device for deep scalp electrodelivery described in any of the above embodiments, including the following steps: S1. Configure device parameters; the device parameters include: working mode.

[0084] In some embodiments, the device operates in three modes: an electrical stimulation mode, a drug delivery mode, and a hybrid mode. Specifically, the user can switch modes using a switch button on the comb handle; for example, a short press (e.g., 1-2 seconds) activates the electrical stimulation mode, a long press (e.g., 4-5 seconds) activates the delivery mode, and two consecutive presses activate the hybrid mode. Other triggering methods can also be used, which will not be described in detail here.

[0085] The electrical stimulation mode refers to a situation where the medication reservoir is not open, and the electrical signal generator produces a pulse voltage of the first amplitude (e.g., 20V-33V), which is then applied to the head via the first and second electrodes to provide specific electrical stimulation. However, in this case, because the user does not apply sufficient pressure when combing their hair with the device, the medication reservoir is not yet open, and therefore only electrical stimulation is being performed.

[0086] The drug electrodelivery mode refers to the opening of the drug storage compartment and the generation of a pulse voltage with a second amplitude (e.g., 20V-33V) by an electrical signal generator, which applies a directional electric field to the head through the first and second electrodes to form a micron-level channel, thereby delivering the drug to deeper layers. Preferably, the first amplitude is the same as the second amplitude, or the first amplitude is smaller than the second amplitude.

[0087] The hybrid mode refers to performing an electrical stimulation mode followed by a drug delivery mode within a single cycle.

[0088] In some embodiments, there is no time interval between the electrical stimulation mode and the drug delivery mode. Users only need to learn how to use the device in advance. For example, when using the device, a small force is first applied to form a circuit between the positive and negative electrodes, but the drug reservoir will not be opened. Then a larger force is applied to open the drug reservoir, which means that the two modes can be switched seamlessly.

[0089] For users with thicker sebum or stronger skin barrier function, this seamless switching method essentially utilizes a continuous strong field to maintain maximum pore size, powerfully propelling the medication to overcome sebum resistance and achieve effective delivery to the deep layers of the hair follicle. More preferably, the first amplitude is smaller than the second amplitude (for example, 30V in electrical stimulation mode and 28V in delivery mode; specifically, the output voltage can be modulated using a voltage modulator). This ensures full utilization of the already opened pores while avoiding irreversible damage to thick sebum areas caused by excessive voltage.

[0090] In other embodiments, for users with thinner sebum or weaker skin barrier function, a time interval T between the electrical stimulation mode and the drug electro-delivery mode is preferred. Preferably, this time interval T is less than the recovery time of the reversible electroporation formed on the hair follicle cell membrane during electrical stimulation. By controlling the time interval within the recovery time of the reversible electroporation, the window of instantaneous increase in cell membrane permeability after electrical stimulation can be utilized, enabling the subsequent drug electro-delivery mode to achieve efficient deep delivery with lower voltage or shorter time, avoiding a decrease in delivery efficiency due to membrane pore closure. More preferably, the time interval T is in the microsecond to millisecond range, and can be experimentally obtained based on electrical stimulation parameters (such as voltage, pulse width, and pulse count) and the type and state of the hair follicle cells, which will not be described in detail here.

[0091] Furthermore, the existence of this time interval T allows for partial repair of the cell membrane from a reversible electroporation state. However, the repair rate varies significantly among different cells (such as epidermal keratinocytes and hair follicle stem cells), thus creating a selective delivery window. When a drug delivery electric field is subsequently applied, drug molecules are more likely to be taken up by deeper target cells that are still in an activated state (such as hair follicle bulge stem cells), thereby achieving precise cell-targeted delivery while avoiding excessive damage to the weakened barrier.

[0092] In some embodiments, since there is a time interval between the electrical stimulation mode and the drug delivery mode, the user needs to apply different pressures to open or close the drug reservoir in accordance with this time interval. Specifically, a voice playback module and a timer can be integrated into the main control module. Once the user selects the hybrid mode, the timer starts counting. In each cycle, if the electrical stimulation mode ends, the main control module controls the voice playback module to play a prompt tone (such as "beep"). When a preset time interval is reached (or before the preset time interval is reached), the main control module controls the voice playback module to play a prompt tone again (such as "beep" or "click") to remind the user. This allows the user to easily distinguish between the two modes and apply different amounts of force according to the two modes. For example, in use, in the electrical stimulation mode, a smaller force is applied first to form a circuit between the positive and negative electrodes, but the drug reservoir will not open. When the prompt voice indicating the end of the preset time interval (or about to end, or the start of the delivery mode) is heard, a larger force is applied to open the drug reservoir, thereby cooperating with the delivery mode for deep delivery of drug molecules.

[0093] S2. When a trigger signal is received, identify the current working mode. If it is the electrical stimulation mode, execute step S3; if it is the drug electrical delivery mode, execute step S4; if it is the mixed mode, execute step S5.

[0094] S3, according to the first preset pulse voltage value, the electrical signal generator in the device generates and sends a corresponding pulse voltage to the first electrode 3 and the second electrode 4 in the device, and forms a directional electric field on the head through the first electrode 3 and the second electrode 4 to perform electrical stimulation.

[0095] S4, according to the second preset pulse voltage value, the electrical signal generator in the device generates and sends a corresponding pulse voltage to the first electrode 3 and the second electrode 4 in the device, and forms a directional electric field on the head through the first electrode 3 and the second electrode 4, so as to open the channel and deliver the drug to the depth of the hair follicles of the head.

[0096] S5, according to the preset interval time T, the electrical stimulation mode and the drug electrical delivery mode are activated sequentially, so that the channel is opened first by the electrical stimulation mode, and then the drug is efficiently delivered through the opened channel by the drug electrical delivery mode.

[0097] Experiment 1: In order to investigate the delivery performance of the device for electrodelivery in this application (hereinafter referred to as the delivery device), different groups were set up, and different devices were used in different groups: (1) AGA model control group (androgenic alopecia model control group): no treatment drug was delivered; (2) Topical group: hair on the head of the experimental animals was removed in advance, and then the treatment drug was applied locally to the scalp where the hair was removed; (3) Aligned comb group: delivery device with first and second electrodes of the same length (both 250 μm long) was used (that is, the difference between this delivery device and the delivery device used in the experimental group is that there is no height difference between the first and second electrodes, and the rest are the same); (4) Experimental group: drug delivery was performed using the delivery device shown in Example 1 above (the height difference between adjacent first and second electrodes is 1.5 mm and the spacing is 14 mm); and then the delivery effect after one delivery was observed using a two-photon microscope. Specifically, the delivered drug molecules are selected from VEGFA plasmid and SRD5A2 siRNA. VEGFA plasmid enhances local metabolism by promoting angiogenesis, while SRD5A2 siRNA inhibits androgen synthesis by reducing the activity of 5α-reductase.

[0098] See Figure 4 A represents the delivery effect images of the four groups observed using a two-photon microscope. Further, images show the distribution of skin tissue observed after cryosectioning (longitudinal section) of the four groups of skin tissue, as shown below. Figure 4 B. By this Figure 4 A and Figure 4 As shown in B, the amount of drug delivered in the experimental group was much greater than that in the aligned comb group and the topical application group; in the control group, almost no drug was delivered to the deep layers.

[0099] Through the Figure 4 The fluorescence intensity PI (used to characterize the delivery concentration / delivery amount of drug molecules) of the red fluorescence signal in image A was analyzed to obtain four sets of fluorescence intensity comparison images, as shown below. Figure 4 C: The fluorescence intensity PI of the experimental group is close to au (see au) Figure 4 (green box in C); while the fluorescence intensity PI of the control group just exceeded au (see au) Figure 4 (orange box in C), while the fluorescence intensity PI of the local application group is less than that of the orange box in C. au (see au) Figure 4 (Purple box in C); the fluorescence intensity PI of the control group was almost 0.

[0100] Through the Figure 4 The red signal intensity (used to characterize drug molecule delivery depth) of slice image B was analyzed to obtain four sets of delivery depth comparison images: As shown by the green curve in 4D, the red signal continues to appear in the slice up to 667μm, which means that the delivery depth of the experimental group can reach more than 660μm. See Figure 4 In D, the orange curve shows a red signal that persists until about 250 μm in the slice, meaning that the delivery depth of the control group can only reach about 250 μm. See Figure 4 In Figure D, the purple curve indicates that the red signal in the slice only persists until about 74 μm, meaning that the delivery depth of the local application group can only reach about 74 μm; while the drug delivery in the control group did not reach the deep tissues.

[0101] The lowest effective voltage was obtained through a transmembrane potential difference test (i.e., drug delivery using the delivery device described in Example 1 above, applying a 30V pulse voltage). See also Figure 4 E and Figure 4 F induces a transmembrane potential exceeding 0.7V, enabling efficient electroporation-mediated drug delivery into follicular cells; moreover, in fact, drug delivery can be achieved as long as the voltage exceeds 0.2V. That is, under specific voltage parameters (approximately 0.2V effective operating voltage), this system can effectively regulate the cell membrane potential, providing a basis for subsequent electroporation delivery.

[0102] See Figure 4 F is a schematic diagram of the delivery device in the experimental group: a directional electric field is formed between the shorter second electrode and the first electrodes on both sides, thereby delivering VEGFA mRNA and SRD5A2 to hair follicle cells simultaneously.

[0103] The content of drug molecules VEGFA mRNA and SRD5A2 siRNA delivered in four groups of skin tissues was analyzed by qPCR. The results are shown in the figure below. Figure 5 G and Figure 5 H: See Figure 4 The green box in G indicates that the delivery device in the experimental group achieved a delivery rate of more than 9 times that of VEGFA mRNA compared to the control group. See Figure 4 The green box in H indicates that the delivery device in the experimental group achieved a delivery rate greater than 15 times that of the control group for SRD5A2 siRNA.

[0104] As can be seen from the qPCR analysis, the levels of VEGFA mRNA and SRD5A2 siRNA in the skin tissue of the experimental group were significantly increased, significantly exceeding those of the control group, the topical application group, and the aligned comb group, thus confirming that the delivery device of this application can achieve effective deep tissue delivery.

[0105] Experiment 2: To evaluate the enhancement effect of the delivery device of the present invention on hair regeneration, a mouse AGA model was established, and the animals were randomly divided into six groups: AGA model control group (androgen-induced alopecia model control group) - G1 group, VEGF plasmid delivery - G2 group, SRD5A2 siRNA delivery - G3 group, simultaneous delivery of VEGF and siRNA - G4 group, finasteride group - G5 group, and minoxidil group - G6 group.

[0106] See Figure 5 Groups A and G1 underwent only hair removal treatment (hair in this group will not regrow without intervention); Groups G2-G4 received the medication once every three days using the delivery device described in this application; Group G5 received oral finasteride per mouse; Group G6 received minoxidil applied daily to the treated area. Preferably, Groups G2-G4 used a delivery device with an electrode array arranged as shown in Figure 1, wherein the height difference between the longer first electrode and the shorter second electrode is 1.5 mm, and the spacing is 14 mm. During the experiment, the body weight of mice in each treatment group did not change significantly.

[0107] After 28 days of treatment, the expression levels of VEGFA and SRD5A2 were measured in the G1-G4 groups, and the results are as follows: Figure 5 B and Figure 5 As shown in C: The expression level of VEGFA in group G4 was more than 8 times that in the control group, meaning that the delivery device in group G4 achieved more than 8 times the delivery level compared to the control group; the expression level of SRD5A2 in group G1 was more than 1 times that in the control group, meaning that the delivery device in group G1 achieved more than 1 times the delivery level compared to the control group.

[0108] Further analysis of protein content in each group was performed using Western blot, yielding the expression levels of VEGFA and SRD5A2 proteins in each group, as shown below. Figure 5 D and Figure 5 E: In all four groups, the expression level of the housekeeping gene GAPDH protein was high. In group G4, the expression level of VEGFA protein was the highest, followed by group G2, and then group G3. In group G1, the expression level of SRD5A2 protein was the highest, followed by group G2, then group G3 and group G4.

[0109] In addition, the hair regrowth of mice was photographed and recorded on days 1, 7, 14, 21, and 28 of the experiment. See [link to relevant documentation]. Figure 5 F, and the number of hair follicles on days 1, 7, 14, 21, and 28 were observed via HE sections, see [reference]. Figure 5 G. Further, staining was performed using the markers CD31 (red) and CD34 (green) to obtain the immunofluorescence staining results of the skin tissue; see [link to relevant documentation]. Figure 5 H. CD31 is a staining marker for blood vessels; CD34 is a marker for hair follicle stem cells. From Figure 5 H indicates that the G4 group had the most hair follicle stem cells, followed by the G3 group, and then the G2 and G5 groups.

[0110] Furthermore, based on Figure 5 H, the recovery area of ​​each group, that is, the area of ​​hair regeneration, is obtained statistically, such as Figure 5 As shown in Figure I: Group G4 had the largest recovery area, almost reaching 100% coverage, followed by Groups G2 and G3, which were not much different from each other. Group G6 had a recovery area of ​​more than 50%, and Group G5 had a recovery area close to 50%. Group G1 had the lowest recovery area.

[0111] An assessment was conducted based on the area, color, and length of hair growth (using hair scoring criteria in this field) to obtain a comprehensive score for each group. See [link to relevant documentation]. Figure 5 J. Therefore, it can be concluded that Group G4 has the highest overall score.

[0112] Furthermore, on Figure 5 The number of hair follicles in G was quantitatively statistically analyzed to obtain the following results: Figure 5 K: Group G4 has the highest number of hair follicles: the largest can reach nearly 400, and the smallest is close to 300. Figure 5 The K-type earth-colored cable box is shown; followed by groups G2 and G6, as... Figure 5 As shown in the orange and purple boxes in K, the others are around 200, or even less than 200.

[0113] Furthermore, separate statistics Figure 5 The fluorescence intensity PI corresponding to CD31 and the fluorescence intensity PI of CD34 in H were obtained. Figure 5 L and Figure 5 M: In group G4, the fluorescence intensity PI of CD31 was the largest, followed by the fluorescence intensity P of CD31 in group G2. That is to say, G4 can significantly promote angiogenesis. In addition, the fluorescence intensity PI of CD34 in group G4 was the largest and much larger than the fluorescence intensity of CD34 in all other groups. That is to say, group G4 can significantly promote hair follicle regeneration.

[0114] In summary, the device provided in this application delivers VEGFA and SRD5A2, which can significantly promote hair follicle regeneration and angiogenesis, thereby promoting the hair regeneration process.

[0115] It should be noted that, in this document, the terms "comprising," "including," or any other variations thereof are intended to cover non-exclusive inclusion, such that a process, method, article, or apparatus that comprises a list of elements includes not only those elements but also other elements not expressly listed, or elements inherent to such a process, method, article, or apparatus. Unless otherwise specified, an element defined by the phrase "comprising one..." does not exclude the presence of other identical elements in the process, method, article, or apparatus that includes that element.

[0116] The embodiments of the present invention have been described above with reference to the accompanying drawings. However, the present invention is not limited to the specific embodiments described above. The specific embodiments described above are merely illustrative and not restrictive. Those skilled in the art can make many other forms under the guidance of the present invention without departing from the spirit and scope of the claims. All of these forms are within the protection scope of the present invention.

Claims

1. A device for deep scalp electrodelivery, characterized in that, It includes an electrical signal generator for generating pulse voltage, a main control module electrically connected to the electrical signal generator, and a comb-shaped housing (1), wherein the electrical signal generator and the main control module are integrated within the comb-shaped housing (1); The device further includes: a plurality of first electrodes (3) and a plurality of second electrodes (4) electrically connected to the electrical signal generator for forming a directional electric field, and a drug supply module; the plurality of first electrodes (3) and the plurality of second electrodes (4) are arranged on the comb-shaped housing (1) according to a preset arrangement rule, wherein the length L1 of the first electrode (3) is greater than the length L2 of the second electrode (4); the comb-shaped housing (1) includes: a comb handle (2), and a comb body (5) connected to one end of the comb handle (2); wherein, The main control module is configured to control the electrical signal generator to generate a corresponding pulse voltage when a trigger signal is received, so as to apply a directional electric field to the target area through the first electrode (3) and the second electrode (4) to deliver the drug to the depth of the hair follicles on the head.

2. The device for deep scalp electrodelivery according to claim 1, characterized in that, The preset layout rules include: two-dimensional planar layout rules and three-dimensional solid layout rules; wherein... The two-dimensional planar layout rule includes: multiple first electrodes (3) and multiple second electrodes (4) are alternately arranged along the length direction of the comb body (5) as a row of comb teeth connected to the comb body (5); The three-dimensional layout rules include: The plurality of first electrodes (3) and the plurality of second electrodes (4) are respectively located on at least two mutually parallel planes, serving as at least two rows of comb teeth connected to the comb body (5); Alternatively, at least two rows of comb teeth are connected to the comb body (5), and multiple first electrodes (3) and multiple second electrodes (4) in each row of comb teeth are alternately arranged along the length direction of the comb body (5); Alternatively, multiple first electrodes (3) and multiple second electrodes (4) are respectively located on multiple mounting surfaces spaced around the comb body, thereby serving as multiple rows of comb teeth spaced around the comb body (5) in a circumferential manner, and multiple first electrodes (3) and multiple second electrodes (4) are respectively mounted on two adjacent mounting surfaces. Alternatively, a plurality of first electrodes (3) and a plurality of second electrodes (4) are respectively located on a plurality of mounting surfaces spaced apart around the comb body (5), thereby serving as a plurality of rows of comb teeth spaced apart circumferentially around the comb body (5), and a plurality of first electrodes (3) and a plurality of second electrodes (4) are alternately arranged on each mounting surface.

3. The device for deep scalp electrodelivery according to claim 2, characterized in that, The second electrode (4) includes a second conductive element (404) extending along the axial direction of the comb teeth. Correspondingly, the drug supply module includes a drug storage chamber (402) built into the second electrode (4). The second conductive element (404) is built into the drug storage chamber (402) and can reciprocate along the axial direction of the drug storage chamber (402); the end of the second conductive element (404) is provided with a conductive sealing member (403) and the end of the second conductive element (404) is provided with an elastic reset member (401). When there is no external force, under the action of the elastic reset member (401), the sealing member (403) at the end of the second conductive element (404) seals the outlet of the drug storage chamber (402); When the end of the first electrode (3) and the sealing member (403) of the second electrode (4) act on the head, under the squeezing action of the head, the sealing member (403) disengages from the outlet of the drug storage chamber (402), thereby allowing the liquid medicine to flow out from the outlet and permeate under the action of the directional electric field formed between the first electrode (3) and the second electrode (4).

4. The device for deep scalp electrodelivery according to claim 1, characterized in that, The drug delivery module includes a drug coating applied to the contact surface of the end of the second electrode (4) that is in contact with the skin.

5. A device for deep scalp electrodelivery according to any one of claims 1 to 4, characterized in that, The difference between the length L1 of the first electrode (3) and the length L2 of the second electrode (4) is greater than 0 mm and less than 2 mm.

6. The device for deep scalp electrodelivery according to claim 5, characterized in that, The distance L3 between the first electrode (3) and the second electrode (4) is greater than 0 mm and less than 14 mm.

7. The device for deep scalp electrodelivery according to claim 3, characterized in that, A first limiting member (405) is fixedly installed inside the drug storage chamber (402), and a second limiting member (406) is detachably installed at the outlet of the drug storage chamber (402). The two ends of the elastic reset member (401) abut against the first limiting member (405) and the second limiting member (406) respectively, and the second conductive element (404) passes through the first limiting member (405) and can reciprocate relative to the first limiting member (405) along the axial direction of the drug storage chamber (402). The second limiting member (406) is provided with a through hole that cooperates with the sealing member (403).

8. The device for deep scalp electrodelivery according to claim 7, characterized in that, The second limiting member (406) is funnel-shaped.

9. A method for deep scalp electrodelivery, characterized in that, An implementation of a device for deep scalp electrodelivery according to any one of claims 1-8 includes the following steps: S1. Configure device parameters; the device parameters include: pulse voltage value; S2. When a trigger signal is received, the electrical signal generator in the device is controlled to generate and send a corresponding pulse voltage to the first electrode (3) and the second electrode (4) in the device according to the preset pulse voltage value. A directional electric field is formed on the head through the first electrode (3) and the second electrode (4) to open the channel and deliver the drug to the depth of the hair follicles of the head.

10. A method for deep scalp electrodelivery, characterized in that, An implementation of a device for deep scalp electrodelivery according to any one of claims 1-8 includes the following steps: S1. Configure device parameters; the device parameters include: working mode, wherein the working mode includes: electrical stimulation mode, drug electrical delivery mode and hybrid mode; S2. When a trigger signal is received, identify the current working mode. If it is the electrical stimulation mode, execute step S3; if it is the drug electrical delivery mode, execute step S4; if it is the mixed mode, execute step S5. S3, according to the first preset pulse voltage value, the electrical signal generator in the device generates and sends the corresponding pulse voltage to the first electrode (3) and the second electrode (4) in the device, and forms a directional electric field on the head through the first electrode (3) and the second electrode (4) to perform electrical stimulation; S4, according to the second preset pulse voltage value, the electrical signal generator in the device generates and sends the corresponding pulse voltage to the first electrode (3) and the second electrode (4) in the device, and forms a directional electric field on the head through the first electrode (3) and the second electrode (4) to deliver the drug to the depth of the hair follicles of the head while opening the channel; S5, according to the preset interval time T, the electrical stimulation mode and the drug electrical delivery mode are activated sequentially, so that the channel is opened first by the electrical stimulation mode, and then the drug is efficiently delivered through the opened channel by the drug electrical delivery mode.

Images