Reverse iontophoresis device comprising microneedle and manufacturing method therefor

Abstract

A reverse iontophoresis device comprising a microneedle according to an embodiment of the present invention comprises a first patch part including a first electrode portion and a second patch part including a second electrode portion, wherein an alternating current power source may be connected between the first electrode portion and the second electrode portion, and the second patch part may further include a drug chamber and a microneedle made of a polymer material.

Description

Reverse ion tophoresis device including micro-needles and method for manufacturing the same

[0001] The present invention relates to a device using reverse ion tophoresis and microneedles and a method for manufacturing the same.

[0002]

[0003] Reverse iontophoresis is a principle that moves substances to the skin using electrical repulsion generated by electrodes. In reverse iontophoresis, substances move toward either the positive or negative electrode depending on the direction of the electric current, and substances passing through the skin generally utilize charged ions. Electroosmosis, which occurs during the reverse iontophoresis process, involves charged substances on the surface attracting ions within the liquid when an electric field is applied; through this, hydrated ions move toward the electrodes, causing fluid movement. In the case of electroosmosis, it is known that the flow is strengthened as the zeta potential, which represents the amount of charge, increases.

[0004]

[0005] Conventional reverse iontophoresis typically involves attaching two electrodes to the human skin, with each electrode connected to an electrical device via a wire. In this process, the substance to be extracted moves out of the skin as voltage is applied, enabling the extraction of bodily fluids.

[0006] However, these existing iontophoresis systems have been operated based on direct current, but due to the Faraday reaction, the system's stability was low, limiting the usage time, and there were disadvantages such as skin inflammation and power consumption issues.

[0007] More specifically, the long-term use of direct current can cause pH changes near the electrodes due to redox reactions, potentially leading to skin damage or inflammation. Additionally, side reactions such as water splitting can result in high power consumption and reduced efficiency, while the generation of hydrogen or oxygen gases near the electrodes can cause problems such as deformation of the system's internal structure. Furthermore, continuous unidirectional direct current can cause ion charge shifting, inducing polarization in the skin, which can turn the skin into a capacitor-like state and lead to an imbalance of ions within the body.

[0008] Furthermore, since it is difficult to effectively extract and deliver large biomolecules using simple diffusion or conventional reverse iontophoresis techniques, there were also problems such as reduced biosensing and drug delivery efficiency and limitations in drug selection.

[0009]

[0010] The present invention is proposed to solve the aforementioned conventional problems, and one of the objectives of the present invention is to provide a stable and efficient reverse iontophoresis system using an alternating current-based electric field and micro-needles having an asymmetric pore structure fabricated through a phase separation process, thereby enabling stable reverse iontophoresis to be used for a long time while simultaneously maximizing the extraction and delivery efficiency of biomolecules.

[0011]

[0012] The embodiments of the present invention aim to solve the following technical problems more specifically.

[0013] 1. AC-based reverse iontophoresis device

[0014] Through the embodiments of the present invention, the inventors aim to increase system stability, reduce power consumption, and resolve skin irritation and inflammation issues by minimizing the Faraday reaction through the use of alternating current power. One objective of the present invention is to stably maintain charge transfer and electroosmotic flow through the repeated application of an alternating current electric field and an electric double layer charge / discharge mechanism, and to effectively extract even large molecular weight biomolecules.

[0015] 2. Microneedles having an asymmetric pore structure

[0016] Furthermore, through the embodiments of the present invention, the inventors intend to form an asymmetric pore structure in which the pore size gradually changes according to the height of the needle by applying a phase separation process during the fabrication of microneedles. This enhances the electroosmotic velocity, effectively controls charge transfer, and maximizes the efficiency of fluid extraction and delivery of polymers or macromolecules, which was difficult with existing technologies. In addition, these structural characteristics ensure excellent electroosmotic performance even in AC environments, thereby expanding the potential for application in various biomolecule extraction and delivery applications.

[0017]

[0018] The present invention aims to overcome the limitations of existing technology through the innovative approach described above and to provide a stable and efficient biomolecular delivery and extraction system.

[0019] However, the purpose of the present invention is not limited to the purpose described above, and all of the inventor's intentions regarding the subject to be demonstrated through each of the embodiments proposed thereafter constitute the purpose of the present invention.

[0020]

[0021] According to one embodiment of the present invention, a reverse iontophoresis device including microneedles can be provided.

[0022] The above device includes a first patch portion including a first electrode portion and a second patch portion including a second electrode portion, wherein an AC power source is connected between the first electrode portion and the second electrode portion, and the second patch portion may additionally include a drug chamber and a polymer micro-needle for extracting substances from the body or injecting drugs.

[0023] According to one embodiment of the present invention, a reverse iontophoresis device may be provided that includes a structure in which both the first patch portion and the second patch portion can be attached to the skin.

[0024] According to one embodiment of the present invention, the micro needle may comprise one or more materials selected from the group consisting of polysulfone, polyethersulfone, cellulose acetate, polylactic acid (PLA), polycaprolactone (PL), polyglycolic acid (PGA), polyurethane, polyvinyl alcohol (PVA), chitosan, hydroxypropyl methylcellulose (HPMC), poly(methyl methacrylate) (PMMA), or polyimide.

[0025] According to one embodiment of the present invention, the micro needles may include a material capable of a phase separation process in relation to a non-solvent.

[0026] According to one embodiment of the present invention, the micro needle may include a plurality of pores, a base substrate, and a needle portion formed on the base substrate.

[0027] According to one embodiment of the present invention, the sum of the heights of the base substrate and the needle portion may be 0.2 mm to 2 mm.

[0028] According to one embodiment of the present invention, in at least a certain region of the micro needles, the average diameter of the pore may have a trend of gradually changing with height.

[0029] According to one embodiment of the present invention, the trend of the average diameter of the pores gradually changing can be formed by the phenomenon of polymer phase separation in a non-solvent.

[0030] According to one embodiment of the present invention, the average pore size of the micro needles on the upper part of the base substrate may be smaller than the average pore size on the lower part of the base substrate.

[0031] According to one embodiment of the present invention, the average pore size of the micro needles on the upper part of the base substrate may be smaller than the average pore size of the needle tip.

[0032] According to one embodiment of the present invention, the average density of the pores in at least a certain region of the micro-needle may have a trend of gradually changing with height.

[0033] According to one embodiment of the present invention, the drug may include a substance having a molecular weight of 10 kDa or more. The drug may have a molecular weight of 100 kDa or less.

[0034] According to one embodiment of the present invention, the reverse ion tophoresis device may further include a biosensor capable of detecting a biomarker.

[0035]

[0036] According to another embodiment of the present invention, a wearable healthcare device including a skin attachment portion may be provided, and the skin attachment portion may include the reverse iontophoresis device.

[0037]

[0038] According to another embodiment of the present invention, a method for manufacturing microneedles can be provided, comprising the steps of: preparing a microneedle mold; introducing a polymer solution into the mold; evaporating a solvent from the mold into which the polymer solution has been introduced; immersing the polymer from which the solvent has been evaporated and the mold in a non-solvent to induce phase separation within the polymer; and separating the polymer in which phase separation has occurred internally from the mold and drying it.

[0039] According to one embodiment of the present invention, the step of evaporating the solvent can be performed at a temperature of 40 to 80 degrees.

[0040] According to one embodiment of the present invention, the polymer solution may have a negative charge.

[0041]

[0042] According to one embodiment of the present invention, the Faraday reaction can be effectively suppressed through a reverse iontophoresis device using an AC power source, thereby reducing problems such as pH changes and skin inflammation. This improves the system stability of the device and provides a drug delivery and biomolecular extraction system capable of long-term use.

[0043] In addition, according to one embodiment of the present invention, the asymmetric pore structure of microneedles fabricated using a phase separation process can improve electroosmotic velocity and charge transfer efficiency due to the gradual change in pore size with height. This enables the effective extraction or delivery of large molecular weight biomolecules, thereby resolving the problem of macromolecule processing that was considered a limitation in existing technologies.

[0044] Furthermore, according to one embodiment of the present invention, stable and efficient drug delivery and biomolecule extraction are possible in various in vivo environments through the combination of an AC power source and asymmetric porous micro-needles. In particular, the stable electric field environment provided by the AC power source expands the applicability to biomolecules with various molecular sizes and charge states.

[0045] In addition, according to one embodiment of the present invention, electroosmotic flow can be optimized by precisely controlling the pore size inside the micro-needle through a phase separation process. This allows for reducing power consumption while maximizing the efficiency of biomolecule extraction and delivery.

[0046]

[0047] In addition, according to one embodiment of the present invention, various polymer materials can be used to fabricate micro-needles, thereby enabling the realization of a device having desired physical properties depending on the application field. This expands the potential for using reverse ion tophoresis devices in various medical applications, such as drug delivery, biosensing, and wearable healthcare devices.

[0048] However, the effects of the present invention are not limited to those described above, but include all effects naturally realized through the various configurations proposed in the present invention.

[0049]

[0050] FIG. 1 is a schematic diagram showing the structure of a reverse ion tophoresis device including microneedles according to one embodiment of the present invention.

[0051] Figure 2 is a schematic diagram comparing the case where an AC power source is connected to both electrodes and the case where a DC power source is connected.

[0052] Figure 3 is a figure illustrating the case where the pores of the micro-needles are formed symmetrically and uniformly, and the case where they are formed asymmetrically with a trend in average size.

[0053] FIG. 4 is a schematic diagram showing the ion flow and electroosmotic rectification phenomena in reverse bias and forward bias states when an AC power source is connected to a micro needle having an asymmetric pore size according to one embodiment of the present invention.

[0054] Figure 5 is an SEM image of an example in which the pore size of the micro-needles is formed differently according to height, according to one embodiment of the present invention.

[0055] FIG. 6 is an overall image of a micro-needle fabricated according to one embodiment of the present invention and an SEM image of a cross-section of the micro-needle.

[0056] FIG. 7 is a schematic diagram showing each step of a method for manufacturing micro-needles according to one embodiment of the present invention.

[0057] FIG. 8 is a schematic diagram showing the process of forming a trend of pore size or pore density according to the height of the micro-needle formed in the phase separation step in a method for manufacturing micro-needles according to one embodiment of the present invention.

[0058] FIG. 9 is a graph showing the results of linear scanning potential (LSV) and membrane conductivity calculation experiments for a microneedle manufactured according to one embodiment of the present invention.

[0059] FIG. 10 is a schematic diagram of an experimental design verifying electroosmotic flow in a micro needle manufactured according to one embodiment of the present invention.

[0060] Figure 11 is a graph showing experimental results of confirming pH changes and verifying electroosmotic flow in microneedles manufactured according to one embodiment of the present invention.

[0061] FIG. 12 is a schematic diagram of an experimental design for verifying the quantification effect of macromolecules in a microneedle manufactured according to one embodiment of the present invention.

[0062] FIG. 13 is a graph showing experimental results verifying the quantification effect of macromolecules in a microneedle manufactured according to one embodiment of the present invention.

[0063]

[0064] The embodiments of the present invention are illustrative for the purpose of explaining the technical concept of the present invention. The scope of rights according to the present invention is not limited to the embodiments presented below or the specific description thereof.

[0065] All technical and scientific terms used in this invention, unless otherwise defined, have the meaning generally understood by those skilled in the art to which this invention pertains. All terms used in this invention are selected for the purpose of further explaining this invention and are not selected to limit the scope of rights according to this invention.

[0066] Expressions such as "comprising," "having," "having," etc. used in the present invention should be understood as open-ended terms implying the possibility of including other embodiments, unless otherwise stated in the phrase or sentence containing such expressions.

[0067] Unless otherwise stated, singular expressions described in the present invention may include the meaning of the plural form, and this applies likewise to singular expressions described in the claims.

[0068]

[0069] Hereinafter, each embodiment of the present invention will be described in detail through the drawings of the present invention and experiments containing the inventors' intentions.

[0070]

[0071] According to one embodiment of the present invention, a reverse iontophoresis device including microneedles can be provided.

[0072] The above device includes a first patch portion including a first electrode portion and a second patch portion including a second electrode portion, wherein an AC power source is connected between the first electrode portion and the second electrode portion, and the second patch portion may additionally include a drug chamber and a polymer micro-needle for extracting substances from the body or injecting drugs.

[0073] At this time, the first patch portion and the second patch portion may be attached to human skin.

[0074] The second electrode may be provided on one side of the micro needle and may be connected to the micro needle to allow current to flow through the needle to deliver drugs or extract substances from the body.

[0075] The above drug chamber is not specified in the form of the present invention and does not necessarily have to be in the form of a physically partitioned chamber. The form of the above drug chamber is not specifically limited as long as it is a structure for storing a drug to be contained or delivered into the body after extracting biomaterials through microneedles.

[0076]

[0077] According to one embodiment of the present invention, a reverse iontophoresis device may be provided that includes a structure in which both the first patch portion and the second patch portion can be attached to the skin.

[0078] According to one embodiment of the present invention, the micro needle may comprise one or more materials selected from the group consisting of polysulfone, polyethersulfone, cellulose acetate, polylactic acid (PLA), polycaprolactone (PL), polyglycolic acid (PGA), polyurethane, polyvinyl alcohol (PVA), chitosan, hydroxypropyl methylcellulose (HPMC), poly(methyl methacrylate) (PMMA), or polyimide.

[0079] All of the above polymer materials are biocompatible micro-needle materials, and micro-needles can be formed by combining one or more polymers.

[0080]

[0081] According to one embodiment of the present invention, the micro needles may include a material capable of a phase separation process in relation to a non-solvent.

[0082] In the embodiments described below, the micro-needles introduce a phase separation process in a manner that forms a trend in pore size and / or density; however, the method of forming a trend in the pore size and / or density of the micro-needles in the present invention is not necessarily limited to a phase separation process. Forming the trend in pore size and / or density through a physical process may also be included within the scope of the present invention.

[0083]

[0084] According to one embodiment of the present invention, the micro needle may include a plurality of pores, a base substrate, and a needle portion formed on the base substrate.

[0085] In one embodiment, the micro-needles may be formed such that a base substrate and a needle portion are distinguished, but in another embodiment, the two portions may not be clearly distinguished. The base substrate and the needle portion may be manufactured through a single process, but depending on the intention, they may be manufactured separately and then joined together.

[0086] According to one embodiment of the present invention, the sum of the heights of the base substrate and the needle portion may be 0.1 mm to 2 mm. If the sum of the heights of the base substrate and the needle portion is less than 0.1 mm, it may be difficult to manufacture or the needle may not penetrate the dermis layer of the actual skin, and if it exceeds 2 mm, it may be difficult to effectively deliver the drug through the needle or the needle may penetrate too deep into the skin layer.

[0087]

[0088] According to one embodiment of the present invention, in at least a certain region of the micro needles, the average diameter of the pore may have a trend of gradually changing with height.

[0089] In one embodiment, the micro-needle includes controlling the average diameter of the pores. In this case, the average diameter of the pores has a trend of gradually increasing or decreasing as it extends in one direction. In this case, the area where the trend is implemented may be the entire area of ​​the micro-needle in one embodiment, but may be limited to a part of the micro-needle in another embodiment. The area can be controlled according to the purpose of the micro-needle.

[0090]

[0091] According to one embodiment of the present invention, the trend of the average diameter of the pores gradually changing can be formed by the phenomenon of polymer phase separation in a non-solvent.

[0092] In one embodiment, the pore trend can be naturally formed through a chemical method, and by utilizing the phase separation phenomenon of the polymer under such a non-solvent, the pore size can be gradually changed even with a simple one-time process.

[0093]

[0094] According to one embodiment of the present invention, the average pore size of the micro needles on the upper part of the base substrate may be smaller than the average pore size on the lower part of the base substrate.

[0095] According to one embodiment of the present invention, the average pore size of the micro needles on the upper part of the base substrate may be smaller than the average pore size of the needle tip.

[0096] As described above, the average pore size may have a gradient within the base substrate in one embodiment, and in another embodiment, the gradient in size may be formed not only in the base substrate but also up to the tip portion, which is the end of the needle portion of the micro-needle.

[0097]

[0098] According to one embodiment of the present invention, the average density of the pores in at least a certain region of the micro-needle may have a trend of gradually changing with height.

[0099] As described above, when a pore size gradient is formed using the phase separation phenomenon, which is a chemical process, the ratio of pores to the polymer ratio naturally changes. In this invention, this is defined as pore density, and thus the average pore density can vary with height. The changing trend of the average pore density, i.e., the gradient, does not necessarily have to be formed through chemical methods as previously explained, but can also be formed by physical processes.

[0100]

[0101] According to one embodiment of the present invention, the micro needle can extract a biomaterial having a molecular weight of 10 kDa or more. The biomaterial may have a molecular weight of 100 kDa or less.

[0102] By using the reverse ion tophoresis method described above and the proposed micro-needles, it is possible to use high molecular weight materials that were previously limited.

[0103] According to one embodiment of the present invention, the reverse ion tophoresis device may further include a biosensor capable of detecting a biomarker.

[0104]

[0105] According to another embodiment of the present invention, a wearable healthcare device including a skin attachment portion may be provided, and the skin attachment portion may include a reverse iontophoresis device of one of the embodiments described above.

[0106]

[0107] According to another embodiment of the present invention, a method for manufacturing microneedles can be provided, comprising the steps of: preparing a microneedle mold; introducing a polymer solution into the mold; evaporating a solvent from the mold into which the polymer solution has been introduced; immersing the polymer from which the solvent has been evaporated and the mold in a non-solvent to induce phase separation within the polymer; and separating the polymer in which phase separation has occurred internally from the mold and drying it.

[0108] According to one embodiment of the present invention, the step of evaporating the solvent may be performed at a temperature of 40 to 80 degrees. Although it is efficient to evaporate the solvent at a temperature higher than room temperature, it is preferable to control the temperature range to the extent described above because excessively high temperatures can damage the polymer.

[0109] The step of evaporating the above solvent may involve evaporating a portion of the solvent at room temperature without introducing a process to specifically raise the temperature.

[0110] According to one embodiment of the present invention, the polymer solution may have a negative charge. However, the polymer solution may not necessarily be limited to a negatively charged material.

[0111]

[0112] <Example>

[0113] Hereinafter, experimental examples to demonstrate the effects of the present invention will be described in detail with reference to the drawings.

[0114] FIG. 1 is a schematic diagram showing the structure of a reverse ion tophoresis device including microneedles according to one embodiment of the present invention.

[0115] As can be seen in Fig. 1, in one embodiment, the reverse ion tophoresis device is largely composed of reverse ion tophoresis electrodes (RI electrodes) and micro-needles for extracting body fluid. In the above embodiment, the drug chamber is configured to serve the role of containing the extracted body fluid. At this time, a biosensor, etc., can be directly coupled to this drug chamber, and through this, it can serve the role of directly measuring biomarkers in the extracted body fluid.

[0116] The reverse iontophoresis electrode functions to extract bodily fluids through the skin by generating an electric current through the application of alternating current from an external power source. One end of the electrode is attached to the skin, while the other is positioned over the micro-needles, generating an electric current from the skin to the micro-needles. For the material used, an Ag / AgCl electrode, commonly used as a general iontophoresis electrode, was prepared in a paste form.

[0117] The micro-needles were designed to physically penetrate the thick stratum corneum of the skin to lower skin resistance, while simultaneously inducing electroosmotic flow (EOF) in one direction, thereby enabling effective extraction of body fluids even with alternating current. The micro-needles were fabricated from polymers, with the height of the needle portion, excluding the base substrate, ranging from 0.5 mm to 1 mm. The polymers used were selected from materials capable of phase separation processes, and were fabricated using one or a combination of materials such as polysulfone, polyethersulfone, and cellulose acetate. Additionally, since electroosmosis occurs within the pores of the micro-needles only when they carry a negative charge, the polymers were fabricated to possess negatively charged functional groups through a process such as sulfonation.

[0118] Biomarkers that can be extracted from the skin can range from substances with molecular weights of hundreds of Da, such as glucose and uric acid, to substances with molecular weights of about tens of kDa, such as DNA and various antigens.

[0119] Figure 2 is a schematic diagram comparing the case where an AC power source is connected to both electrodes and the case where a DC power source is connected, showing the reason why the Faraday current is significantly reduced when the AC power source is connected and processes 1 and 2 are repeated.

[0120] Figure 3 illustrates the case where the pores of the micro-needles are formed symmetrically and uniformly, and the case where they are formed asymmetrically with a trend in average size, and shows the reason why micro-needles having asymmetric pore sizes with an average diameter having a trend according to height were manufactured in one embodiment of the present invention.

[0121] FIG. 4 is a schematic diagram showing the ion flow and electroosmotic rectification phenomena in reverse bias and forward bias states when an AC power source is connected to a micro needle having an asymmetric pore size according to one embodiment of the present invention.

[0122] Figure 5 is an SEM image of an example in which the pore size of the micro-needles is formed differently according to height according to one embodiment of the present invention, showing that the difference in pore size and ratio is formed differently depending on the evaporation time of the polymer solution.

[0123] As can be seen in the images of Fig. 5, the pore structure and size of the micro-needle portion change depending on the solution evaporation time, and it was confirmed that the pore density at the smallest pore and the pore density at the largest pore also change. Since rectification can occur effectively when the difference in the ratio of pore size and density is greatest, micro-needles formed with an evaporation time of 3 hours were used in the examples described below.

[0124] FIG. 6 is an overall image of a micro-needle fabricated according to one embodiment of the present invention and an SEM image of a cross-section of the micro-needle.

[0125] FIG. 7 is a schematic diagram showing each step of a method for manufacturing micro-needles according to one embodiment of the present invention.

[0126] FIG. 8 is a schematic diagram showing the process of forming a trend of pore size or pore density according to the height of the micro-needle formed in the phase separation step in a method for manufacturing micro-needles according to one embodiment of the present invention.

[0127] In the following examples, microneedles were fabricated using negatively charged sulfonated polysulfone. At this time, microneedles were fabricated by immersing a PDMS mold sprayed with the solution into a container of water, which is the non-solvent of the polysulfone solution. At this time, the ratio (density) of pores within the polymer of each sample was varied by varying the evaporation time of the solution before causing phase separation by immersing the solution in the non-solvent.

[0128]

[0129] FIG. 9 is a graph showing the results of linear scanning potential (LSV) and membrane conductivity calculation experiments for a microneedle manufactured according to one embodiment of the present invention, and the ion rectification action of the asymmetric pores can be confirmed by the current difference according to the voltage direction.

[0130] The fabricated micro-needles should exhibit a dominant electroosmotic flow in one direction in a reverse iontophoresis system using alternating current. The inventors intended to verify the ion rectification phenomenon by verifying the change in current according to voltage. Through the difference between the increase in current from -3 to 0 V and the increase in current from 0 to 3 V, it was found that a difference in ion flow occurred depending on the direction of voltage. It can be inferred that the electroosmotic flow will be stronger in the direction where the current increases slowly, as the electrical double layer is formed thicker due to ion depletion. The change in membrane conductance according to voltage could be calculated and represented using the gradient of the current according to voltage.

[0131]

[0132] FIG. 10 is a schematic diagram of an experimental design verifying electroosmotic flow in a micro needle manufactured according to one embodiment of the present invention, and through this experiment, electroosmotic rectification can be confirmed through the PBS movement amount.

[0133] In the experiment shown in Fig. 10, PBS solutions were placed on both sides of a microneedle having asymmetric pores, and the amount of PBS solution flow was measured by applying DC and AC voltages. The experimental results confirmed that as the AC frequency increases, the electroosmotic flow rate decreases because the time for ion movement through rectification within the pores becomes shorter. This implies that electroosmotic flow can be controlled according to frequency, and it was confirmed that optimization is possible to a frequency value where the electroosmotic flow rate is slower than DC but there is no change in pH.

[0134]

[0135] Figure 11 is a graph showing experimental results of confirming pH changes and verifying electroosmotic flow in microneedles manufactured according to one embodiment of the present invention.

[0136] In the experiment shown in Figure 11, when direct current was used, redox reactions occurred continuously near the electrodes and rapid changes in pH occurred, resulting in locally high pH changes. On the other hand, when alternating current was used, the polarity of the electrodes was periodically switched, suppressing redox reactions and showing a tendency for pH changes to be significantly mitigated.

[0137]

[0138] FIG. 12 is a schematic diagram of an experimental design for verifying the quantification effect of macromolecules in a microneedle manufactured according to one embodiment of the present invention.

[0139] FIG. 13 is a graph showing experimental results verifying the quantification effect of macromolecules in a microneedle manufactured according to one embodiment of the present invention.

[0140] In FIGS. 12 and 13, the inventors confirmed how possible extraction is through a microneedle from a gel containing cytochrome c molecules having a large molecular weight of 12 kDa.

[0141]

[0142] As a result, similar results were obtained at passive and DC 1V, which is below the water splitting voltage, and it was confirmed that approximately five times more cytochrome c migrated under AC conditions with no change in pH. From this, the efficiency of AC reverse iontophoresis using microneedles with an asymmetric porous structure could be verified.

[0143]

[0144] The foregoing description is merely an illustrative explanation of the technical concept of the present invention, and those skilled in the art to which the present invention pertains may make various modifications and variations within the scope of the essential characteristics of the present invention. Accordingly, the embodiments disclosed in the present invention are intended to explain, not limit, the technical concept of the present invention, and the scope of the technical concept of the present invention is not limited by these embodiments. The scope of protection of the present invention shall be interpreted by the claims below, and all technical concepts within an equivalent scope shall be interpreted as being included within the scope of rights of the present invention.

Claims

1. In a reverse iontophoresis device for injecting charged ions into the skin, A first patch portion including a first electrode portion; and A second patch portion including a second electrode portion; comprising, An alternating current power source is connected between the first electrode part and the second electrode part, and The above second patch part additionally, drug chamber; and A polymer micro-needle for extracting substances from the body or injecting drugs; further comprising Reverse ion tophoresis device including microneedles.

2. In Paragraph 1, The first patch portion and the second patch portion are both attached to the skin. Reverse ion tophoresis device including microneedles.

3. In Paragraph 1, The above micro needles are, Comprising one or more selected from the group consisting of polysulfone, polyethersulfone, cellulose acetate, polylactic acid (PLA), polycaprolactone (PL), polyglycolic acid (PGA), polyurethane, polyvinyl alcohol (PVA), chitosan, hydroxypropyl methylcellulose (HPMC), poly(methyl methacrylate) (PMMA), and polyimide, Reverse ion tophoresis device including microneedles.

4. In Paragraph 1, The above micro-needles include a material capable of phase separation in relation to a non-solvent, Reverse ion tophoresis device including microneedles.

5. In Paragraph 1, The above micro-needles include a plurality of pores, and Base Finance Department; and A needle portion formed on the above base substrate; comprising Reverse ion tophoresis device including microneedles.

6. In Paragraph 5, The sum of the heights of the base material part and the needle part is 0.2 mm to 2 mm. Reverse ion tophoresis device including microneedles.

7. In Paragraph 5, In at least a certain region of the micro-needles, the average diameter of the pores has a trend of gradually changing with height, Reverse ion tophoresis device including microneedles.

8. In Paragraph 7, The gradually changing trend of the average diameter of the above pores is, formed by the polymer phase separation phenomenon in a non-solvent, Reverse ion tophoresis device including microneedles.

9. In Paragraph 5, The above micro needles are, The average pore size of the upper part of the base substrate is smaller than the average pore size of the lower part of the base substrate. Reverse ion tophoresis device including microneedles.

10. In Paragraph 5, The above micro needles are, The average pore size of the upper part of the base substrate is smaller than the average pore size of the needle tip, Reverse ion tophoresis device including microneedles.

11. In Paragraph 5, In at least a certain region of the micro-needles, the average density of the pores has a trend of gradually changing with height. Reverse ion tophoresis device including microneedles.

12. In Paragraph 1, The above micro-needles are capable of extracting biomaterials with a molecular weight of 10 kDa or more, Reverse ion tophoresis device including microneedles.

13. In Paragraph 1, The above-mentioned reverse ion tophoresis device is, A biosensor capable of detecting biomarkers, which further includes a biosensor Reverse ion tophoresis device including microneedles.

14. A wearable healthcare device including a skin attachment portion, The above skin attachment part is, A reverse ion tophoresis device comprising the micro-needles of claim 1, Wearable healthcare device including micro-needles.

15. Step of preparing the micro-needle mold; A step of introducing a polymer solution into the above mold; A step of evaporating the polymer solvent in a mold into which the above polymer solution is introduced; A step of inducing phase separation within the polymer by immersing the polymer from which the solvent has been evaporated and the mold in a non-solvent; and The method comprising the step of separating the polymer, in which the phase separation has proceeded internally, from the mold and drying it; Method for manufacturing micro-needles for reverse ion tophoresis devices.

16. In Paragraph 15, The step of evaporating the above solvent is performed at a temperature of 40 to 80 degrees, Method for manufacturing micro-needles for reverse ion tophoresis devices.

17. In Paragraph 15, The above polymer solution is negatively charged, Method for manufacturing micro-needles for reverse ion tophoresis devices.

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