KR20230099191A - Biodegradable metallic microneedle patch electrodes for enhanced transdermal drug delivery - Google Patents

Abstract

The present invention provides an electrode-type biodegradable metallic microneedle patch for enhanced drug delivery, which induces active ingredients to penetrate effectively and quickly into tissues of the skin. According to the present invention, the electrode-type biodegradable metallic microneedle patch comprises: an electrode unit including an anode electrode and a cathode electrode disposed to be spaced apart from the anode electrode; a power supply unit electrically connected to the electrode unit to apply a voltage; and a plurality of microneedles connected to the electrode unit, formed at regular intervals along the electrode unit, and passing through the stratum corneum of the skin to directly deliver active ingredients to the inner tissue of the skin. The electrode unit generates hydrogen gas (H_2) from an electrochemical reaction by a predetermined voltage applied from the power supply unit.

Description

Biodegradable metallic microneedle patch electrodes for enhanced transdermal drug delivery}

The technical idea of the present invention relates to a skin treatment device, and more particularly, to an electrode-type biodegradable metal microneedle patch capable of enhancing drug delivery to a patient by applying an external voltage.

The microneedle is a system that delivers a drug by physically piercing a small hole in the stratum corneum of the skin and using the passage, and can deliver the drug at a speed about 100 times higher than that of conventional transdermal delivery systems. The microneedle-based delivery method, which has recently been used or is being developed, is a solid form in which a drug is applied after forming a hole in the skin, and a form in which the drug is delivered by needle administration itself, that is, a melted drug contained in a needle or applied to the needle surface. It can be divided into coating types.

In general, microneedles are used for delivery of active substances such as drugs and vaccines in vivo, detection of analytes in the body, and biopsy. The purpose of delivery of a pharmaceutically or chemically active ingredient using a microneedle is to deliver the active material through the skin rather than through a biological circulatory system such as blood vessels or lymphatic vessels. Therefore, the microneedles must have sufficient physical strength to allow penetration of the skin, and preferably have low pain. In order to reduce pain as much as possible, it is advantageous to have a shorter skin application time of the microneedle, and in this case, the active substance must be rapidly delivered.

However, such a conventional microneedle may cause pain to the patient because it takes a long time for the drug or cosmetic ingredient contained or coated in the needle to penetrate into the skin tissue, and also, the microneedle is easily broken in the process of penetrating into the skin. There is a problem that it is very harmful to the human body when it is left in the body.

The present invention is to solve various problems, including the above problems, by applying voltage from the outside to induce drugs or cosmetic ingredients to penetrate into tissues within the skin effectively and quickly, and even if they remain in the body, they are safe and harmless biodegradable An object of the present invention is to provide an electrode-type biodegradable metal microneedle patch for enhancing drug delivery containing Mg as a material.

However, these tasks are exemplary, and the technical spirit of the present invention is not limited thereto.

According to one embodiment of the present invention, the electrode portion having an anode electrode and a cathode electrode disposed spaced apart from the anode electrode; a power supply unit electrically connected to the electrode unit to apply voltage; and microneedles connected to the electrode unit, formed in plural at regular intervals along the electrode unit, and passing through the stratum corneum of the skin to directly deliver the active ingredient to the inner tissue of the skin; Including, but, the electrode unit generates hydrogen gas (H ₂ ) from an electrochemical reaction by a predetermined voltage applied from the power supply unit, providing an electrode-type biodegradable metal microneedle patch for enhancing drug delivery.

The power supply unit may apply a voltage of 0.8V to 1.6V to the electrode unit.

An electric field may be formed in the electrode part by a voltage applied from the power supply part.

The active ingredient exposed to the electric field may move in a specific direction by the principle of electrophoresis.

The electrode part and the microneedle may include a biodegradable metal material.

The electrode part and the microneedle include magnesium (Mg) or zinc (Zn), but may be provided to be integrally formed.

An adhesive sheet may be formed on one surface in contact with the skin so that the electrode unit can be adhered to the skin.

The power supply unit may provide DC power, AC power, RF power, or pulse power to the electrode unit.

The power source may include a battery composed of an iron electrode, a hydrogel, and a magnesium electrode.

The microneedles may be formed in a pointy shape with a width gradually decreasing from a connection portion with the electrode to a tip so as to easily pass through the stratum corneum of the skin.

Further comprising a substrate on which the electrode unit is disposed, wherein the substrate is made of polyimide, polydimethylsiloxane (PDMS), poly(methyl methacrylate) (PMMA), polyvinylpyrrolidone (PVP), polyvinyl alcohol (PVA), poly(lactic-co-glycolic acid) (PLGA), polycaprolactone (PCL), poly glycolic acid (PGA), poly lactic acid (PLA), poly glycerol sebacate (PGS), and polybutylene adipate terephthalate (PBAT).

According to the technical concept of the present invention, it is possible to provide an electrode-type biodegradable metal microneedle patch for enhancing drug delivery that can ensure safety by including a biodegradable material that can be degraded even if it remains in the body.

In addition, by penetrating the microneedle into the skin and applying an external voltage, an electrode type for enhancing drug delivery capable of inducing effective penetration of active ingredients such as drugs or cosmetic ingredients into tissues within the skin on the surface of the microneedle in a short time. A biodegradable metal microneedle patch can be provided.

The effects of the present invention described above have been described by way of example, and the scope of the present invention is not limited by these effects.

1 is a cross-sectional view showing an electrode-type biodegradable metal microneedle patch for enhancing drug delivery according to an embodiment of the present invention.
FIG. 2 is a perspective view showing in detail the electrode part and microneedles of the electrode-type biodegradable metal microneedle patch for enhancing drug delivery of FIG. 1 according to an embodiment of the present invention.
3 is an electrode-type biodegradable metal microneedle patch for enhancing drug delivery made of pure magnesium and magnesium alloy (Mg-0.05Ca-1Zn) according to an embodiment of the present invention, according to the magnitude of the applied external voltage This is a graph showing the amount of hydrogen generated by the electrode reaction.
Figure 4 shows the process and result of penetration of active ingredients such as drugs or cosmetic ingredients into skin tissues on the surface of the microneedle according to an embodiment of the present invention.

Hereinafter, several preferred embodiments of the present invention will be described in detail with reference to the accompanying drawings. The embodiments of the present invention are provided to more completely explain the present invention to those skilled in the art, and the following examples may be modified in many different forms, and the scope of the present invention is as follows It is not limited to the examples. Rather, these embodiments are provided so that this disclosure will be thorough and complete, and will fully convey the spirit of the invention to those skilled in the art. In addition, the thickness or size of each layer in the drawings is exaggerated for convenience and clarity of explanation. Hereinafter, embodiments of the present invention will be described with reference to drawings schematically showing ideal embodiments of the present invention. In the drawings, variations of the depicted shape may be expected, depending on, for example, manufacturing techniques and/or tolerances. Therefore, embodiments of the inventive concept should not be construed as being limited to the specific shape of the region shown in this specification, but should include, for example, a change in shape caused by manufacturing.

1 is a cross-sectional view showing an electrode-type biodegradable metal microneedle patch 100 for enhancing drug delivery according to an embodiment of the present invention.

2 is a perspective view showing in detail the electrode part 120 and the microneedle 150 of the electrode-type biodegradable metal microneedle patch 100 for enhancing drug delivery of FIG. 1 according to an embodiment of the present invention.

1 and 2, the electrode-type biodegradable metal microneedle patch 100 for enhancing drug delivery includes a substrate 110, an electrode unit 120, a microneedle 150, and a power supply unit 160. do.

An electrode unit 120 is disposed on the substrate 110 . Substrate 110 is an optional component and may be omitted. The substrate 110 may include various non-conductive materials. The substrate 110 may include a material capable of providing flexible characteristics or may include a flexible substrate having a thickness. The substrate 110 may include, for example, glass, ceramic, fiber, carbon fiber, polymer material, etc., and for example, polyimide, polydimethylsiloxane (PDMS), PMMA, ecoflex, or dragon skin. -skin), PVP, PVA, poly(lactic-co-glycolic acid (PLGA), silk fibroin, polycaprolactone (PCL), poly glycolic acid (PGA), poly lactic acid (PLA), poly glycerol sebacate (PGS), PBAT , It may include at least one of collagen and rice paper, agarose gel, and polyanhydrides More preferably, the substrate is polyimide, PDMS (polydimethylsiloxane), PMMA (Poly (methyl methacrylate)), PVP (Polyvinylpyrrolidone) , polyvinyl alcohol (PVA), poly(lactic-co-glycolic acid (PLGA), polycaprolactone (PCL), poly glycolic acid (PGA), poly lactic acid (PLA), poly glycerol sebacate (PGS) and polybutylene adipate terephthalate (PBAT) ) may include at least one of them.

The electrode unit 120 may provide an electrical signal by contacting the patient's skin. The electrode unit 120 may include an anode electrode 130 and a cathode electrode 140 disposed spaced apart from the anode electrode 130 . The electrode unit 120 includes a conductive material but is a biodegradable metal material that can be biodegraded in the body, for example, magnesium (Mg), iron (Fe), zinc (Zn), molybdenum (Mo), tungsten (W), It may include calcium (Ca), potassium (K), sodium (Na), silicon (Si), a-IGZO, germanium (Ge), or an alloy thereof, preferably magnesium (Mg). .

The power supply unit 160 may be electrically connected to the electrode unit 120 to apply a predetermined voltage to the electrode unit 120 . The power supply unit 160 may be connected to the electrode unit 120 through a wire 170 . The power supply unit 160 may provide DC power, AC power, RF power, or pulse power to the electrode unit 120 . The power supply unit 160 may be composed of a galvanic battery or a triboelectric generator. The power supply unit 160 may include a battery composed of an iron electrode, a hydrogel, and a magnesium electrode. The triboelectric generating element may be formed using metal deposition on a biodegradable polymer film.

The microneedles 150 may be connected to the electrode unit 120 and formed in plurality at regular intervals along the electrode unit 120 . The microneedles 150 may be formed along one side of the electrode unit 120 , along both sides of the electrode unit 120 , or along the central portion. The microneedles 150 can pass through the stratum corneum of the skin and directly deliver active ingredients such as drugs or cosmetic ingredients to the inner tissue of the skin. The microneedle 150 may include a biodegradable metal material. The biodegradable means a material that can be absorbed in the human body and is harmless after absorption. The microneedle 150 is, for example, magnesium (Mg), iron (Fe), zinc (Zn), molybdenum (Mo), tungsten (W), calcium (Ca), potassium (K), sodium (Na), Silicon (Si), a-IGZO, germanium (Ge), or an alloy thereof may be included, and preferably magnesium (Mg) may be included.

The electrode part 120 and the microneedle 150 are made of the same biodegradable material, for example, magnesium (Mg) or zinc (Zn), and the electrode part 120 and the microneedle 150 are integrally formed. can have

When an external voltage is applied to the electrode part 120 by the power supply part 160, an electric field is formed, and the active ingredient exposed to this electric field can be moved in a specific direction by the principle of electrophoresis and delivered to the inside of the skin. there is.

In addition, the anode electrode 130 and the cathode electrode 140 of the electrode unit 120 to which the voltage is applied operate as an electrolytic cell, and an electrochemical reaction may occur. Thus, the anode electrode 130 can generate hydrogen gas (H 2 ) through, for example, an oxidation reaction of Mg electrode material, and the cathode electrode 140 can generate hydrogen gas (H ₂ ) through a reduction reaction of water present in body fluid inside the skin. Hydrogen gas (H ₂ ) can be generated.

3 is an electrode-type biodegradable metal microneedle patch for enhancing drug delivery made of pure magnesium and magnesium alloy (Mg-0.05Ca-1Zn) according to an embodiment of the present invention, according to the magnitude of the applied external voltage This is a graph showing the amount of hydrogen generated by the electrode reaction.

Referring to FIG. 3 , it can be confirmed that the amount of hydrogen gas generated by the electrochemical reaction increases as the magnitude of the applied voltage increases. At this time, an appropriate amount of hydrogen gas can physically promote the diffusion of the drug, but when hydrogen gas bubbles are excessively generated, there is a problem of hindering the movement of active ingredients. That is, the delivery of the active ingredient to the inside of the skin can proceed more easily as the electric field size increases in proportion to the applied voltage, but when the voltage is applied in a range exceeding a predetermined value, excessive hydrogen gas bubbles cause There is a problem that the movement of the active ingredient can be inhibited.

Thus, the predetermined voltage applied to the electrode unit 120 may have a value within the range of, for example, 0.8V to 1.6V, and preferably, may have a value within the range of 0.8V to 1.4V. When the magnitude of the voltage applied to the electrode unit 120 is less than 0.8V, there is a problem in that the magnitude of the generated electric field is insufficient to move the active ingredient. When the magnitude of the voltage applied to the electrode part 120 exceeds 1.6V, the excessively generated hydrogen gas bubbles excessively inhibit the movement of the active ingredient into the skin, so it is more effective than when the applied voltage is 0V. There is a problem that the increase in the migration force of the components may be insignificant.

On the other hand, the applied voltage at which the same hydrogen is generated is different depending on the type of biodegradable metal. For example, in FIG. 3, the applied voltage representing an arbitrary amount of hydrogen generation (0.75ml/cm ² per hour, dotted line) is about 1.07V for pure magnesium, whereas it is about 1.32V for Mg-0.05Ca-1Zn alloy. However, since the applied voltage varies depending on the composition of the biodegradable metal, it is possible to specify an appropriate use range in which excessive hydrogen is not generated through a hydrogen generation test.

Hereinafter, the operating principle of the electrode-type biodegradable metal microneedle patch 100 for enhancing drug delivery will be described.

As the electrode-type biodegradable metal microneedle patch 100 for enhancing drug delivery is attached to the human skin, the microneedle 150 is inserted into the human skin. The microneedle 150 is electrically connected to the electrode unit 120, and the microneedle 150 and the electrode unit 120 are formed as an integrated magnesium structure, for example, including magnesium (Mg) and provided as one body. It can be.

A part of the microneedle 150 is electrically connected to the anode electrode 130 of the electrode unit 120, and another part of the microneedle 150 is electrically connected to the cathode electrode 140. The power supply unit 160 may apply a predetermined external voltage, for example, a voltage in the range of 0.8V to 1.6V, to the anode electrode 130 and the cathode electrode 140 .

As the external voltage is applied to the electrode unit 120 by the power supply unit 160, an electric field is formed between the anode electrode 130 and the cathode electrode 140, and active ingredients exposed to the electric field are moved by the principle of electrophoresis. . Here, the moving direction of the active ingredient is determined by the type of charge of the active ingredient particle and the characteristics of the voltage signal applied from the power supply unit 160 .

Electrophoresis is a phenomenon in which microparticles with positive and negative charges in an electric field are driven by a Coulomb force and move. That is, particles with a positive charge move to the negative electrode, and particles with a negative charge move to the positive electrode. The movement characteristics of particles by electrophoresis may vary depending on the amount of charge, the size of the particles, the electrical, chemical, and physical properties of the medium or the strength of the electric field.

In addition, when an external voltage is applied to the electrode unit 120 by the power supply unit 160, a potential difference is generated between the anode electrode 130 and the cathode electrode 140, and this potential difference causes the anode electrode 130 and the cathode electrode 140 to ) At each electrode, an electrochemical reaction takes place.

The electrode unit 120 operates as an electrolytic cell, and a reaction as shown in the following chemical formula may proceed at each electrode. For example, the anode electrode 130 may generate hydrogen gas (H ₂ ) through an oxidation reaction of a magnesium electrode material as shown in the following reaction formula, and the cathode electrode 140 may generate body fluid inside the skin as shown in the following reaction formula. Hydrogen gas (H ₂ ) can be generated through a reduction reaction of water present in.

Anode: Mg → Mg ²⁺ + 2e ^-

Mg + 2H ₂ O → Mg(OH) ₂ + H ₂

Cathode: 2H ₂ O + 2e ^- → H ₂ + 2OH ^-

Since the microneedle 150 and the electrode unit 120 contain a biodegradable metal, for example, magnesium, when they are removed from the skin after their functions are over, even if residues remain in the skin, they can be absorbed into the body and disappear. In addition, since the microneedles 150 are naturally decomposed in the body, infections caused by residues and side effects may be minimized.

On the other hand, the electrode unit 120 has a flexible property in the shape of a thin rectangular plate, so that it can be naturally deformed and adhered to according to the shape and curvature of the human skin, like a dynamic compression plate (DCP). In addition, an adhesive sheet is formed on one surface of the electrode unit 120 in contact with the skin, so that the electrode unit 120 can be more firmly adhered to the human skin.

A plurality of microneedles 150 are formed at regular intervals along both sides of the thin plate-shaped electrode unit 120, and can pass through the stratum corneum of the skin to directly deliver active ingredients to the inner tissue of the skin. More specifically, the microneedle 150 is formed so that the width gradually decreases toward the tip at the connection portion with the electrode unit 120 so that the microneedle 150 can easily pass through the stratum corneum of the skin, and the tip is formed in a pointed shape. It can be. As such, the microneedle 150 may be formed in a cone shape, triangular pyramid shape, or quadrangular pyramid shape with a pointed tip, and the shape may not be particularly limited as long as it can penetrate through the stratum corneum of the skin.

In addition, when the microneedle 150 penetrates the inside of the skin, the surface of the microneedle 150 is coated with an active ingredient so that the active ingredient can also penetrate into the skin, or is formed on one surface of the microneedle 150. A groove may be formed and the active ingredient may be filled in the groove. An active ingredient penetrated into the skin along with the microneedle 150 may be a kind of physiologically active substance as a drug. The physiologically active substances refer to compounds and molecules that induce biological responses when applied to hosts, animals, and humans, and include, for example, therapeutic substances such as vaccines, antibodies, antitumor agents, insulin, analgesics, and hair growth agents. substances) or cosmetic substances such as retinol with anti-aging and whitening effects. In addition, the physiologically active substance may include a lipolysis substance for diet or a non-therapeutic substance such as an anesthetic.

As described above, the active ingredient, which is a kind of the physiologically active material, is formed in the form of an electrolyte or non-electrolyte solution or gel, and is coated on the surface of the microneedle 150 or filled in the groove formed on one surface of the microneedle 150. can be

In the conventional case, when trying to deliver a drug or physiologically active substance to the biodegradable metal microneedle 150, there are the following problems. Drugs injected along a needle coated on a needle or penetrating the stratum corneum and epidermal layer depend purely on diffusion, and a complicated mechanism is required to increase or precisely control the drug injection rate. Therefore, in order to solve this problem, a means capable of accelerating the drug injection from the microneedle 150 is required.

Figure 4 shows the process and result of penetration of active ingredients such as drugs or cosmetic ingredients into skin tissues on the surface of the microneedle according to an embodiment of the present invention.

4(a) and 4(b), in the electrode-type biodegradable metal microneedle patch 100 for enhancing drug delivery according to the technical idea of the present invention, the microneedle 150 is inserted into the skin When an external voltage is applied to the electrode unit 120 by the power supply unit 160, drug molecules, which are ionizable active ingredients coated on the surface of the microneedle or injected along the surface by the electrophoresis principle, are applied to the electric field in the direction of the opposite electrode. It can move quickly and be delivered to the inside of the skin. That is, it is possible to confirm the efficient intradermal delivery process of the active ingredient by the effect of adding the diffusion effect by the electric field to the diffusion by concentration. In addition, the hydrogen gas bubbles generated from each of the anode electrode 130 and the cathode electrode 140 enhance the delivery power of the above-mentioned active ingredient into the skin, so that the above-mentioned active ingredient penetrates into the tissue within the skin effectively and quickly. There is an effect that can be done. In addition, referring to FIG. 4(c), it is shown that a difference may occur in the diffusion area according to each electric field generated according to the magnitude of the applied voltage. It is confirmed that the movement of the active ingredient can be rather hindered by the hydrogen gas bubbles.

The battery-powered device can be connected to the patch with a power supply and electrical control device to control drug release and diffusion during attachment, and both direct current and alternating current can be used. In addition, it can be used by connecting an electric energy harvesting device such as a triboelectric force harvesting device that can be operated by human motion and a piezoelectric generator. For example, it can be used in the form of activating the function of the patch by attaching it to the inside of a cosmetic puff, etc., and actually generating electricity although it looks like a makeup operation on the outside.

The technical spirit of the present invention described above is not limited to the foregoing embodiments and the accompanying drawings, and various substitutions, modifications and changes are possible within the scope of the technical spirit of the present invention. It will be clear to those skilled in the art to which it pertains.

100: Electrode-type biodegradable metal micro-needle patch for enhancing drug delivery
110: substrate,
120: electrode unit,
130: anode electrode,
140: cathode electrode,
150: microneedle
160: power supply
170: wiring

Claims (11)

An electrode unit having an anode electrode and a cathode electrode disposed spaced apart from the anode electrode;
a power supply unit electrically connected to the electrode unit to apply voltage; and
a plurality of microneedles connected to the electrode unit and formed at regular intervals along the electrode unit, passing through the stratum corneum of the skin and directly delivering active ingredients to the inner tissue of the skin; Including,
the electrode part
Generating hydrogen gas (H ₂ ) from an electrochemical reaction by a predetermined voltage applied from the power supply unit,
Electrode-type biodegradable metal microneedle patch for enhancing drug delivery. According to claim 1,
the power supply
Applying a voltage of 0.8V to 1.6V to the electrode part,
Electrode-type biodegradable metal microneedle patch for enhancing drug delivery. According to claim 1,
An electric field is formed in the electrode part by the voltage applied from the power supply part.
Electrode-type biodegradable metal microneedle patch for enhancing drug delivery. According to claim 3,
The active ingredient exposed to the electric field moves in a specific direction by the principle of electrophoresis,
Electrode-type biodegradable metal microneedle patch for enhancing drug delivery. According to claim 1,
The electrode part and the microneedle contain a biodegradable metal material,
Electrode-type biodegradable metal microneedle patch for enhancing drug delivery. According to claim 5,
The electrode part and the microneedle
Including magnesium (Mg) or zinc (Zn), but provided to be integrally formed,
Electrode-type biodegradable metal microneedle patch for enhancing drug delivery. According to claim 1,
the electrode part
An adhesive sheet is formed on one surface in contact with the skin so as to be adhered to the skin.
Electrode-type biodegradable metal microneedle patch for enhancing drug delivery. According to claim 2,
the power supply
Providing DC power, AC power, RF power, or pulse power to the electrode unit,
Electrode-type biodegradable metal microneedle patch for enhancing drug delivery. According to claim 2,
The power supply unit includes a battery composed of an iron electrode, a hydrogel, and a magnesium electrode,
Electrode-type biodegradable metal microneedle patch for enhancing drug delivery. According to claim 1,
The microneedle
In order to easily pass through the stratum corneum of the skin, the width is gradually smaller toward the tip at the connection portion with the electrode portion, so that the tip is formed in a pointed shape.
Electrode-type biodegradable metal microneedle patch for enhancing drug delivery. According to claim 1,
Further comprising a substrate on which the electrode unit is disposed,
The substrate is polyimide, polydimethylsiloxane (PDMS), poly(methyl methacrylate) (PMMA), polyvinylpyrrolidone (PVP), polyvinyl alcohol (PVA), poly(lactic-co-glycolic acid (PLGA), polycaprolactone (PCL), poly glycolic acid acid (PGA), poly lactic acid (PLA), poly glycerol sebacate (PGS) and PBAT (Polybutylene adipate terephthalate),
Electrode-type biodegradable metal micro-needle patch for enhancing drug delivery.

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