KR20190005062A - Device mounted on mask pack comprising burn treatment, mask pack and kit comprising the same - Google Patents

Abstract

A device mounted for iontophoresis drug delivery, and an iontophoresis drug delivery device and kit comprising the same. The device mounted for iontophoresis drug delivery, and the iontophoresis drug delivery device comprising the same according to one aspect of the present invention, the iontophoresis drug delivery device is well adhered to the site of application, for example, the skin, and improves the delivery of a bioactive material through the skin, and uses a device having an electrode to prevent itching, pain, burning, and erythema which may occur in a process of delivering the bioactive material to the skin. The device mounted for iontophoresis drug delivery includes antipyrotic; a battery; and an intermediate sheet.

Description

FIELD OF THE INVENTION [0001] The present invention relates to an iontophoresis drug delivery system comprising an iontophoresis drug delivery system comprising a therapeutic agent, an iontophoresis drug delivery system comprising the same,

An iontophoresis drug delivery system comprising the same, and an iontophoresis drug delivery system and kit comprising the same.

Generally, in the field of cosmetics, the seat iontophoresis drug delivery device is a product that can obtain moisturizing and cleansing effects by attaching a sheet type manufactured in the form of a face without needing to be worn by hand. Sheets are available in various forms such as sheets divided into two sheets on the top and bottom, and sheets tailored to specific areas such as under the eyes, eyes, and mouth.

The general iontophoresis drug delivery device is limited in the delivery of materials useful for the skin because the physiologically active substance is delivered locally and percutaneously. It is important for the iontophoresis drug delivery device to be able to adhere well to the skin for the delivery of useful materials to the skin. In addition, various attempts have been made to further enhance the cosmetic effect, one of which is the use of an iontophoresis device.

Iontophoresis is a drug delivery method that allows charged molecules to pass through tissues easily. 1 is a schematic view of a conventional iontophoresis device. Referring to FIG. 1, an iontophoresis device is a technique for penetrating an ionic material into the skin using a direct current. In order to utilize a repulsive force acting between ions having the same polarity, + 'Electrode, and the ionic material having a negative characteristic is applied to the' - 'electrode so that the ionic material easily penetrates into the skin. Unlike traditional transdermal methods where the drug is passively absorbed, iontophoresis devices provide active transport within the electric field.

However, the conventional iontophoresis device has a problem that the oxidation reaction occurs on the surface of the electrode attached to the skin, causing itching, pain, burning, and erythema on the user's skin using the iontophoresis device.

Thus, the iontophoresis drug delivery device is well adhered to the skin, and the substance in the iontophoresis drug delivery device is delivered to the skin efficiently, It is required to develop an iontophoresis drug delivery device using the iontophoresis principle that can prevent itching, pain, burning, and erythema that may occur during the delivery.

One aspect is to provide an iontophoresis drug delivery device that is well adhered to the skin, enhances delivery of the physiologically active substance through the skin, and specifically provides a physiologically active substance at a desired site, for example, A device mounted on iontophoresis drug delivery which can transmit more, and which can prevent side effects that may occur during the process of transferring a useful substance to the skin using a cell having an electrode, and an iontopore Sis drug delivery device. The technical problem to be solved by this embodiment is not limited to the above-mentioned technical problems, and other technical problems can be deduced from the following embodiments.

One aspect is an apparatus mounted on an iontophoresis drug delivery device comprising a burn therapeutic agent, the burn treatment device comprising: A battery having a cathode and an anode; And an intermediate carrier sheet electrically connected to the charge carrier, wherein the intermediate carrier sheet is configured to allow current generated from the charge carrier to flow to a material-containing sheet of the iontophoresis drug delivery device, And to provide a device that is mounted on a drug delivery device.

Another aspect relates to the apparatus; And a substance-containing sheet wherein the intermediate sheet of the apparatus is connected to the opposite surface of the surface connected to the electrode.

Another aspect is to provide a kit comprising the device, or the iontophoresis drug delivery device, and a container containing an aqueous solution for activating the device.

According to one aspect of the present invention, there is provided an iontophoresis drug delivery device for use in an iontophoresis drug delivery device, and an iontophoresis drug delivery device including the iontophoresis drug delivery device, The delivery of the physiologically active substance through the skin is improved and the effect of preventing the itching, pain, burning, and erythema that may occur during the process of transferring the physiologically active substance to the skin by using the device having electrodes have.

1 is a schematic view of a conventional iontophoresis device.
2 is a diagrammatic representation of an apparatus mounted in an iontophoresis drug delivery device in accordance with one embodiment.
Figure 3 is a diagrammatic representation of the top surface of an iontophoresis drug delivery device in accordance with one embodiment.
4 is a diagrammatic view of a perspective view of an iontophoresis drug delivery device in accordance with one embodiment.
5 is a diagrammatic view of a perspective view of an iontophoresis drug delivery device according to another embodiment.
6 is a diagram illustrating a side view of an iontophoresis drug delivery device using a reverse electrodialysis cell according to one embodiment.
FIG. 7 is a diagram illustrating the activation principle of an iontophoresis drug delivery device using a reverse electrodialysis cell according to one embodiment; FIG.
7A shows the electrolyte flow in the reverse electrodialysis cell in the pre-activation state,
FIG. 7B shows the electrolyte flow of the reverse electrodialysis cell at the start of activation,
Figure 7c shows the electrolyte flow in an activated electrodialysis cell.
8 is a photograph of an apparatus mounted in an iontophoresis drug delivery device manufactured according to one embodiment.
FIG. 9 is a photograph showing that the iontophoresis drug delivery device manufactured according to one embodiment is applied to pig skin divided into a control group (left panel) and an experimental group (right panel).
10 is a photograph showing the mass transfer effect when the iontophoresis drug delivery device manufactured according to one embodiment is applied to pig skin.

Although the terms used in the present embodiments have been selected in consideration of the functions in the present embodiments and are currently available in common terms, they may vary depending on the intention or the precedent of the technician working in the art, the emergence of new technology . Also, in certain cases, there are arbitrarily selected terms, and in this case, the meaning will be described in detail in the description part of the embodiment. Therefore, the terms used in the embodiments should be defined based on the meaning of the terms, not on the names of simple terms, and on the contents of the embodiments throughout.

In the descriptions of the embodiments, when a part is connected to another part, it includes not only a case where the part is directly connected but also a case where the part is electrically connected with another part in between . Also, when a component includes an element, it is understood that the element may include other elements, not the exclusion of any other element unless specifically stated otherwise. The term " ... ", " module ", as used in the embodiments, means a unit for processing at least one function or operation, and may be implemented in hardware or software, or a combination of hardware and software Can be implemented.

It should be noted that the terms such as " comprising " or " comprising ", as used in these embodiments, should not be construed as necessarily including the various components or stages described in the specification, Some steps may not be included, or may be interpreted to include additional components or steps.

Also, terms used in the embodiments, including ordinal numbers such as " first " or " second, " can be used to describe various objects, but the objects should not be limited by the terms. These terms are only used for the purpose of distinguishing one object from another.

The following description of the embodiments should not be construed as limiting the scope of the present invention and should be construed as being within the scope of the embodiments of the present invention. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS Exemplary embodiments will now be described in detail with reference to the accompanying drawings.

One aspect provides an apparatus that is mounted to an iontophoresis drug delivery device.

The iontophoresis drug delivery device may be a mask pack. Accordingly, another aspect may be to provide a device to be mounted to a mask pack, a mask pack comprising the same, and a kit.

The "burn treatment" may include without limitation materials for the treatment of burns. Specifically, the therapeutic agent includes a protein therapeutic agent including an antibody, a peptide therapeutic agent, an aptamer, a small interfering RNA (siRNA), an antisense oligonucleotide, and miRNA (microRNA) as therapeutic agents that can be included in a drug delivery device ≪ / RTI > oligonucleotide therapeutic agents, or combinations thereof.

The device mounted on the iontophoresis drug delivery device may comprise an burn treatment agent. Specifically, the image therapeutic agent may include, for example, a sequence represented by SEQ ID NO: 1-20 below.

SEQ ID NO: 1: MGLQENLKDIMLQ;

SEQ ID NO: 2: MGLHDNLKQLMLQ;

SEQ ID NO: 3: LTSAAPKVET TTLNIQ;

SEQ ID NO: 4: RNIPPFEGCI WN;

SEQ ID NO: 5: NIPPFEGCIW N;

SEQ ID NO: 6: IPPFEGCIWN;

SEQ ID NO: 7: PPFEGCIWN;

SEQ ID NO: 8: PFEGCIWN;

SEQ ID NO: 9: FEGCIWN;

SEQ ID NO: 10: RNIPPFEGCI W;

SEQ ID NO: 11: RNIPPFEGCI;

SEQ ID NO: 12: RNIPPFEGC;

SEQ ID NO: 13: PPFEGCIW;

SEQ ID NO: 14: PPFEGCI;

SEQ ID NO: 15: PPFEGC;

SEQ ID NO: 16: PPFEG;

SEQ ID NO: 17: PPFE;

SEQ ID NO: 18: PPF;

SEQ ID NO: 19: RNIPPFEGCI WNLVINSVPM DFAR;

SEQ ID NO: 20: RNIPPFEGCI WNLVINSVPM DFARPVSFKN ADIGRC.

2 is a diagrammatic representation of an apparatus 101 mounted to an iontophoresis drug delivery device according to one embodiment.

Referring to FIG. 2, the device mounted in the iontophoresis drug delivery device includes: a battery 110 having a cathode and an anode; And an intermediate sheet 116 electrically connected to the battery 110.

In one embodiment, the battery 110 can be any cell capable of generating current. For example, the battery unit may include a reverse electrodialysis cell, a primary cell, or a secondary cell, and more specifically, a flexible battery, an alkaline cell, a dry cell, a mercury cell, a lithium cell, A battery, a nickel-hydrogen battery, a lithium ion secondary battery, and a lithium ion polymer secondary battery. The reverse electrodialysis cell will be described in detail with reference to FIGS. 6 and 7. FIG. The battery 110 may be located at any position on one side of the intermediate sheet 116.

The cathode 131 and the anode 132 are connected to each other by the connection portions 118 and 119 of the intermediate sheet 116 and the intermediary sheet 116, As shown in FIG. The material that can be used for the electrode may include a conductive material such as silver, silver epoxy, palladium, copper, aluminum, gold, titanium, palladium, chromium, nickel, platinum, silver / silver chloride, Silver ion, or mercury / silver oxide.

In one embodiment, intermediate intermediate sheet 116 may be configured to allow current generated from the cell 110 to flow into the material-containing sheet 120 of the iontophoresis drug delivery device. The intermediate intermediate sheet 116 partially includes an insulating portion and the current generated from the cathode 131 and the anode 132 of the battery is electrically connected by the insulating portion of the intermediate intermediate sheet 116 It may not be. For example, the intermediate intermediate sheet 116 may be partially coated with a conductive material 117 as a mesh structure to form a circuit. The circuit can form two separate circuits, one circuit connected to the anode and the other connected to the cathode.

The intermediate intermediate sheet 116 may comprise at least a partially conductive material of the intermediate intermediate sheet 116 or may be coated with a conductive material or may be formed of a conductive woven or nonconductive non- (For example, a nonwoven fabric). Also, for example, the intermediate intermediate sheet 116 may be in a dry form. The conductive fabric, for example, the conductive fabric may include a first layer comprising a synthetic resin from the side connected to the material-containing sheet 120, a second layer comprising a conductive material and a synthetic resin formed on the first layer, A third layer comprising a conductive material formed on the second layer, a fourth layer comprising a conductive material and a synthetic resin formed on the third layer, and a fifth layer comprising a synthetic resin formed on the fourth layer . The synthetic resin may include an acrylic resin, a urethane resin, a silicone resin, a styrene resin, an aniline resin, an amino resin, an amino alkyd resin, a vinyl acetate resin, an alkyd resin, an epoxy resin, a toluene resin, or a combination thereof. The conductive material may be selected from the group consisting of carbon, gold, silver, aluminum, copper, steel use stainless (SUS), and combinations thereof. For the coating of the conductive material, the conductive material may be any one selected from the group consisting of carbon paste, gold paste, silver paste, aluminum paste, copper paste, SUS paste and combinations thereof. The coating of the conductive material may be coated by a method known to a person skilled in the art and may be coated by, for example, gravure printing, offset printing, digital printing, or transfer. One of ordinary skill in the art can determine the appropriate manner and amount of paste to be printed on the intermediate sheet to obtain the desired conductivity value.

Further, the intermediate sheet 116 may further include connecting portions 118 and 119 for electrically connecting to the battery unit 110. The connection portions 118 and 119 may be the same as the conductive material 117.

In one embodiment, the intermediate sheet 116 may serve to flow the current generated from the battery 110 to the material-containing sheet 120. The intermediate intermediate sheet 116 may be disposed on a region of interest of the face to which the substance is to be delivered in the application of the iontophoresis drug delivery device. For example, the substance to be delivered to the object is applied to the entire substance-containing sheet 120, and the iontophoresis drug delivery device is applied to the entire face, but a specific region of the face, for example, , The location of the acne, and the like, the material in the iontophoresis drug delivery device can be better delivered. One of ordinary skill in the art can appropriately determine the size and shape of the intermediate medial sheet so that the material can well transfer to the region of interest of the face.

The intermediate intermediate sheet 116 may form a circuit such that the current generated in the electrode section 110 flows over the entire applied area. For example, the intermediate intermediate sheet may have a conductivity of 0.1 ohm / cm to 10 ohm / cm. < / RTI > In detail, the conductivity may be 10 ohm / cm or less, 8 ohm / cm or less, 6 ohm / cm or less, 4 ohm / cm or less, 2 ohm / cm or less, 1 ohm / cm or less.

In one embodiment, the iontophoresis drug delivery device can be made to adhere well to the skin by pressing the mask sheet directly contacting the skin due to the presence of the intermediate material sheet coated with the conductive material.

In addition, the iontophoresis drug delivery device according to one embodiment of the present invention uses a cell having an electrode to transmit a physiologically active substance to the skin, thereby improving the delivery of the substance and preventing side effects have.

In other embodiments, the device may include one or two charge sections 110. In the case where the battery unit is two units, the battery unit 110 may be disposed on the same surface of the intermediate sheet 116. Each anode 132 of the two cells 110 is electrically connected by a conductive portion 117 of the intermediate sheet 116 and each cathode 131 is also electrically connected to the intermediate sheet 116 Or may be electrically connected by a conductive portion 117 (e.g., a portion coated with a conductive material). As described above, the anode 132 and the cathode 131 of the two battery units 110 are connected to the insulating portion of the intermediate sheet 116 (for example, a portion where the conductive material is not coated) The current generated from the cathode 131 and the anode 132 of the battery may not be electrically connected.

Another aspect provides an iontophoresis drug delivery device comprising the device.

Referring to Figures 3 to 5, the iontophoresis drug delivery device includes the device 101; And a material-containing sheet 120 connected to the opposite surface of the intermediate medium sheet 116 of the apparatus, which surface is connected to the electrode unit 110.

The device 101 is as described above.

In one embodiment, the iontophoresis drug delivery device comprises: a charge section 110 having an anode and a cathode; An intermediate sheet 116 electrically connected to the positive electrode and the negative electrode of the battery unit, respectively; And one or two first or second material-containing sheets (120) connected to one side of one of the two intermediate sheets (116) or one side of each of the two intermediate sheets (116) The intermediate sheet 116 may be configured to allow the electric current generated from the sheet to flow to the material-containing sheet 120. In addition, the substance-containing sheet 120 may be configured to transmit the substance in the substance-containing sheet 120 to the object by the electric current generated from the charge section 110.

The first or second substance-containing sheet 120 may include a substance to be delivered to a subject, the substance to be delivered to the subject may be contained in both the first and second substance-containing sheets 120, (Not shown). In addition, the material-containing sheet 120 may be in a wet form. The material-containing sheet 120 may be configured so that a substance to be delivered to a subject is contained in an electrolyte solution, essence, hydrogel, cellulose, agarose, gelatin or collagen. For example, when the material-containing sheet 120 is a cellulosic material, the iontophoresis drug delivery device may be a cellulosic material, and in the case of collagen, the iontophoretic drug delivery device may be a collagen pack. The cellulosic pack or iontophoresis drug delivery device is used as is commonly known in the art. Thus, the substance-containing sheet may refer to a common sheet for use as a conventional iontophoresis drug delivery device. The material containing sheet may also include an electrolyte, such electrolyte may include NaCl, MgCl _2, AgCl, CuCl _2, CaCl _2, or in a combination of the two. The concentration of the electrolyte contained in the material-containing sheet is, for example, 0.01% to 0.2%, 0.02% to 0.18%, 0.05% to 0.18%, 0.08% to 0.15%, 0.08% to 0.12%, or 0.08% %, 0.1%, or 1.1%. By including the low concentration electrolyte in the material-containing sheet, the material-containing sheet can have an appropriate conductivity value without deteriorating the feeling of use of the material-containing sheet, so that the substance in the material-containing sheet can be more easily transferred to the application site. In addition, the substance-containing sheet may further comprise a water-soluble polysaccharide, for example, arabiogalactan. By adding the water-soluble polysaccharide in the substance-containing sheet, the conductivity can be further increased.

In addition, the material-containing sheet 120 may contain a substance having charge or polarity. The substance may be a substance to be delivered to a subject. The substance-containing sheet 120 may be provided with a substance to be delivered to a subject, or may be provided with a substance to be delivered to a subject in the form of a kit in a separate container, May be provided.

Further, for example, the material-containing sheet 120 may include an aqueous solution or buffer solution, a hydrogel or a matrix containing or containing a substance having charge or polarity. The substance contained in the substance-containing sheet may be mixed with an enhancer substance having a property of promoting mass transfer. The enhancer can roughly be divided into an enzymatic enhancer and a non-enzymatic enhancer. Enzyme enhancers include proteolytic enzymes such as papain, trypsin, pepsin and bromelain. Non-enzymatic enhancers include lactam compounds, ethyl acetate, ethyl alcohol, dioxolane, nonionic surfactants, , Caprylic acid, capric triglyceride, and n-decyl methyl sulfoxide. These enhancers can be suitably mixed and used depending on the substance to be delivered. Also, the matrix material may include an acrylic or methacrylic resin such as an ester of acrylic acid or methacrylic acid and a polymer of alcohol. The alcohol may include butanol, pentanol, isopentanol, 2-methylbutanol, 3-methylpentanol, 2-ethylbutanol, isooctanol, decanol or dodecanol. In addition, the polymer may contain not only a homopolymer but also an acrylic acid, methacrylic acid, acrylamide, methacrylamide, N-alkoxymethylacrylamide, N-alkoxymethylmethacrylamide, Nt-butyl acrylamide, itaconic acid, N-branched alkylmaleimide glycol diacrylate, or mixtures thereof. ≪ Desc / Clms Page number 5 > Other matrix materials include natural or synthetic rubbers such as styrene butadiene, butyl ether, neoprene, polyisobutylene, polybutadiene and polyisoprene, polyvinyl acetate, urea formaldehyde resins, phenol formaldehyde resins, resorcinol formaldehyde resins Cellulose derivatives such as ethyl cellulose, methyl cellulose, nitrocellulose, cellulose acetate butyrate and carboxymethyl cellulose and natural gums such as guar, acacia, pectin, starch, dextrin, albumin, gelatin, casein and the like. These materials may include adhesives and stabilizers as is well known in the art. In addition, the subject to which the substance-containing sheet is contacted and to which the substance is delivered may be, for example, a human or a mammal for other purposes.

The substance having electric charge or polarity included in the substance-containing sheet 120 may be a substance which is charged or polarized by charging the substance itself in the ion conductive medium in the substance-containing sheet, solvation, or the like. The substance having the charge or polarity may include a physiologically active substance or drug. The molecular weight (MW) of the material may be, for example, from about 100 to about 2000, from about 200 to about 2000, from about 300 to about 1000, from about 300 to about 800, or from about 400 to about 7000. In addition, the materials may include whitening agents, anti-wrinkle agents, agents, or combinations thereof. Examples of the whitening agent include mulberry extract, niacinamide, adenosine, arbutin, ethyl ascorbyl ether, oil soluble licorice extract, ascorbyl glucoside, ascorbyltetraisopalmitate ascorbyl tetraisopalmitate, magnesium ascorbyl phosphate, alpha-bisabolol or combinations thereof. Examples of the anti-wrinkle agent include retinol, retinyl palmitate, adenosine, polyethoxylated retinamide, acetyl hexapeptide-3 or 8, acetyl octapeptide Acetyl Octapeptide-3, Acetyl tetrapeptide-5, Palmitoyl pentapeptide, Copper peptide, Palmitoyl oligopeptide, Palmitoyl dipeptide-10 ), Palmitoyl tripeptide-1, palmitoyl tetrapeptide-7, palmitoyl pentapeptide-3, palmitoyl hexapeptide-12, pentapeptide -18, Leuphasyl), or a combination thereof. The substance may also be a protein. The protein may be a modified protein or an ionized or ionizable form of the protein so as to be contained in a substance and delivered.

6 and 7, the operation principle of the iontophoresis drug delivery device in the case where the battery 110 is an electrodialysis cell will be described in detail. The reverse electrodialysis cell unit 110 includes a cation exchange membrane 111; An anion exchange membrane 112 disposed apart from the cation exchange membrane 111; And chambers 113 and 114 that are at least partially defined for the cation exchange membrane 111 and the anion exchange membrane 112 or that are disposed between the cation exchange membrane 111 and the anion exchange membrane 112, Wherein the cation exchange membrane 111 and the anion exchange membrane 112 are alternately disposed and the chamber includes a chamber 113 containing a high concentration of electrolyte and a chamber containing a low concentration of electrolyte disposed in an alternate manner 114 Lt; / RTI >

The intermediary mediation sheet 116 may be connected to the electrode portions (the cathode 131 and the anode 132) existing on both outer sides of the reverse electrodialysis unit 110. A chamber (e.g., a nonwoven fabric) for containing an electrolyte on the outer surface and a cathode 131 when the cation exchange membrane 111 is present, and a chamber (e.g., a nonwoven fabric) And the anode 132 when the anion exchange membrane 112 is present. At this time, electrons are produced by the oxidation reaction in the cathode 131, and electrons are consumed by the reduction reaction in the anode 132 as described below.

(Cathode) Ag -> Ag ^- + e ^-

(Positive electrode) AgCl + e ^- - > Ag + Cl ^-

In one embodiment, the iontophoresis drug delivery device 100 comprises two to seventy, five to sixty, seven to forty , A plurality of cation exchange membranes 111, anion exchange membranes 112, and chambers 113 and 114 that contain electrolyte, with 10 to 35 or 15 to 30 layers.

One side of the material-containing sheet 120 may be in contact with a target S to which the material is to be injected, so that the current generated from the reverse electrodialysis cell 110 flows through the intermediate- Containing sheet 120 to transfer the substance in the substance-containing sheet 120 to the object S. For example, the cation (Na ⁺ ) in the chamber 113 containing the electrolyte at a high concentration passes through the cation exchange membrane 111 and moves to the chamber 114 containing the electrolyte at a low concentration. On the similar principle, anion within the chamber 114 contains a low concentration (Cl ^-) are moved into the chamber 114 including the electrolyte at a low concentration then passes through the anion exchange membrane (112). The migration of the ions occurs in all the cation exchange membranes 111, the anion exchange membranes 112, and the chambers 113 and 114. As described above, the oxidation reaction occurs to produce electrons to replenish the relatively insufficient positive ions in the cathode 131 with the movement of the ions as an electromotive force. In the anode 132, relatively small anions are supplemented , A reduction reaction occurs and consumes electrons. Therefore, the reverse electrodialyzing unit 110 generates an ion current and outputs a current.

Thereafter, a negative charge is charged in the conductive portion 117 of the intermediate sheet 116 connected to the cathode 131 of the battery unit 110 through the connecting portion 119, so that the cationic material contained in the material- (D ⁺ ) and repulsive force can act. Similarly, a positive charge is charged in the conductive portion 117 of the intermediate sheet 116, which is connected to the anode 132 of the battery 110 via the connecting portion 118, so that the anionic Material (D ^- ) and repulsive force can act. Therefore, for example, in the case of the material-containing sheet 120 connected to the cathode 131 of the battery unit, the cation (D ⁺ ) can penetrate (transfer) In the case of the material-containing sheet 120 connected with the anion (D), the anion (D ^- ) can penetrate (transfer) the substance through the skin.

The voltage or current formed in the reverse electrodialysis unit 110 can be controlled by adjusting the type and thickness of the cation exchange membrane 111 and the anion exchange membrane 112 or the volume of the chambers 113 and 114 . The thickness of the chambers 113 and 114 that accommodate the electrolyte is determined by the thickness of the chambers 113 and 114 existing in the middle portion of the cell 110 and the thickness of the chambers 113 and 114 existing in the outer portion of the cell 110 0.0 > 114, < / RTI > In this way, the voltage or current output from the battery section 110 can be increased. The range of voltages output from the cell section may be at least about 0.5 Volt or more, such as about 0.5 volt to about 15 volts, about 1.0 volt to about 10 volt, about 1.5 volt to about 8.0 volt, about 2.0 volts to about 4.0 volts, or about 2.0 volts to about 3 volts. The range of current output from the cell section is at least about 0.1 mA, such as from about 0.1 mA to about 10 mA, from about 0.2 mA to about 8 mA, from about 0.4 mA to about 6 mA, from about 0.5 mA to about 4 mA mA, from about 0.5 mA to about 2 mA, or from about 0.5 mA to about 1 mA. The current may be different depending on the skin resistance, and the skin resistance may be about 1000 to 3000 Ohm.

As used herein, the term " Reversed Electrodialysis (RED) "can refer to the salinity gradient energy resulting from the difference in salt concentration between two solutions, and in one embodiment, the iontophoresis drug Which means that a current flows through the delivery device 100. Therefore, the reverse electrodialysis unit 110 may refer to a device that generates electric current using reverse electrodialysis. For example, in the present specification, the reverse electrodialysis cell 110 may generate an electric current by a difference in ion concentration of an electrolyte in a solution between a high-concentration electrolytic solution and a low-concentration electrolytic solution.

Further, since the iontophoresis drug delivery device 100 according to one embodiment uses reverse electrodialysis, a separate power source or electrode may not be required, or may have no separate power source or electrode. For example, the battery part may be the only source of current for delivering the material to the object. The iontophoresis drug delivery device 100 may be a current source for transferring a substance to a target body, or may be made of only the electrode part, and the battery part may have no separate power source or electrode. The cell portion may use an electrolyte solution to form a current using the reverse electrodialysis cell 110. As used herein, the term "electrolyte" may mean a material that is dissolved in a solvent such as water to dissociate into ions to flow a current, and the electrolyte solution may mean a solution such as water in which an electrolyte is dissolved. Therefore, the electrolyte may be contained in the electrolyte solution. The reverse electrodialysis unit 110 generates a current through a difference between the high concentration electrolyte solution and the low concentration electrolyte solution. The amount of the electrolyte in the chamber 113 containing the high concentration of the electrolyte is lower than that of the low concentration electrolyte solution. May be higher than the amount of electrolyte in the electrolyte 114. The chamber 114 containing the electrolyte at a low concentration may include an electrolyte-free chamber. For example, the electrolyte is contained in an electrolyte solution, and the chamber 113 containing the electrolyte at a high concentration contains about 0.1 to about 20 mol / L, about 0.5 to about 15 mol / L, about 0.7 to about 10 mol / L, about 1.0 to about 8.0 mol / L, about 1.0 to about 2.0 mol / L, or about 1.2 to about 1.8 mol / L, and the concentration of the electrolyte in the chamber 114 ) Does not contain an electrolyte or is present in an amount of about 0.005 to about 10 mol / L, about 0.005 to about 8 mol / L, about 0.01 to about 6 mol / L, about 0.05 to about 6.0 mol / L, / L, or about 0.1 to about 2.0 mol / L, and the ion concentration of the electrolyte solution in the chamber 113 containing the electrolyte at a high concentration is lower than the ion concentration of the electrolyte solution in the chamber 114 ) ≪ / RTI > of the electrolyte solution in the electrolyte solution.

In another embodiment, the chamber 113, 114 comprising the electrolyte may comprise an electrolyte paste. The electrolyte paste may include a water-soluble polymeric binder and an electrolyte. The water-soluble polymeric binder is selected from the group consisting of, for example, a cellulose resin, xanthan gum, polyvinylpyrrolidone, polyvinyl alcohol, water-soluble (meth) acrylic resin, polyether-polyol, and polyetherurea-polyurethane It can be more than one. The electrolyte-containing polymer binder and the electrolyte are mixed to prepare an electrolyte paste, whereby a chamber containing the electrolyte paste can be manufactured. The electrolyte contained in the chamber can be made into an electrolyte paste to lower the resistance, so that the electrolyte in the chamber can move more easily.

In another embodiment, the chambers 113 and 114 containing the electrolyte may be those containing electrolyte containing the hydrogel. For example, the chamber 113 containing the electrolyte at a high concentration contains a solid material including a high concentration electrolyte or a hydrogel containing a high concentration electrolyte, or the chamber 114 in which the electrolyte is contained at a low concentration It may be that a solid material containing an empty or low concentration electrolyte or a low concentration electrolyte contains a contained hydrogel. When the solid material or the hydrogel is contained, for example, the solid state salt (NaCl) is contained, when the water is introduced into the chamber, the solid material or the hydrogel is dissolved in water, Ion flow can be generated. The solid material or hydrogel may be water-soluble, or permeable to an ionic material, and may be used without limitation as long as it has appropriate mechanical properties. Examples of such solid materials or hydrogels include agar, poly ethylene glycol diacrylate (PEGDA), poly (2-hydroxyethyl methacrylate) PHEMA, alginic acid such as sodium alginate, calcium alginate, or potassium alginate. can do. The solid material or hydrogel may also comprise a solid powder form of the ionic binding material.

The chamber 113, 114 containing the electrolyte may be composed of a fabric or non-fabric capable of absorbing aqueous solution. For example, the non-woven fabric may be a nonwoven fabric. When the chamber 113, 114 containing electrolyte is composed of a fabric capable of absorbing an aqueous solution, the electrolyte may be contained in the chamber in the form of a powder. If the electrolyte is present in the form of a powder on the fabric, the flow of ions may occur when a solution, such as water, is introduced into the chamber, the electrolyte dissolved in water to form an electrolyte aqueous solution. In addition, the chambers 113 and 114 may be a fabric impregnated with electrolyte or a non-fabric. The electrolyte-impregnated or non-woven fabric can be produced, for example, by a hot air rolling process after the nonwoven fabric is placed in a NaCl solution. For example, the chamber 113 containing a high concentration of electrolyte can be manufactured through a hot air rolling process after putting a fabric or non-woven fabric capable of absorbing an aqueous solution into a NaCl solution at a high concentration, 114) can be prepared by a hot air rolling process after inserting a fabric or non-woven fabric capable of absorbing the aqueous solution into the NaCl low concentration solution. Further, the chamber 114 containing a low concentration of electrolyte may be composed of a fabric or a non-fabric capable of absorbing an aqueous solution without impregnating NaCl.

In addition, the amount of the electrolyte or the ion concentration of the electrolyte solution in the chamber 113 containing the electrolyte at a high concentration and the chamber 114 containing the electrolyte at a high concentration may be at least about 0.5 volts or more, for example, about 0.1 volt or more To about 15 volts, from about 0.2 volts to about 10 volts, from about 1.0 volt to about 8.0 volts, from about 2.0 volts to about 6.0 volts, from about 2.0 volts to about 4.0 volts, or from about 2.0 volts to about 3 volts It may be contained at different amounts or ionic concentrations. About 0.1 mA to about 10 mA, from about 0.2 mA to about 8 mA, from about 0.4 mA to about 6 mA, from about 0.5 mA to about 4 mA, from about 0.5 mA to about 2 mA , Or from about 0.5 mA to about 1 mA. Examples of the electrolyte may include _{NaCl, MgCl 2, AgCl, CuCl} 2, CaCl 2, or in a combination of the two.

 As used herein, the term " ion-exchange membrane "may refer to a membrane that tends to pass either a cation or an anion. The ion exchange membrane may be a synthetic resin, for example, the synthetic resin may be crosslinked. The cation exchange membrane 111 is negatively charged, so that ions having a negative charge can pass ions having a positive charge without repelling them, and can be, for example, a cation exchange membrane 111 having a sulfone group. Conversely, the anion exchange membrane 112 is positively charged, and ions having a positive charge can pass ions having a negative charge without repelling and passing through them. For example, the anion exchange membrane 112 may be anion exchange membrane 112 having tetravalent ammonium. Examples of the monomer forming the cation exchange membrane 111 include sulfonic acid-type monomers such as 2- (meth) acrylamide-2-methylpropanesulfonic acid, 2- , 3-sulfopropane (meth) acrylate, 10-sulfodecane (meth) acrylate) and salts thereof; For example, 2- (meth) acryloylethylphthalic acid, 2- (meth) acryloylethylsuccinic acid, 2- (meth) acryloylethylsuccinic acid, Acryloylethylmaleic acid, 2- (meth) acryloylethylmaleic acid, 2- (meth) acryloylethyl-2-hydroxyethylphthalic acid ), 11- (meth) acryloyloxydecyl-1,1-dicarboxylic acid, and salts thereof; And a sulfuric acid-type monomer such as 2- (meth) acryloyloxyethyl dihydrogenphosphate, 2- (meth) acryloyloxyethylphenylhydrogenphosphate (2 (meth) acryloyloxyethyl phenyl hydrogenphosphate, 10- (meth) acryloyloxydecyl dihydrogenphosphate, 6- (meth) acryloyloxyhexyl dihydrogenphosphate (6 - (meth) acryloyloxyhexyl dihydrogenphosphate, and salts thereof. Examples of the monomer forming the anion exchange membrane 112 include N, N-dimethylaminoethyl (meth) acrylate, N, N-diethylaminodetyl (meth) N, N-diethylaminoethyl (meth) acrylate, N, N-dimethylaminoethyl (meth) acrylate / methyl chloride, And may include ethyl (meth) acrylate / methyl chloride (N, N-diethylaminoethyl (meth) acrylate / methyl chloride). The ion exchange capacity (IEC) of the cation exchange membrane 111 or the anion exchange membrane 112 may be about 0.5 meg / g or more, or about 1.0 meg / g or more, for example, about 0.5 to about 20.0 meg / About 1.0 to about 10.0 meg / g, about 2.0 to about 10.0 meg / g, and about 5.0 to about 10.0 meg / g. Also, the permeation selectivity of the cation exchange membrane 111 or the anion exchange membrane 112 may be about 70% or about 80% or more, such as about 80 to about 100%, about 90 to about 100%, or about 95 to about 100% %. ≪ / RTI >

In one embodiment, the iontophoresis drug delivery device 100 may further include a spacer (not shown) for separating the cation exchange membrane 111 and the anion exchange membrane 112 from each other. The spacers may be the same as the chambers 113 and 114 that receive the electrolyte. The spacer may prevent the ion exchange membranes from sticking to each other, and may include, for example, a net made of polypropylene or polyetylon, a sponge, an adhesive tape, or a fabric such as cloth or nonwoven fabric . In addition, the spacer may serve as a support for supporting the cation and anion exchange membranes 112, and the chambers 113 and 114 that contain the electrolyte. The support may be, for example, a gasket.

The back electrodialysis cell unit 110 may further include a container 115 for accommodating the back electrodialysis cell unit 110. The container 115 may be configured to expose a part of the reverse electrodialysis cell 110 to be administered with a solution for activating the reverse electrodialysis cell 110. And can play a role for holding and supporting the components in the reverse electrodialysis unit 110. Further, for example, the vessel 115 can prevent the solution in the chambers 113 and 114 from leaking. Also, a part of the container 115 may serve as a spacer (not shown), for example, a double-sided tape, as described above. Further, the container may be an insulator, and any material conventionally used may be used as the material of the container. Examples of optional materials include cellophane, cellulose acetate, ethylcellulose, plasticized vinyl acetate-vinyl chloride copolymer, polyethylene terephthalate, nylon, polyethylene, polypropylene, polyvinylidene chloride, rubber strings, , Metal plates, wood plates, paper, cloth, and aluminum foils.

Referring to FIG. 7, a specific example in which a reverse electrodialysis cell is activated is schematically shown. 7A, the reverse electrodialysis cell is a sidewall of the chambers 113 and 114, and at least a portion of the sidewall located between the cation exchange membrane 111 and the anion exchange membrane 112 The water permeable membrane 140 may be disposed. The water supply part 130 for supplying water to the chambers 113 and 114 may be connected to at least a part of the side walls of the chambers 113 and 114. The water supply unit 130 and the chambers 113 and 114 may be in fluidic communication by a flow channel or a channel (not shown). And may further comprise means or valves capable of controlling the fluid communication. In the above, the side wall may refer to a side of the chambers that is not facing. 7B, the water in the water supply portion 130 flows into the chambers 113 and 114 through the water permeable membrane 140, whereby the flow of the ions described above, as shown in FIG. 7C, Can be formed. In addition to the water permeable membrane or water supply described above, the device can be activated via any means that produces a difference in electrolyte ion concentration in the chamber (113, 114) of the device. For example, the device may be activated by supplying water to activate the device before or after the user has contacted the skin with the skin.

Another aspect provides a kit comprising an iontophoresis drug delivery device or an iontophoresis drug delivery device comprising the same.

The kit may comprise a container containing an aqueous solution (e. G., Water) to activate the device mounted to the iontophoresis drug delivery device. The aqueous solution may comprise an electrolyte. The electrolyte is the same as described for the electrolyte contained in the material-containing sheet.

The kit may further comprise a container containing a substance to be delivered to the subject. For example, the iontophoresis drug delivery device may be provided with the iontophoresis drug delivery device as a kit together with a substance contained in a specific container in the absence of the substance to be delivered to the subject. The substance to be delivered to the subject may be provided in the form of a composition containing the substance or a powder of the substance. For example, the composition comprising the material may be provided in the form of a cream, gel, liquid, essence, serum or the like comprising the material. The composition comprising the substance has a viscosity of at least a predetermined value and the user can deliver the substance in vivo by applying the substance to the substance-containing sheet. A person skilled in the art can appropriately select the form of the drug, the constitution of the substance-containing sheet and the constituent thereof according to the use mode. When the iontophoresis drug delivery device, the substance, and / or the aqueous solution is provided as a kit, the user applies the drug to an iontophoresis drug delivery device and uses an aqueous solution to deliver the iontophoresis drug delivery By activating the device, the substance can be delivered in vivo by contacting the skin of the subject or someone else.

8 is a photograph of an apparatus mounted in an iontophoresis drug delivery device manufactured according to one embodiment. As the intermediate sheet, a nonwoven fabric was used, and 0.5 g of silver paste (Daesu Electronics Co., Ltd.) was printed on the nonwoven fabric. Ethylcarbitol acetate was used as a solvent for viscosity control. After the silver paste was printed, a thermal process was performed at 120 ° C for 3 to 4 hours to remove harmful substances to the human body, and cooling and deodorization processes were simultaneously performed through the air process for 1 hour or more. Then, in order to perforate the intermediary intermediate sheet, the silver paste is marked by marking the printed roll, and the mark is sensed at the time of perforation so that it can be perforated within an error range. The conductivity of the intermediate sheet obtained through this process was about 1 ohm / cm. A reverse electrodialysis cell was used as the battery. Specifically, as the chamber for containing the electrolyte, a nonwoven fabric having a thickness of about 0.2 to 0.5 mm was used. Cation exchange membrane and anion exchange membrane were purchased from ASAHI GLASS Co. SBX tape (CROSS company, SBX tape) was used as a spacer, a container, or a support for attaching the nonwoven fabric, the cation exchange membrane, and the anion exchange membrane. The SBX tape was punched to allow ion exchange to ensure a space for placing the solution in the chamber housing the electrolyte. In addition, the NaCl powder was placed on the nonwoven fabric by a predetermined amount so that the concentration of the chamber containing the electrolyte at a high concentration was 1.72 M and the concentration of the chamber containing the electrolyte at a low concentration was 0.011 M. Each configuration of the reverse electrodialysis cell unit was prepared as described above, and each configuration was stacked in the order of stacking the reverse electrodialysis cell units described above. The area of the chamber was 1.5 cm x 1.3 cm, and the chamber was used as one layer to fabricate a reverse electrodialyzing cell having 31 layers. The voltage and current were measured by contacting the copper copper plate to a reverse electrodialysis cell with a digital multimeter 34410A of an ammeter Keysight.

The connection between the sheet and the intermediate sheet was performed by an ultrasonic process. The process of inserting the back electrodialysis cell into the support (i.e., the container) was manually performed and the cell portion was connected to the sheet. The lower part of the support, the silver paste of the intermediate sheet, and the electrode of the battery and the silver paste were printed by ultrasonic process.

As described above, a device mounted on the iontophoresis drug delivery device was manufactured, and the material-containing sheet was applied to the skin using a wet-type micro-sized mask (PNC Industry, Korea). As an aqueous solution for activating the iontophoresis drug delivery device, an aqueous solution containing 0.1% of NaCl was used. Whether or not the iontophoresis drug delivery device was adhered well was evaluated through sensory evaluation. Specifically, the test group and the control group were applied to the skin of 20 persons who were collected, and then a sensory evaluation was performed to determine whether the skin was well adhered to the skin. Iontophoresis drug delivery device was applied randomly to the participants in the experiment, and scores of 1 (low adhesion sensitivity) to 5 (high adhesion strength) were evaluated for the degree of skin adhesion, Are shown in Table 1.

Experimental group Control group Adhesion to skin 4.45 3.81

In addition, as shown in Figs. 9 and 10, whether or not the substance was delivered well was applied to pig skin. Specifically, as a test group, the iontophoresis drug delivery device according to one embodiment was applied for 30 minutes on pig skin, and a mask pack without RED battery was applied for 30 minutes as an experimental group. Calcein (M.W. 622.55 g / mol, Sigma-Aldrich), 0.5 mM, a fluorescent reagent, was used for the substance-containing part. The pig skin was then sampled and sectioned for fluorescence microscopy analysis. Specifically, a frozen block was prepared, cut into a frozen section having a size of 7 mu m, placed on a cover slip, and observed with a fluorescence microscope. The results are shown in Fig. As shown in FIG. 10, in the control group, fluorescence remained without passing through the horny layer, whereas the iontophoresis drug delivery device according to one embodiment was able to be confirmed by transmitting fluorescence deeply through the stratum corneum.

As a result, the iontophoresis drug delivery device according to one embodiment of the present invention is well adhered to the skin, and the delivery of the physiologically active substance through the skin is improved, and by using the device having the electrode, It was confirmed that there is an effect of preventing itching, pain, burning, and erythema which may occur during the delivery.

100: iontophoresis drug delivery device 101: device mounted on iontophoresis drug delivery device
110: electrode part 111: cation exchange membrane
112: anion exchange membrane 113, 114: chamber
115: container 116: intermediate sheet
117: conductive part 120: material-containing sheet
130: water supply part 140: water permeable membrane
131: cathode 132: anode

Claims (1)

An apparatus mounted on an iontophoresis drug delivery device,
Burn Therapeutics;
A battery having a cathode and an anode; And
And an intermediate sheet electrically connected to the sheet portion,
Wherein the intermediate mediated sheet is configured to flow the current generated from the electrode section to a substance containing sheet of the iontophoresis drug delivery device.

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