KR101698147B1 - Iontophoresis device using reversed electrodialysis and method for deliverying drug using the same - Google Patents

Abstract

An iontophoresis device using reverse electrodialysis and a method for delivering a drug using the same are provided. The iontophoresis device has an effect of improving the transfer of drug through the skin and preventing side effects that may occur in the course of transferring the drug to the skin.

Description

TECHNICAL FIELD [0001] The present invention relates to an iontophoresis device using reverse electrodialysis, and a method for delivering a drug using the iontophoresis device using reversed electrodialysis,

Iontophoresis device using reverse electrodialysis, and a method for delivering a drug using the same.

Methods for delivering a drug into the body for the purpose of skin cosmetic treatment or treatment include oral administration, topical administration, intravenous administration, intramuscular injection, intracutaneous injection and subcutaneous injection. With the exception of topical administration, where the drug is delivered locally to a particular site of the body, the above-described drug delivery methods generally result in delivery of the drug throughout the body. Such a drug delivery method is not suitable for local delivery of a drug to a specific body tissue.

Therefore, other methods have been developed for drug delivery to specific body tissues such as Natural Orifice Transluminal Endoscopic Surgery (NOTES) and iontophoresis. 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 of penetrating an ion material into a skin using a DC current. In order to utilize a repulsive force acting between ions of the same polarity, ', And the ionic material having a negative characteristic is applied to the' - 'electrode so that the ionic material is easily penetrated 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. Accordingly, there is a need to develop an iontophoresis device capable of preventing itching, pain, burning, and erythema that may occur during the process of delivering a drug to the skin using an iontophoresis device having electrodes .

Korean Patent Publication No. 10-2014-0137860

One aspect includes a Reversed Electrodialysis (RED) cell that generates current through a difference in ion concentration between a high-concentration electrolyte solution and a low-concentration electrolyte solution; And a substance-containing portion connected to one surface of the electrode portion and including a substance having charge or polarity, wherein an electric current generated from the reverse electrodialysis cell portion flows through the substance containing portion, To an iontophoresis device capable of delivering an iontophoresis device.

In another aspect, the present invention provides a method for forming an iontophoresis device, comprising: supplying water to a chamber of the iontophoresis device to form a current between ions in the iontophoresis device; And delivering the substance in the substance-containing portion including the substance having charge or polarity to the object through the generated electric current.

One aspect includes a Reversed Electrodialysis (RED) cell that generates current through a difference in ion concentration between a high-concentration electrolyte solution and a low-concentration electrolyte solution; And a substance-containing portion connected to one surface of the electrode portion and including a substance having charge or polarity, wherein an electric current generated from the reverse electrodialysis cell portion flows through the substance containing portion, To an iontophoresis device.

Referring to FIG. 2, 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 a chamber (113, 114) at least partially defined (disposed between the cation exchange membrane and the anion exchange membrane) for receiving the electrolyte and for the cation exchange membrane (111) and the anion exchange membrane (112) The chamber 111 and the anion exchange membrane 112 may be alternately arranged such that the chamber 113 in which the electrolyte is highly concentrated and the chamber in which the electrolyte is contained in the low concentration are alternately arranged. One side of the substance-containing portion 120 including the charge or the substance having polarity may be in contact with the object S to which the substance is to be administered, so that the electric current generated from the reverse electrodialysis cell 110 is the substance Containing portion 120 to transfer the substance in the substance-containing portion 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, 114 within the negative ions (Cl ^-) is movable in a chamber 114 containing the electrolyte is at a low concentration then passes through the anion exchange membrane (112). The ions move in all of the cation exchange membrane 111, the anion exchange membrane 112 and the chambers 113 and 114, and an ion current is generated in the reverse electrodialyzer 110 to output a current. That is, the anion (Cl < ^- >) may be emitted to the anion exchange membrane 112 disposed at the lowermost portion of the battery. Thereafter, the anion (Cl ^- ) moves to the substance containing part (120) connected to the anion exchange membrane (112) disposed at the lowermost part of the electrode part and the anionic substance (D ^- ) contained in the substance containing part Lt; / RTI > Similarly, the cation (Na ⁺ ) moves to the substance-containing portion 120 connected to the cation exchange membrane 111 disposed at the end, so that repulsive force can act on the substance (D ⁺ ) of the cation contained in the substance- have. Therefore, for example, in the case of the substance containing section 120 connected to the cation exchange membrane 111 arranged at the lowermost part of the electrode section, the cation (D ⁺ ) can penetrate (transfer) the object through the skin, In the case of the substance containing part 120 connected to the anion exchange membrane 112 arranged at the lowermost part of the anion exchange membrane 112, the anion D ^- can penetrate (transfer) the substance through the skin. In addition, the voltage or current formed in the reverse electrodialysis unit can be controlled by adjusting the type and thickness of the cation exchange membrane, the anion exchange membrane, or the volume of the chamber. 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.

In one embodiment, the iontophoresis device may be a patch, or a patch form, for delivery of material through the skin. One side of the substance-containing layer 120 of the patch may be attached to the reverse electrodialysis cell 110 and the opposite side may be attached to a protective layer (not shown) and may include an adhesive material. Therefore, the patch can be adhered to the skin or the like when the protective layer is removed at the time of use. In addition, the shape of the patch may have any shape, for example, a shape such as a square, a circle, an ellipse, and a hexahedron.

As used herein, the term " Reversed Electrodialysis (RED) "may refer to the salinity gradient energy resulting from the difference in salt concentration between the two solutions, and in one embodiment, the iontophoresis device The current flowing through the resistor R may flow. Thus, the reverse electrodialysis cell unit may refer to a device that uses reverse electrodialysis to generate current. For example, in the present specification, the reverse electrodialysis cell unit 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.

In addition, since the iontophoresis device 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 device may be a current source for transferring a substance to a target object, and may include 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 by using the reverse electrodialysis cell portion. 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 cell unit 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 containing the high concentration of the electrolyte is higher than the amount of the electrolyte in the chamber containing the low concentration electrolyte. Lt; / RTI > The chamber in which the electrolyte is contained at a low concentration may also include an electrolyte-free chamber. For example, a chamber containing a high concentration of said electrolyte to form a flow of ions may comprise about 0.1 to about 20 mol / L, about 0.5 to about 15 mol / L, about 0.7 to about 10 mol / L, L, about 1.0 to about 2.0 mol / L, or about 1.2 to about 1.8 mol / L, and the chamber containing the electrolyte at a low concentration comprises 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 / And the ion concentration of the electrolyte solution in the chamber containing the electrolyte at a high concentration may be higher than the ion concentration of the electrolyte solution in the chamber containing the electrolyte at a low concentration. The amount of the electrolyte or the ionic concentration of the electrolyte solution in the chamber containing the high concentration of the electrolyte and the low concentration may be at least about 0.5 volts or more, for example, about 0.5 volt to about 15 volts, May be included at different amounts or concentrations of ions to output a voltage of about 10 volts, about 1.5 volts to about 8.0 volts, about 2.0 volts to about 6.0 volts, about 2.0 volts to about 4.0 volts, or about 2.0 volts to about 3 volts have. 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 is negatively charged, so that ions having a negative charge can pass ions having a positive charge without repelling them, and for example, can be a cation exchange membrane having a sulfone group. Conversely, the anion exchange membrane is positively charged, and ions having a positive charge can pass ions having a negative charge without repelling and passing them, and for example, they can be anion exchange membranes having tetravalent ammonium. Examples of the monomer forming the cation exchange membrane include sulfonic acid-type monomers such as 2- (meth) acrylamide-2-methylpropanesulfonic acid, 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 include N, N-dimethylaminoethyl (meth) acrylate, N, N-diethylaminodetyl (meth) N-diethylaminoethyl (meth) acrylate, N, N-dimethylaminoethyl (meth) acrylate / methyl chloride, ) Acrylate / methyl chloride (N, N-diethylaminoethyl (meth) acrylate / methyl chloride). The ion exchange capacity (IEC) of the cation exchange membrane or anion exchange membrane is about 0.5 meg / g or more, or about 1.0 meg / g or more, such as about 0.5 to about 20.0 meg / g, about 1.0 to about 10.0 meg / g, from about 2.0 to about 10.0 meg / g, and from about 5.0 to about 10.0 meg / g. Also, the permeation selectivity of the cation exchange membrane or anion exchange membrane can 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%. In one embodiment, the iontophoresis device may further comprise a spacer for separating the cation and the anion exchange membrane. The spacer may serve to prevent the ion exchange membranes from sticking to each other when the electrolyte solution is housed in the chamber. For example, the spacer may be formed of a polyhedron, a sponge, or a fabric made of polypropylene or polyethelon, .

The material containing portion may include any material known in the art if it is an ion conductive medium. The substance containing portion may include, for example, an aqueous solution or buffer solution, a hydrogel or a matrix containing or enclosing a substance having charge or polarity. The substance contained in the substance-containing portion 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. Examples of the object to which the substance-containing part is to be delivered in contact with the substance-containing part include humans and other mammals, and specifically, humans, monkeys, mice, rats, rabbits, sheep, Pigs, and the like.

The substance having a charge or polarity contained in the substance-containing portion may be a substance having charge or polarity by charging the substance in the ion-conducting medium in the substance-containing portion or by 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, arbutin, ethyl ascorbyl ether, oil soluble licorice extract, ascorbyl glucoside, ascorbyl tetraisopalmitate, They may include combinations thereof. Examples of the anti-wrinkle agent may include retinol, retinyl palmitate, adenosine, polyethoxylated retinamide, or a combination thereof. Examples of such agents include a complex agent selected from the group consisting of alkaloids, NSAIDs, alpha 2 adrenergic agonists, opioids, NMDA antagonists, GABA agonists, non-opioid central anesthetics and anti-inflammatory agents. Specifically, the alkaloid may include caffeine or nicotine. An NSAID and an alpha 2 adrenergic agonist, an NSAID and an opioid, an NSAID, an opioid and an alpha 2 adrenergic agonist, an NMDA antagonist, an alpha 2 adrenergic agonist and an NSAID, respectively. Also examples of such agents may include amorolfine, ascorbic acid, hyaluronate, argireline, or a combination thereof. For example, antiviral agents and anesthetics (e.g., opioids, topical anesthetics, capsaicin) may be included for viral diseases accompanied by pain and skin lesions such as herpes zoster or herpes. In addition, for cancer pain or chronic pain, for example, opioids and opioid antagonists may be included. The above-mentioned NSAID may be selected from the group consisting of acetaminophen, acelophenac, celecoxib, choline magnesium trisalicylate, diclofenac sodium, etodolac, fenoprofen, ibuprofen, indomethacin, ketoprofen, ketorolac, Tromethamine, rhonozolac calcium, meloxicam, naproxen, pyrosicam, rofecoxib, salcalate, sulindol, and tenoschim. The alpha 2 adrenergic agonist may include clonidine, tizanidine, medetomidine, paradomidine, and brimonidine. Opioids include but are not limited to morphine, codeine, fentanyl, alfentanil, sufentanil, remifentanil, hydro morphine, oxymorphin, hydrocodone, levorphanol, methadone, meperidine, buprenorphine, butorphanol, pentazocine and nalbuphine . NMDA antagonists may include ketamine, and dextromethorphan. GABA agonists may include midazolam, diazepam, lorazepam, and baclofen. Steroids may include prednisolone, dexamethasone, triamcinolone, betamethasone, diflucortolone, monometasone, methylprednisolone, hydrocortisone, clobetasol, clomethasone, clomethasone, and fluorocinolone. Non-opioid central anesthetics include tramadol, and antiviral agents may include acyclovir, palmclover, valacyclovir, and the like. Local anesthetics may include tetracaine, lidocaine, mefibacaine, bupivacaine, lopivacaine, levo-bupivacaine, and the like. Opioid antagonists may include naloxone and naltrexone. Further, the substance may be a protein, for example, a therapeutic 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.

3, the apparatus includes a second reverse electrodialysis cell 110 'and a second substance containing a substance having charge or polarity and connected to one surface of the second electrode unit 110' Section 120 '. In addition, the second 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 a chamber 113 ', 114' disposed between the cation exchange membrane 111 'and the anion exchange membrane 112' and containing an electrolyte, wherein the cation exchange membrane 111 'and the anion exchange membrane 112' And the chambers 113 'and 114' may be alternately arranged in a chamber 113 'containing a high concentration of electrolyte and a chamber 114' containing a low concentration of electrolyte. The reverse electrodialecting unit 110 and the second reverse electrodialecting unit 110 'are formed by a chamber containing a high concentration of salt bridges or electrolytes formed on the uppermost cation or anion exchange membrane of each of the cells, It may be connected. In addition, the ion exchange membranes connected to the substance containing section 120 and the second substance containing section 120 'may be ion exchange membranes having mutually opposite charges. For example, the ion exchange membrane connected to the substance containing section 120 is a cation exchange membrane, and the ion exchange membrane connected to the second substance containing section 120 'may be a cation exchange membrane and vice versa. In addition, it may be to deliver a substance having a positive charge or polarity or a substance having a negative charge or polarity to the object via the substance containing section 120 or the second substance containing section 120 ', respectively. For example, the substance-containing portion 120 may contain a substance having a positive charge or polarity, and the second substance-containing portion 120 'may include a substance having a negative charge or polarity. In one embodiment, by arranging the second reverse electrodialecting cell and the second substance containing portion in connection with the reverse electrodialysis cell and the substance containing portion, the ion flow can be improved and more substance can be delivered to the object .

3, the iontophoresis device may further include a container 115 for accommodating a reverse electrodialecting cell and a substance containing portion. The container 115 may be disposed to expose at least a portion of one surface of the material containing portion 120 that contacts the object while receiving the device. In this specification, the container 115 may mean that it serves to receive the device and to hold and support the components in each device. For example, the container 115 may be an adhesive tape (not shown) to prevent the solution in the chambers 113 and 114 from leaking. Also, a part of the container 115 is a spacer (not shown) and can serve as a spacer as described above. The container may be an insulator, and the reverse electrodialecting cell and the second reverse electrodialysis cell may be separated. As the material of the container, any material conventionally used may be used. Any material can be used, for example, cellophane, cellulose acetate, ethylcellulose, plasticized vinyl acetate-vinyl chloride copolymer, polyethylene terephthalate, nylon, polyethylene, polypropylene, polyvinylidene chloride, paper, .

Referring to FIG. 4, a specific example in which the iontophoresis device is activated is shown schematically. In one embodiment, as shown in FIG. 4A, as side walls of the chambers 113 and 114, at least a part of the side wall positioned between the cation exchange membrane 111 and the anion exchange membrane 112 is provided with a 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. 4B, water in the water supply portion 130 flows into the chamber through the water permeable membrane 140, whereby the above-described flow of ions can be formed, as shown in FIG. 4C . In addition to the water permeable membrane or water supply described above, the device can be activated through any means that creates a difference in electrolyte ion concentration in the chamber of the apparatus. 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. In addition, the chamber containing the electrolyte at a high concentration may accommodate a solid material containing a high concentration of electrolyte or a hydrogel containing a high concentration of electrolyte. In addition, the chamber in which the electrolyte is contained at a low concentration may be empty, or may contain a solid material containing a low concentration electrolyte or a hydrogel containing a low concentration electrolyte. 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 as described above, the solid material or the hydrogel is dissolved in water Thereby forming an electrolyte aqueous solution, so that the flow of ions can occur. 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.

5, the reverse electrodialecting cell 110, the substance containing unit 120, the second reverse electrodialecting cell 110 'and the second substance containing unit 120' (Not shown) formed at the bottom of the cation exchange membrane 111 or the anion exchange membrane 112 at the lowermost part of each repeating unit or a chamber 113 containing a high concentration of electrolyte ≪ / RTI > In addition, the substance-containing portion 120 may not be disposed in the lowermost cation exchange membrane 111 or the anion exchange membrane 112 to which the respective repeating units are connected. In addition, the number of repeating units may be 2 to 10, for example, 2, 3, 4, or 5.

Further, in another embodiment, the iontophoresis device may comprise a control for controlling the flow of ions. The control unit may be disposed at a portion connecting the reverse electrodialysis unit and the second reverse electrodialysis unit, or at a portion connecting each of the repeated units. The control unit may include a switch device, a pH sensor, or a salt sensor. For example, the sensor may sense the flow of ions or the output of current in the device to regulate the flow of ions or the output of current through the switch device. The control unit may contain information on the transfer characteristics of the substance (drug) contained in the substance-containing part to the skin. For example, the control unit may include a microprocessor having data on the iontophoresis characteristic for a specific substance (drug) included in the iontophoresis device. The data includes correlations between these conditions and delivery rates when a particular substance (drug) is delivered into the body through the skin by an ionophore system as described above under conditions of flow of a specific current and / or ion . The microprocessor may include a control algorithm according to the transfer characteristics of the substance contained in the substance containing part to the skin. Alternatively, the object or physician may determine the basal administeration level of the substance (drug), i.e., the intensity of the baseline current, according to the data contained in the microprocessor, and administer the substance (drug) . When the necessity of additional administration to the subject occurs during the administration of the substance according to the basic administration rate, for example, when the subject has pain and the substance (drug) administered at the basic rate is an analgesic agent, If the pain is not reduced by the basal administration, additional substance (drug) delivery may be provided. In this case, the condition of the substance (drug) delivery can be determined based on the correlation between the substance (drug) administration condition stored in the microprocessor and the administration rate. The controller may be configured to adjust the intensity of current supplied to the user's skin. The intensity of the current does not necessarily have to be automatically adjusted, but may be such that the intensity of current can be adjusted according to the needs of the patient or the operator. In addition, the controller may be configured to automatically turn on / off the current supplied to the user's skin at predetermined time intervals. The configuration of the electric circuit performing the current control function as described above will be apparent to those skilled in the art and will not be described in further detail herein.

In another embodiment, the iontophoresis device may include a display portion electrically connected to the control portion. The display unit may display an amount of a substance (drug) to be administered under specific conditions, a rate, and a remaining amount of a substance (drug) according to the data included in the control unit. The display portion includes any display device known in the art. For example, it may be an LCD, a PDP, a bank tube, an LED, or the like. In an embodiment of the present invention, a display unit is connected to the control unit, and the display unit displays the amount of the substance (drug) to be delivered, the amount of the substance (drug) The amount of the substance to be delivered (drug), and the amount of the substance to be delivered (drug). The doctor or physician may determine whether to further administer or discontinue the substance (drug) based on the dose of the substance (drug) displayed on the display section, the rate of administration, and the like.

In another aspect, the present invention provides a method for forming an iontophoresis device, comprising: supplying water to a chamber of the iontophoresis device to form an electric current by forming a flow of ions by a cation or an anion exchange membrane between adjacent chambers, The method comprising delivering a substance in a substance containing section comprising a substance having a specific activity to a subject.

In one embodiment, a method of delivering a substance to a subject includes generating a flow of ions between adjacent chambers in a chamber containing a high concentration of electrolyte and a low concentration of electrolyte; Generating a current by the flow of ions; And transferring the substance in the substance-containing portion including the substance having charge or polarity to the object by the generated electric current. The method may further comprise the step of supplying an aqueous solution to the chamber before generating the flow of ions between adjacent chambers to generate a difference in ion concentration of the electrolyte solution in the chamber. Thus, a method according to one embodiment includes generating an electrical current using reverse electrodialysis; And transferring the substance in the substance-containing portion containing the substance having charge or polarity to the object by the generated electric current.

The iontophoresis device and configurations that may be included therein are as described above.

In one embodiment, the method may further comprise the step of contacting the iontophoresis device with the object. The contacting step may be performed before or after the step of generating a difference in the electrolyte ion concentration between the chambers, or the step of generating the current by forming the flow of ions between the adjacent chambers.

The step of generating the current may be generated by the flow of ions formed by the difference in ion concentration of the electrolyte solution in two or more chambers as described above. For example, the reverse electrodialysis as described above may be used Thereby generating an electric current.

The method may be without the step of supplying power to deliver the substance to the subject. For example, the method may be such that there is no step of supplying power to deliver the substance to the object, except for the reverse electrodialysis cell part introduced into the iontophoresis device.

According to one aspect, an iontophoresis device and a method of delivering a substance can improve the delivery of drug through the skin and can occur in the process of delivering the drug to the skin using an iontophoresis device equipped with an electrode Itching, pain, burning, and erythema can be prevented.

1 is a schematic view of a conventional iontophoresis device.
FIG. 2 is a schematic diagram illustrating a reverse electrodialysis cell and a containing portion of an iontophoresis device according to an embodiment.
FIG. 3 is a schematic diagram illustrating a reverse electrodialysis cell and a containing portion of the iontophoresis device according to one embodiment.
4 is a diagram illustrating the activation principle of the iontophoresis device according to one embodiment.
FIG. 5 is a diagram illustrating a reverse electrodialysis cell and a containing portion of the iontophoresis device according to one embodiment.

Hereinafter, the present invention will be described in more detail with reference to examples. However, these examples are for illustrative purposes only, and the scope of the present invention is not limited to these examples.

Example : Iontophoresis  Fabrication of devices and drug delivery using them

One. Iontophoresis  Production of devices

An iontophoresis device using reverse electrodialysis was prepared by the following method.

(AEM) and anion exchange membrane (CEM) (ASAHI GLASS CO. Product Name: CMV (cation exchange membrane), AMV (anion exchange membrane) ). The double-sided tape with the exchange membrane was piled up in such a way that the AEM and the CEM were stacked alternately, and the top of the patch was attached with a double-sided tape having a large hole instead of the two holes. The bottom of the patch was coated with a hydrogel containing the drug to be injected to prepare an iontophoresis device.

2. Iontophoresis  Drug delivery with devices

The drug delivery efficacy in the rat was confirmed using the patch prepared above.

Specifically, Ketoprofen (Sigma Aldrich, Lot # SLBH0842V), an anti-inflammatory analgesic, was administered at a dose of 0.43 mg / cm ² The patched patch patch was attached to three rats (Orient, SD variety. ~ 250g). As a control, a blank patch prepared in the same manner as the above-mentioned patch was applied in the same manner, and the patch was attached to three rats. The general patch is a patch using a simple spreading method. Blood of the rats was collected at 1 hour, 2 hours, 4 hours, 6 hours, 8 hours, 12 hours and 24 hours after the patches of the test group and the control group were attached to the rats, chromatography, high performance liquid chromatography) method, and the results are shown in FIG.

6 is a graph showing the drug delivery efficiency of the iontophoresis device according to one embodiment.

delete

As shown in FIG. 6, it was found that the iontophoresis device according to one embodiment delivered about two times more drug than the control. Also, when using the iontophoresis device according to one embodiment, it was found that the time required to reach the highest drug concentration of the control patch was only one hour. Therefore, it can be confirmed that the iontophoresis device according to one embodiment can deliver more drugs to the subcutaneous blood vessels through the skin.

100: iontophoresis device 110: reverse electrodialysis cell
111: Cation exchange membrane 112: Anion exchange membrane
113, 114: chamber 115: container
120: Adhesive part 130: Water supply part
140: Water permeable membrane

Claims (24)

First and second reversed electrodialysis (RED) cells for generating a current through a difference in ion concentration between the high-concentration electrolytic solution and the low-concentration electrolytic solution; And
And a first material containing portion and a second material containing portion connected to one surface of the first and second reverse electrodialecting cell portions and including a substance having charge or polarity,
And an electric current generated from the first and second reverse electrodialysis cell units flows through the first and second substance containing portions to transfer the substances in the first and second substance containing portions to the object, ) Apparatus,
The first reverse electrodialecting cell unit and the second reverse electrodialysis cell unit each include a cation exchange membrane; An anion exchange membrane disposed apart from the cation exchange membrane; And a chamber which is at least partly defined with respect to the cation exchange membrane and the anion exchange membrane and accommodates an electrolyte, wherein the cation exchange membrane and the anion exchange membrane are alternately arranged, and the chamber comprises a chamber containing a high concentration of electrolyte and an electrolyte The chambers containing low concentration are alternately arranged,
The first reverse electrodialysis cell and the second reverse electrodialysis cell are connected by a chamber containing a salt bridge or an electrolyte formed on the uppermost cation or anion exchange membrane of each cell,
Further comprising a control unit disposed at a portion connecting the first reverse electrodialysis cell unit and the second reverse electrodialysis cell unit and for controlling the flow of ions. delete The iontophoresis device of claim 1, wherein the first and second electrodialysis cell units are the only current sources for delivering the material to a target. The chamber according to claim 1, wherein the electrolyte is contained in an electrolyte solution, the chamber containing the electrolyte at a high concentration comprises an ion concentration of the electrolyte solution of 0.1 to 20 mol / L, Or an ion concentration of the electrolyte solution in the range of 0.1 to 20 mol / L, and the ion concentration of the electrolyte solution in the chamber containing the electrolyte at a high concentration is not more than the ion concentration of the electrolyte solution in the chamber containing the electrolyte at a low concentration Lt; RTI ID = 0.0 > Ion < / RTI > The iontophoresis device according to claim 1, wherein the chamber in which the electrolyte is contained at a high concentration and the chamber in which the electrolyte is contained at a low concentration includes an electrolyte of different amount or ion concentration so as to output a voltage of from 0.5 volt to 15 volts. . The iontophoresis device of claim 1, wherein the iontophoresis device is a patch for delivery of material through the skin. The iontophoresis device of claim 1, wherein the cation or anion exchange membrane has an ion exchange capacity (IEC) of greater than or equal to 0.5 meg / g and a permeance selectivity of greater than or equal to 70%. The iontophoresis device according to claim 1, wherein the electrolyte is any one selected from the group consisting of NaCl, MgCl ₂ , AgCl, CuCl _2, CaCl _2, and combinations thereof. The chamber according to claim 1, wherein the chamber containing the electrolyte at a high concentration contains a solid material containing a high concentration electrolyte or a hydrogel containing a high concentration electrolyte, or the chamber containing the electrolyte at a low concentration may contain an empty or low concentration electrolyte Or a hydrogel containing a low concentration of electrolyte. ≪ RTI ID = 0.0 > Ion < / RTI > delete The iontophoresis device according to claim 1, wherein the ion exchange membranes connected to the first substance containing portion and the second substance containing portion are ion exchange membranes of mutually opposite charges. The iontophoresis device according to claim 1, wherein the iontophoresis device transfers a substance having a positive charge or polarity or a substance having a negative charge or polarity to the object through the first substance containing portion or the second substance containing portion, respectively Iontophoresis device. The method according to claim 1, wherein a plurality of repeating units including the first reverse electrodialecting cell unit and the first substance containing unit and the second reverse electrodialecting cell unit and the second substance containing unit are connected, And a chamber containing a high concentration of a salt or electrolyte formed under the lowermost cation or anion exchange membrane of the iontophoresis device. delete The container according to claim 1, further comprising a container for accommodating the first and second reverse electrodialecting cell units and the first and second substance containing portions, wherein the container has one surface of the first and second substance- Is exposed to expose a portion of the iontophoresis device. The iontophoresis device according to claim 1, further comprising a spacer for separating the cation and the anion exchange membrane. 2. The iontophoresis device of claim 1, wherein the first and second substance containing portions are or contain hydrogels containing the substance. The iontophoresis device of claim 1, wherein the material is a whitening agent, a wrinkle remover, a medicament, or a combination thereof. [Claim 19] The method of claim 18, wherein the whitening agent is selected from the group consisting of mulberry extract, arbutin, ethyl ascorbyl ether, oil soluble licorice extract, ascorbyl glucoside, ascorbyl tetraisopalmitate or a combination thereof and wherein said wrinkle remover is retinol, retinyl palmitate, adenosine, polyethoxylated retinamide or a combination thereof, said medicament being selected from the group consisting of lidocaine, ketopro Wherein the iontophoresis device is selected from the group consisting of a pen, nicotine, caffeine, Amorolfine, Fentanyl, Ascorbic acid, Hyaluronate, Argireline or a combination thereof. Supplying water to the chamber of the iontophoresis device of claim 1 to generate a current between ions in the iontophoresis device by forming a flow of ions by the cation or anion exchange membrane between adjacent ones of the chambers;
And delivering the substance in the first and second substance-containing portions including the substance having charge or polarity through the generated electric current to the object. The method of claim 20, further comprising contacting the iontophoresis device of claim 1 to a target. 21. The method of claim 20 wherein there is no step of supplying power to deliver a substance to a subject except for the first and second reverse electrodialytic cell portions introduced into the iontophoresis device. The method according to claim 20, wherein the electrolyte is contained in an electrolyte solution, the chamber containing the electrolyte at a high concentration comprises an ion concentration of the electrolyte solution of 0.1 to 20 mol / L, Or an ion concentration of the electrolyte solution in the range of 0.1 to 20 mol / L, and the ion concentration of the electrolyte solution in the chamber containing the electrolyte at a high concentration is not more than the ion concentration of the electrolyte solution in the chamber containing the electrolyte at a low concentration / RTI > 14. The iontophoresis device according to claim 13, further comprising a control section for controlling the flow of ions, and the control section is disposed at a part connecting the respective repeating units.

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