JP4477865B2 - Iontophoresis device - Google Patents

Description

  The present invention relates to an iontophoresis device for noninvasively taking out in vivo components from a living body.

  2. Description of the Related Art Conventionally, a method for noninvasively diagnosing from outside the body using ultrasound, CT scan, X-ray, or the like is known. In addition to this, a method of taking blood invasively and measuring enzymes, proteins, sugars, lipids, antibodies, antigens and the like contained therein is also widely used. However, since this method is invasive, there is a problem that it is painful at the time of puncture, or that there is a possibility that infection will occur from the puncture site thereafter.

On the other hand, for example, Patent Document 1 discloses an apparatus that non-invasively measures a glucose concentration in a living body using iontophoresis.
This device attaches an electrode to the skin and passes an electric current to generate a flow of ions and water in the electrode-skin-in-vivo-skin-electrode path, and the in-vivo glucose is extracted by this flow. Is to measure. As a result, diabetes diagnosis and blood glucose level monitoring can be performed. In this case, an electrode can be attached to the mucous membrane such as the oral cavity instead of the skin. Moreover, this apparatus can detect and quantify an extracted substance by providing a sensor device.
Japanese National Patent Publication No. 10-506293

Patent Document 2 discloses an iontophoresis device structure and a method for detecting in-vivo components.
This device is equipped with an applicator having a detection member configured to adsorb in vivo components by iontophoresis, and is applied to the skin or mucous membrane for immunology of in vivo components moved by iontophoresis. Detection by chemical or chemical methods. In this method, qualitative measurement can be performed by, for example, the color density and the number of stained cells by processing the detection member to which the in vivo component is adsorbed.
Japanese Patent Laid-Open No. 11-347014

  By the way, the skin has a barrier function to prevent the invasion of foreign substances from the outside, and also plays a role to prevent the volatilization of moisture in the living body. Extraction is not sufficient and there are problems in measurement error and sensitivity. The iontophoresis device described above can be applied not only to the skin but also to the mucous membrane, but the device structure particularly suitable for application to the mucous membrane is not shown. Unlike the case of skin, attaching an electrode for iontophoresis to a mucous membrane such as the oral cavity is a heavy burden for a person who wears it, and thus it is desirable to reduce this burden in practice.

  Accordingly, an object of the present invention is to provide an iontophoresis device suitable for use in mucous membranes for noninvasively taking out in vivo components from the living body.

An object of the present invention is an iontophoresis device for noninvasively taking out in-vivo components from a living body, comprising a plurality of electrode structures and a power supply device connected to the electrode structure, One of the electrode structures has an in-vivo component extraction pad to be applied to the mucous membrane, and the time for applying electrical energy to the living body by the power supply device is set to 30 seconds to 20 minutes. Achieved by an iontophoresis device. Here, the electrode structure having the in vivo component extraction pad can include an ion exchange resin or an ion exchange membrane. In addition, the electrode structure having the in vivo component extraction pad can be provided with a device for quantifying the in vivo component or a device for qualitative measurement. This in vivo component may be a drug administered for treatment.
Furthermore, an iontophoresis device according to the present invention includes two electrode structures, a fixing member that fixes each electrode structure, and a spring provided between the fixing members that are rotatably arranged to cross each other. A member and a power supply device connected to each of the electrode structures, wherein at least one of the electrode structures has an in vivo component extraction pad to be applied to the mucous membrane. One of the electrode structures may be an electrode structure on the oral mucosa application side, and the other may be an electrode structure on the skin application side.

The in vivo component analysis method according to the present invention is a method for non-invasively extracting and analyzing an in vivo component using iontophoresis. Applied to the mucous membrane, applies electrical energy to the living body through iontophoresis through the pad for 30 seconds to 20 minutes, quantifies in vivo components extracted by the pad, or qualitatively measures is there. Here, the in vivo component extraction pad can be applied to the oral mucosa, and can be used, for example, for extraction of glucose.
By configuring in this way, it can be used for mucous membranes, particularly oral mucosa, for non-invasive extraction of in vivo components such as biologically derived components and administered drugs from the living body for quantitative or qualitative evaluation. A suitable iontophoresis device can be obtained.

  ADVANTAGE OF THE INVENTION According to this invention, the iontophoresis apparatus suitable for using for a mucous membrane for taking out in-vivo components non-invasively from the living body can be obtained.

  FIG. 1 is a diagram showing an embodiment of an iontophoresis device according to the present invention. This device is provided between an electrode structure 11 on the oral mucosa application side, an electrode structure 12 on the skin application side, fixing members 13 and 14 of each electrode structure, and a fixing member disposed so as to be rotatably intersected. A spring member 15 provided and a power supply device 16 connected to each electrode structure 11, 12 are provided.

  FIG. 2 is a schematic view showing an example of the electrode structure 11 on the oral mucosa application side, where (a) is a plan view, (b) is a sectional view, and (c) to (e) are other sectional views. As shown in FIGS. 2A and 2B, the electrode structure 11 includes an extraction pad 21 for extracting a biological component (substance), a ring portion 22 surrounding the extraction pad, an extraction pad and a ring. A support 24 that supports the electrode, an electrode part 25 disposed between the extraction pad and the support, and an electrode terminal 26 connected to the electrode part. The extraction pad 21 collects in vivo components extracted from the mucous membrane. The ring portion 22 is necessary to securely fix the extraction pad 21 so that it does not come off. The electrode terminal 26 has a series of structures with the electrode portion 25 immediately below the extraction pad, and is covered with an insulator 27 except for the portion connected to the power supply device.

  Examples of the material for the extraction pad 21 include fibers such as nonwoven fabric, gauze, and absorbent cotton, agar, gelatin, polyacrylic acid and salts thereof, polyvinylpyrrolidone and a copolymer of polyvinylpyrrolidone and vinyl acetate, methylcellulose and derivatives thereof, Pectin, polyethylene oxide, methyl vinyl ether maleic anhydride copolymer, polyvinyl alcohol and derivatives thereof or saponified products thereof, acrylic, silicon-based, SlS-based, SBS-based, urethane-based, natural rubber-based pressure-sensitive adhesive, and mixtures thereof, These tackifiers may contain a tackifier such as rosin, hydrogenated rosin, rosin ester, terpene resin, terpene phenol resin, petroleum resin, coumarone resin, coumarone-indene resin. Such a thing is mentioned, However It is not limited to this. Among these, it is desirable to use an aqueous base.

  It is preferable to provide an ion exchange resin or an ion exchange membrane in the extraction pad 21 or at another appropriate position. In FIG. 2 (c), the ion exchange resin 28 is dispersed and / or mixed in the extraction pad 21. In FIG. 2 (d), the ion exchange membrane 29 is disposed in the extraction pad 21 in parallel with the electrode portion 25. This is provided to separate the extracted in-vivo component from the electrode unit 25 because the extracted in-vivo component may affect the determination when it comes into contact with the electrode unit 25. As the ion exchange resin, a cation exchange resin or an anion exchange resin can be used.

  Examples of the cation exchange resin include Amberlite XT-1004, IR120B, IR-122, IR-124, 252, XT-1031, 200C, IRC-50, IRC-76 (manufactured by Organo), Diaion SK-1B, SK-104, SK-110, PK-208, PK-216, WK-10, WK-11, WK-20 (manufactured by Mitsubishi Kasei), Dowex HCR-S, HGR-W2, 88, MWC-1H (Dow・ Chemical), Duolite C-20, C-26, C-264, C-3, C-433, C-464 (Rohm & Haas), Imac C-12, C-16P, Z-5 , GT-73, Lewatit S-100, SP-112, SP-120, S-109, CNP-80 (manufactured by Bayer) or inorganic ions Exchangers such as Bio-Rad ZP-1, ZM-1, ZT-1, AMP, KCF-1, HZO-1, HTO-1 (manufactured by Bio-Rad), AMD-Erba, HMD-Erba, HAP-Erba, ZPH-Erba, TDO-Erba, COX-Erba, AAO-Erba, CUC-Erba, CUS-Erba (manufactured by Carlo Erba), Zerwat, Relaxation Z (manufactured by Dia-Prosim 100), Ionac C, , C102, M-50 (manufactured by Ionac. Chem. Comp.), Decalsco (F, Y), Zeo-Dur, Zerolite Green Sand (manufactured by Permit), IXE-300, IXE-400, IXE-100, IXE -500, IXE-1000 (Toa Gosei Chemical) (Manufactured by Kogyo Co., Ltd.).

  Examples of the anion exchange resin include Amberlite IRA-400, IRA-401, IRA-402, IRA-420, XT-5007, IRA-900, IRA-904, IRA-938, IRA-458, IRA-958, IRA-410, IRA-411, IRA-416, IRA-910, IRA-68, IRA-35 (manufactured by Organo), Diaion SA-10A, SA-11A, SA-12A, PA-306, PA-312, PA -318, SA-20A, SA-21A, PA-406, PA-412, PA-418 (manufactured by Mitsubishi Kasei), Dowex SBR, SBR-P, 11, MSA-1, SAR, MSA-2, 66, WGR-2 (manufactured by Dow Chemical Company), Duolite A-113 plus, A-147, A-16 , A-132, A-116 plus, A-162, A-368, A-7 (made by Rohm & Haas), Imac A-34, A-33, A-31, A-32, A205, A- 28, Lewatit M-500, MP-500, AP-247A, M-600, MP-600, MP-62, OC-1059, CA-9222 (manufactured by Bayer), cholestyramine and the like are used. In the present invention, any of these is used, but an anion exchange resin is preferably used, and more preferably a quaternary ammonium salt containing chlorine ions in the anion exchange resin. In addition, styrene, acrylic, methacrylic and the like are generally used as the polymer substrate. However, the polymer substrate is not limited to these, and any polymer substrate for ion exchange resin may be used. In addition, a soluble resin or a hardly soluble resin can be used as long as the functionality is not affected.

  As the ion exchange membrane, a cation exchange membrane or an anion exchange membrane can be used. Examples of the cation exchange membrane include those containing a sulfone group in a copolymer of divinylbenzene and styrene. Examples of the anion exchange membrane include those containing an amino group in a copolymer of divinylbenzene and styrene.

  Moreover, the electrode structure 11 can be equipped with the apparatus which quantifies the in-vivo component, or the apparatus which measures qualitatively. Examples of the device for quantifying in vivo components include a glucose sensor. Examples of the apparatus for qualitatively measuring in-vivo components include a general antigen-antibody sensor.

  In FIG.2 (e), a glucose sensor is provided in the electrode structure on the oral mucosa application side. The glucose sensor has at least two electrodes 41, 42 and a detector 43 connected between the electrodes. Glucose oxidase (GO) is immobilized on one surface (for example, electrode 41) of the two electrodes 41,. When the iontophoresis device is energized for a predetermined time, glucose (G) is extracted from the oral mucosa to the extraction pad 21. Here, glucose is oxidized by the catalytic action of glucose oxidase on the electrode 41 on which glucose oxidase is immobilized, and electrons are generated at this time. By detecting this as a potential difference between the electrodes 41 and 42 with the detector 43, glucose can be quantified. The detector 43 includes circuits for amplification, calculation, display, and the like of a potential difference, and these circuits can be mounted on a common substrate with the power supply device 16. In addition, the antigen-antibody sensor can be configured in the same manner.

Applying a current density of iontophoresis is used as an electrical energy extraction efficiency, 0.01～2MA terms of skin irritation due to the current / cm ² C., preferably from 0.05～1MA / cm ^2. The voltage at this time is 50 V or less, preferably 20 V or less, more preferably 10 V or less. Although there is no limitation in particular as an electricity supply pattern, DC, a pulse, or pulse depolarization etc. which are generally used are mentioned. The material of the electrode part is not particularly limited, and examples thereof include platinum, gold, and carbon. Silver can be used for the anode and silver / silver chloride can be used for the cathode. The electrode material is preferably carbon from the viewpoint of cost, and silver and silver / silver chloride are preferable from the viewpoint of not causing pH change by energization.

  3A and 3B are schematic views showing an example of the electrode structure 12 on the skin application side, where FIG. 3A is a plan view and FIG. 3B is a cross-sectional view. The electrode structure 12 includes a control pad 31 that is paired with the extraction pad 21 described above, a ring portion 32 that surrounds the extraction pad, a support 34 that supports the control pad and the ring portion, and a space between the control pad and the support. And an electrode terminal 36 connected to the electrode part. The electrode terminal 36 is covered with an insulator 37.

  As the material of the control pad 31, the same material as that in the above-mentioned electrode structure 11 on the oral mucosa side can be used. In this case also, it is desirable to use an aqueous base.

  This iontophoresis device is used as follows. In FIG. 1, first, the ends of the fixing members 13 and 14 are expanded against the tensile force of the spring member 15. Accordingly, the gap between the electrode structures 11 and 12 is increased, so that the electrode structure 11 is brought to the oral cavity side, and the electrode structure 12 is brought to the cheek side, and both electrode structures are pulled by the tensile force of the spring member 15. And fix with cheeks. Here, the electrode structure 11 is applied to the oral mucosa, and the electrode structure 12 is applied to the cheek skin. Thereafter, the operation of the power supply device 16 is started, and electrical energy is loaded on the living body via the electrode structures 11 and 12. The load time of electrical energy by the power supply device 16 will be described later. After loading the electric energy for a predetermined time, the operation of the power supply device 16 is stopped and the iontophoresis device is removed from the living body. Then, the in-vivo component extracted by the extraction pad 21 of the electrode structure 11 is analyzed. The method for measuring the extracted in-vivo component is not particularly limited, but can be measured by an enzymatic reaction or electrochemically. These measuring devices may be attached to the extraction pad or may be arranged outside the extraction pad.

  The in vivo component extracted by iontophoresis is desirably ionic, but is not limited thereto. As long as it dissolves in water, it is extracted according to the flow of water generated by energization, so glucose and the like can be extracted. In particular, glucose measurement is essential for diabetic patients, and frequent measurement is required, so that the apparatus of the present invention is very useful.

  In addition, blood concentration measurement of substances in the living body is necessary not only for substances derived from living bodies for diagnosis but also for drugs (physiologically active substances) and their metabolites administered from outside the body. There is. In fact, in the field of medicine, therapeutic drug monitoring (TDM: Therapeutic) is used for drugs (physiologically active substances) that have little difference in the effective therapeutic blood concentration of drugs (bioactive substances) and their metabolites and their side effects. Measurement of blood concentration after drug administration is called drug monitoring. However, in order to measure the blood concentration of a drug or the like in the blood, blood collection by puncture is necessary, and it has been a heavy burden on the patient to perform this frequently. The present invention extracts an in-vivo drug or the like without puncturing, and is an effective method that does not place a burden on the patient.

  Examples of drugs that perform TDM using the device of the present invention include ethosuximide, carbamazepine, clonazepam, diazepam, nitrazepam, sodium valproate, phenytoin, phenobarbital, primidone and other antiepileptic drugs, chlorpromazine, haloperidol and other psychotropic drugs, Antidepressants such as amitriptyline hydrochloride, imipramine hydrochloride and maprotiline hydrochloride, antidepressants such as lithium carbonate, bronchodilators such as aminophylline, choline theophylline and theophylline, cardiac glycosides such as digoxin and digitoxin, aprindine, quinidine, disopyramide, Antiarrhythmic drugs such as procainamide, mexiletine and lidocaine, antibacterial drugs such as amikacin sulfate, gentamicin sulfate and tobramycin, immunosuppressive drugs such as cyclosporine, antipyretic analgesic and anti-inflammatory drugs such as aspirin Dried and concentrated human antithrombin III, dipyridamole, ticlopidine, anti-thrombotic agents such as heparin sodium and the like. The present invention can be used for the measurement and prediction of the blood concentration of the drug as described above, but is not limited thereto.

  By the way, in iontophoresis, when application to the skin and mucous membrane is compared, the permeability of the substance is higher in the mucosa than in the skin. For example, in an example using calcitonin as a model compound, absorption from the mucous membrane is about 6 times higher than in the case of skin. This is true not only when a drug is administered from the skin or mucous membrane, but also when an in vivo component is extracted from the skin or mucous membrane. That is, when the same current is applied using iontophoresis, more in-vivo substances can be extracted through the mucosa than through the skin. Furthermore, when the resistance of skin and mucous membrane was measured, the skin was 4.5 times higher. Therefore, if the upper limit of the voltage is considered to be the same, a 4.5 times higher current can be applied. That is, by changing the extraction site from the skin to the mucous membrane, it is possible to shorten the energization time and improve the accuracy in terms of permeability and resistance. Even when the in vivo components are taken out through the skin, some in vivo components can be taken out and quantified by energization for 15 minutes. The longer the energization time is, the more in-vivo components can be extracted. However, by applying the mucous membrane to the application site as in this iontophoresis device, the energization time is reduced to 1 minute or less as follows. Is possible.

That is, as described above, the extraction time through the skin requires 15 minutes, the skin resistance is 4.5 times higher than the mucosal resistance, and the absorption from the mucosa is in the case of skin The extraction time through the mucosa is about 6 times higher than
15 × 60 / (4.5 × 6) = 33.333 (about 30 seconds)
Necessary. Therefore, the load time of electrical energy in the present iontophoresis device applied to the mucous membrane is at least 30 seconds.

  On the other hand, since the present iontophoresis device is applied to the mucous membrane, mainly the oral mucosa, the shorter the application time, the better. Therefore, the invasive measurement method for collecting blood with a currently used needle was compared with a device applied to the oral mucosa, and a preferable application time was examined. As shown in the experimental examples to be described later, if the maximum time that can be applied at one time is 20 minutes or less, it is the same as the current invasive measurement method or better than the invasive measurement method, but it is necessary to shorten the time ( It was easy to use but could not be said to be good), and the overall result was slightly better. If it is 15 minutes or less, it is better than the invasive measurement method, but the time is required to be shortened (it is easy to use but not good), and it can be said that it is superior to the present. Furthermore, if it is 10 minutes or less, there is an opinion that “it is superior to invasive measurement methods. By shortening the application time to 5 minutes, 2 minutes, and 1 minute, it can be said that the ratio of being superior to the present is increased and it is quite excellent. Further, assuming use outside the home, if it was not less than 5 minutes, there was no person to use, and the desired application time was 2 minutes or less, more desirably 1 minute or less. That is, the application time is preferably 20 minutes or less, preferably 10 minutes or less, more preferably 5 minutes or less, more preferably 2 minutes or less, and most preferably 1 minute or less.

(Experimental example)
Example 1
An iontophoresis device applied to the oral mucosa as shown in FIG. 1 was used to apply to 10 persons, and the applicable time was examined. At this time, it was not actually energized, and it was investigated how long it could be applied. As an index of time, it was compared with the measurement of glucose by invasive blood sampling that is currently most used (conventional method).
Results of Example 1 Table 1 shows the results.

  As shown in Table 1, when this apparatus is applied for 30 minutes, 6 out of 10 people feel that the application time is too long, and the conventional method is simple (the invasive measurement method is better) It was. The four responded that they had almost the same ease of use (equivalent to an invasive measurement method) because they were painless, although the time was long. Overall, it cannot be said that 30-minute application is effective. When applied for 20 minutes, there are 8 people who feel almost equivalent (equivalent to invasive measurement method), and 2 people who answered that it is better than the conventional method (invasive measurement method). The result was slightly better. Furthermore, in the application for 15 minutes, half of the results were equivalent to the conventional method, and the remaining half were better than the conventional method. If it is applied for 10 minutes, most people have answered that it is superior to the conventional method. In less than 5 minutes, the number of people who answered that it was superior to the conventional method and that it was easier to use was 6 people, and in 2 minutes or less, this number increased to 8 people. By setting it to 1 minute or less, all 10 responded that it was superior to the conventional method and was easier to use.

Example 2
Using the same apparatus as in Example 1, a survey on application time was performed assuming use outside the home. If the device of the present invention is used outside the home, how long should it be used? It was also examined how many minutes the appropriate application time was.
Results of Example 2 Tables 2 and 3 show the results.

  As shown in Table 2, the maximum allowable time was 5 minutes. Further, as shown in Table 3, the preferred application time was 1 person for 2 minutes or less and 9 persons who answered 1 minute or less.

Example 3
Beagle dogs under pentobarbital anesthesia, anode electrode pad containing 1000 units of salmon calcitonin (pad for extraction of electrode structure on the oral mucosa application side) to oral mucosa, cathode electrode (control pad for electrode structure on the skin application side) Applied to the ear. A 0.2 mA current was applied for 30 minutes from a pulse depolarizing iontophoresis device, and the salmon calcitonin concentration in the blood was measured after 30 minutes. Quantification was performed using an RIA kit (ROIK6003, Peninsula).
Comparative Example 1
In the same manner as in Example 3, a beagle dog was administered with salmon calcitonin under pentobarbital anesthesia. However, the anodic electrode pad was not applied to the oral mucosa but applied to the skin (abdomen). The cathode electrode was applied to the ear. Other conditions were the same as in the example.

Results of Example 3 and Comparative Example 1 FIG. 4 is a graph showing blood concentrations 30 minutes after application of the present apparatus to the oral mucosa (Example 3) and skin (Comparative Example 1). When salmon calcitonin was administered to dogs from the oral mucosa (Example 3), the blood concentration after 30 minutes was about 530 pg / ml, whereas when administered from the skin (Comparative Example 1) About 90 pg / ml. It is said that calcitonin is ionized in a large amount and permeated by a flow of water (convective flow) generated at that time rather than permeated by a direct electric driving force of iontophoresis. Therefore, although the direction is different, even a non-ionized in vivo component such as glucose shows about 6 times higher permeability when permeated (extracted) from the mucosa.

Example 4
Using a conductive gel, a direct current of 0.2 mA was applied to the dog oral mucosa, and the resistance was measured.
Comparative Example 2
Using a conductive gel, a direct current of 0.2 mA was applied to dog skin, and the resistance was measured.

Results of Example 4 and Comparative Example 2 FIG. 5 is a graph showing resistance in the oral mucosa (Example 4) and skin (Comparative Example 2), respectively. As a result of measuring the resistance of the oral mucosa in Example 4, it was about 8 KΩ, whereas it was about 36 kΩ on the skin. The skin resistance was about 4.5 times higher than the oral mucosal resistance. Therefore, when this apparatus is applied to the mucous membrane at the same voltage as that of the skin, a 4.5 times higher current can be loaded, and more in vivo components can be extracted.

  As described above, the present invention is a device for non-invasively taking out in-vivo components from a living body for diagnosis, and extracts from the transmucosal membrane using electrical energy. In this case, the time for applying the electric energy for extraction is preferably about 30 seconds to 20 minutes, more preferably about 30 seconds to 15 minutes, and about 30 seconds to 10 minutes. Is more preferably about 30 seconds to 5 minutes, more preferably about 30 seconds to 2 minutes, and even more preferably about 30 seconds to 1 minute. Electrical energy is supplied using iontophoresis. An ion exchange resin or an ion exchange membrane can be provided in the mucosa application pad of the iontophoresis device. The ion exchange membrane can be a cation exchange membrane or an anion exchange membrane, and the ion exchange resin can be a cation exchange resin or an anion exchange resin. The iontophoresis device can also be equipped with a device for quantifying or qualifying in vivo components. The in vivo component to be extracted is, for example, glucose. Extraction from the oral mucosa using an iontophoresis device is preferred.

  The present invention can be used in the medical field, and is particularly preferably applied to an iontophoresis device used for a mucous membrane for noninvasively taking out in vivo components from the living body.

It is a figure which shows one Embodiment of the iontophoresis apparatus which concerns on this invention. It is the schematic which shows an example of the electrode structure on the oral mucosa application side, (a) is a top view, (b) is sectional drawing, (c)-(e) is another sectional drawing. It is the schematic which shows an example of the electrode structure by the side of skin application, (a) is a top view, (b) is sectional drawing. It is a graph which shows the blood concentration 30 minutes after applying this apparatus with respect to an oral mucosa (Example 3) and skin (Comparative Example 1). It is a graph which shows each resistance in an oral mucosa (Example 4) and skin (comparative example 2).

Explanation of symbols

DESCRIPTION OF SYMBOLS 11, 12 Electrode structure 13, 14 Fixing member 15 Spring member 16 Power supply device 21 Extraction pad 22, 32 Ring part 24, 34 Support body 25, 35 Electrode part 26, 36 Electrode terminal 27, 37 Insulator 31 Control pad

Claims (3)

An electrode structure on the oral mucosa application side, an electrode structure on the skin application side, a fixing member for fixing each electrode structure, and a spring member provided between the fixing members disposed so as to intersect with each other in a rotatable manner When the a power supply connected to each electrode structure, the oral mucosal application side of the electrode structure have a physiological substance extraction pad applied to mucous membranes, and ion-exchange resins or ion-exchange membrane Or an iontophoresis device comprising a device for quantifying in vivo components or a device for qualitative measurement .   2. The iontophoresis device according to claim 1, wherein a time for applying electric energy to the living body by the power supply device is set to 30 seconds to 20 minutes. 3. The iontophoresis device according to claim 1, wherein the in vivo component is a drug administered for treatment.

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