JPH041634B2 - - Google Patents

Description

[Detailed description of the invention]

The present invention relates to a device for iontophoresis. Iontophoresis has recently attracted increasing attention as an effective topical administration method that promotes transdermal absorption of ionic drugs (Glass JM et al., Int.J.
Dermatol.19 519 (1980); Russo J., Am.J.
Hosp.Pharm.37 843 (1980) Gangarosa LP et
al., J.Pharmacol.Exp.Ther.212 377 (1980);
Kwon BS et al., J.Infect.Dis.140 1014
(1979); Hill JM et al., Ann.NY.Acad.Sci.284
604 (1977) and Tannebaum M.Phys.Ther.60
792 (1980), etc.). Iontophoresis in these prior art technologies usually involves connecting the output terminal of a continuous current generator or an intermittent current generator to a conductor such as a conductor such as a metal plate covered with absorbent cotton impregnated with a chemical solution, or a similar structure. Since it is administered in succession with a guan inductor, it is quite complicated to implement, and although it is an extremely effective medication method, its widespread use has been limited. In addition, this iontophoresis is used by using continuous or intermittent plain current that has the same polarity as the drug to be administered, but the skin has an ohmic current as shown in the skin equivalent circuit diagram in Figure 1. Polarization impedance Z consisting of resistance Rdc, polarization resistance Rpol, and polarization capacitance Cpol
It has In normal iontophoresis, such as continuous current, which uses this ohmic resistance Rdc as the exclusive current path, Rdc has an extremely high resistance, so in order to administer the amount of drug necessary for treatment, a high voltage must be applied to the skin. As a result, it was highly irritating to the skin and could cause burns, redness, etc. Furthermore, it has been extremely difficult to administer the required amount when low voltage is used to prevent damage to the skin. In addition, the ohmic resistance Rdc of the skin S is a simple resistance of about 10KΩ・cm to 1MΩ・cm that does not depend on the frequency of the power supply, but the polarization impedance Z is substantially zero when the frequency of the voltage used is, for example, 10KHz or higher. It is known that it converges to
(Yamamoto, et al., Med. & Biol. Eng. &
Comput., (1978) 16.592−594; Yamamoto et al. , Medical Electronics and Bioengineering (1971) Vol. 11 No. 5 337-
342.) Therefore, when a high frequency voltage is applied to the human body, the polarization impedance Z decreases, making iontophoresis possible at a low voltage, but the polarization impedance Z of the skin S is equivalent to the skin equivalent in Figure 1. Polarization resistance Rpol and polarization capacitance as shown in the circuit diagram
Since it is represented by a parallel circuit with Cpol, Figure 2a
Even if a DC pulse as shown in Figure 1 is simply applied, the polarization capacitance Cpol repeats charging and discharging, and when the pulse output is stopped, the residual charge (polarization) is discharged (de-energized) very slowly through the polarization resistor Rpol. (polarization), the current involved in drug introduction is essentially the same as when using a continuous current, as shown in Figure 2b, and the skin impedance does not decrease even if a high-frequency DC pulse is simply applied. It couldn't have happened. In addition, as shown in Figure 2c, it is possible to shorten the output time of the DC pulse and increase the interval of the pulse pause time until the current value becomes sufficiently low even if residual charge (polarization) occurs due to the polarization capacitance Cpol. According to
In other words, it is possible to lower the skin impedance Z by reducing the duty ratio, but this poses a problem in terms of introduction efficiency because the residual electrode (polarization) is an electric charge that remains on the skin and is not involved in drug administration. It was hot. The present invention solves the above-mentioned drawbacks, and can sufficiently reduce skin impedance, thereby enabling use at low voltage and high current, and furthermore, even when high voltage is applied, skin irritation is avoided. The purpose of the present invention is to provide a safe device for iontophoresis with little risk of burns, redness, etc. Another object of the present invention is to provide an iontophoresis device that consumes low power by effectively recovering the residual charge stored in the polarization capacitor when outputting a therapeutic pulse. A further object of the present invention is to provide a small and lightweight iontophoresis device, particularly an iontophoresis device that is extremely easy to operate and has a lightweight structure that can be directly attached to human skin. Hereinafter, a first embodiment of the present invention will be described in detail with reference to FIGS. 3 to 6. In FIG. 3, reference numeral 1 indicates an iontophoresis device shown in a block diagram. 2 is a power source, for example, a 6 [V] dry battery. 3 is a pulse oscillation mechanism,
This is a mechanism for oscillating a DC pulse of approximately 50 KHz, for example, as shown in FIG. 6a. 4 is a seki conductor containing an ionic drug, and 5 is a non-seki conductor.
Reference numeral 6 denotes a human body connected to the above-mentioned Kankan conductor 4 and Insenkan inductor 5. 7 is a capacitor for recovering residual charge, which is connected in parallel with the power supply 2. 8 is an inductor. This inductor 8 is connected to a switch mechanism 9. This switch mechanism 9 is configured such that, at the same time as the treatment pulses 10, 10, . 5
It is provided to form a closed circuit connected in series to the pulse oscillation mechanism 3, and is connected in parallel to the pulse oscillation mechanism 3. Next, the method of use and operation of the device for iontophoresis of the present invention constructed as described above will be explained. First, the Guan inductor 4 and the inkan inductor 5 are attached to the human body 6. Through this operation, the drug introduction circuit shown in FIG. 4 is formed. That is, the pulse oscillation mechanism 3 outputs the pulse 10 shown in FIG. 6a. During the output time T of the pulse 10, a current flows mainly through the polarization impedance Z of the skin S of the human body 6 (pulse current Ia), and the ionic drug in the separator 4 is absorbed transdermally mainly through the polarization resistance Rpol. The switch mechanism 9 is turned on at the same time as the treatment pulse 10 is stopped, that is, the pulse oscillation mechanism 3 is turned off, and the residual charge recovery circuit shown in FIG. 5 is formed. With this circuit, the residual charge charged in the polarization capacitance Cpol of the polarization impedance Z of the skin S of the human body 6 when the treatment pulse 10 is output is caused by the L-C resonance between the polarization capacitance Cpol and the inductor 8.
The residual charge is collected by the capacitor 7 for collecting the remaining charge. This recovered charge is then discharged when the next therapeutic pulse 10 is output. In addition, this action causes the residual charge (polarization) charged in the polarization capacitance Cpol to be discharged (depolarization) during the pause time of the treatment pulse 10 (depolarization current Ib), and the potential between both conductors is maintained at a predetermined level. below the value, preferably at the same level. In addition, in the above embodiment, an explanation has been given of a method using L-C resonance as a means for depolarizing and recovering residual charge, but the present invention is not limited to this, and a capacitor for recovering residual charge is simply provided. Alternatively, any means may be used as long as the residual charge can be recovered, such as a structure in which the residual charge is recovered by R-C resonance. Furthermore, considering drug introduction efficiency and residual charge recovery efficiency, a transformer, charge pump type booster circuit,
It may be provided with a mechanism for boosting the pulse voltage, such as a DC-DC converter. Further, a large peak current flows through the human body at the rise and fall of the treatment pulse, and an output current limiting circuit may be provided to limit this peak current. Furthermore, the power supply voltage, pulse width, and oscillation frequency may be arbitrarily changed depending on the characteristics and application of the drug to be introduced, but the duty ratio is usually 0.1.
~0.7, frequency of about 1KHz to 500KHz, preferably duty ratio of 0.1 to 0.4, frequency of 5K
Hz to 200KHz may be suitably used. Further, a mechanism for varying these may be provided to enable control delivery including fine adjustment based on individual differences. In addition, the degree of depolarization referred to in the present invention is sufficient as long as the residual polarization voltage that is constantly applied to the skin does not cause skin irritation (stimulation), and the usage conditions such as the pulse voltage used etc. Although the residual voltage can be determined as appropriate, the residual voltage is usually preferably within 3 [V], more preferably 1.5
It is within [V]. If this is expressed as a ratio of the amount of depolarizing current to the amount of pulse current, the amount of depolarizing current is usually about 50% or more, preferably 60% or more, more preferably about 60% or more of the pulse current.
70% or more. Furthermore, from another point of view, a range in which the depolarization current value is a steady value substantially close to zero level is preferable. On the other hand, it is clear that a constant steady bias voltage or the like may be further applied at the same time as the pulse voltage, as long as skin irritation does not occur. That is, pulsed iontophoresis and weak plain current iontophoresis can be used together within the above range. Further, in the above embodiments, a general example of the skin equivalent circuit has been described, but substantially the same can be said when considering the electrical characteristics of the conductor. As is clear from the above explanation, according to the iontophoresis device of the present invention, when the same power supply voltage is applied, the iontophoresis device of the present invention has a power of approximately 10 times to several 10 times as much as that of a device using a continuous current or a simple intermittent current. Current will flow, resulting in an ionic drug introduction effect several to several tens of times greater. In addition, because the required amount of drug can be administered at a low voltage, or even when applying a high voltage such as 50 [V], irritation to the skin is extremely low, there is little risk of burns or redness, and it can be used for a long time. A device for iontophoresis that is also suitable for use can be obtained. Furthermore, the residual charge stored in the polarized capacitance of the skin is a waste charge that is not involved in drug introduction;
According to the iontophoresis device of the present invention,
Since the residual charge is very effectively collected and discharged when the next treatment pulse is output, it has the effect of significantly reducing power consumption. Furthermore, due to the low power consumption, it is possible to introduce a prescribed drug with a relatively small capacity and small battery, which can be extremely effective in reducing the size and weight of the device itself. Although periodic pulses have been explained above from a practical point of view, essentially the same effect can be obtained even with non-periodic pulses, and the pulse waveform etc. is not limited to rectangular waves. Of course it is voluntary. Next, each component and embodiment of the iontophoresis device of the present invention will be described in more detail. In Figure 7, a transformer is provided to boost the pulse voltage, the secondary winding of this transformer is used as an inductor, and the L-C between this inductor and the load capacitance is
This is an example of a circuit that uses resonance to depolarize and recover residual charge in a load capacitor. In the figure, reference numeral 2 denotes a power source, which uses a 3 [V] lithium battery shaped like a button, for example, in order to make the entire device 1 smaller and lighter. This power source 2 is connected to a pulse oscillation mechanism 3. This pulse oscillation mechanism 3 is formed of, for example, an unstable multivibrator circuit, and is configured to output pulses with a frequency of 50 KHz and a duty ratio of 0.2. 11 is a transformer. This transformer 11 is provided to boost the pulse voltage, and has a winding ratio of 1:3, for example. Further, the secondary side of this transformer 11 is configured to act as an inductor 8 for L-C resonance. 9 is a switching transistor. This switching transistor 9 is configured to operate the transformer 11 by the pulse output from the pulse oscillation mechanism 3.
This is provided to turn on and off the primary side of the 12 is a diode for circuit protection.
7 is a capacitor for recovering residual charge. Reference numerals 4 and 5 are connected to the human body 6 by means of a conductor and a conductor. The operation and effect of this embodiment are the same as those of the above embodiment, so the explanation thereof will be omitted. Next, a second embodiment of the circuit of the iontophoresis device of the present invention will be explained in detail with reference to FIG. Omitted. This embodiment is a circuit in which a transformer for inducing an induced current is provided, and the residual charge of the load capacitance is depolarized and recovered by the action of the transformer. In the figure, 15 is an induced current induction transformer. This transformer 15 is connected in series between both conductors 4 and 5 on the primary side, and the secondary side 17 is connected to a secondary battery 19 via a diode 18 for preventing reverse current.
It is connected to the. 3 is a pulse oscillation mechanism connected to the secondary battery 19 and connected to the first and second
is connected to the gates of FETs 20 and 21. Next, the operation of this embodiment will be explained. First, the pulse oscillation mechanism 3 generates a pulse 10 as shown in FIG. 6 using the secondary battery 19 as a power source. This pulse 1
At the same time as 0 rises, conduction occurs between the drain and source of the FET 20. Therefore, during the output time T of the pulse 10, the current flows mainly through the polarization impedance Z of the skin S of the human body 6 (pulse current Ia), and the ionic drug in the separator 4 is absorbed transdermally mainly through the polarization resistance Rpol. Ru. Then, at the same time as pulse 10 stops, FET20 turns OFF, and FET21
is conductive. Therefore, the residual charge charged in the polarization capacitance Cpol of the polarization impedance Z is instantaneously depolarized by the closed circuit including the primary side 16 of the induced current induction transformer 15. At the same time, an induced current is induced in the secondary side 17 by the transformer 15. This induced current is efficiently recovered by the secondary battery 19 via the diode 18. Incidentally, in the above embodiment, an explanation has been given of a case in which the residual charge is collected in a secondary battery, but a structure in which the residual charge is collected in a capacitor may also be used. Further, the winding ratio of the transformer may be appropriately changed in consideration of the induced current induction efficiency and the charging efficiency of the secondary battery or the capacitor. Next, an example of the overall configuration of the iontophoresis device of the present invention will be described in detail below. 9 and 10 show a first embodiment. In the figure, reference numeral 30 denotes an iontophoresis device that is integrally attached to the skin, that is, in the form of a plaster, and has a separator 31 and a separator 32.
The conductor 31 includes an ionic drug-containing conductive gel layer 33 formed in the form of a flexible sheet or film;
It is integrally formed by laminating a current dispersion conductive member layer 34 formed of metal foil such as aluminum foil, conductive rubber or resin film, carbon film, conductive paint, or the like. Further, the indifferent conductor 32 is integrally formed by laminating a conductive gel layer 35 formed in the shape of a flexible sheet or film and a current dispersion conductive member layer 36 formed of aluminum foil or the like as described above. It was formed. A power supply unit 37 is installed approximately at the center of the upper surface of the conductor 31. This power supply unit 37 includes a power source, for example, a so-called button-shaped battery, a pulse oscillation mechanism, a means for bringing the potentials of both conductors 31 and 32 to the same level when the treatment pulse of this pulse oscillation mechanism is stopped, and a residual charge. A means for recovering the current is provided therein, and one of the output terminals, for example, the (-) terminal, is installed so as to be in contact with the current dispersion conductive member layer 34. Further, the (+) terminal of the power supply unit 37 is connected to the current dispersion conductive material layer 38 of the indifferent conductor 32 by a lead wire 38 made of, for example, aluminum foil, whose lower surface except near both ends is coated with an insulator.
It is connected to the. 39 is an insulating backing layer. This insulating bulking layer 39 is made of, for example, a non-conductive synthetic resin formed in the form of a flexible sheet or film.
are spaced apart and fixed to this insulating backing layer 39. That is, the inductor 31, inductor 32, and power supply unit 37 are integrally supported and connected by the insulating backing layer 39. Next, the operation and usage of the iontophoresis device constructed as described above will be explained. First, the guide element 31 is attached so as to be in contact with the desired treatment position on the human body. At the same time, Seki Douko 31 and Inkan Douko 32
forms a closed circuit, pulse oscillation is started, and transdermal penetration of the ionic drug in the ionic drug-containing conductive gel layer 33 of the conductor 31 is accelerated. According to this example, an iontophoresis device can be obtained which is extremely easy to operate and lightweight, and which can be directly attached to the human skin, and which can provide a sufficient drug administration effect. Next, with reference to FIGS. 11 and 12, a second embodiment in which the iontophoresis device of the present invention is configured to be integrally attached to the skin, that is, in the form of a plaster, will be described in detail. In the figure, 40 is an iontophoresis device, 41 is a seki conductor, and 4 is a device for iontophoresis.
2 indicates an indifferent conductor. The conductive material layers 43 and 44 for current dispersion of the conductor 41 and the conductor 42 are 5
They are arranged at a distance of about mm, and an ionic drug-containing conductive gel layer 45 formed extremely thin, for example, about 0.3 mm, is adhered to the lower surface thereof.
Further, the non-conducting conductor 42 and the disconducting conductor 43 are integrally supported and connected by an insulating backing layer 46. 47 and 48 are Seki conductor 41 and Inkan conductor 4, respectively.
This is the terminal connected to 2. This terminal 47, 48
The top portion of the power supply unit 49 protrudes through the insulating backing layer 46, and the power supply unit 49 is electrically connected and mechanically supported and connected by the terminals 47 and 48. The method of using the iontophoresis device of this example is the same as that of the first example, so the description thereof will be omitted. According to this embodiment, the Seki conductor 41 and the Inkan conductor 4
Since the conductive gel layers laminated in the conductive gel layers 2 and 2 are the same, i.e., one ionic drug-containing conductive gel layer 45 is attached to each of the current dispersion conductive member layers 43 and 44, there is a slight gap between each conductor. However, since the conductive gel layer itself has resistance and the distance between the conductive member layers 43 and 44 is extremely large compared to the thickness of the conductive gel layer 45, the ionic drug does not penetrate the skin. It has almost no effect on the effect. According to this embodiment, in addition to the effects of the first embodiment, the manufacturing process is extremely simple and efficient. In other words, a device can be obtained by simply attaching terminals and a power supply to a single belt-shaped sheet in which a conductive gel layer, a conductive material layer, and an insulating backing layer are laminated and cut at predetermined intervals, and mass production is possible. This has a very useful effect when considering the following. Furthermore, if the spacing between both terminals is narrowed and the power supply is placed approximately in the center of the top surface of the device as in the example, the size of the power supply has almost no effect on the entire device, and it can be attached to the curved surface of the human body. It can be used satisfactorily with almost no loss in flexibility even when Next, a third embodiment of the iontophoresis device of the present invention will be described in detail with reference to FIG. 13 of the drawings. In the figure, 51 is a device for iontophoresis, and 52 is an indifferent conductor. Reference numeral 54 denotes a power supply, the (-) terminal of which is connected to the current dispersion conductive material layer 55 of the conductor 52, and the (+)
The terminal is connected to the current dispersion conductive member layer 57 of the indifferent conductor 53 via a lead wire 56. According to the configuration of this embodiment, the guan conductor and the guan conductor can be attached to the human body at any distance within the length of the lead wire, and when the attachment site is small or has a relatively large curvature. It can also be used easily on surfaces such as Furthermore, even when the skin sweats profusely due to use in hot and humid conditions, a plaster structure can be obtained that is completely unaffected by the current flowing through the epidermis because the conductors are separated from each other. Next, a fourth embodiment of the iontophoresis device of the present invention will be described in detail with reference to FIG. 14 of the drawings. In the figure, 61 is a device for iontophoresis, 62 is an inductor thereof, and 63 is an inductor thereof. Both conductors 62 and 63 are connected to a power supply 65 via a lead wire 64. This power supply 65 includes a power source such as four AA batteries, a pulse oscillation mechanism using a transformer, and a switch mechanism for making the potentials of both conductors 62 and 63 equal to the same level when the treatment pulse is stopped. Means for recovering the electric charge is provided therein. Furthermore, this power supply 65 includes an output current variable circuit and a timer circuit. According to this embodiment, since the power supply is separate from both conductors, the circuit space can be increased and a large capacity dry cell battery can be used. Furthermore, since both conductors are simply film-like ultra-light sheets, it is extremely easy to attach them to the human body. Furthermore, since a variable output current circuit is installed, the amount of output current can be controlled arbitrarily depending on the skin resistance of the user, the type of drug to be introduced, the required amount, etc. Furthermore, since a timer circuit is provided, it has the advantage of being able to prevent excessive administration of drugs. In the above example, a conductive gel containing an ionic drug was used as the conductor, but the present invention is not limited to this.
Paper materials such as water-absorbing paper, cloth materials such as gauze, fiber materials such as absorbent cotton, sponges or porous materials such as open synthetic resin foams or water-absorbing resins, as long as they can be impregnated with and retain ionic drugs or electrolyte solutions. It can be anything. In addition, in the examples, the conductive gel layer of the conductor was described as containing an ionic drug in advance, but the ionic drug was applied to the conductor and/or the skin during use. Also good. That is, a conductive gel layer that does not contain an ionic drug is used, and at the beginning of treatment, an ointment, cream, etc. containing an ionic drug is applied to the conductor and/or the skin to form a film. It may also be an iontophoresis device to which a conductor is attached for treatment. Furthermore, a polarity switching means may be added to the device so as to freely change the yin and yang of the conductor depending on the yin and yang of the effective drug ion species. In addition, especially when the biological condition changes depending on the drug dose, or when the drug dose must be controlled according to the biological condition, the output current can be automatically adjusted while monitoring the biological condition. It is also possible to have a configuration in which a feedback mechanism for controlling the speed is internally provided. For example, when it is necessary to control the dose based on the blood sugar level, especially when administering insulin, a sensor that monitors the blood sugar level can be connected to the power supply, and the detection output of this sensor can be used to automatically control the dose. A feedback mechanism for controlling output current and/or output time may be provided. With this configuration, it is possible to perform optimal drug administration according to the biological condition, which was impossible with conventional administration methods. Each component of the plaster structure of this example will be explained in more detail as follows. Conductive gel layer This layer is preferably made of natural resin polysaccharides such as karaya gum, gum tragacanth, xanthan gas, or partially saponified polyvinyl alcohol, vinyl resins such as polyvinyl formal, polyvinyl methyl ether and its copolymers, polyvinyl pyrrolidone, polyvinyl methacrylate, etc. Polyacrylic acid and its sodium salt, polyacrylamide and its partially hydrolyzed product, partially saponified polyacrylic ester, poly(acrylic acid-acrylamide)
Various hydrophilic natural or synthetic resins such as acrylic resins such as acrylic resins are softened and plasticized with water and/or alcohols such as ethylene glycol and glycerin to produce flexible films or sheets that have self-shape retention and skin adhesion. Supplied as a gel. On the other hand, electrolytes such as sodium chloride, sodium carbonate, potassium citrate, etc. are added in a required amount (usually about 1 to 15%) to impart sufficient electrical conductivity. The conductive gel layer suitable for the present invention obtained in this way is in the form of a flexible film or sheet and can adhere to the skin, so it has low skin contact resistance and is effective for percutaneous penetration of drug ions. Not only that, but it also has the advantage of being able to adhere and support the entire structure to the skin without requiring other skin adhesion means such as adhesive tape. In particular, when a natural resin polysaccharide such as Karaya gas is used as a base material for the gel layer, its natural polymeric acid structure provides PH buffering and skin protection properties, extremely high water retention capacity, moderate skin adhesion, etc. Not only can a gel with good electrochemical conductivity be provided, but also suitable skin compatibility can be obtained. In addition, when formulating the composition of these gel layers, it goes without saying that electrochemical considerations should be made in much the same way as in the case of so-called electrophoresis gels, but the main consideration is the type of drug used and the required dosage (dose). ), the application time, the output of the battery used, the skin contact area, etc., are appropriately carried out so that the ion mobility or conductivity reaches the required value. Here, the preferred conductive gel layer in this example, as well as some more specific examples, are as follows: 1. The average molecular weight is 440,000, and the degree of saponification is approximately 60 using a conventional method.
Prepare 30g of % polyvinyl alcohol powder,
To this, 40 g of distilled water containing 10% NaCl and 30 g of glycerin, which had been preheated to 80°C, were added and stirred.
The resulting mixture was then heated and pressed for about 20 minutes at a pressure of 0.6 kg/cm ² using a hot press heated to 80° C. to obtain a flexible sheet with a thickness of 3 mm.
This flexible sheet-like material has sufficient skin adhesion and its DC specific resistance (hereinafter the same) is 0.8K.
It was Ω・cm. 2 A flexible sheet-like conductive gel layer was manufactured using the following composition in the same manner as in 1 above. Composition example A Polyvinylpyrrolidone (PVP- manufactured by GAF)
K90; average molecular weight 360,000)...20g Distilled water containing 10% NaCl...40g Glycerin...40g The obtained sheet had strong skin adhesion and its specific resistance was 0.2KΩ·cm. Composition example B Polyvinyl formal (average molecular weight 1.6 million,
Degree of formalization: 15%; degree of saponification of raw material polyvinyl alcohol: 60%) ...15g Distilled water containing 5% NaCl ...70g Propylene glycol ...15g The obtained sheet has sufficient skin adhesion and its specific resistance was 1.0KΩ・cm. Composition example C Polyvinyl acetoacetal (average molecular weight 44
(30% acetalization degree; 70% saponification degree of starting polyvinyl alcohol) ...40g Distilled water containing 15% NaCl ...50g Ethylene glycol ...10g Sufficient skin adhesion, specific resistance 0.75K
Ω・cm. 3 Sodium polyacrylate (Aronbis SS manufactured by Nippon Pure Chemical Industries, Ltd.; average molecular weight 3 million to 5 million) 20 g at 5%
12g of distilled water containing NaCl and 68g of glycerin solution
The mixture was mixed uniformly with the mixture and heated and pressed at 80°C for 10 minutes to obtain a flexible sheet. This sheet has moderate skin adhesion and its specific resistance after being left for one day and night.
It was 0.5KΩ・cm. 4 30g of Karaya gas and 30g of distilled water containing 5% NaCl
and 40 g of glycerin were mixed and heated and pressed to prepare a sheet in the same manner. Specific resistance 0.65KΩ・
cm. 5 Sodium polyacrylate (Aronbis S manufactured by Nippon Pure Chemical Industries, Ltd.; average molecular weight 3 million to 5 million) 20 g 7%
A sheet was prepared in the same manner by mixing with 80 g of NaCl-containing purified water and applying heat and pressure. Specific resistance 0.47KΩ・cm. In addition, especially from an electrochemical point of view, basic drugs such as prapranolol, insulin, lidocaine, and cysteine are made of polyacrylic acid, methyl vinyl ether/maleic anhydride copolymer (GAF
GANTREZ ^R AN-169, etc.), carboxypolyethylene (CARBOPOL ^R, manufactured by GOODRICH)
etc.), ascorbic acid, salicylic acid, nitrous acid, riboflavin phosphate, betamethasone phosphate, tretinoin (trans-retinoic acid, etc.).
It will be understood that highly efficient transfer of target drugs can be achieved by using basic polymers such as polyacrylamide as gel bases for acidic drugs such as Acid). For example, an example of a gel composition for propranolol is as follows. Carbopol ^R 491 or GANTREZ ^R AN−
169 30 parts by weight Glycerin 45 parts by weight Water 15 parts by weight Propranolol 10 parts by weight In addition, this gel composition is made into a self-adhesive film with a thickness of about 0.1 to 0.5 mm, as described above. It is extremely suitable for use as a conductor-integrated film electrode. Additionally, it will be appreciated that non-ionic polymers such as polyvinyl alcohol, polyvinylpyrrolidone, etc. may also provide gels with relatively high electrochemical efficiency. As is clear from the above, the gel base material composition or range of the conductive gel layer of the present invention is not limited to a specific one, and a wide range of hydrophilic polymers can be softened and plasticized with water and/or alcohols. However, in order to have shape retention, the composition is usually selected within the range of 10 to 70% by weight of the hydrophilic polymer and the balance water and/or alcohol. Each of the above-mentioned conductive gel layers has sufficient skin adhesion by itself, but if desired, a pressure-sensitive adhesive component such as an acrylic adhesive or a vinyl acetate emulsion adhesive may be added. It's okay. In this way, by arranging the skin-adhesive and conductive gel layer around the periphery or end of the structure, the entire structure can be attached to the skin without the need for any other fixing means such as adhesive tape. It is held fixed. In addition, if the conductive gel layer is the husband of Seki Doko,
In each of the above-mentioned gel compositions, it is sufficient to add and dissolve a required ionic drug in place of part or all of the electrolyte component, ie, sodium chloride. If necessary, the water-retaining member layer may be made removable, and the member impregnated with a chemical solution may be placed at a predetermined position in the structure during use and used for treatment. Furthermore, it is clear that in place of the water-absorbing member, non-adhesive hydrogels commonly used in the field of electrophoresis, such as agar gel and gelatin gel, may be used. An example of an agar water gel composition is as follows. Agar water 4.0 parts by weight Purified water 100.0 〃 Vitamin C 5.0 〃 (Ascorbic acid: its Na salt ~ 1:1) This type of hydrogel piece may be layered on the structure in advance, or as described above during use. It may be arranged. In addition, when using a non-adhesive hydrogel such as agar gel in this way, it is natural that skin-adhesive fixing means such as adhesive tape may be optionally added to the outer extension of the structure in this example. It is. Ionic drugs All ion dissociative drugs can be used, but
Some examples of those already widely used in the field of iontophoresis are as follows: iodopotassium, procaine hydrochloride, melicol, various skin vitamins such as vitamin B ₁ , B ₂ , B ₆ , C, and histamine. , sodium salicylate, dexamethasone, betamethasone phosphate, epinephrine, hydrocordyline, idoxolidine, propranolol, nitrites, bleomycin, undecylene hydrochloride, sodium salt of dexamethasone phosphate, brednisolone sodium phosphate, alimemazine, chlorpheniramine , clemastine, dibenclamide, colchicine, diclofenac,
Chlorpromazine, chlordiazepoxide, clonazepam, digipramine, isopramine, atropine, ergotamine, nifedipine, alprenolol, indenolol, oxprenolol,
Isoprenaline, propranolol, betanidine, clonidine, guanethidine, hydralazine,
Prazodine, efuedrine, salbutamol, terbutaline, metoclopramide, etc. Usage Example 1 Examples and usage examples of the Kan inductor and Inkan inductor of the iontophoresis device of the present invention will be described in more detail as follows. That is, the conductive gel layers of both conductors are made of 20% by weight of Carbopol ^R 491, 30% by weight of distilled water, and 40% by weight of glycerin, and have a thickness of 1.5 mm and an area of 48 cm ^{2 .}
It is a viscoelastic gel, and the ionic drug-containing conductive gel layer of Seki Doko is further added with 5% by weight of sodium salicylate, and the conductive gel layer of Sekidoko contains approximately 3% by weight of sodium chloride. is added. A power supply that outputs 10KHz treatment pulses (duty ratio 30%) is connected to a 6V power supply and is laminated and attached to the unit. In addition, the plaster structure in this usage example is used as an analgesic/anti-inflammatory agent, but in this case, a bias voltage is applied simultaneously within a range that does not cause skin irritation, or a similar range after depolarization is applied. Maintaining a certain level of residual polarization voltage within the body is combined with so-called galvanization, which has a vasodilatory effect, so it has a synergistic effect on diseases such as neuralgia, arthralgia, and rheumatoid arthritis. It will be understood that this is an indication of effectiveness. Usage example 2 1 Metoprolol (antiarrhythmic drug) Electrode sheets containing 10% metoprolol (Ciba-Geigy) and having the composition shown in Table 1 below (each electrode 1 mm thick, area 50 cm ² )
31 years old, weight 75Kg and () age 39 years, weight 56Kg
One Seki conductor and one Inkan conductor were fixed on the left forearm of each healthy male subject at a random distance of 1 cm from each other at 50 KHz, a duty ratio of 20% (pulse width 4 μs), and a voltage of 10 [ Iontophoresis was performed using the depolarization method of the present invention under the conditions of [V] (average pulse current: 50 mA). After energization, 20 ml of blood was collected from the right arm vein using a heparinized tube at Ohr, 4 hr, and 8 hr, and this was used as a sample. Tomeprolol concentration in blood plasma fraction is
Degen and Riess (J. Chromat. 121, 72-75
(1976)) using a Hitachi model 163 equipped with an ionization detector.
Measurements were made at a temperature of 220°C in the injection chamber and 200°C in the oven. Column is 2
A QF-1 glass column (2 m) packed with % silicon was used. The measurement results are shown in Table 2. In addition, there was no skin irritation such as redness during the above treatment.

【table】

[Table] 2. Diclofenac sodium (anti-inflammatory agent) Electrode sheets (thickness 1 mm, area 50 cm ² ) containing 2% diclofenac sodium (Ciba-Geigy) and having the composition shown in Table 3 below were used at different ages. 35
2 on the left forearm of a healthy male subject aged 55 kg.
The sheets were pasted and fixed with a distance of about 1 cm between each other, and electricity was applied under the same conditions as in the usage example for metoprolol. After 5 hours, 20 ml of blood was collected to obtain each blood sample, and the blood plasma fraction was collected. Got ready. The concentration of diclofenac sodium in the blood plasma fraction was determined by Geiger, Degen and Sioufi (J.
Chromat.111, 293-298, (1976)) using a gas-liquid chromatography method with slight modifications to the Hitachi model 163 equipped with an ionization detector.
The measurement was carried out under the same temperature conditions as in the previous example.
The column is made of glass filled with 2% silicon.
A QF-1 column (2m) was used. As a result, 5
The blood plasma level at hour was approximately 128 ng/ml.

[Table] * Polyacrylamide: Manufactured by Mitsui Cyanamid Co., Ltd. It is clear that the plaster structure of the type shown in Use Example 1 above is useful for the treatment of various skin diseases and the penetration of beauty nutrients. . For example, if the conductive gel layer of both conductors is
GANTREZ ^R AN-169 20% by weight, 15% by weight of distilled water containing 20% NaCl, and 65% by weight of glycerin, formed from a viscoelastic gel with skin adhesive properties with a thickness of 1.5 mm and an area of approximately 12 cm ² , and its use At this time, 1 to several ml of a 3% sodium ascorbate-containing aqueous solution (stored in ampules) is dripped into the conductive gel layer of the conductor, and the entire structure is then applied to the affected area to begin the treatment. As is well known, vitamin C (ascorbic acid) or its derivatives (sodium ascorbate, etc.)
is effective for pigmentation disorders such as so-called melasma, sparrow spots, and various types of melasma, and treatment using iontophoresis is already known to be useful in cosmetics and dermatology. However, as mentioned above, it is not widely used due to the complicated operation. However, this example allows the treatment to be performed with extremely simple operations, and can be said to be revolutionary as a therapeutic or cosmetic plaster. Other gel base materials Some preferred examples of the gel base material for the conductive gel layer of the present invention are as described above, but various hydrophilic polymer materials known as so-called biological electrode materials may also be selected at will. It is once again pointed out that it can be used. For example, JP-A No. 95895 of 1972, No. 77489 of 1974, No. 52742 of 1975, No. 81635 of 1975, No. 129035 of 1973, No. 15728 of 1973, No. 63939 of 1972, No. 36940 of 1972, No. 56 60534, 1956, 89270, 1956, 28505, 1957, 49431, 1957, 52463, 1957 55132, 1957, 131428, 1957 160439, 1957, 57 No. 164064, No. 166142, No. 1957, No. 168675, No. 1957, No. 4569, No. 10066, No. 1958, No. 80689, No. 1973, No. 135706, No. 1983 No. 138603, No. 1956, No. 93305, No. 1983 Various hydrophilic polymer materials disclosed in 1957 No. 179413, 1957 No. 185309, etc. can be used as the gel base material of the conductive gel layer of the present invention by appropriately adjusting their water content. As described above, the gel base material of the conductive gel layer of the present invention is a hydrophilic polymer which is softened and plasticized with water and/or alcohol to preferably provide a skin-adhesive viscoelastic gel. However, the base material composition is not limited to a specific material, and the composition of the base material is determined in consideration of compatibility with the drug used, skin compatibility, electrical conductivity, etc. Furthermore, these gel layers can be disposable or replaced with other materials.

[Brief explanation of drawings]

Fig. 1 is an explanatory diagram in which the skin is replaced with an equivalent circuit, Fig. 2 shows the waveform in conventional iontophoresis, a is the pulse voltage waveform diagram, and b is the current waveform flowing through the human body when the waveform a is applied. Figure, c is a
A current waveform diagram is shown when a pulse with a reduced duty ratio is applied. Fig. 3 is a block circuit diagram showing an embodiment of the iontophoresis device of the present invention, Fig. 4 shows a closed circuit diagram when the therapeutic pulse is output, and Fig. 5 shows a closed circuit diagram when the therapeutic pulse is stopped. show. FIG. 6a shows a therapeutic pulse voltage waveform diagram output from the conductor,
b shows a waveform diagram of the current flowing through the human body when the waveform of a is applied. 7 and 8 are block circuit diagrams showing a more detailed embodiment of the iontophoresis device of the present invention. 9 and 10 show a first embodiment of the overall configuration of the iontophoresis device of the present invention, FIG. 9 is a sectional view taken along the - line, and FIG. 10 is a bottom view. Figures 11 and 12 show the second embodiment, and Figure 11 is XI.
A sectional view taken along the line -XI, and FIG. 12 a perspective view. FIG. 13 and FIG. 14 show the third and fourth embodiments, with FIG. 13 showing a sectional view thereof, and FIG. 14 showing a perspective view thereof. S...skin, Rdc...ohmic resistance, Z...polarization impedance, Rpol...polarization resistance, Cpol...polarization capacitance,
1... Device for iontophoresis, 2... Power supply,
3...Pulse oscillation mechanism, 4...Separate conductor, 5...Separate conductor, 6...Human body, 7...Capacitor (residual charge recovery capacitor), 8...Inductor, 9...Switching transistor, 10, 10...Treatment pulse , 11
...Transformer, 15...Induced current induced transformer, 16
...Primary side, 17...Secondary side, 19...Secondary battery, a
... Pulse current, b... Depolarization current, 30, 40,
51, 61...Device for iontophoresis, 3
1, 41, 52, 62...Seki Deiko, 32, 42, 5
3,63... Indifferent conductor, 33,45... Ionic drug-containing conductive gel layer, 35... Conductive gel layer, 37,
49, 54, 65...Power supply unit.

Claims (1)

[Scope of Claims] 1. In an iontophoresis device having a power source, a pulse oscillation mechanism, an inductor and an inductor, depolarizing between the two inductors when the treatment pulse of the pulse oscillation mechanism is stopped; , an iontophoresis device characterized in that it is provided with means for recovering residual charges stored in a polarization capacitor. 2 An inductor is provided in series between both conductors, and the residual charge stored in the polarization capacitance is depolarized and recovered by L-C resonance between the inductance and the load capacitance. The iontophoresis device according to item 1. 3. The iontophoresis device according to claim 1 or 2, wherein the inductor utilizes a transformer for boosting pulse voltage. 4 In order to depolarize and recover the residual charge stored in the polarization capacitor, an induced current induction transformer is provided, and the primary side of this transformer is connected in series between both conductors, and the secondary side is connected to a secondary battery. The iontophoresis device according to claim 1, characterized in that the device is connected to a capacitor or a capacitor.