JPH0316573A - Element for percutaneous administration - Google Patents

Abstract

PURPOSE:To constitute an ideal portable power supply for iontophoresis by simultaneously bringing a semiconductor electrode lower in standard single-pole potential and a matrix containing an ionic permeable drug into contact with the skin. CONSTITUTION:A semiconductor cathode 3 is connected to an anode metal 1 by a conductor 4 to be brought to a conductive coupling state and brought into contact with the surface of the skin of a living body along with the conductive matrix 2 containing an ionic permeable drug (M<->) brought into conductive contact with the anode metal 1. As a result, a free electron (e<->) flows out toward the anode metal 1 from the semiconductor cathode 3 by the standard single-pole potential of a cathode and an anode and the conductive zone of the semiconductor cathode 3 becomes an electron insufficient state and the energy hand thereof is inclined. At this time, a Schottky potential barrier betais formed in the skin contact surface of the semiconductor cathode 3 and a depletion layer is formed but, when a low resistance oxide semiconductor cathode is used, effective electromotive force can be held stably.

Description

DETAILED DESCRIPTION OF THE INVENTION [Industrial Field of Application] The present invention relates to a transdermal drug device that utilizes the action of iontophoresis.

[Conventional technology]

Drug administration methods used to treat diseases in living organisms include injection, rectal administration, and oral administration methods that rely on the transport effect of venous blood flow, and transdermal administration methods that rely on the local diffusion and osmosis effect of drugs. The former is mainly effective in treating systemic symptoms and diseases caused deep within the body, while the latter is mainly effective in treating local diseases. In recent years, with the improvement of transdermal administration methods, it has become possible in some cases to continuously supply drugs at a constant concentration to living organisms, allowing them to continue living their daily lives while being treated. Typical uses include treating musculoskeletal and connective tissue disorders, preventing angina pectoris attacks, and calming bronchial inflammation caused by colds. These transdermal medications usually involve applying a drug containing an effective ingredient to the skin, and supplying a constant concentration of the active ingredient to the affected area while maintaining a constant diffusion rate. However, drug components that exhibit curing effects on diseases are generally polymeric compounds and have complex three-dimensional structures, so relying only on simple concentration diffusion phenomena often does not provide sufficient therapeutic effects. In particular, it has been pointed out that transdermal administration is inappropriate in cases of acute illness or severe symptoms. Therefore, in recent years, iontophoresis,
In other words, the transdermal absorption method of ionic drugs using electrophoresis has been attracting attention. Iontophoresis itself has been known since the early 20th century and has been used in some cases, but in recent years, ionic drugs effective for facial neuralgia, fixed plasters, and electrode materials (including matrices for ionic drugs) have been developed. Its effectiveness has been highlighted through the development of high-performance, compact, and portable external power supplies that are capable of electrophoresis.

To perform iontophoresis, an ionic drug containing an active ingredient is held in a conductive paste or water-containing gauze and applied to the affected area, and a current-carrying electrode (active electrode) is placed on top of the ionic drug. A counter electrode called an indifferent electrode (or ground electrode) is placed in close contact with the skin, and a power source is connected between both electrodes to supply electricity. In this case, which electrode is positively biased depends on the effective precept charge to be penetrated into the living body. For example, if salicylic acid, which has an anti-inflammatory and analgesic effect, is used as a sodium salt, the active electrode is connected to the cathode of a power source because salicylic acid is negatively charged, and the electrical repulsion forces the salicylic acid into the current-carrying path in the skin. It causes electrophoresis and penetration.

The current density to be applied varies greatly depending on the necessity of the effective supply concentration, but is usually said to be on the order of several to several hundred μA/cd (for example, JP-A-58-130054).
It has been reported that by employing iontophoresis, the rate of effective in-vivo supply is increased by more than one order of magnitude compared to the case of simple diffusion and osmosis (for example,
Compare No. 149168, Tables 1 to 4). Therefore, transdermal administration using iontophoresis is effective for antibiotics such as penicillin, cefazo, and phosphorus, anti-inflammatory analgesics such as salicylic acid and flufenamic acid, antiepileptic drugs such as bentobarbital and secobarbital, and other vitamins and hormones. It is likely to be used for the administration of many drugs, including anti-arrhythmic drugs and anti-arrhythmic drugs.

[Problem to be solved by the invention]

Since iontophoresis causes electrophoresis of ionic drugs by biasing from an external power source, a small portable battery must be used as a power source in order to apply it to an active living body (for example, JP-A-60-188176). ．． However, after using a dry cell battery for a certain period of time, the electromotive force will be consumed and it will no longer be able to fulfill its purpose, or if the situation in contact with the skin changes,
For example, there are problems such as the skin resistance changes greatly due to sweating, etc., and a large current flows, causing burns on the living body's skin. As a measure to prevent this, two types of metals with different ionization tendencies are electrically connected, and an electromotive force is generated using the electrical closed circuit that occurs when the skin is in contact with the skin. Iontophoresis has been proposed in which a sex drug metal salt is applied to the skin-contacting surface of the anode (Japanese Patent Laid-Open No. 203270/1983). This method attempts to use the biological skin surface as an electrolyte, and uses an external power supply (
Compared to the above-mentioned conventional technology using a battery, this method uses the internal reaction of the battery (oxidation-reduction reaction between electrodes).

Therefore, even if a large change in skin resistance or a short circuit between the electrodes occurs, the electromotive ability of the battery will only stop, and there is an advantage that it is safe.

However, this method has major drawbacks. In other words, when a cathode and anode are brought into skin contact to form an electrical closed circuit, electrons flow from the cathode, which has a strong tendency to ionize, to the anode, and the cathode metal becomes oxidized. Since the electrons transferred from the cathode to the anode negatively charge the anode, the anionic drug component placed under the anode migrates into the living body and is absorbed by the electrical repulsion. However, an electron-depleted (oxidized) cathode is in a chemically unstable ``active state,'' so it attracts highly electronegative electrons and tends to form compounds.

In JP-A-60-203270, (3) upper right column 1
Lines 4 to 16 state that ``(the cathode under this condition) absorbs anions in the body, which accumulates as metal salts. It is obvious that if the cathode is surrounded by water molecules, an oxide is immediately formed according to the following reaction formula before absorbing anions in the body.

Me”+20H−→Me(○H)z→M e O +
H 2 0 (Me” is a cathode structure metal ion)
In particular, when the magnesium alloy recommended as suitable in this literature example is used for the cathode, it exhibits a strong oxidizing effect, so MgO-based oxides are quickly deposited on the cathode surface.
Cover the surface. Since MgO-based oxide is an insulator, the internal resistance of the battery increases as the oxide begins to form.
The electromotive force begins to decrease, and as the oxide film becomes thicker, there is no conduction at all. In other words, iontophoresis is no longer induced.

The present invention was made in order to eliminate the drawbacks of the above-mentioned portable iontophoresis power source. In other words, the main purpose of the present invention is to take advantage of the safety of an internal reaction type battery (biocell) that utilizes the action of biological skin electrolytes while continuously performing electrode reactions as stable as an externally powered battery. The objective is to configure a portable power source for iontophoresis. Another object of the present invention is to not only permeate the ionic drug from the anode side into the living body, but also to simultaneously permeate the cathode constituent substances into the living body by electrophoresis, depending on the needs of the symptoms, so that interferon can be absorbed into the living body. The aim is to make it possible to enhance physiologically active effects by inducing drugs, etc.

[Means to solve the problem]

In order to achieve the above object, the present invention provides a gold I7X electrode having a higher standard terminal potential that is in conductive contact with the back side of a conductive matrix containing an ionic penetrating drug (effective amount), and a gold I7X electrode having a higher standard terminal potential. A device for transdermal administration is disclosed, which comprises a connected semiconductor electrode having a lower standard terminal potential, and is characterized in that the semiconductor electrode and a conductive matrix containing the ionic penetrant drug are brought into skin contact at the same time.

When an electrical closed circuit is formed by skin contact, electrons immediately flow out (reduced), so using a semiconductor for the cathode, which is extremely susceptible to oxidation, stabilizes the electrode reaction of this internal reaction type battery. In other words, it is extremely effective in allowing iontophoresis to continue for a long period of time.

In order to reduce the internal resistance of the battery and increase the effective current density, it is useful to use a low-resistance semiconductor with a resistivity of Ω(1) or less, especially an electron-supplying conductive semiconductor, for the cathode. Such low-resistance conductive oxides include zinc oxide (Zn
○), bismuth oxide (Bl203)e antimony oxide (
s b203), tin oxide (Sn○2), etc., but these compounds are a type of non-stoichiometric oxide, and the ones containing oxygen defects have higher conductivity (lower resistance). Therefore, although it is possible to use oxide semiconductors for the cathode from the beginning, it is also possible to use these as metals (Zn, Bi, Sb, Sn) at first.
), it can also be used as a cathode in contact with the skin. This is faster especially when used in wet conditions, but when an electrical closed circuit is formed by simultaneous cathode and anode skin contact, electrons flow out of the metal, resulting in the immediate formation of a thin oxide film on the skin contact surface. do. The oxide film grows to a thickness of several to several tens of micrometers over time when the current is applied, but since the oxide film acts as a good low-resistance electron-supplying semiconductor, it can be used in this way. .

Furthermore, when a substance such as germanium, its compound, or mixture, silicon, its compound, or mixture, or rare earth compound or its mixture is used as a semiconductor cathode, these substances are cationized by contact with the skin and permeate into the living body. As a result, it is known that a unit of interferon, etc., is induced in the body in proportion to the osmotic concentration, and the generated interferon cytotoxicity strengthens the biological activity of the body, resulting in a more favorable effect on treatment. .

[Effect]

When the semiconductor cathode of the present invention is used in an internal reaction type battery for iontophoresis, it stably generates a constant electromotive force for the following reasons. That is, as shown in FIG. 1(a), the semiconductor cathode 3 is connected to the anode metal 1 by a conductive wire 4 for conductive connection, and the ionic penetrant drug (
When the conductive matrix 2 (herein, matrix does not refer to a grid pattern but refers to a base material) containing a conductive matrix 2 (M-) is brought into contact with the skin of a living body, the standard ends of the cathode and anode as shown in the figure. Due to the electrode potential difference, free electrons (e-) flow from the semiconductor cathode 3 toward the anode metal 1, and the conduction band of the semiconductor cathode 3 becomes electron-deficient, as shown in FIG. 1(b). The energy band of 3 is tilted. At this time, a Schottky potential barrier β is formed on the skin contact surface of the semiconductor cathode 3, creating a depletion layer. However, when a low-resistance oxide semiconductor is used for the cathode, electrons are thermally excited from the continuous defect levels formed by oxygen defects as shown in the figure and supplied to the conduction band, resulting in stable and effective activation. Electricity is conserved. At this time, the source of electrons that are thermally excited via the defect level is the filled zone of the oxide semiconductor, so holes (h+) are generated in the filled zone from the loss of electrons. Since the holes are self-biased in the forward direction within the semiconductor, they flow toward the skin-contacting surface as shown. As a result, the oxide semiconductor molecules are cationized at the surface in contact with the skin, but because the ionic bond between the highly electronegative oxygen atom and the metal atom is strong, the bonding force between adjacent atoms overcomes the repulsive force, and the oxide semiconductor molecule is normally separated from the crystal. The cations do not dissociate and penetrate into the skin of a living body. The holes directly flow into the living body's skin and oxidize the living body's ions (e.g. iron ions) present in this area (Fe"+h+ → Fe3+). On the other hand, if a non-oxide crystal such as germanium is used as the semiconductor cathode, , the semiconductor atoms (or molecules) that are cationized at the skin contact surface by the holes generated by the process shown in Figure 1 (b) have much weaker interatomic attraction than oxides (due to strong covalent bonding). ) In an unstable state, it dissociates from the crystal due to the repulsion between adjacent cations of the same type and the action of electrolytes on the skin surface, and penetrates into the body as semiconductor cations.As mentioned above, germanium ions, etc. It has the function of producing cytokines such as interferon and interleutin in the body.Since physiological effects are activated, the healing effect may be enhanced in conjunction with the action of therapeutic ionic drugs that penetrate into the body from the anode side. In this case, iontophoresis occurs on the cathode side at the same time as on the anode side.In addition, in this case, cations dissociate one after another on the skin contact surface of the cathode semiconductor, so fresh atomic surfaces are generated. When a semiconductor cathode is used instead of a metal anode, a Schottky disorder β is formed at the skin contact surface as shown in Figure 1 (b) when the cathode is in contact with the skin, and the biological skin conduction band is Because the bottom of the conduction band and the bottom of the semiconductor conduction band are discontinuous at this location, even if the semiconductor atoms become cationized at the skin contact surface, electrons will not flow in from the skin surface and electrically neutralize them.Therefore, This makes it possible to ionize semiconductor cations and penetrate the body.
When metal is used for the cathode as in No. 203270,
Since the bottom of the electron conduction band is continuous between the skin surface and the metal, electrons are supplied from the living body to the metal side. In other words, if a noble metal is used for the cathode instead of a base metal that is easily oxidized, such as a magnesium alloy, for the anode, no oxide film will be formed on the skin surface even after long-term use, and electrons will not be generated. Since the metal is continuously replenished from the living body, cationization and ionization of the metal do not occur. However, in this case, it is obvious that a noble metal having a standard terminal potential higher than that of the cathode must be used as the anode.

Note that the anode metal 1 of the present invention is usually in conductive contact with the gel matrix 2, and as the ionic drug salt contained in the matrix 2 is ionized and the permeated ions M- are permeated into the living body, the matrix 2 changes. Since the pH changes, it is desirable to use metals that are resistant to corrosion, such as noble metals. In addition, when a transdermal drug device is in contact with the skin for a long period of time, problems such as irritation of the skin surface due to pH change (alkalinization) may occur. The matrix composition should be determined taking into account the occurrence of neutralization reactions, such as the use of insoluble salt production or esterification by blending with alcohol.

〔Example〕

(Part 1) As shown in Fig. 2, @3tm metal cathodes 3 were placed on the outside of a mesh-like gold electrode with a diameter of 2o at intervals of 10 mm, and both electrodes 1 and 3 were short-circuited with a conductive wire 4. ．． The mesh-like gold electrode 1 is an anode, and a conductive matrix 2 containing an ionic penetrant drug is disposed in close contact with the lower surface of the mesh-shaped gold electrode 1. This device for transdermal administration was placed in skin contact with the back of a white rabbit whose hair had been shaved and its hair removed, and it was fixed with adhesive tape, and the administration effect was examined over time. In order to compare the penetration effect, a mesh gold electrode (1) in which conductive matrix 2 containing 0.4 mol of sodium salicylate was simply combined was prepared and similarly applied to the back of a white rabbit. The conductive matrix base material was polyvinylpyrrolidone gel, and the ionic penetrant drugs were selected as sodium salicylate, sodium ascorbate, and calcium tretinoin, and 0.4 mol of each was dispersed in the gel base material and formed into a sheet. is the conductive matrix 2.

Further, the material of the metal anode 3 was a magnesium alloy or zinc.

In order to increase the adhesion of the cathode and anode during skin contact, a mist of pure water was sprayed onto each skin contact surface, and after skin contact, the skin contact site was kept at the same position throughout the test period. After skin contact 6, 12, 18. 24
Blood was collected from each rabbit over time and the concentration of ionic drug in the blood was measured as a function of time. Each rabbit was treated with a specific drug and a specific cathode metal only once, and the concentration was measured by collecting superior vena cava blood from a catheter inserted into the ear vein of the test rabbit. The results are shown in FIG.

FIG. 3 shows that each of the ionic drugs salicylic acid, ascorbic acid, and tretinoin induces iontophoresis by using the device shown in FIG. 2, and permeates into the rabbit body. In other words, for comparison, the transdermal absorption concentration of salicylate ions (...×...
This clearly shows that the blood concentration is higher due to iontophoresis. However, the penetration effect when a magnesium alloy is used as the metal cathode is significantly lower than when zinc is used. When a magnesium alloy is used, the blood concentration decreases after skin contact, reaching a peak in the data over time, and finally converges to a value that is not much different from the blood concentration due to concentration diffusion.

The reason for this lies in the nature of the oxide film formed on the surface of the cathode metal 3 during the iontophoresis process.

When the devices of each rabbit used in the iontophoresis experiment were removed 24 hours after being in contact with the skin and the skin contact surface of the cathode metal 3 was examined, it was a grayish white color without exception. The grayish white color is due to an oxide film with a thickness of 5 to 30 μm. When only the cathode metal 3 was separated from the element and conductivity was examined, zinc showed good conductivity (specific resistance of 0.6Ω), but magnesium In the case of alloy, an insulating film was formed and there was no conduction at all. In order to investigate the progress of oxide film formation, only the conductive matrix 2 of the anode was removed from the device shown in FIG. 2, pure water was sprayed onto the cathode metal, and the device was placed in skin contact with the back of a white rabbit whose hair had been shaved and depilated. In this case, the cathode gold gt3 was attached to a zinc element and a magnesium alloy element at two places on the back of a white rabbit, and the cathode was removed after a certain period of time to examine how the cathodes were attached to the skin. As a result, an oxide film began to form on the skin contact surface for both the zinc cathode and the magnesium alloy cathode after only about 2 hours had passed after skin contact.
It was recognized with the naked eye. The oxide film thickness increases over time. In the case of the magnesium alloy cathode, an increase in resistance was observed 2 hours after skin contact (specific resistance number + Ωa
n). After 4 hours had elapsed, the specific resistance had rapidly increased to several KΩ, but in the case of the zinc cathode, the specific resistance remained below 0.1 Ω even after 4 hours had elapsed. In other words, when a magnesium alloy cathode is used, the specific resistance rapidly decreases due to the formation of an oxide film, so the circuit resistance of the electrical closed circuit between the element and the rabbit in Figure 2 increases rapidly, and the circuit power supply in Figure 2 increases. The performance of the internal reaction type battery rapidly deteriorates, and iontophoresis stops in a relatively short period of time (about 10 hours after skin contact). In contrast, in the case of a zinc cathode, the zinc oxide semiconductor film formed on the surface in contact with the skin sufficiently serves as an electron supply source, so iontophoresis continues for a long time. In the case of a zinc cathode, the specific resistance remains at around 1Ω even after 72 hours have passed after contact with the skin, so the internal resistance as a battery is sufficiently small and it is effective as a power source for iontophoresis. Therefore, the gradual saturation characteristic of the drug blood concentration at the zinc cathode (effectively the zinc oxide cathode) shown in Figure 3 is not due to deterioration of the cathode properties, but rather a balance between the supply and excretion of each ionic drug to the living body. This is thought to be due to

(Part 2) The device has the shape shown in FIG. 2, and the anode metal 1 is made of a nickel plate plated with a platinum thin film (approximately 2 μl in thickness), and the conductive matrix 2 is gelatin gel coated with a thin platinum film (approximately 2 μl thick). It is an ionic drug source with 8 moles of sodium citrate dispersed in it,
For the cathode 3, five types of internal reaction type electromotive force-based transdermal medication elements were formed, each using zinc, bismuth, button, antimony, and tin metal as starting materials. For comparison, a nickel plate having a diameter of 2 aa and a gelatin gel matrix in which 0.8 mol of sodium citrate was dispersed was electrically bonded (no cathode was used) was separately prepared. Each element and the comparative pad (using only concentration diffusion) were attached with adhesive tape to the back of another white rabbit that had been shaved and depilated, and after 24 hours, the blood of each test rabbit was collected and citrate was added to the blood. I checked the concentration. As a result, Table 1 was obtained.

Table 1 shows that iontophoresis using the device shown in Figure 2 works effectively even after being in contact with the skin day and night. It can be seen that transdermal absorption by iontophoresis is 6 to 10 times higher than absorption by simple diffusion. The element current in Figure 2 after 24 hours is 8 μA.
Met. This value is almost the same as about 9 μA at the start of skin contact.

Furthermore, after 24 hours had elapsed, the device was removed and the surfaces in contact with the cathode metal were examined, and it was found that all surfaces were covered with an oxide film semiconductor.

Next, the cathode 3 of the device shown in FIG.
An annular plate was formed by sputtering a 10 μm zinc oxide film. That is, an element using a low-resistance oxide semiconductor for the cathode 3 was manufactured before the skin contact started. Anode metal 1 and conductive matrix 2 are the same as samples A-F. When this device was applied to the shaved area on the back of a white rabbit, blood was collected after 24 hours and the citric acid concentration in the blood was measured.
80 μg/mQ, and almost the same results as Sample A in Table 1 were obtained. This fact indicates that in the device for transdermal medication using internal reaction electromotive force of the present invention, a conductive oxide semiconductor can be used as the cathode in advance, and the conductive oxide semiconductor can be quickly removed when electricity is applied to the skin. This shows that it is also possible to employ metals such as those listed in Table 1, which have a similar shape.

(Part 3) A 10 square, 0.2+m thick silver plate is used as the anode metal 1, and the lc
An m-square, 0.5 mm thick n-type germanium single crystal plate (carrier concentration I x 10"cm-') was used as the semiconductor cathode 3, and as shown in FIG. 4, both were arranged at 5rLn intervals and copper wires 4 were soldered. A conductive connection was made by the anode metal l.
A gelatinous matrix 2 consisting of polyvinyl pyrrolidone containing 0.3 mol of dexamethasone, glycerin, and 10% saline was applied to the back side of the device to form a transdermal drug device (device G). Moreover, the semiconductor cathode 3 of this element is
An element (element H) in which phosphorous-doped n-type SiC (carrier concentration I x 10"an-3) was chemically vapor-deposited to a thickness of 15 μm on the surface of a 1cII 1 square tin plate, and the semiconductor cathode 3 were replaced with a 10 square tin plate. A separate element (element ■) was also prepared in which the iron plate surface was replaced with one in which lanthanum boride (L a B 6 ) was deposited to a thickness of 0.5 μm.

Each of these devices was attached to the shaved back hair of a different CaH mouse (male) using adhesive tape, and changes in the blood concentrations of dexamethasone and interferon over time were examined. For the experiment, three groups of four CaH type mice were prepared, and elements G, H, and F were attached to each group, and one mouse was taken out from each group every 6 hours and blood was collected for examination. Ta. For comparison, we prepared a device (device J) in which the semiconductor cathode shown in FIG.
The blood concentrations of dexamethasone and interferon were examined 12 hours and 24 hours later, respectively. The results are shown in FIG. Regardless of which device is used, due to the effect of iontophoresis, the concentration of dexamethasone in the body increases over time after skin contact, reaching a saturation point after 24 hours. At the same time, what is characteristic is that in devices G, H, and I, the concentration of interferon'a in the blood increases over time compared to device J using an oxide cathode. On the other hand, in the case of device J, the interferon concentration increases only slightly due to skin contact with the device. In order to clarify the reason for this, we investigated the lanthanum concentration in the blood of mice to which the device was attached.

As a result, it was found that the lanthanum concentration increased over time from the zero level before the device was attached. In addition, considerable amounts of germanium and silicon were detected in the blood of mice 24 hours after attaching elements G and H, respectively. On the other hand, in the blood of mice 24 hours after attaching element J, zinc concentration was only detected at the same level as before attaching the element. therefore,
It can be concluded that the increase in interferon concentration in the blood of rats to which devices G, H and device were attached was caused by the semiconductor material of the cathode penetrating into the mouse body as a result of iontophoresis. These elements (G, H
, ■) The surface in contact with the cathode skin was hardly oxidized even after 24 hours.

(Part 4) In the transdermal drug device shown in Figure 2, the anode gold pA1
is gold, the conductive layer 71 placed on the bottom surface is an agar gel containing 0.1 mole of potassium nalidixate, and the cathode semiconductor 3 is a phosphorus-doped n-type zinc sulfide (carrier concentration) coated on a copper plate. 8X101ff, -3) thin film (approximately 0.5 μm thick) (device K), and in the case of an iron boride FeB film (approximately 1 μm thick) in which the cathode semiconductor 3 is deposited on a copper plate (device L). ), we conducted an experiment to attach the device to living skin. As in the previous example, the back hair of a CaH type mouse (male) was shaved, elements K and L were attached to different mice, and 48 hours later, the blood of the mouse was collected to examine the blood concentration of the drug. .

As a result, it was confirmed that iontophoresis was induced not only under the anode but also on the cathode side. That is, the blood of both mice contained 50 to 60 I of nalidixic acid.
In addition to detecting Lg/n+Q, the blood concentration of zinc in mice to which Element K was attached was more than three times higher than that in mice to which Element L was attached; Approximately 20% higher iron content was detected than in mice with K attached.

This is because the cathode semiconductor 3 is cationized in contact with the skin, as described in the [Operation] section, and is dissociated from the crystal in molecular units due to the electrical repulsion between adjacent cations and the surface catalytic action of the skin. , which has penetrated into the living body. Zinc and iron are rare constituent elements of living organisms, and are preferable elements for living organisms as long as they are not ingested in excess.

〔Effect of the invention〕

As described above in detail in the Examples, in the case of the biocell-type transdermal medication device using the semiconductor cathode of the present invention, skin resistance change is a concern when using a portable external power source such as a dry battery or storage battery. There is no need to worry about the application of an excessively large current or a decrease in electromotive force over time, and it is possible to supply an extremely safe and stable transcutaneous current for a long time to a living body during daily activities. In addition, the ionic drug active ingredient placed on the anode can be transdermally absorbed for a much longer period of time compared to previous biocell-type skin dosing devices that use a metal with insulating resistance as the cathode. It was shown that it is very effective in treating the affected parts of living bodies. Furthermore, if a low-resistance material is used as the cathode semiconductor, which is a non-oxide and whose penetrating ions contain elements that are physiologically active for living organisms, iontophoresis will be induced not only under the anode but also under the cathode. This is advantageous because the therapeutic effect of the original ionic drug can be further enhanced.

With the present invention, transdermal medication has become a more effective biological treatment method than ever before.

[Brief explanation of the drawing]

FIG. 1 is a diagram for explaining the principle of the present invention, FIGS. 2 and 4 are diagrams showing different structures of elements for transdermal administration of the present invention, and FIGS. 3 and 5 are diagrams, respectively. This is another example data of the present invention. In the figure, 1 is the anode metal, 2
3 is a conductive matrix containing an ionic penetrant drug, 3 is a semiconductor cathode, and 4 is a conductive wire.

Claims (3)

[Claims] (1) consisting of a metal electrode with a higher standard unipolar potential that is in conductive contact with the back surface of a conductive matrix containing an ionic penetrant drug, and a semiconductor electrode with a lower standard unipolar potential that is conductively connected to the metal electrode, A device for transdermal administration, characterized in that the semiconductor electrode and the conductive matrix containing the ionic penetrant drug are brought into skin contact at the same time. (2) The semiconductor electrode is an electron-supplying conductive oxide semiconductor or a metal made of zinc, bismuth, lead, antimony, and tin that forms the semiconductor by surface oxidation on the skin contact surface when the element is used in skin contact. The transdermal drug device according to claim 1, characterized in that it is formed from at least one of the following. (3) The method according to claim 1, wherein the semiconductor electrode is formed of a semiconductor made of an element or a compound thereof that exhibits a physiologically active effect by inducing interferon when ions permeate into a living body. Element for skin dosing.