JP2797118B2 - Transdermal drug delivery device - Google Patents

Description

Description: TECHNICAL FIELD The present invention relates to an element for transdermal administration utilizing the action of iontophorase.

[Conventional technology]

Drug administration methods used for treating diseases of the living body include injection, rectal administration, and oral administration methods that rely on the transport action of venous blood flow, and transdermal administration methods that rely on local diffusion and penetration of the drug.
The former is effective mainly for treating systemic symptoms and diseases caused deep inside the body, and the latter is effective mainly for treating local diseases. In recent years, it has become possible in some cases to provide a constant concentration of a drug to living organisms in an active manner and to carry out daily life while treating while improving the transdermal administration method. Typical examples include treatment of diseases of the musculoskeletal system and connective tissue, prevention of attacks of angina, and suppression of bronchial inflammation due to colds. In these transdermal administrations, a drug containing an active ingredient is usually in contact with the skin, and a constant concentration of the active ingredient is supplied to the affected part while maintaining a constant diffusion rate of the ingredient. However, since a drug component showing a curative action for a disease is generally a polymer compound and has a complicated three-dimensional structure, a sufficient therapeutic effect cannot be often obtained only by relying on a simple concentration diffusion phenomenon. In particular,
It has been pointed out that transdermal administration is not suitable for acute illness or severe symptoms.

In recent years, iontophoresis, ie, transdermal absorption of ionic drugs using electrophoresis, has been spotlighted as a means of dramatically improving the efficiency of in vivo delivery of active ingredients by transdermal administration. 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,
Its utility has been highlighted by the development of fixed plaster, electrode material (including matrix for ionic drugs), and high performance small portable external power supply capable of electrophoresis.

In order to perform iontophoresis, an ionic drug containing an active ingredient is held in a conductive paste or a hydrated gauze or the like to be in skin contact with the affected area, and an energizing electrode (active electrode) is arranged thereon. In this vicinity, a counter electrode called an indifferent electrode (or a ground electrode) is in contact, and a power source is connected between the two electrodes to energize. In this case, which electrode is biased positively depends on the charge of the active ingredient that penetrates the living body. For example, if salicylic acid, which has an anti-inflammatory and analgesic effect, is used as a sodium salt, the active ingredient salicylic acid is negatively charged, so the active electrode is connected to the cathode of the power supply, and the salicylic acid migrates to the current path in the skin by electrical repulsion.・ We let you penetrate. The current density to be energized varies greatly depending on the necessity of the active ingredient supply concentration, but is generally said to be about several to several hundred μA / cm ² (for example, Japanese Patent Application Laid-Open No. 58-130054). The adoption of iontophoresis increases the rate of in vivo delivery of active ingredients,
It has been reported that the value is increased by one digit or more compared to the case of simple diffusion and infiltration (for example, JP-A-61-149168,
Tables 1 to 4). Therefore, the transdermal administration method using iontophoresis is based on antibiotics such as penicillin and cefazolin, anti-inflammatory analgesics such as salicylic acid and flufenamic acid, antiepileptic drugs such as pentobarbital and secobarbital, and other vitamins and hormones. I am in the fortune to use it for the administration of many drugs such as antiarrhythmic drugs.

[Problems to be solved by the invention]

Since iontophoresis causes electrophoresis of an ionic drug by a bias from an external power source, a small portable battery must be used as a power source for application to an active living body (for example, JP-A-60-188176). . But,
The use of a dry battery consumes electromotive force after a certain period of use, making it impossible to fulfill its purpose, or a change in the condition of the skin contact surface, for example, perspiration causes a drastic change in skin resistance. There are problems such as occurrence. As a measure to prevent this, two types of metals with different ionization tendencies are conductively connected and an electromotive force is generated using an electrical closed circuit generated at the time of skin contact, and ionicity using the same type of metal as the anode side metal An iontophoresis using a drug metal salt applied to a skin contact surface of an anode has been proposed (JP-A No.
No. 60-203270). This method uses the skin surface of a living body as an electrolyte, and uses an internal reaction (oxidation-reduction reaction between electrodes) of the battery as compared with the above-described conventional technology using an external power supply (battery). Therefore, there is an advantage that even if a large change in skin resistance or a short circuit occurs between the electrodes, the electromotive force of the battery is only stopped, which is safe.

However, this method has major drawbacks. That is, when an electrically closed circuit is formed by contacting the negative anode, electrons flow from the cathode having a high ionization tendency to the anode, and the cathode metal is oxidized. Since the electrons transferred from the cathode to the anode charge the anode negatively, the anionic drug component disposed under the anode migrates into the living body and is absorbed by the electric repulsion. However, since the cathode without electrons (oxidized) is in a chemically unstable “active state”, electrons having high electronegativity are attracted to easily form a compound. JP
In No. 60-203270, (3) In the upper right column, lines 14 to 16, "(The cathode under this condition) absorbs anions in the body and thereby accumulates as metal salts."
However, if the cathode is trapped in water molecules as in this literature example, it is obvious that oxides are immediately formed by the following reaction formula before absorbing anions in the body. is there.

^{Me +2 + 2OH - → Me (} OH) 2 → MeO + H 2 O ( provided that, Me ⁺² cathode structure metal ions) when particularly using a magnesium alloy, which is recommended as a preferred in this document examples cathode Since it exhibits a strong oxidizing action, the MgO-based oxide coats the cathode surface within a short time. Since the MgO-based oxide is an insulator, the internal resistance of the battery increases with the start of the formation of the oxide. Therefore, the electromotive force starts to decrease, and as the oxide film thickness increases, conduction stops at all. That is, iontophoresis does not occur.

The present invention has been made to solve the above-mentioned drawbacks of the portable iontophoresis power supply. That is, the main object of the present invention is to make the electrode reaction as stable as that of an external power supply battery while continuously utilizing the safety of an internal reaction type battery (biocell) utilizing the action of a biological skin electrolyte. A portable iontophoresis portable power supply. Another object of the present invention is to allow not only the penetration of the ionic drug into the living body from the anode side but also the penetration of the cathode constituent substance into the living body by electrophoresis at the same time, depending on the necessity of the symptom. It is to be able to enhance the physiological activity by inducing.

[Means for solving the problem]

In order to achieve the above object, according to the present invention, there is provided a metal electrode having a higher standard monopolar potential in conductive contact with the back of a conductive matrix containing an ionic penetrant drug (active ingredient), and a standard electrode conductively connected to the metal electrode. A transdermal drug delivery device comprising a semiconductor electrode having a lower unipolar potential, wherein the semiconductor electrode and the conductive matrix containing the ionic penetrant are simultaneously in skin contact with each other.

The use of a semiconductor for the cathode, which is extremely susceptible to oxidation, stabilizes the electrode reaction of this internal reaction type battery because electrons flow out (reduction) as soon as an electrically closed circuit is formed by skin contact. In other words, it is extremely effective in performing iontophoresis continuously for a long 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 having a specific resistance of 1 Ωcm or less, particularly, an electron-supplying conductive semiconductor for the cathode. Such low-resistance conductive oxides include zinc oxide (ZnO), bismuth oxide (Bi ₂ O ₃ ), antimony oxide (Sb ₂ O ₃ ), and tin oxide (SnO ₂ ). Is a non-stoichiometric oxide having a higher electrical conductivity (lower resistance) if it contains oxygen defects. Therefore,
The cathode can be used in the form of an oxide semiconductor from the beginning, but it can also be initially used as a cathode while keeping the metal (Zn, Bi, Sb, Sn, etc.). Especially when used in a wet state, it is quicker, but when an electrical closed circuit is formed by simultaneous anode and anode contact, electrons flow out of the metal and as a result, a thin oxide film is immediately generated on the skin contact surface. I do. The oxide film grows to a thickness of several to several tens [mu] m with the passage of current, but since the oxide film acts as a good low-resistance electron supply type semiconductor, such a method can be used. However, when the metal is oxidized while being in contact with the metal, a good oxide film is often not formed with a constant thickness due to uneven position of the oxidation. Therefore, the metal surface on which these non-stoichiometric oxides are formed is thinned in advance (several hundreds of μm to 1 μm).
It is preferable that the oxide film is formed beforehand and then contacted. Oxidation after skinning progresses relatively uniformly due to this oxide film / metal double layer structure, and reaches the stable oxide film thickness described above.

Further, when a material such as germanium, the same compound, a mixture, silicon, the same compound, a mixture, a rare earth compound, or a mixture is used as a semiconductor cathode, these are converted into cations by skin conduction and penetrate into a living body. As a result, it is known to induce interferon or the like in a unit proportional to the osmotic concentration in a living body, and the generated cytokine such as interferon enhances the biologically active action of the living body, and thus has a more favorable effect on the treatment.

[Action]

When the semiconductor cathode of the present invention is used in an internal reaction battery for iontophoresis, a stable and constant electromotive force is generated for the following reasons. That is, as shown in FIG. 1 (a), the semiconductor cathode 3 is connected to the anode metal 1 by the conductive wire 4 to be conductively connected, and the conductive matrix containing the ionic penetrant (M ⁻ ) brought into conductive contact with the anode metal 1 2 (here, the matrix is not a grid-like shape, but a substrate), when it comes into skin contact with the skin surface of the living body, as shown in the figure, due to the standard unipolar potential difference of the negative anode, 3 toward the anode metal 1 from the free electrons (e ^-) flows out, the conduction band of the semiconductor cathode 3 as shown in Figure 1 is an electron deficient (b), the semiconductor cathode 3
Energy band is inclined. At this time, the semiconductor cathode 3
A Schottky potential barrier β is formed on the surface in contact with the skin, and a depletion layer is formed. However, when a low-resistance oxide semiconductor is used for the cathode, electrons are thermally excited from a continuous defect level formed by oxygen defects as shown in the figure and supplied to the conduction band, so that the effective oscillation is constantly stabilized. Power is preserved. At this time, the source of the electrons thermally excited through the defect level is a full band of the oxide semiconductor, and thus, in the full band, holes (h ⁺ ) are generated. Since the holes are self-biased in the forward direction in the semiconductor, they flow toward the skin contact surface as shown in the figure. As a result, the oxide semiconductor molecules are positively ionized on the surface in contact with the skin. Cations do not dissociate and penetrate into living skin. The holes flow into the living skin as it is,
Biological ions (for example, iron ions) existing in this region
^Is oxidized (Fe ²⁺ + h ⁺ → Fe ³⁺ ).

On the other hand, when a non-oxide crystal such as germanium is used as the semiconductor cathode, the semiconductor atoms (or molecules) cationized on the skin contact surface by holes generated by the process shown in FIG. Is in an unstable state because it is much weaker than oxide (due to strong covalent bonding)
It is dissociated from crystals by the repulsion between adjacent homogeneous cations and the electrolytic action of the skin surface (catalytic action of the electrolyte), and penetrates into the body as semiconductor cations. As described above, germanium ions and the like have a function of producing cytokines such as interferon and interleukin in vivo.
Since the physiological action is activated, the healing effect is often increased in conjunction with the action of the therapeutic ionic drug permeating into the living body from the anode side. In this case, iontophoresis occurs on the cathode side as well as on the anode side. Further, in this case, the cations are successively dissociated at the skin contact surface of the cathode semiconductor, so that a fresh atomic surface is in skin contact.

When a semiconductor cathode is used instead of a metal cathode, the Schottky barrier β at the skin contact surface as shown in FIG.
Is formed, and the bottom of the conduction band of the living body and the bottom of the conduction band of the semiconductor become discontinuous at this part. Therefore, even if semiconductor atoms are cationized on the skin contact surface, electrons flow from the skin surface and become electrically neutral. There is no sum. Therefore, ionization of the semiconductor cation and permeation into the living body are possible. On the other hand, JP-A-60-20
When a metal is used for the cathode as in No. 3270, electrons are replenished from the living body to the metal side because the skin surface and the metal are in contact with the skin and the bottom of the electron conduction band is continuous. In other words, if a noble metal such as a magnesium alloy is used for the cathode instead of a readily oxidizable base metal, if noble metal is used for the cathode, electrons will not be formed from the living body without forming an oxide film even after long-term use on the skin contact surface. Since replenishment continues, metal cationization and ionization do not occur. However, in this case, it is obvious that a noble metal having a higher standard monopolar potential than the cathode side must be used as the anode.

In addition, the anode metal 1 of the present invention is usually a gel matrix 2
Since the pH of the matrix 2 changes due to the infiltration of the ionic drug salt contained in the matrix 2 into the living body by the permeation of the ion M ^−, a metal that is resistant to corrosion, such as a noble metal, It is desirable to use. In addition, when the transdermal administration device is in contact with the skin for a long period of time, a problem such as a rash on the skin of the living body due to a pH change (alkalization) occurs. Use of insoluble salt formation reaction by blending, use of esterification by blending alcohol, etc.
Matrix composition determinations should take into account the occurrence of neutralization reactions.

〔Example〕

(Part 1) As shown in FIG. 2, a metal cathode 3 having a width of 3 mm with an interval of 1 cm outside a mesh electrode 1 (using gold) having a diameter of 2 cm.
, And both electrodes 1 and 3 were short-circuited by the conducting wire 4. The electrode 1 using mesh-shaped gold is an anode, and a conductive matrix 2 containing an ionic drug to be penetrated is disposed in close contact with the lower surface thereof. The transdermal administration element was in intimate contact with the back of a white rabbit that had been shaved and then depilated, and was fastened with an adhesive tape to examine the administration effect over time. In order to compare the permeation effect, an electrode 1 using mesh-like gold was prepared by combining a conductive matrix 2 containing 0.4 mol of sodium salicylate,
Similarly, the skin contacted the back of the white rabbit. The conductive matrix base material is polyvinylpyrrolidone gel, and the ionic permeating agent is selected from sodium salicylate, sodium ascorbate, and tretinoin calcium, and 0.4 mol of each is dispersed in the gel base material. The matrix 2 is used. The material of the metal cathode 3 was a magnesium alloy or zinc (zinc oxide).

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

FIG. 3 shows that each of the ionic drugs of salicylic acid, ascorbic acid and tretinoin uses the element shown in FIG. 2 to induce iontophorase and permeate the rabbit body. That is, for comparison, the blood concentration by iontophoresis was clearly higher than the percutaneous absorption concentration of salicylate ion (… ×… ×…) by the element that only causes concentration diffusion in contact with rabbits. I have. However, the penetration effect when using a magnesium alloy as the metal cathode is significantly lower than when using zinc. In the case of using a magnesium alloy, the blood concentration was reduced as a result of time lapse data even after skin contact, and finally fell to a value not much different from the blood concentration due to concentration diffusion.

This is because the cathode metal 3 during iontophoresis
In the nature of the oxide film formed on the surface. The element of each rabbit used in the iontophoresis experiment was removed 24 hours after skin contact, and the skin contact surface of the cathode metal 3 was examined. The gray-white color is due to an oxide film having a film thickness of 5 to 30 μm. When only the cathode metal 3 was separated from the device and the conduction was examined, zinc showed good conduction characteristics (specific resistance 0.6 Ωcm). In the case, the insulating film was formed and there was no conduction at all. In order to examine the progress of the formation of the oxide film, only the conductive matrix 2 of the anode was removed from the device shown in FIG. 2, and pure water was sprayed on the cathode metal and the skin was in contact with the back of a white rabbit which had been subjected to shaving and depilatory treatment. In this case, the element made of zinc and the element made of magnesium alloy were independently in contact with each other at two places on the back of one white rabbit, and the cathodes were turned on at regular intervals. It was removed and the skin was examined. As a result, it was visually observed that an oxide film began to form on the skin contact surface only about 2 hours after skin contact with both the zinc cathode and the magnesium alloy cathode. The oxide film thickness increases with time, but in the case of a magnesium alloy cathode, the resistance rises from 2 hours after skin contact (resistivity number + Ωcm), and after 4 hours, the resistivity is several However, the specific resistance remained below 0.1 Ωcm even after 4 hours in the case of the zinc cathode. That is, when a magnesium alloy cathode was used, the circuit resistance of the electrical closed circuit composed of the element and the rabbit in FIG. The performance of the reactive battery suddenly decreases, and iontophoresis stops in a relatively short time (about 10 hours after skin contact). On the other hand, in the case of a zinc cathode, the zinc oxide semiconductor film formed on the skin contact surface sufficiently serves as an electron supply source, so that iontophoresis is maintained for a long time. In the case of zinc cathode, the specific resistance is 1 Ωcm even after 72 hours since skin contact
Therefore, the internal resistance of the battery is sufficiently small and effective as a power source for iontophoresis. Therefore, the zinc cathode of FIG. 3 (effectively a zinc oxide cathode)
It is considered that the gradual saturation characteristic of the drug blood concentration in the above is not due to the deterioration of the cathode characteristics but to the balance between supply and discharge of each ionic drug to the living body.

(Part 2) It has the element shape shown in FIG. 2, the anode metal 1 is a material in which a platinum thin film (about 2 μm in thickness) is plated on a nickel plate surface, and the conductive matrix 2 is 0.8 mol in gelatin gel. Is an ionic drug source in which sodium citrate is dispersed,
The cathode 3 formed five types of transdermal drug delivery devices using an internal reaction type electromotive force, in which the starting materials were zinc, bismuth, lead, antimony, and tin metals each having a thin oxide film chemically formed on the surface thereof. Further, for comparison, a gel (without using a cathode) in which 0.8 mol of a sodium citrate-dispersed gelatin gel matrix was conductively adhered to a nickel plate having a diameter of 2 cm was separately prepared. Each element and a comparative pad (using only concentration diffusion) were adhered to the back of another white rabbit, which had been subjected to shaving and depilatory treatment, with an adhesive tape. After 24 hours had elapsed, the blood of each test rabbit was collected and citrated into the blood. The concentration was examined. As a result, Table 1 was obtained.

Table 1 shows that the iontophoresis using the device shown in FIG. 2 still functions effectively after day and night skin contact. It can be seen that transdermal absorption by iontophoresis is 6 to 10 times higher than absorption by simple diffusion. The device current in FIG. 2 after 24 hours was 8 μA. This value is almost the same as about 9 μA at the start of skin contact. After 24 hours, the device was removed, and the skin contact surface of the cathode metal was examined. As a result, it was found that all surfaces were covered with a stable milky white oxide semiconductor.

Next, the cathode 3 of the element shown in FIG.
An annular plate formed by sputtering a zinc oxide film having a thickness of about 10 μm was formed. That is, an element using a low-resistance oxide semiconductor for the cathode 3 before the start of skinning was produced. The anode metal 1 and the conductive matrix 2 are the same as the samples A to F. This element was in skin contact with the back shaved part of a white rabbit, and after 24 hours, blood was collected and the citrate concentration in the blood was measured.
μg / ml, and almost the same results as those of Sample A in Table 1 were obtained. This fact indicates that, in the transdermal administration device using the internal reaction type electromotive force of the present invention, only the conductive oxide semiconductor is used in advance as the cathode, or the conductive oxide semiconductor is It shows that it is also possible to adopt a metal as shown in Table 1 which is formed quickly or a metal which can form a non-stoichiometric oxide as shown in Table 1 having a very thin oxide film formed on the surface.

(Part 3) A 1 cm square, 0.2 mm thick silver plate was used as the anode metal 1 and a 1 cm square,
A 0.5 mm thick n-type germanium single crystal plate (carrier concentration 1 × 10 ¹⁸ cm ⁻³ ) was used as the semiconductor cathode 3, and both were arranged at 5 mm intervals as shown in FIG. . Next, dexamethasone is placed on the back of the anode metal 1.
A gel matrix 2 comprising 0.3 mol of polyvinylpyrrolidone, glycerin and 1% saline was applied to form a device for transdermal administration (device G). In addition, the semiconductor cathode 3 of this device was replaced with a device obtained by chemically vapor-depositing phosphorus-doped n-type SiC (carrier concentration: 1 × 10 ¹⁸ cm ⁻³ ) to a thickness of 15 μm on the surface of a 1 cm square tin plate (device H). , And the semiconductor cathode 3 were replaced with one obtained by vapor-depositing a 0.5 μm-thick lanthanum boride (LaB ₆ ) on the surface of a 1 cm square iron plate.

These elements were shaved from the back hairs of different C3H mice (male) and attached to the site with viscous tape, and the changes in dexamethasone and interferon blood concentrations over time were examined. In the experiment, three groups of C3H type mice were prepared as a group of four mice, and elements G, H and I were attached to each group,
One animal was taken out of each group every 6 hours and blood was collected and examined. For comparison, the semiconductor cathode of FIG.
An element (element J) having a thick zinc oxide film formed on the surface of an m-sized zinc plate was prepared and attached to the back skin of two C3H-type mice (males), and after 12 hours and 24 hours, respectively. The blood levels of dexamethasone and interferon were examined.
The result is shown in FIG. Regardless of which element is used, the concentration of dexamethasone in the body increases as time elapses after skin contact due to the effect of iontophoresis, and reaches a saturation point 24 hours later. At the same time, what is characteristic is the element
In G, H and I, compared to the element J using an oxide cathode,
The interferon concentration in the blood is increasing over time. On the other hand, in the case of the device J, the increase in the interferon concentration due to the skin contact of the device is only slight.
To clarify the reason, the concentration of lanthanum in the blood of the mouse to which the element I was attached was examined. As a result, it was found that the lanthanum concentration increased with time from the zero level before the element was attached. Further, the elements G and H
Significant amounts of germanium and silicon were also detected from the blood of the mouse 24 hours after the application of the. On the other hand, from the blood of the mouse 24 hours after the attachment of the element J, only the same zinc concentration as that before the attachment of the element was detected. Therefore, it can be concluded that the increase in the interferon concentration in the blood of the rats to which the devices G, H and I were applied was caused by the cathode semiconductor material penetrating into the mouse as a result of iontophoresis. The cathode skin contact surfaces of these devices (G, H, I) were hardly oxidized even after 24 hours.

(Part 4) In the device for transdermal administration shown in FIG.
Is a phosphorous doped n-type zinc sulfide (carrier concentration of 8 × 10 ¹⁷ cm) in which a conductive matrix 2 disposed on the lower surface is an agar gel containing 0.1 mol of potassium nalidixate and a cathode semiconductor 3 is adhered on a copper plate. ^-3 ) thin film (thickness about 0.5μ)
m) (element K) and the iron boride FeB film (thickness: about 1 μm) in which the cathode semiconductor 3 was deposited on a copper plate (element L), a living skin contact experiment of the element was performed. As in the previous example, the back hair of a C3H-type mouse (male) was shaved, and elements K and L were attached to separate mice, and 48 hours later, the blood of the mouse was collected and the blood concentration of the drug was examined. . As a result, it was confirmed that iontophoresis was induced not only below the anode but also on the cathode side. That is, nalidixic acid was detected in the blood of both mice in the amount of 50-60 μg / ml, and the blood concentration of zinc was three times higher in the mouse with element K than in the mouse with element L. Strong detection,
Conversely, in the mouse to which the element L was attached, about 20% higher iron content was detected than in the mouse to which the element K was attached. This is because, as described in the section above, the cathode semiconductor 3 becomes cationized at the skin contact portion, and dissociated from the crystal in a molecular unit by the electric repulsion between adjacent cations and the surface catalysis of the skin. , Which have permeated the body. Zinc and iron are rare constituent elements of living organisms, and are preferable elements for living organisms if they are not excessively consumed.

〔The invention's effect〕

As described above in detail in Examples, in the case of a biocell-type transdermal drug delivery device using a semiconductor cathode of the present invention, skin resistance change that is a concern when a portable external power source such as a dry battery or a storage battery is used. Therefore, it is possible to supply an extremely safe and stable transcutaneous current for a long period of time to a living body during daily activities without fear of excessively large current flow or a decrease in electromotive force over time. In addition, compared to the conventional biocell-type parenteral administration device in which the oxide film uses a metal having insulating resistance for the cathode, the active ingredient of the ionic drug placed on the anode is transdermally absorbed for a much longer time than the conventional biocell-type drug administration device. It was shown to be very effective in treating the affected area of a living body. Furthermore,
If a low-resistance material that is non-oxide and contains ions that are bioactive in living organisms is used as the cathode semiconductor, iontophoresis occurs not only under the anode but also under the cathode, and This is advantageous because the therapeutic effect of the ionic drug can be further enhanced.

According to the present invention, transdermal administration has become a more effective biological treatment method than before.

[Brief description of the drawings]

FIG. 1 is a diagram for explaining the principle of the present invention, FIGS. 2 and 4 are diagrams each showing another transdermal drug administration element structure of the present invention, and FIGS. 9 is data of another embodiment of the present invention. In the figure, 1 is an anode metal (or mesh electrode), 2 is a conductive matrix containing an ionic permeating agent, 3 is a semiconductor cathode or metal cathode, and 4 is a conductor.

──────────────────────────────────────────────────続 き Continued on front page (58) Field surveyed (Int.Cl. ⁶ , DB name) A61N 1/30

Claims (3)

(57) [Claims] 1. A metal electrode having a higher standard monopolar potential in conductive contact with the back of a conductive matrix containing an ionic permeating agent, and a lower standard monopolar semiconductor electrode conductively connected to the metal electrode. A transdermal administration device, wherein the semiconductor electrode and the conductive matrix containing the ionic drug penetrate simultaneously. 2. The semiconductor electrode according to claim 1, wherein said semiconductor electrode is an electron-supply-type conductive oxide semiconductor or zinc, bismuth, lead, antimony and tin whose at least a surface layer is a conductive oxide semiconductor and a lower layer of said semiconductor is formed by surface oxidation. 2. The transdermal administration device according to claim 1, wherein the device is a bilayer formed of at least one metal consisting of: 3. The semiconductor device according to claim 1, wherein said semiconductor electrode is formed of a semiconductor made of an element or a compound thereof which exhibits a physiologically active action upon interferon induction or the like when ion-permeated into a living body. Transdermal dosage element.