JP2000237326A - Iontophoresis apparatus - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide an iontophoresis apparatus which administers an ionic medicine. SOLUTION: An iontophoresis electrode section 1 comprises an electrode material 11 which is connected to a power source of the same kind of the polarity as the polarity of the electrification ions of the ionic medicine, a conductive medium 12 which is disposed at the electrode material, an ion exchange membrane 13 which selects the ions opposite to the electrification ion of the ionic medicine, the ionic medicine 14 which is disposed on the ion exchange membrane for selecting the ions opposite to the electrification ion of the ionic medicine and an ion exchange membrane 15 which is disposed at the ionic medicine and selects the ions of the same kind as the electrification ions of the ionic medicine. A ground electrode section 2 comprises an electrode material 21 which is disposed adjacently to the iontophoresis electrode section, is integrally constituted. and has the polarity opposite to the polarity of the electrode material of the iontophoresis electrode section and an ion exchange membrane 23 which is disposed at the conductive medium and selects the ions opposite to the electrification ions of the ionic medicine.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a device used for percutaneously administering various ionic drugs (transdermal drug delivery) by iontophoresis (hereinafter referred to as an iontophoresis device). ). More specifically, according to the present invention, a stable energized state (constant current and / or constant voltage) is ensured for a long time in the iontophoresis electrode section (working side electrode section) and the ground electrode section (non-working side electrode section). Therefore, the positively (+) or negatively (-) charged drug component of the ionic drug can be efficiently transported (driven) to the skin (or mucous membrane) side in the iontophoresis electrode portion. The electrode portion (working-side electrode portion) and the ground electrode portion (non-working-side electrode portion) contribute to maintaining the above-mentioned stable energized state, and can eliminate the adverse effect on the skin due to the electrode reaction. Operability (convenience) can be improved because the toforease electrode and the ground electrode are integrated, and the iontophoresis electrode and the ground electrode are alternated. An ionic drug by integrating a plurality of sets may be percutaneously delivered to a desired depth, it relates to the iontophoretic device having excellent characteristics that.

[0002]

2. Description of the Related Art An electromotive force for driving an ionic drug (ionic chemical substance) placed on the skin or mucous membrane (hereinafter simply referred to as skin) at a desired site is applied to the skin. A method of introducing (penetrating) these ionic drugs into the body through the skin is called iontophoresis (iontophoresis, iontophoresis, iontophoresis, iontophoresis) (the iontophoresis of the iontophoresis). For the definition, see, for example, JP-A-63-352.
No. 66 is helpful).

As mentioned above, iontophoresis (io)
In ntophoresis, an ionizable ionic drug placed on the skin is driven (transported) under a predetermined electromotive force to penetrate the skin. For example, positively charged ions are driven (transported) into the skin on the anode side of the electrical system of the iontophoresis device. On the other hand, negatively charged ions are driven (transported) into the skin on the cathode side of the electrical system of the iontophoresis device.

[0004] Examples of the ionic drugs applied to the above-mentioned iontophoresis include the following. (1). Positively charged ionic drugs: anesthetics (procaine hydrochloride, lidocaine hydrochloride, etc.), drugs for gastrointestinal diseases (carnitine chloride, etc.), skeletal muscle relaxants (banklonium bromide, etc.), antibiotics (teotracycline) Formulations, kanamycin formulations, gentamicin formulations). (2). Negatively charged ionic drugs: vitamin (hereinafter abbreviated as V) agents (VB ₂ , VB ₁₂ , VC, VE, folic acid, etc.), adrenocortical hormones (hydrocortisone-based water-soluble preparations, dexamethasone-based water-soluble agents) Preparations, prednisolone aqueous solutions, etc.), antibiotics (penicillin aqueous solutions,
Chromium phenicol aqueous solution).

A method of administering an ionic drug by iontophoresis and a device to be applied to the method have been studied and developed for a long time, and various types have been proposed. As a conventional technique relating to this type of iontophoresis, there is a technique using an ion exchange membrane. As will be described later in detail, the present invention also belongs to a category using an ion exchange membrane. Therefore, in order to help understand the difference between the present invention using an ion exchange membrane and the prior art,
Hereinafter, a conventional technique using an ion exchange membrane will be described in detail.

[0006] 1. Patent Application Publication No. 3-504343 (hereinafter referred to as Conventional Technique 1) (1). This Conventional Technique 1 is used as an iontophoresis electrode for (i) an electrode plate, and (ii) ionic properties to be permeated. A reservoir containing (or ionizable) drug; (iii) an ion exchange disposed outside the reservoir (on the side in contact with the skin) and having an ion of the same polarity as the ionic drug. And a membrane. (2). According to the prior art 1, when the function of the ion exchange membrane is transferred (driven) to the skin side of the ionic drug, the ion exchange membrane moves to the electrode side beyond the interface between the electrode and the skin by the ion exchange membrane. Constraining the movement of oppositely charged ions that are to migrate,
For example, it describes reducing the movement of sodium, chlorine, and other ionic species that may be present in the skin and create ionic current paths different from ionic drugs. (3) Also, in the prior art 1, since the ion exchange membrane can reduce the amount of other mobile charged carriers in the reservoir containing the ionic drug, the administration efficiency of the ionic drug can be reduced. It can be increased.

[0007] 2. U.S. Pat. No. 4,722,726 (hereinafter referred to as "prior art 2") (1). This prior art 2 is described as a related art in the above-mentioned prior art 1 publication. The iontophoresis electrode is divided into (i) an upper chamber filled with a buffer solution (buffer solution) and a lower chamber filled with an ionic drug, and (ii) the upper chamber is a lower chamber by an ion exchange membrane. An electrode having a structure isolated from the electrode is disclosed. (2) This prior art 2 explains that the upper chamber filled with a buffer solution (buffer solution) mitigates the adverse effect of water hydrolysis, and that the ion exchange membrane separates the ionic drug from the contents of the upper chamber. are doing. However, the technique using the buffer solution disclosed in the prior art 2 clearly increases the concentration of additional ionic species in the system, and thus obviously lowers the transport efficiency of charged ions of the active drug component of the ionic drug. It also has undesirable aspects. Therefore, attention should be paid to the technique of simply using a buffer solution.

[0008] 3. JP-A-3-94771 (hereinafter, referred to as "
This is referred to as Conventional Technology 3. (1). This prior art 3 is (i) a moisture holding portion surrounded by a flexible supporting member and having an electrode plate therein, and (ii) disposed on the front surface (skin side) of the moisture holding portion. Ion exchange membrane,
And (iii) an electrode for iontophoresis comprising a drug layer (ionic drug layer) disposed on the front surface (skin side) of the ion exchange membrane. (2) The prior art 3 attempts to administer the drug at a high concentration while preventing dilution with water when administering the ionic drug. (3) For this reason, the prior art 3 uses a water-permeable ion-exchange membrane that is substantially impermeable to a drug, and spray-drys the drug on the living body (skin) contact surface. An electrode for iontophoresis is formed by using a material adhered or adhered by spraying or the like.

4. JP-A-4-297277 (hereinafter referred to as prior art 4) (1). This prior art 4 relates to an earlier application filed by the present applicant, and for example, in FIG. (Working electrode section) (In the case of FIG. 2, the cathode is the working electrode section in relation to the polarity of ions of the ionic drug to be used.) The cathode plate / gauze / cation containing the ionic drug It discloses a multilayer structure composed of an exchange membrane / a gauze containing an ionic drug / anion exchange membrane. (2). The iontophoresis technology disclosed in the prior art 4 is a subject of improvement of the present invention, and the limitations of the prior art 4 will be described in detail in the description of the present invention described later. .

In the above-mentioned prior art, the prior art 4
When attention is paid to the number of ion exchange membranes used (arranged), the conventional techniques 1 to 3 have a single-layer structure using one ion exchange membrane, whereas the conventional techniques 1 to 3 use two ion exchange membranes. This is different from the others in that a multi-layer structure is disclosed. Focusing on the number of used ion-exchange membranes, the present invention belongs to a multi-layer structure as in the above-mentioned prior art 4. However, the present invention is based on a technical idea completely different from that of the prior art 4, which will be described in detail later. The ground electrode (ground electrode,
There is a significant feature in that a three- or four-layer structure in which an ion-exchange membrane is provided also for the neutral electrode portion).

[0011]

As described above, in a method of transdermally administering an ionic drug by iontophoresis, there is a technique using an ion exchange membrane. However, the above-described iontophoresis technology using the conventional ion exchange membrane involves electrochemical reaction on the electrode plate surface in the iontophoresis electrode section (working side electrode section) and / or the ground electrode section (non-working side electrode section). Lack of initiative or creativity to prevent or eliminate various disadvantages based on reactions. In other words, the conventional iontophoresis technology using an ion-exchange membrane is based on the total overall electrochemical reaction between the iontophoresis electrode (working electrode) and the ground electrode (non-working electrode). And lacks an attitude to eliminate the drawbacks induced thereby and to establish high value-added iontophoresis technology.

For this reason, the iontophoresis technology using the conventional ion exchange membrane, more specifically, the ion exchange membrane is used in the working side electrode portion as seen in the above-mentioned conventional technology, but the ground electrode is used. The conventional iontophoresis technology, which is not used in some parts, has the following disadvantages.

(I) It is difficult to administer an ionic drug (drug delivery) under a stable power supply state for a long period of time (operation under conditions of constant voltage or current stable for a long period of time) Is difficult to do). For example, the polarity of the working electrode portion differs depending on the polarity of the charged ions of the active ingredient of the ionic drug, but in the positive (+) working electrode portion, a physiological medium, which is a conductive medium, is applied at the electrode plate interface. The gas is decomposed to generate bubbles (oxygen gas, chlorine gas, etc.), which increases the current-carrying resistance and rapidly reduces the iontophoresis effect (ion transport efficiency) with time. The above is also caused by bubbles (such as hydrogen gas) generated in the negative (-) pole ground electrode portion.

(Ii) At the contact surface between the working electrode and / or the ground electrode and the skin, burns, inflammations (current burns induced by the current itself, H ⁺ generated by electrolysis)
Or OH ^- and the like pH-induced burns due to sudden change in pH. ) Etc. occur.

(Iii) The electrode plate (for example, +
At the contact surface between the skin and the skin, hypochlorous acid based on harmful substances generated by sweat on the skin surface or electrolysis of saline as a conductive medium, for example, Cl ⁻ (chlorine ion) (Known as a suitable oxidizing agent), causing skin damage and the like.

(Iv) At the contact surface between the electrode plate (eg, one pole) of the ground electrode portion and the skin, harmful substances generated by electrolysis of sweat on the skin surface or saline as a conductive medium, for example, High alkalinity (NaOH) causes skin damage and the like.

The present invention has been made in view of the disadvantages and limitations of the conventional iontophoresis technology using the above-mentioned ion exchange membrane. The present inventors have intensively studied a conventional iontophoresis technique using an ion exchange membrane in order to increase the added value.

As a result, the present inventor has proposed that the configuration of the iontophoresis electrode section (working-side electrode section) of the iontophoresis apparatus be based on the effectiveness of the ionic drug disclosed in Japanese Patent Application Publication No. 3-504343. An iontophoresis electrode material (working-side electrode material) connected to a power source of the same type as the charged ions of the drug component, an ionic drug disposed on the front surface of the iontophoresis electrode material, and a front surface of the ionic drug An ion-exchange membrane that selects the same type of ions as the charged ions of the active drug component of the ionic drug disposed on the side of the part that contacts the skin. The configuration between the iontophoresis electrode material and the ionic drug is viewed from the iontophoresis electrode material side, and (i) at least the iontophoresis electrode material Along with disposing a conductive medium such as physiological saline on the front part, (ii) an ion exchange membrane for selecting an ion opposite to the charged ion of the active drug component of the ionic drug is provided on the front part of the conductive medium. It has been found that when arranged and configured, the above-mentioned drawbacks in the iontophoresis electrode section are eliminated.

Furthermore, the present inventor has never known that an ion exchange membrane is provided on the side of a ground electrode (non-working electrode) in a conventional iontophoresis apparatus using an ion exchange membrane. However, when the configuration of the ground electrode portion (the non-working side electrode portion) is viewed from the electrode material side of the ground electrode portion, (iii). A conductive medium such as saline is disposed at least on the front surface of the ground electrode material. And (iv). When an ion exchange membrane for selecting an ion opposite to the charged ion of the active drug component of the ionic drug is arranged on the front surface of the conductive medium, the above-mentioned drawbacks in the ground electrode portion are disadvantageous. Found that it will be resolved.

The present invention is based on the above-mentioned findings, and comprises an iontophoresis electrode section (working-side electrode section) and a ground electrode section (non-working electrode section) integrating the above-mentioned constitutions (i) to (iv). The present invention is to provide an iontophoresis device incorporating a side electrode portion). ADVANTAGE OF THE INVENTION According to this invention, the administration efficiency of an ionic drug is high under the stable electricity supply state (state of constant current and / or constant voltage) for a long time, and the biosafety which prevented the burn and inflammation of the skin surface was improved. Administration of ionic drugs with high iontophoresis (drug delivery)
Is provided, a novel iontophoresis device capable of realizing the following.

[0021]

SUMMARY OF THE INVENTION In general, the present invention is directed to an iontophoretic electrode (operating electrode) connected to a power source used to administer an ionic drug by iontophoresis. And an iontophoresis device having a ground electrode portion (non-working side electrode portion)
(1) .The iontophoresis electrode section is (1) -1. An electrode material connected to a power source having the same polarity as the charged ions of the ionic drug, (1) -2. (1) -3. An ion exchange membrane for selecting an ion opposite to a charged ion of the ionic drug disposed on the front surface of the conductive medium, (1) -4. An ionic drug disposed on the front surface of the ion exchange membrane to select an ion opposite to the charged ion, and (1) -5 of the same type as the charged ion of the ionic drug disposed on the front surface of the ionic drug. An ion exchange membrane for selecting ions.

Further, the present invention provides (2): The ground electrode portion is adjacent to the iontophoresis electrode portion, and
In addition to being integrally formed, (2) -1. An electrode material having a polarity opposite to that of the electrode material of the iontophoresis electrode portion, and (2) -2. A conductive medium disposed at least in front of the electrode material. And (2) -3. An ion exchange membrane, which is disposed on the front surface of the conductive medium and selects an ion opposite to the charged ion of the ionic drug. About.

The present invention also provides a method for improving the performance of an iontophoresis device having the above-mentioned iontophoresis electrode section (working side electrode section) and a ground side electrode section (non-working side electrode section). The conductive medium of the iontophoresis electrode section and the ground electrode section is characterized by being composed of a substance containing a substance which is easily oxidized or reduced, and more specifically, (ii). The conductive medium of the toforase electrode portion and the ground electrode portion is composed of a material containing ferrous sulfate and ferric sulfate, or an organic acid and / or a salt thereof as a substance easily oxidized or reduced. It is a feature.

Further, according to the present invention, in order to improve the performance of the iontophoresis device, the ground electrode portion (non-working side electrode portion) is constituted by using a combination of a cation exchange membrane and an anion exchange membrane. It is characterized by the following. It should be noted that one ion exchange membrane (the ion selectivity of the ion conversion membrane differs depending on the charging polarity of the ionic drug) is used for the above-mentioned ground electrode part, and further, the ion selectivity differs for the ground electrode part. The use of two types of ion exchange membranes is not found at all in the prior art.

Hereinafter, the technical structure of the present invention will be described in more detail. First, in order to gain an understanding of the present invention, a conventional method of administering an ionic drug by iontophoresis using the basic configuration diagram of the iontophoresis device of the present invention and its problems, and furthermore, the ionic drug of the present invention The features of the method of administration will be described. Next, a specific configuration of the iontophoresis device of the present invention will be described. Although the drawings are referred to for explaining the technical configuration of the present invention, those shown in the drawings should be interpreted as merely one embodiment, and the present invention is not limited to these drawings. There is no such thing.

FIGS. 1 and 2 show the basic configuration of the iontophoresis device (X) of the present invention. 1 is a perspective view, and FIG. 2 is a sectional view of a main part. 1 and 2
FIG. 3 also shows a method of administering an ionic drug (drug delivery) by a new iontophoresis realized by the iontophoresis device (X) of the present invention.

FIG. 3 is a diagram showing the basic configuration of the iontophoresis device (X) when the administration of the ionic drug is performed under the following conditions in the iontophoresis device (X) of the present invention shown in FIG. FIG. (i) As an ionic drug, a sodium (Na) salt of ascorbic acid (vitamin C) (hereinafter sometimes abbreviated as As ⁻ Na ⁺ ) is used. (ii). Physiological saline (Na ⁺ Cl ⁻ aqueous solution) is used as the conductive medium. In the present invention, as the physiological saline, in order to remove defects caused by the electrode reaction,
In some cases, ferrous sulfate and ferric sulfate having a redox potential lower than the electrolytic potential of water or a substance to which a substance which is easily redox-reduced such as an organic acid is added. (iii) The iontophoresis electrode section (working-side electrode section) is used as a cathode (negative pole). (iv). Connect the ground electrode (non-working side electrode) to the anode (+
Pole). (v). The type (selective permeability of ions) of the ion exchange membrane to be used and the arrangement site are as shown in the figure.

FIG. 4 shows a basic configuration diagram of the iontophoresis device (X) of the present invention in which the performance of the iontophoresis device (X) shown in FIG. 3 is further improved. As shown in FIG. 4, the ion exchange membrane of the ground electrode portion (2) in FIG. 4 is a combination of the cation exchange membrane (23) and the anion exchange membrane (25), as compared with that of FIG. It is different in that it is configured.

In FIGS. 1 to 4, the reference numerals in the drawings correspond to the reference numerals of the respective components of the iontophoresis device described in the section of "Means for Solving the Problems". For example, “(1) -1” as a component of the iontophoresis device (X) of the present invention is indicated as “11” in the figure.

The greatest feature of the iontophoresis device (X) of the present invention is that the purpose of this type of iontophoresis is to apply an ionic drug to the body through the skin (or mucous membrane) under a predetermined electromotive force. It is well known in the prior art that the amount of ions that move with a certain electromotive force (this depends on the ion concentration, the ion mobility, and the valence of the ions). ), The present invention focuses on the electrochemical reaction of each electrode part, and particularly focuses on the disadvantageous factor (negative factor) based on the electrochemical reaction, from which the iontophoresis is performed. The technology is being rebuilt.

In iontophoresis, the electrode portion necessarily undergoes an electrochemical reaction, that is, an oxidation reaction (anode) and a reduction reaction (cathode). Then, by the electrochemical reaction, for example, the generation of harmful substances by the electrolysis of physiological saline as a conductive medium (for example, hypochlorite caused by Cl ⁻ , which is known as a strong oxidant at the anode) Acid formation), rapid pH changes (rapid acidification at the anode, rapid alkalinization at the cathode), or the formation of bubbles (eg, H ₂ gas at the cathode, O ₂ gas or Cl ₂ at the anode). The generation of gas) causes fatal defects in iontophoresis, such as adverse effects on human skin, skin irritation, and inability to conduct electricity (increase in resistance due to gas generation).

The present invention aims at improving the iontophoresis technology and increasing the value of the iontophoresis technology based on the elimination of the drawbacks caused by the electrochemical reaction occurring at the electrode portion in the iontophoresis.

The iontophoresis device (X) of the present invention
FIG. 2 shows a conventional method for administering an ionic drug in order to eliminate the above-mentioned drawbacks.
As shown in FIG. 3, (i). As the configuration of the iontophoresis electrode section (working-side electrode section) (1), the above-described technical components (1) -2 to (1) of the present invention are used. 3 (indicated by reference numerals 12 to 13 in FIGS. 2 and 3), and (ii) a ground electrode portion (non-working side electrode portion).
As the configuration of (2), the technical components of the present invention described above (2)
-2 to (2) to 3 (reference numerals 22 to 23 in FIGS. 2 to 3)
Indicated by And (iii) adopting a configuration in which the iontophoresis electrode section (working-side electrode section) (1) and the ground electrode section (2) are integrated.
Has a feature point.

The iontophoresis device (X) according to the present invention, as shown in FIG. 4, is different from the conventional iontophoresis device (X) in that (iv). As a configuration, a cation exchange membrane (2
3) using an anion exchange membrane (25) in combination, and
(v). The ground electrode part (2) having the above-mentioned feature point (iv)
There is a feature in adopting a configuration integrated with the iontophoresis electrode portion (working side electrode portion) (1) having the feature point (i) described above.

In short, the iontophoresis device (X) of the present invention is used in view of the use of an ion exchange membrane in order to eliminate the above-mentioned drawbacks caused by the electrode reaction in the conventional ionic drug administration method. It is noted that two ion-exchange membranes are used for the iontophoresis electrode and at least one ion-exchange membrane is used for the ground electrode while paying attention to the permselectivity of ions.

Furthermore, the iontophoresis device (X) of the present invention is provided with a specific ion exchange membrane as described above in order to eliminate the above-mentioned drawbacks caused by the electrode reaction in the conventional ionic drug administration method. In addition to the arrangement of the above, (vi). A material containing a substance which is easily oxidized or reduced as compared with electrolysis of water as a conductive medium for both electrode portions (iontophoresis electrode portion and ground electrode portion) There is a characteristic point in adopting.

Hereinafter, the iontophoresis device of the present invention will be described.
The above-mentioned features of (X) can be used as ionic drugs.
Sodium scorbate (As^-Na⁺)
Will be explained in the following. In this case, the active drug component of the ionic drug
Charged ions are anions (As ^- )
But it is not. For this reason, it is shown in FIGS.
Thus, the iontophoresis electrode (1) is connected to the cathode (-
Pole) and the ground electrode (2) becomes the anode (+ pole).
You. Needless to say, ionic drugs
Is dissociated into positively charged ions,
Electrode polarity and ion exchange membrane type (selection characteristics of ions)
Gender) are, of course, the opposite.
That is.

1 to 4 showing the basic structure of the iontophoresis device (X) of the present invention, reference numeral 1 denotes an iontophoresis electrode portion (working side electrode portion), and 2 denotes a ground electrode portion (non-working side electrode portion). ), 3 indicates a power supply device, and 4 indicates skin (or mucous membrane).

As shown in FIGS. 3 and 4, the iontophoresis electrode section (working side electrode section) (1) has (i).
Negative (-) electrode (11), (ii). Conductive medium (12), specifically, 0.9% NaCl aqueous solution containing ¹ MAs ^- Na ⁺ (iii). Cation exchange membrane (13), (iv) ). An ionic drug (14), specifically, a 1 MAs ^- Na ⁺ aqueous solution, and (v) an anion exchange membrane (15).

In the case of FIG. 3, the ground electrode section (2) is composed of (i) a positive (+) pole (21), and (ii) a conductive medium (2).
2), specifically, a 0.9% NaCl aqueous solution, and (iii) a cation exchange membrane (23).

In the present invention, as shown in FIG. 4, the ground electrode portion (2) has a positive (+)
From the direction of 1) to the skin (4), (i). Positive (+) pole (21), (ii). Conductive medium (22), specifically 1M
0.9% NaCl aqueous solution containing As ^- Na ⁺ , (iii).
An anion exchange membrane (25), (iv). A conductive medium (24),
Specifically, 0.9% NaCl containing ¹ MAs ^- Na ⁺
An aqueous solution, (v) a cation exchange membrane (23).

In the present invention, the two electrode portions (1, 2)
The conductive medium (12, 22) may be composed of a compound containing a compound which is easily oxidized and reduced as compared with the electrolysis reaction of water (oxidation and reduction reaction of water).
Further, in the present invention, the conductive medium (12, 22) of the two electrode portions (1, 2) has a lower oxidation-reduction potential of the ionic drug (for example, As ^- Na ⁺ ) than water in general. These ionic drugs may be contained as a compound which is easily oxidized and reduced. The same can be said for the conductive medium (24) of the ground electrode section (2) shown in FIG.

Hereinafter, referring to the basic configuration diagram of the iontophoresis device (X) of the present invention, a more specific configuration of the iontophoresis device (X) for realizing a new administration method of an ionic drug, That is, the specific configuration of the iontophoresis electrode section (working side electrode section) (1), and then the specific configuration of the ground electrode section (non-working side electrode section, ground electrode section) (2) will be described in this order. .

In the iontophoresis device (X) of the present invention, the iontophoresis electrode section (working side electrode section)
The electrode material (11) of (1) may be made of a desired material. In addition, the electrode material (12) of the ground electrode portion (non-working side electrode portion) (2) may be configured as desired. For example, an inert electrode made of a conductive material such as carbon or platinum may be used.

In the iontophoresis device (X) of the present invention, the electrode material (11, 12) may be an active electrode known in the field of iontophoresis instead of the inactive electrode. Good thing. As an example of the above-mentioned active electrode, when the drug component of the ionic drug is a positive (+) ion, specifically, morphine hydrochloride or lithium chloride (in this case, morphine ion as a drug component, In the case of using lithium ion as a positive ion and chlorine as a counter ion as a negative ion), there is a silver electrode or the like which reacts with these counter ions as an anode (+) material. In the case of the above-described active electrode, the silver electrode and chlorine ion (Cl ⁻ ) easily react with each other, and Ag + Cl ⁻ → AgC
Insoluble AgCl is produced by l + e ⁻ . The advantage of using the active electrode is that the electrolysis reaction of water can be prevented because the standard potential of the reaction is lower than the standard potential of the electrolysis reaction of water at the anode (+). Accordingly, rapid acidification at the anode (positive electrode) based on H ⁺ ions and rapid alkalinization at the cathode (negative electrode) based on OH ⁻ ions are prevented.

However, in the iontophoresis apparatus (X) of the present invention, as described above, since the iontophoresis system uses at least three or more ion exchange membranes having different ion selectivities, the active electrode Insoluble substances (insoluble fine particles) such as silver chloride (AgCl) generated in step (1) may hinder the properties of the ion exchange membrane. From the above, the iontophoresis device (X) of the present invention uses a plurality of ion exchange membranes having different ion selectivities,
It is preferable to use a more economical inactive electrode without using a special electrode material called an active electrode. In addition, in the iontophoresis system, metal ions and the like which are inevitably generated from the electrode material are also transported, and the iontophoresis effect is reduced by that amount, so that the iontophoresis device (X) of the present invention is used as an electrode material. Is preferably a carbon electrode.

In the iontophoresis device (X) of the present invention shown in FIG. 3, the iontophoresis electrode unit (1) is disposed so as to be in contact with the negative (-) electrode material (11) of the electrode unit (1). The conductive medium (12) is made of a material containing a compound that is easily reduced. In the iontophoresis device (X) of the present invention shown in FIG.
The conductive medium (22) disposed so as to be in contact with the periphery of the positive (+) electrode material (21) of the ground electrode portion (2) includes:
It is composed of a compound containing a compound that is easily oxidized. The site for disposing the compound that is easily oxidized or reduced,
It goes without saying that the reaction corresponds to the electrochemical reaction in each electrode plate, that is, the reduction reaction at the negative (-) electrode and the oxidation reaction at the positive (+) electrode.

In the iontophoresis electrode section (1) of the iontophoresis apparatus (X) of the present invention shown in FIG. 3, a conductive medium (12) containing a compound which is easily reduced and an ionic drug as shown in the figure. (As ^- Na ⁺ ) (14)
A cation exchange membrane (13) is provided in the middle of the above. The present invention relates to the conductive medium (1) containing the compound which is easily reduced in relation to the above-described configuration.
2) is disposed so as to be in contact with the negative electrode material (11). The conductive medium (12) is, as described later,
It plays an important role. This is the same for the conductive medium (22) containing a compound that is easily oxidized on the side of the ground electrode (2).

In the present invention, the conductive medium (12)
As the compound which is easily oxidized or reduced, those which are excellent in biosafety, economical efficiency (inexpensive and easily available) and the like are preferable. For example, inorganic compounds such as ferrous sulfate and ferric sulfate , Ascorbic acid (vitamin C)
Pharmaceutical agents such as sodium and sodium ascorbate; acidic compounds such as lactic acid present on the skin surface; or organic acids such as oxalic acid, malic acid, succinic acid, and fumaric acid and / or salts thereof.

Among the compounds which are more likely to be oxidized or reduced than the above-mentioned electrolytic reaction of water (oxidation at the positive electrode and reduction at the negative electrode), for example, ferric sulfate is such that ferric ions are easily converted to ferrous ions at the negative electrode. Reduce to ions. In addition, ferrous sulfate easily oxidizes ferrous ions to ferric ions at the positive electrode. As a result, as will be described later in detail, it is possible to eliminate the drawbacks caused by the electrolysis reaction of water, and to provide excellent performance such as high biosafety related to the specific ion exchange membrane arrangement of the present invention. An iontophoresis device (X) is provided.

In the present invention, the conductive medium (12)
Are for ensuring electrical conductivity, and a typical example is a saline solution or a physiological saline solution. In the iontophoresis device (X) of the present invention, the configuration for housing or holding the conductive medium (12) may be any desired configuration. Also,
The conductive medium (12) may be, for example, a solution type or a type in which a desired medium (gauze, water-absorbing polymer material, etc.) is impregnated.

Here, as the conductive medium (12),
The advantages of using a compound containing the compound which is easily oxidized or reduced will be described in detail. In the iontophoresis electrode section (1) and the ground electrode section (2), an electrochemical reaction occurs, and decomposition of the electrolyte solution and decomposition of the ionic drug occur. As a result, air bubbles are generated in the electrode chamber, and contact between the electrode part and the electrolytic chamber solution is hindered. For example, a negative electrode is H ₂ gas, and a positive electrode is Cl ₂ and O _2.
2 gas is generated. When such a situation occurs, the resistance increases due to bubbles, and no current flows even if a voltage is applied. In the case of As ^- Na ⁺ delivery described above,
Stable energization for a long time (30 minutes or more) becomes impossible. This is a very serious problem from the viewpoint of the practicality of the iontophoresis device.

In order to remove the above-mentioned instability factor and to stably perform iontophoresis, it is extremely important to suppress the generation of bubbles. In order to achieve the above-mentioned object, it is useful to put a substance which is susceptible to oxidation or reduction reaction into each electrode chamber without generating bubbles. That is, when water is oxidized or reduced, oxygen or hydrogen is generated. To suppress these reactions, for example, ferrous sulfate, ferric sulfate, ascorbic acid or a sodium salt thereof is added to the electrode chamber solution. (Electrode solution). For example, when sodium ascorbate is used, sodium ascorbate is oxidatively decomposed instead of oxygen at the electrode where the oxidation reaction occurs, and sodium ascorbate is reductively decomposed instead of hydrogen at the electrode where the reduction reaction occurs. However, this can suppress the generation of oxygen or hydrogen bubbles which impair the stability of the current-carrying characteristics.

As described above, a substance which is more easily oxidized or reduced than water (a substance having a redox potential lower than that of water) in an electrochemical reaction such as sodium ascorbate is sacrificed. By
The generation of gas (gas) in the electrode chamber can be suppressed, and an iontophoresis device (X) capable of more stable operation can be obtained. In the present invention, in addition to the above-described ferrous sulfate, ferric sulfate, and ascorbic acid, any of the sacrificial substances may be used as long as the sacrificial substance undergoes oxidation-reduction to suppress the decomposition of water. It goes without saying that you can do it. In the case of sodium ascorbate as the sacrificial substance, sodium ascorbate is used for (i) an electrode (-electrode) where a reduction reaction occurs, to CO ₂ or H ₂ CO ₃ , and (ii) an oxidation reaction. At the electrode (+ electrode) where occurs, it changes to dehydroascorbic acid, 2,3 diketo 6-gulonic acid, and the like.

In the iontophoresis device (X) of the present invention, a desired cation exchange membrane (13) can be used. As described above, the iontophoresis device (X) of the present invention comprises a cation exchange membrane (13).
In addition, an anion exchange membrane (15) is used. Here, specific examples of both the cation exchange membrane (13) and the anion exchange membrane (15) used in the present invention will be described.

In the present invention, the cation exchange membrane (1)
3) Neosepta (CM) manufactured by Tokuyama Corporation
-1, CM-2, CMX, CMS, CMB, etc.).

In the present invention, the anion exchange membrane (1)
5) includes Neosepta (AM) manufactured by Tokuyama Corporation.
-1, AM-3, AMX, AHA, ACH, ACS, A
CS-3) can be used.

In the iontophoresis device (X) of the present invention, the configuration for containing or holding the ionic drug (As ^- Na ⁺ ) (14) may be any desired configuration. The ionic drug (14) may be, for example, a solution type or a type in which a desired medium (gauze, water-absorbing polymer material, etc.) is impregnated.

In the iontophoresis device (X) of the present invention, the ion-exchange membrane provided on the front surface of the ionic drug (As ⁻ Na ⁺ ) (14), that is, on the skin side, component of charged ions (as ^-) anion exchange membrane (15) having an ion selectivity of the same type are used.

With the technical configuration of the iontophoresis electrode section (1) of the iontophoresis apparatus (X) of the present invention, a longer and more stable iontophoresis effect and biosafety can be obtained than in the conventional method. Can be. That is,
With the above-described technical configuration, a long-term and stable current-carrying property can be obtained. In other words, an ionic drug can be efficiently penetrated into the body through the skin (4) (drug delivery), Further, generation of harmful substances due to the electrolysis reaction in the electrode portion can be eliminated.

Next, the configuration of the ground electrode (+ electrode) (2) of the iontophoresis device (X) of the present invention will be described.

The prior art relating to iontophoresis is
Regarding the configuration of the ground electrode part (earth electrode part), it is suggested that the simple idea of simply taking the ground (earth) works strongly, and that consideration is given to securing stable current-carrying characteristics and securing biological safety. It has not been done yet. This is described in Japanese Patent Application Laid-Open Publication No. 3-504343 and Japanese Patent Laid-Open Publication No.
No. 4771 and Japanese Unexamined Patent Publication No.
It is justified by looking at 297277.

The present invention relates to an iontophoresis device (X)
In addition to the configuration of the iontophoresis electrode section (1), in connection with the overall configuration of the device, it is possible to administer the ionic drug by iontophoresis stably for a long period of time, and to have a high level of biosafety. The ground electrode portion (2) is also different from the conventional technology in terms of the convenience of operation and the desired iontophoresis effect (adjustment of the depth of administration of the ionic drug, etc.). It adopts a strategic configuration.

As shown in FIGS. 1 and 2, the ground electrode section (2) of the iontophoresis device (X) of the present invention.
Is the electrode material (1) of the iontophoresis electrode section (1).
An electrode material (21) having a polarity opposite to that of 1), the electrode material (2)
The conductive medium (2) disposed at least on the front side of (1)
2) and an ion-exchange membrane (23) disposed on the front surface of the conductive medium (22), that is, on the side of the skin (4), for selecting ions opposite to charged ions of the ionic drug. And an integral part of the iontophoresis electrode section (1).

In the iontophoresis device (X) of the present invention, the point that an ion exchange membrane (23) is provided in the ground electrode portion (2) in order to enhance biosafety is a large feature not found in the prior art. It is a feature point. Further, in the iontophoresis device (X) of the present invention, in order to achieve long-term stable operation with biosafety, the ground electrode portion (1) as well as the conductive medium (12) of the iontophoresis electrode portion (1). The conductive medium (22) of 2) may be composed of a material containing a substance having a redox potential lower than the redox potential of water. And disposing an ion exchange membrane (23) on the ground electrode section (2);
Combining the use of a substance that is easily oxidized and reduced to form a high value-added iontophoresis device (X) is also a major feature not found in the prior art.

In the iontophoresis device (X) of the present invention, as shown in FIG. 2, the ground electrode portion (2) is a single ion exchange membrane (2) having a predetermined ion selectivity.
3) may be configured. The advantage of disposing the ion exchange membrane (23) on the ground electrode section (2) will be described later with demonstration data. Further, the conductive medium (22) of the ground electrode portion (2)
The advantage of adding a substance which is easily oxidized and reduced is that the conductive medium (1) of the iontophoresis electrode unit (1) has already been added.
As described in 2).

As shown in FIG. 3, the ionic drug is negative (-) such as sodium ascorbate (As ^- Na ⁺ ).
When the electrode material (2) is charged in the ground electrode portion (2) of the iontophoresis device (X) of the present invention,
1) is composed of an anode (+), the conductive medium (22) is composed of, for example, physiological saline, and the ion exchange membrane (23) is composed of a cation exchange membrane.

In the present invention, the conductive medium (22) of the ground electrode portion (2) is made of a substance which is easily oxidized and reduced, for example, ferric sulfate or ferric sulfate containing ferrous sulfate (both of them). Molar solution), physiological saline containing ascorbic acid, sodium ascorbate and the like. Further, as shown in FIG. 4, the ground electrode section (2) of the present invention may use two types of ion exchange membranes having different ion selectivities as the ion exchange membrane.

In the method of administering an ionic drug by iontophoresis described with reference to the iontophoresis device (X) shown in FIG. 3, as described above, the active drug component of the ionic drug is negative (-). Charged sodium ascorbate
(As ^- Na ⁺ ). In the present invention, even if the active drug component of the ionic drug is positively (+) charged, it can be similarly administered.

The active drug component of the ionic drug that is positively (+) charged includes, for example, procaine hydrochloride and lidocaine hydrochloride as anesthetics. In this case, it goes without saying that the polarity of each electrode material (11, 12) and the ion-exchange characteristics of the ion-exchange membrane must be completely opposite to the case of the administration of sodium ascorbate (As ^- Na ⁺ ). That is. When the positively (+) charged ionic drug is used, the features of the present invention can be easily understood by analogizing the administration case of the negatively (−) charged sodium ascorbate.

The power supply unit (3) shown in FIGS.
Can be used as desired. In the present invention, as the power supply device (3), a battery, a constant voltage device, a constant current device, a constant voltage / constant current device (galvano device)
Etc. can be used.

Next, an experimental device equivalent to the basic configuration diagram of the iontophoresis device (X) shown in FIGS.
An experimental example / comparative experimental example in the case where sodium ascorbate (As ⁻ Na ⁺ ) was administered as an ionic drug using an experimental apparatus manufactured by modifying the above experimental apparatus for collecting comparative data was described. . From the experimental examples / comparative experimental examples described below, in the iontophoresis device (X) of the present invention, it is possible to understand particularly the importance of disposing an ion exchange membrane on the ground electrode section (2). .

FIGS. 5 to 8 are schematic views of the experimental apparatus used. 5 and 6 show an apparatus for a comparative experiment. FIG.
FIG. 8 shows an experimental device equivalent to the iontophoresis device (X) of the present invention. The meanings of the reference symbols of the experimental devices are as follows. (1). Reference numerals 11, 21, 12, 13, 14, 15, 2
2, 23, 24, and 25 are the same as those in FIGS. As the cation exchange membranes (13, 23) and the anion exchange membranes (15, 25), Neoceptor CMX (cation) and AMX (anion) manufactured by Tokuyama Corporation were used, respectively. (2). Reference numeral 4 denotes a virtual skin tank that simulates the skin. (3). Reference symbol PP is a porous polypropylene membrane (AN filter, AN manufactured by Nippon Millipore Limited).
06). (Note) PP has no selective permeability for ions. (4) Reference numerals A to E indicate tanks partitioned by an ion exchange membrane or PP.

1. Iontophoresis experiment with the experimental device shown in Fig. 5 (a). Experimental conditions (1). Electrode solution in chamber A (iontophoresis electrode chamber, negative electrode chamber) is composed of conductive medium (12) and ionic drug. (14), and 0.9% N in which 1M As ⁻ Na ⁺ is dissolved.
aCl aqueous solution was used. (2). As a medium of room B (virtual skin room simulating skin)
A 0.9% NaCl aqueous solution was used. (3) 0.9% NaCl aqueous solution was used as the conductive medium (22) in the room C (ground electrode room). (4). Energizing conditions: voltage 30V (initial setting value), current 10mA (constant current),
Energizing time 30 minutes. (b). Experimental results: As experimental results, pH of each room (A to C)
The changes are shown in Table 1 below.

[0075]

[Table 1]

[0076] (c) Discussion:. (1) .A chamber reduction reaction, the oxidation reaction occurs in the C chamber, the chamber A As - ^(ascorbate ions) are transported to the B compartment. Obviously, the pH shifts from neutral to alkaline in the room A, and changes from neutral to strongly acidic in the room C. Therefore, the case of the present experiment where the ground electrode (21) in the room C and the skin (4) in the room B are in direct contact is in a very dangerous state. This can be seen from the fact that the chamber B has been shifted to an acidic state, and that the shift to the acidic side is due to the acid (HClO ₃ ) generated in the chamber C. The hypochlorous acid is known as a strong oxidizing agent. (2). Room A, which is an iontophoresis electrode room, and skin (B)
Although the anion exchange membrane (15) is present between the chambers (A), the chamber A is somewhat prevented from becoming alkaline, but the OH ^- ions in the chamber A are not exchanged with the anion exchange membrane (15).
It is thought that the skin surface is locally alkaline because it passes by electrophoresis to the room B side via the. That is, it is considered that in the room B, it is thought that the pH tends to be more acidic, but it stops at pH = 4.20, OH ^- ions reach the skin surface, and the pH is locally shifted to the alkaline side. . (3) From the above, when performing iontophoresis, the mode of using only one ion exchange membrane as in this experiment should be avoided from the viewpoint of biosafety. (4). The amount of As ⁻ (ascorbate ion) administered in this experiment was about 300 μmol (theoretical value: 560 μmo).
1), which substantially corresponds to the decrease amount of the room A and the increase amount of the room B. However, the dose is about 1/2 of the theoretical value.
, And the large amount in the A chamber OH ^- ions are generated, which As ^- to be transported with the As ^- transporting 50%
Obstructing. Also from this point, this experimental apparatus is unsuitable as an iontophoresis apparatus.

2. Iontophoresis experiment with the experimental device shown in FIG. 6 (a). Experimental conditions: room A and B of the experimental device shown in FIG.
The configuration of the chamber (skin) was changed as shown in the figure to the cation exchange membrane (1).
3) and an anion exchange membrane (15) were used, and the experimental apparatus reconfigured was used, and the conductive medium (12) and the ionic drug (12) were used as the electrode solution in the room A and the ionic drug solution in the room B, respectively. 0.9) dissolved in 1M As ^- Na ⁺ containing 14)
The experiment was performed in the same manner as in the above “1”, except that a% NaCl aqueous solution was used. (b). Experimental results: As experimental results, pH of each room (A to D)
The changes are shown in Table 2 below.

[0078]

[Table 2]

(C). Discussion (1). An iontophoresis electrode chamber (A chamber) and a solution chamber (B) containing As ⁻ Na ⁺ as an ionic drug as an administration reagent.
By separating the chamber B) with the cation exchange membrane (13), the pH of the chamber B can be kept constant. This prevents the skin surface (C room) from becoming alkaline. Further, the ion permeation amount is improved as compared with the experiment of the above “1”, and a value substantially close to the theoretical value is obtained. (2). However, the pH of the room C (virtual skin tank) (4) is lowered. This suggests the effectiveness of partitioning between the chamber C and the chamber D, that is, between the ground electrode chamber (D) and the virtual skin bath (4) with an ion exchange membrane instead of a simple membrane (pp). . Furthermore, in the ground electrode chamber (D), there is a risk that hypochlorite ions are generated by oxidative decomposition of physiological saline as a conductive medium and diffused into the skin.

3. (A). Experimental conditions: Room C and D of the experimental apparatus shown in FIG.
The experiment was carried out in the same manner as in the above "2", except that the PP membrane between the chambers was changed to the cation exchange membrane (23). (b). Experimental results: Table 3 below shows the changes in pH in each room (A to D) as experimental results.

[0081]

[Table 3]

(C). Discussion: This experiment corresponds to an experiment using the iontophoresis device (X) of the present invention.
This experimental apparatus is characterized in that it is configured by arranging one cation exchange membrane (23) on the ground electrode section (2). (1) Although a change in pH was observed in each of the electrode chambers, that is, the chambers A and D, the As ^- Na ⁺ solution chamber (room B) and the skin (C
The change in pH in the chamber is suppressed and is effective. Further, a cation exchange membrane (23) is provided in the ground electrode chamber (D chamber).
The harmful anions such as hypochlorite ions can be kept in the room D without contacting the skin. (2) Since the permeation amount of ascorbate ion shows almost the theoretical value, this experimental apparatus is useful as an iontophoresis apparatus. (3). However, as an improvement of this experimental apparatus, in the ground electrode chamber (D room) in contact with the virtual skin bath (C room), H generated by electrolysis of water on the ground electrode (21) was used.
⁺ Ions migrate through the cation exchange membrane (23) and
This has led to acidification of the chamber, which should be improved. For this reason, it is preferable to employ two types of ion exchange membranes, that is, a cation exchange membrane and an anion exchange membrane, on the ground electrode side as well as on the intzeze electrode side.

4. (A). Experimental conditions: In the experimental apparatus shown in FIG. 7,
An anion exchange membrane (25) is arranged in the illustrated manner in addition to the cation exchange membrane (23) in the ground electrode chamber (D chamber), and as an electrode solution for a newly partitioned ground electrode chamber (E chamber). The experiment was performed in the same manner as in the above “3”, except that a 0.9% NaCl aqueous solution in which 1M As ⁻ Na ⁺ was dissolved was used. (b). Experimental Results As experimental results, the changes in pH in each room (AE) are shown in Table 4 below.
Shown in

[0084]

[Table 4]

(C). Consideration: (1) Two ion exchange membranes (13, 1) were placed on the iontophoresis electrode side shown in FIG.
5) and two ion exchange membranes (2
In iontophoretic devices were provided with 3,25), iontophoresis electrode section side (from A~B chamber) in the human body (C chamber) As ^- only is supplied, and a ground electrode portion (E to Na ⁺ from the room D) to the human body (room C)
Only as a result, sodium ascorbate (As ⁻ Na ⁺ ) is injected into the body. Since no substances other than those described above are injected into the body, the present experimental device is an extremely safe and effective means of administering (drug delivery) ionic drugs. (2). PH change is hardly observed in the B, C and D rooms. This is, (i) in the iontophoresis electrode section, B chamber ascorbate ion. (As ^-) moved to a virtual skin chamber (C chamber), and Natoumuion (N
a ⁺ ) has moved to the iontophoresis electrode chamber (chamber A), and (ii) D
This indicates that the sodium ion (Na ⁺ ) in the room has moved to the virtual skin chamber (room C) and the ascorbate ion (As ⁻ ) has moved to the ground electrode chamber (room E). No change occurred.

[0086]

Next, an embodiment of an iontophoresis device (X) used for administering an iontophoretic ionic drug of the present invention will be described in detail with reference to the drawings. In the reference drawings, the ion-exchange membranes (13, 15, 23, 25) are indicated by wavy lines for clarity of illustration, and some constituent elements (members) and a combination of constituent elements (members) are combined. The style or hatching is omitted. However, configurations omitted in the drawings can be easily understood from the description of each embodiment and other attached drawings.

FIG. 9 is a view for explaining a first embodiment of the iontophoresis device (X) of the present invention, and is a longitudinal sectional view. The iontophoresis device (X) according to the first embodiment of the present invention is roughly divided as shown in FIG.
(i). Cylindrical iontophoresis electrode (1), (ii).
A ground electrode part (2) integrally formed on the periphery of the cylindrical iontophoresis electrode part (1);
ii) Constant voltage / constant current power supply (3).

The iontophoresis device of this type includes the iontophoresis electrode section (1) and the land electrode section (2).
Are separate from each other, and during administration of the ionic drug, the user is forced to hold the ground electrode portion (2) by hand in order to ground (ground). However, the iontophoresis device (X) of the present invention is excellent in operability and convenience because the elements of the iontophoresis electrode unit (1) and the ground electrode unit (2) are integrated as described above. I have. In addition, since both elements (1, 2) are integrated, the dose and administration of the ionic drug can be established by setting the interval between the two elements (1, 2) as desired or by integrating a plurality of sets of both elements. Can be adjusted.

In the present invention, the main reason why the two elements (1, 2) can be integrated is that the biological safety of the ground electrode portion (2) is much better than before. Therefore, in the iontophoresis device (X) of the present invention,
The ground electrode part (2) integrated with the iontophoresis electrode part (1) has nothing to do with it even when it comes into contact with skin parts that are more susceptible to fever, inflammation and irritation than the skin of the hands. Thus, the ionic drug can be safely and efficiently administered by ion.

In the iontophoresis device (X) of the present invention, the ground electrode section (2) is integrated with (integral with) the iontophoresis electrode section (1). The meaning of “integrated (integrally configured)” means that it is integrated with a part of the constituent members of the iontophoresis electrode unit (1) as shown in the figure. In the present invention, the integration is not limited to the embodiment shown in FIG. 9, and the integration should be interpreted in the broadest sense.

The iontophoresis device (X) shown in FIG. 9 is configured on the assumption that Na ascorbate (As ^- Na ⁺ ) is administered as an ionic drug (14) by iontophoresis. I have. For this reason, in the iontophoresis device (X) shown in FIG.
The reference numerals of each component mean the following. (i) The electrode plate of the iontophoresis electrode part (1) shown in (11) has a (-) electrode, and (ii) the conductive medium of the iontophoresis electrode part (1) shown in (12). Is a saline solution, (iii). The ion exchange membrane of the iontophoresis electrode part (1) shown in (13) is a cation exchange membrane, (i)
v). The ionic drug of the iontophoresis electrode part (1) shown in (14) is sodium ascorbate (As ⁻
Na ⁺ ), (v). The ion exchange membrane of the iontophoresis electrode part (1) shown by (15) is an anion exchange membrane, (v)
i). The electrode plate of the ground electrode part (2) shown in (21) is a (+) pole, and the conductive medium of the ground electrode part (2) shown in (vii). , And (viii).
The ion exchange membrane of the ground electrode portion (2) shown by (23) indicates a cation exchange membrane.

As shown in FIG. 9, in the iontophoresis device (X) according to the first embodiment of the present invention, the elements of the iontophoresis electrode section (1) and the ground electrode section (2) are integrated. In the following, for convenience of explanation, the description will be made by dividing each element.

In the iontophoresis device (X) according to the first embodiment of the present invention, the iontophoresis electrode section (1) is largely divided as shown in FIG.
(i) a non-conductive cylindrical outer cylinder (a), and (ii) a non-conductive cylindrical inner cylinder (b),
Under these elements (a, b), the reference numerals (11
Elements 15 to 15) are held or accommodated. The ground electrode part (2) is integrated with the outer peripheral edge of the insulating cylindrical body (a) so that both elements (1, 2) are substantially flush with the skin (4) surface. It is composed by being connected to.

The iontophoresis electrode section (1) shown in FIG. 9 has a circular plan view as shown in FIG. The iontophoresis electrode section (1) is configured to have a desired size (outer diameter and height), for example, because it is gripped by hand and brought into contact with a desired diseased part. Further, as shown in FIG. 9, the outer cylindrical body (a) and the inner cylindrical body (b) are screwed together by screwing via a screw portion formed on the contact surface between them. belongs to. However, in the present invention, the outer cylinder (a) and the inner cylinder (b) may be combined in any other manner, such as an engagement type, a locking type, and an insertion type. It may be.

In the cylindrical outer cylinder (a), the parts constituting the iontophoresis electrode section (1) are, as shown, (i) cooperating with the inner cylinder (b). Cation exchange membrane (1) for fixing the cation exchange membrane (13)
3) Support portion (a1), (ii). Ion drug (14) storage portion (a) for storing the ionic drug (14)
2), (iii) a support (a3) for anion exchange membrane (15) for fixing anion exchange membrane (15), (iv) anion exchange membrane for fixing anion exchange membrane (15) ( 15) A pressure ring (a31), and (v) a fixing pin (a32) for fixing the anion exchange membrane (15).

On the other hand, the cylindrical inner cylinder (b) cooperates with the support (a1) for the cation exchange membrane (13) of the outer cylinder (a) as shown in the figure. Pressing part (b1) for cation exchange membrane (13) for fixing cation exchange membrane (13) by pressing, (ii). Housing for conductive medium (12) for housing conductive medium (12) (B2), (iii) a support portion (b) for the electrode plate (11) for supporting the electrode plate (11).
3), (iv) a guide hole (b4) for a lead wire (31) for guiding a lead wire (31) from a power supply unit (3), and (v) a lead wire (31) for supporting the lead wire (31). ) Support (b
5), (vi) a top disk portion (b6).

As shown in FIG. 9, the iontophoresis electrode section (1) composed of the cylindrical body (a) and the inner cylindrical body (b) having the above-described structure is composed of a (-) electrode plate (11), a gauze or A conductive medium (12) containing a substance easily oxidized and reduced impregnated in a water-absorbing polymer material, a cation exchange membrane (13), an ionic drug (As ⁻ Na ⁺ ) (14),
And the anion exchange membrane (15) can be reliably held or accommodated inside. In the configuration of the outer cylinder (a) and the inner cylinder (b), when both are screwed together, the inner cylinder (b) is displaced relatively to the outer cylinder (a). Thereby, the anion conversion film (15) can be brought into close contact with the skin (4), and the iontophoresis effect can be improved.

Next, a ground electrode section (1) integrally formed with the iontophoresis electrode section (1) of the iontophoresis apparatus (X) of the first embodiment shown in FIG. 9 of the present invention. The configuration 2) will be described. In the present invention, the two elements (1, 2) may be integrated by, for example, integral molding of a non-conductive plastic material.

As shown in FIG. 9, in the cylindrical outer cylinder (a), the parts constituting the ground electrode part (2) are roughly divided into (i). Ground electrode part (2). Plate (21) for accommodating the side electrode plate (21) and the conductive medium (22) and the accommodating portion (a) for the conductive medium (22)
4), (ii) a support section (a5) for the cation exchange membrane (23) for fixing the cation exchange membrane (23) on the side of the ground electrode section (2), and (iii) a side of the ground electrode section (2). Cation exchange membrane (2) for fixing the cation exchange membrane (23) of
3) a pressing ring (a51, a52) and (iv) a fixing pin (a53) for fixing the cation exchange membrane (23) on the side of the ground electrode (2). The reference numerals (21 to 2)
The element shown in 3) is held or accommodated.

In FIG. 9, the ground electrode portion (2)
The lead wire (32) from the power supply section (3) is buried integrally. However, in the ground electrode portion (2), the arrangement of the lead wire (32) is such that the lead wire is supported by the support (b5) like the inner cylinder (b) of the iontophoresis electrode portion (1). This may be done.

In FIG. 9, the element (5) disposed on the front surface of the anion exchange membrane (15) of the iontophoresis electrode section (1) and the cation exchange membrane (23) of the ground electrode section (2) comprises: A medium, such as gauze, impregnated with a conductive liquid such as physiological saline for improving conductivity between the ion exchange membranes (15, 23) and the skin (4) is shown. In the present invention, it goes without saying that the element (5) may be omitted. In this case, since the anion exchange membrane (15) and the skin (4) are in contact, the ion transport number (the transport number of charged ions of the ionic drug) is improved.

In the iontophoresis device (X) of the present invention shown in FIG. 9, although not shown for clarity of illustration, the iontophoresis electrode unit (1) and / or the ground electrode unit (2) are Supply path for conductive medium (12, 22) or ionic drug (14), each electrode plate (11, 12)
It goes without saying that a vent hole for the gas generated from the gas or a housing portion for the adsorbent for adsorbing the gas may be provided.

FIG. 10 is a view for explaining a second embodiment of the iontophoresis device (X) of the present invention.
FIG. The iontophoresis device (X) of the second embodiment of the present invention can be said to be a modification of the first embodiment shown in FIG.

The iontophoresis device (X) of the second embodiment shown in FIG. 10 of the present invention is different from that of the first embodiment shown in FIG. 9 only in the following configuration. Yes, other configurations are substantially the same. (i) The iontophoresis electrode (1) is connected to the inner cylinder (b) of the iontophoresis electrode (1) of the first embodiment by two.
And an inner cylinder (b) and an intermediate cylinder (c). The components (a,
The specific configuration of (b, c) is clear from FIG.
The zone (m,
In (n), the (m) zone is a zone for administering an ionic drug, and the (n) zone is a zone for guiding a current flowing in the skin to a ground (earth) electrode portion. In the drawing, (mn) indicates an insulating portion (shield portion) of the negative electrode (11) and the positive electrode (21).

In the present invention, as a modified example of the second embodiment shown in FIG. 10, instead of the structure in which the cation exchange membrane (13) is held by the outer cylinder (a) and the intermediate cylinder (c), the inner cylinder is replaced by an inner cylinder. It goes without saying that a configuration in which the body (b) and the intermediate cylinder (c) are held may be adopted. In this case, the support portion (a1) for the cation exchange membrane (13) of the outer cylinder (a) is removed, and for example, an intermediate cylinder (c) provided with a protrusion inside the lower portion is used, and , The inner cylinder (b) having the structure of the first embodiment shown in FIG.
The cation exchange membrane (13) may be held by the projection of the intermediate cylinder (c) and the lower end of the inner cylinder (b) (see b1 in FIG. 9).

FIG. 11 is a view for explaining a third embodiment of the iontophoresis device (X) of the present invention.
It is a figure corresponding to 0. The iontophoresis device (X) of the third embodiment of the present invention can be said to be a modification of the second embodiment shown in FIG.

The iontophoresis device (X) of the third embodiment shown in FIG. 11 of the present invention is different from that of the second embodiment shown in FIG. 10 only in the following configuration. Yes, others are substantially the same. (i). The conductive medium (1) of the iontophoresis electrode (1)
The configuration of the inner cylinder (b) and the intermediate cylinder (c) was reconfigured so that the accommodation section of 2) divides the upper part of the electrode plate (11) into the lower two parts. (ii) The conductive medium (22) housed in the housing part (a4) of the conductive medium (22) of the ground electrode part (2) was composed of a physiological saline containing a substance which is easily oxidized and reduced.

FIG. 12 is a view for explaining a fourth embodiment of the iontophoresis device (X) of the present invention.
FIG. However, the iontophoresis electrode section (1) is omitted. FIG. 12 is an enlarged view of a main part of the ground electrode part (2).

The iontophoresis device (X) of the fourth embodiment shown in FIG. 12 of the present invention is different from that of the first embodiment shown in FIG. 9 only in the following configuration. Yes, other configurations are substantially the same. (i) The configuration of the electrode plate (21) of the ground electrode portion (2) and the accommodation portion (a4) for the conductive medium (22) are added to the components (21, 22, 23) shown in FIG. Further, it is configured to be able to accommodate the conductive medium (24) and the anion exchange membrane (25). The conductive medium (24) and the anion exchange membrane (25) are held or housed in the housing part (a4) by the members (a6, a7) shown. That is, the anion exchange membrane (25) is provided with the holding member (a
6), the cation exchange membrane (23) is held by the holding member (a7), and the conductive medium (24) is accommodated between both ion exchange membranes (23, 25). (ii). Components (5) disposed in front of the anion exchange membrane (15) (not shown) of the iontophoresis electrode (1) and the cation exchange membrane (23) of the ground electrode (2). Was removed.

The iontophoresis device (X) of the fourth embodiment shown in FIG. 12 has two cation exchange membranes and two anion exchange membranes for each of the iontophoresis electrode section (1) and the ground electrode section (2). In this case, a total of four ion exchange membranes are provided, which is different from those of the other embodiments. The iontophoresis device (X) according to the fourth embodiment has an excellent effect as demonstrated in an iontophoresis experiment using the experimental device shown in FIG. In the iontophoresis device (X) of the fourth embodiment shown in FIG. 12, the cation exchange membrane (23) of the ground electrode section (2) is replaced with the anion exchange membrane (not shown) of the iontophoresis electrode section (1). (15)
Needless to say, it is preferable to dispose them so that they are flush with each other.

The iontophoresis electrode of the present invention (1)
Various modifications are possible for the iontophoresis device (X) in which the electrode and the ground electrode portion (2) are integrated.

(I) FIG. 13 shows a configuration of an iontophoresis device (X) of the present invention in which a plurality of (m1 to mX) concentrically provided ionic drug administration zones as shown in the figure. Indicates that you can do it. The ground (earth) zones are indicated by (n1) to (nX). A specific configuration of the iontophoresis device (X) of the fifth embodiment capable of forming the concentric ionic drug administration zone shown in FIG. 13 of the present invention described above is, for example, the second configuration of FIG. It can be easily understood from the embodiment. Therefore, the illustration of the iontophoresis device (X) of the fifth embodiment is omitted.

(Ii). FIG. 14 shows a configuration of the iontophoresis device (X) of the present invention in which a plurality (m1 to mX) of ionic drug administration zones are provided in series as shown in the figure. Indicates that you can do it. The ground (earth) zones are indicated by (n1) to (nX). The specific configuration of the iontophoresis device (X) of the sixth embodiment capable of forming the ionic drug administration zone shown in FIG. 14 of the present invention described above is, for example, that of the second embodiment of FIG. It can be easily understood from things. For this reason, the iontophoresis device (X) of the sixth embodiment
Are not shown.

In FIGS. 13 and 14, an insulating portion (shield portion), that is, a (mn) zone shown in FIG. 10 should be shown at the boundary between each administration zone and the ground (earth) zone. Is (m
n) Zones are omitted.

The iontophoresis device (X) according to the fifth or sixth embodiment capable of forming the administration zone and the ground (earth) zone shown in FIGS.
By setting the width of each administration zone as desired, the degree of penetration of the ionic drug into the skin (depth of penetration from the skin surface)
Can be adjusted.

[0116]

According to the present invention, an iontophoresis device having the following excellent characteristics is provided. (i) Since the iontophoresis electrode section (working side electrode section) and the ground electrode section (non-working side electrode section) can maintain a stable energized state (conduction current and / or constant voltage) for a long time, The positively (+) or negatively (-) drug component of the ionic drug can be efficiently transported (drug delivery) to the skin (or mucous membrane) at the toforase electrode portion. (ii). The iontophoresis electrode section (working-side electrode section) and the ground electrode section (non-working-side electrode section) contribute to maintaining the above-mentioned stable energized state, and use (arrangement) of a specific ion exchange membrane. According to the embodiment, adverse effects on the skin (skin irritation, fever, inflammation, etc.) due to the electrode reaction can be eliminated. (iii) Since the iontophoresis electrode section (working-side electrode section) and the ground electrode section (non-working-side electrode section) are integrated, the treatment person has a ground (ground) as in the past.
Work is released, and operability and convenience are improved. Further, by disposing a plurality of pairs of the iontophoresis electrode portion and the ground electrode portion of the integrated structure,
The degree of penetration of the ionic drug into the skin (depth of penetration from the skin surface) and the administration area of the ionic drug can be adjusted as desired.

[Brief description of the drawings]

FIG. 1 is a diagram (schematic perspective view) illustrating a basic configuration of an ion and an apparatus (X) of the present invention.

FIG. 2 is a diagram (schematic sectional view) for explaining a basic configuration of the iontophoresis device (X) of the present invention.

FIG. 3 is a diagram illustrating a basic configuration of an iontophoresis device (X) of the present invention used when administering sodium ascorbate (As ⁻ Na ⁺ ) as an ionic drug.

FIG. 4 is a diagram illustrating another basic configuration of the iontophoresis device (X) of the present invention used when administering sodium ascorbate (As ⁻ Na ⁺ ) as an ionic drug.

FIG. 5 is a schematic diagram of a first experimental device (a device to be compared with the present invention) for testing the iontophoresis effect.

FIG. 6 is a schematic diagram of a second experimental device (a device to be compared with the present invention) for testing the iontophoresis effect.

FIG. 7 is a schematic diagram of a third experimental device (device according to the present invention) for testing the iontophoretic effect.

FIG. 8 is a schematic diagram of a fourth experimental device (the device according to the present invention) for testing the iontophoresis effect.

FIG. 9 is a diagram illustrating an iontophoresis device (X) according to the first embodiment of the present invention.

FIG. 10 is a diagram illustrating an iontophoresis device (X) according to a second embodiment of the present invention.

FIG. 11 is a diagram illustrating an iontophoresis device (X) according to a third embodiment of the present invention.

FIG. 12 is a diagram illustrating an iontophoresis device (X) according to a fourth embodiment of the present invention.

FIG. 13 is a view for explaining an iontophoresis device (X) according to a fifth embodiment of the present invention.

FIG. 14 is a diagram illustrating an iontophoresis device (X) according to a sixth embodiment of the present invention.

[Explanation of symbols]

X ... Iontophoresis device 1 ... Iontophoresis electrode part 11 ... Electrode material 12 ......... Conductive medium 13 ......... Ion (cation) exchange membrane 14 ... ………………………………………………………………………………………………………………………………………… Ion (anion) exchange membrane 2 ………………………………………………………………………………………. Conductive medium 23 ... Ion (cation) exchange membrane 3 ... Power supply unit 31, 32 ... Lead wire 4 ... Skin 5 ... Gauze impregnated with conductive liquid a ……………………………………………………………………………………………………………………………………………………………………………………………………………………. ……… Support for ion exchange membrane (15) a31 ………… ... Pressing ring for ion exchange membrane (15) a32 ... Fixing pin a4 ... Electrode plate (21) and conductive medium (2)
2) accommodation section a5 ...... support section for ion exchange membrane (23) a51, a52 ... press ring for ion exchange membrane (23) a53 ...... fixing pin a6, a7 ... ... Holding member b ... Inner cylinder body b1 on the side of the iontophoresis electrode (1) b1 ... Pressing part for ion exchange membrane (13) b2 ... ... for conductive medium (12) Housing part b3 ... Support part for electrode plate (11) b4 ... Guide hole for lead wire (31) b5 ... Support for lead wire (31) b6 ... Top disk part c ………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………….

 ────────────────────────────────────────────────── ─── Continued on the front page (72) Inventor Takehiko Matsumura 22-2 Kitaminemachi, Ota-ku, Tokyo (72) Inventor Yoriko Kobayashi 2-38-7 Motomiya, Otsu-shi, Shiga F-term (reference) 4C053 HH02 HH04

Claims (6)

[Claims] 1. An iontophoresis having an iontophoresis electrode section (working side electrode section) and a ground electrode section (non-working side electrode section) connected to a power supply used for administering an ionic drug by iontophoresis. In the rese apparatus, (1) the electrode portion of the iontophoresis is connected to a power source having the same polarity as the charged ion of the ionic drug, (1) -1. (1) -3. An ion exchange membrane for selecting an ion opposite to the charged ion of the ionic drug disposed on the front surface of the conductive medium, (1) -3. An ionic drug disposed on the front of an ion exchange membrane that selects an ion opposite to the charged ion of the ionic drug, and (1) -5. Electrification of the ionic drug disposed on the front of the ionic drug An ion exchange membrane that selects the same type of ions as the ions, And (2) the ground electrode portion is adjacent to the iontophoresis electrode portion and is integrally formed, and (2) -1.the iontophoresis electrode portion (2) -2.A conductive medium disposed at least on the front surface of the electrode material, and (2) -3.Ions disposed on the front surface of the conductive medium. Ion-exchange membrane, which selects the opposite ion to the charged ion of the active agent,
And an iontophoresis device. 2. A ground electrode section comprising: (2) -2. A conductive medium disposed at least in front of said electrode material; and (2) -3.
An ion exchange membrane that selects the opposite ion from the charged ion of the ionic drug disposed on the front surface of the conductive medium and an ion exchange membrane that selects the opposite ion. The iontophoresis device according to claim 1. 3. The iontophoresis device according to claim 1, wherein the conductive medium of the iontophoresis electrode portion and the ground electrode portion is formed of a material containing a substance which is easily oxidized or reduced. 4. The method according to claim 3, wherein the conductive medium of the iontophoresis electrode portion and the grant electrode portion is composed of a solution containing ferrous sulfate and ferric sulfate as substances that are easily oxidized or reduced. The iontophoresis device according to claim. 5. The method according to claim 3, wherein the conductive medium of the iontophoresis electrode section and the ground electrode section is composed of a solution containing an organic acid and / or a salt thereof as a substance which is easily oxidized or reduced. Iontophoresis device. 6. An iontophoretic electrode section comprising: (2) -3. An ion conversion membrane for selecting an ion opposite to a charged ion of an ionic drug disposed on the front surface of the conductive medium; Claims: (1) -5. An ion exchange membrane for selecting ions of the same kind as the charged ions of the ionic drug disposed on the front surface of the ionic drug. Item 3. The iontophoresis device according to item 1 or 2.