JP2008086538A - Iontophoresis apparatus, ion-exchange membrane laminated body, and bipolar ion-exchange membrane - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide an iontophoresis apparatus capable of solving the problems of decline of the efficiency in dosing medical ions and sudden variation of pH values on the dermal interface which may occur in a conventional iontophoresis apparatus equipped with an ion-exchange membrane laminated body with two layered ion-exchange membranes of opposite conductive types. <P>SOLUTION: An electrode structure is composed by using the ion-exchange membrane laminated body or a bipolar ion-exchange membrane. The ion-exchange membrane laminated body is adjusted so that the density of ion-exchange groups of at least one of the two ion exchange membranes of opposite conductive types is low on the interface of the ion-exchange membranes and high on the opposite face. The bipolar ion-exchange membrane comprises a first membrane thickness part to which the ion-exchange groups of a first conductive type are introduced on the front surface side, a second membrane thickness part to which the ion-exchange groups of a second conductive type are introduced on the rear surface side, and a third membrane thickness part with a lower density of ion-exchange groups than the first or second membrane thickness part in the middle between the first and second membrane thickness parts. <P>COPYRIGHT: (C)2008,JPO&INPIT

Description

  The present invention is suitable for iontophoresis devices for administering ionically dissociated drug ions to a living body driven by a voltage having the same conductivity type as the drug ions, and for administering drug ions by iontophoresis. The present invention relates to an ion exchange membrane laminate and an ambipolar ion exchange membrane that can be used in the present invention.

  An iontophoresis device generally includes a working electrode structure that holds drug ions dissociated into positive or negative ions, and a non-working electrode structure that serves as a counter electrode of the working electrode structure. Drug ions are administered into the living body by applying a voltage of the same conductivity type as that of the drug ions to the working electrode structure in a state where both the electrode structures are in contact with the living body skin.

  Patent Document 1 discloses an iontophoresis device that has high drug ion administration efficiency and can prevent degradation of the drug during energization.

  FIG. 6 is an explanatory diagram showing an iontophoresis device disclosed in Patent Document 1. In FIG.

  As illustrated, the iontophoresis device of Patent Document 1 includes an electrode 111 to which a first conductivity type voltage is applied from a power supply 130, an electrolyte solution holding unit 112 that holds an electrolyte solution, and a second conductivity type ion. A working electrode structure 110 having an exchange membrane 113, a chemical solution holding part 114 for holding a chemical solution containing drug ions of the first conductivity type, and a first conductivity type ion exchange membrane 115, and a voltage of the second conductivity type from the power source 130. Electrode 121, electrolyte solution holding part 122 holding electrolyte solution, first conductivity type ion exchange membrane 123, electrolyte solution holding part 124 holding electrolyte solution, and second conductivity type ion exchange membrane 125 A non-working side electrode structure 120.

  In this iontophoresis device, since the ion exchange membrane 115 is interposed between the drug solution holding unit 114 and the skin, the transfer of biological counter ions to the drug solution holding unit 114 is blocked. Therefore, the amount of current consumed by the movement of biological counter ions decreases, and as a result, the administration efficiency of drug ions increases. Further, since the migration of drug ions to the electrolyte solution holding unit 112 is blocked by the ion exchange membrane 113, the drug ions are prevented from being decomposed in the vicinity of the electrode 111 during energization.

  The applicant of the present application has devised an iontophoresis device in which the working electrode structure 110 in the iontophoresis device of Patent Document 1 is further improved, which is referred to as US Provisional Patent Application No. 60/69668 (hereinafter referred to as “Application”). 1)).

  FIG. 7A is an explanatory view showing a working electrode structure 210 disclosed as one embodiment in the first application.

  As shown in the figure, the working electrode structure 210 includes an electrode 211 to which a voltage of the first conductivity type is applied and an electrolyte solution holding unit 212 that holds the electrolyte solution, on the front side of the electrolyte solution holding unit 212. The ion exchange membrane stack S composed of the second conductivity type ion exchange membrane 213 and the first conductivity type ion exchange membrane 215 is arranged, and the ion exchange membrane 215 is doped with the first conductivity type drug ions. Has been.

  In the iontophoresis device provided with the working electrode structure 210, the ingress of biological counter ions into the device is blocked by the ion exchange membrane 215, so that the drug ion administration efficiency is increased and the drug ion electrolyte is retained. Since the transition to the unit 212 is blocked by the ion exchange membrane 213, the same effect as that of the iontophoresis device of Patent Document 1 can be achieved, such as prevention of drug decomposition during energization.

  In addition, in the iontophoresis device provided with the working electrode structure 210, drug ions are held by the ion exchange membrane 215, which is a member arranged closest to the living skin, so that the administration efficiency of the drug ions is high. Further, the drug ions are held in a state of being bonded to the ion exchange groups in the ion exchange membrane 215, so that the stability and storage stability of the drug ions are improved. Additional effects such as simplification of the manufacturing process due to the omission of the chemical solution holding part 114 that had to be handled in the state are achieved.

  The present applicant has devised a further iontophoresis device related to the improvement of the iontophoresis device of Patent Document 1, and filed this as Japanese Patent Application No. 2005-222893 (hereinafter referred to as “Application 2”). ing.

  FIGS. 7B and 7C are explanatory views showing a working electrode structure 310 and a non-working electrode structure 320 disclosed as embodiments in the application 2. FIG.

  As shown in the drawing, the working electrode structure 310 holds an electrode 311 to which a voltage of the first conductivity type is applied, an electrolyte solution holding unit 312 that holds the electrolyte solution, and a chemical solution that contains drug ions of the first conductivity type. A chemical solution holding unit 314 and a first conductivity type ion exchange membrane 315 are provided, and a second conductivity type ion exchange membrane 313 and a first conductivity type ion exchange are provided between the electrolyte solution holding unit 312 and the chemical solution holding unit 314. An ion exchange membrane stack S made of membrane 313 'is arranged.

  The non-working-side electrode structure 320 includes an electrode 321 to which a second conductivity type voltage is applied, an electrolyte solution holding unit 322 that holds the electrolyte solution, an electrolyte solution holding unit 324 that holds the electrolyte solution, and a second conductivity type ion. An exchange membrane 325 is provided, and an ion exchange membrane stack S composed of a first conductivity type ion exchange membrane 323 and a second conductivity type ion exchange membrane 323 'is provided between the two electrolyte solution holding portions 322 and 324. Has been placed.

  Since the iontophoresis device including the working electrode structure 310 includes the ion exchange membranes 313 and 315, drug ion administration efficiency is increased and decomposition of the drug during energization is prevented. An effect similar to that of the iontophoresis device of the present invention is achieved.

  In addition, in the working side electrode structure 310, the ion exchange membrane laminate S composed of two ion exchange membranes 313 and 313 ′ having opposite conductivity types is disposed between the electrolytic solution holding unit 312 and the chemical solution holding unit 314. In addition, the migration of ions between the electrolytic solution holding unit 312 and the chemical solution holding unit 314 during storage of the apparatus can be blocked. Therefore, an additional effect is achieved that the alteration of the drug during storage of the apparatus due to the migration of the first or second conductivity type ions of the electrolyte solution holding unit 312 to the chemical solution holding unit 314 can be achieved. Note that in the working electrode structure 310, in order to ensure energization from the electrolyte solution holding unit 312 to 314 during drug administration, at least one of the ion exchange membranes 313 and 313 ′ has an ion having a low transport number to some extent. An exchange membrane is used.

In the iontophoresis device including the non-working side electrode structure 320, an ion exchange membrane laminate including two ion exchange membranes 323 and 323 ′ having opposite conductivity types between the electrolyte solution holding unit 322 and the electrolyte solution holding unit 324. Since S is arranged, it is possible to block ion migration between the two electrolyte holding units 322 and 324 during storage of the apparatus. Therefore, the electrolyte solution holding unit 322 uses an electrolyte solution that is excellent in inhibiting electrode reactions and has a buffering effect, and the electrolyte solution holding unit 324 uses a highly safe electrolyte solution for the living body. Can be used, it is possible to prevent the electrolytes in both electrolyte holding parts from being mixed during storage of the apparatus. Also in the non-working side electrode structure 320, an ion exchange membrane having a somewhat low transport number is used for at least one of the ion exchange membranes 323 and 323 ′ in order to ensure energization during drug administration.
International Publication No. 03/037425 Pamphlet

  The iontophoresis devices disclosed in the applications 1 and 2 have various excellent characteristics as described above, but the type of drug to be administered, the characteristics of the ion exchange membrane used, or the voltage applied to the electrodes. Depending on the conditions such as, the iontophoresis devices disclosed in Applications 1 and 2 cannot obtain a sufficient drug administration rate, or abrupt pH fluctuation may occur at the skin interface. It was issued.

  The present invention further improves the iontophoresis device disclosed in Application 1 or 2, and may be caused by conditions such as the type of drug administered, the characteristics of the ion exchange membrane used, or the power supply voltage. It is an object of the present invention to provide an iontophoresis device that can prevent or alleviate the decrease in the administration rate.

  The present invention further improves the iontophoresis device disclosed in Application 1 or 2, and prevents pH fluctuations at the skin interface that may occur depending on conditions such as the characteristics of the ion exchange membrane used and the power supply voltage. Another object of the present invention is to provide an iontophoresis device that can be reduced.

  The present invention relates to an ion exchange membrane laminate or a bipolar ion exchange membrane that can be suitably used for the iontophoresis device disclosed in the application 1 or 2, wherein the type of drug to be administered and the ion exchange membrane to be used Another object of the present invention is to provide an ion exchange membrane laminate or a bipolar ion exchange membrane capable of preventing or reducing a decrease in drug administration rate that may be caused by conditions such as the above-mentioned characteristics or power supply voltage.

  The present invention is an ion exchange membrane laminate or a bipolar ion exchange membrane that can be suitably used in the iontophoresis device disclosed in the application 1 or 2, and the characteristics of the ion exchange membrane used, the power supply voltage, etc. It is another object of the present invention to provide an ion exchange membrane laminate or a bipolar ion exchange membrane capable of preventing or reducing pH fluctuation at the skin interface that may occur depending on conditions.

  The inventor of the present application, in the iontophoresis device disclosed in the application 1 or application 2, the drug ion that may be generated depending on the type of drug to be administered, the characteristics of the ion exchange membrane used, or the power supply voltage. As a result of studying the problem of the decrease in the administration rate of the drug or the rapid pH fluctuation at the skin interface, the cause of these phenomena is the two ion exchanges in the ion exchange membrane laminate provided in the iontophoresis device of the applications 1 and 2. The iontophoresis can be used to clarify the electrolysis of water at the interface of the membrane and eliminate or reduce the electrolysis of water in the ion-exchange membrane stack without increasing the number of components or adversely affecting other device characteristics. The race system was completed.

That is, the present invention comprises a first conductivity type first ion exchange membrane having a front surface and a back surface,
A second ion exchange membrane of a second conductivity type having a front surface and a back surface,
An iontophoresis provided with an electrode structure having an ion exchange membrane laminate in which the first and second ion exchange membranes are laminated by bringing the back surface of the first ion exchange membrane into contact with the back surface of the second ion exchange membrane. A cis device,
An iontophoresis device, wherein the iontophoresis device is inclined so that an ion exchange group density of at least one of the first and second ion exchange membranes is high on the front surface and low on the back surface (Claim 1). Or
A first ion exchange membrane of a first conductivity type having a front surface and a back surface;
A second ion exchange membrane of a second conductivity type having a front surface and a back surface,
An ion exchange membrane laminate in which the back surface of the first ion exchange membrane is brought into contact with the back surface of the second ion exchange membrane and the first and second ion exchange membranes are laminated,
An ion exchange membrane laminate for iontophoresis, wherein the ion exchange group density of at least one of the first and second ion exchange membranes is inclined so as to be high on the front surface and low on the back surface. (Claim 7).

  In the following description, the first or second ion exchange membrane having an ion exchange group density gradient that is high on the front surface and low on the back surface in the first and seventh aspects will be referred to as a “gradient ion exchange membrane”.

  The ion exchange membrane laminate according to claims 1 and 7 includes a first conductivity type first ion exchange membrane and a second conductivity type second ion exchange membrane laminated thereon. Therefore, this ion exchange membrane laminate can serve as the ion exchange membrane laminate in applications 1 and 2.

  Furthermore, in the ion exchange membrane laminate of claims 1 and 7, at least one of the first and second ion exchange membranes is a tilted ion exchange membrane, and the ion exchange group density on the back side of the tilted ion exchange membrane is low. Therefore, it is possible to suppress electrolysis of water at the interface between the first and second ion exchange membranes during energization.

  On the other hand, by sufficiently increasing the ion exchange group density on the surface side of the gradient ion exchange membrane, the function of the iontophoresis device according to Application 1 or 2 can be fully exhibited.

  That is, in the ion exchange membrane stack of the iontophoresis device of application 1, an ion exchange membrane having the same conductivity type as that of drug ions (in the case of the working electrode structure 210, the ion exchange membrane 215) is used as a gradient ion. In the case of an exchange membrane, the ion exchange group density on the surface side can be sufficiently increased to increase the drug administration efficiency, and the ion exchange membrane (working side electrode structure having the opposite conductivity type to the drug ion) In the case of 210, when the ion exchange membrane 213) is a tilted ion exchange membrane, the migration of drug ions to the electrolyte is suppressed by sufficiently increasing the ion exchange group density on the surface side, Decomposition of drug ions during energization can be prevented.

  Similarly, with respect to the iontophoresis device of application 2, two ion exchange membranes constituting the ion exchange membrane laminate (in the case of the working electrode structure 310, ion exchange membranes 313 and 313 ′, non-action) In the case of the side electrode structure 320, one or both of the ion exchange membranes 323 and 323 ′) can be a tilted ion exchange membrane, and the ion exchange group density on the surface side of the tilted ion exchange membrane can be sufficiently increased. By making it higher, the migration of the drug ions in the working electrode structure to the electrolyte and the migration of the ions in the electrolyte to the chemical solution holding part are prevented, or the two electrolytes in the non-working electrode structure are mixed. Can be prevented.

  The first and second ion exchange membranes of the present invention are typically ion exchange membranes in the form of a sheet (planar) having at least a front surface and a back surface.

  The “back surface” in the first and second ion exchange membranes of the present invention is the surface on the side where the first ion exchange membrane and the second ion exchange membrane are in contact, and the “surface” is the surface on the opposite side. .

  The gradient of the ion exchange group density in the gradient ion exchange membrane of the present invention may be such that the ion exchange group density continuously increases from the back surface side to the front surface side, and increases stepwise. Also good. Further, it is not always necessary that the ion exchange group density is maximized on the surface of the gradient ion exchange membrane or minimized on the back surface, and may be maximized or minimized between the front surface and the back surface.

  The method of imparting a gradient to the ion exchange group density in the gradient ion exchange membrane of the present invention is arbitrary, but as an example, by introducing an ion exchange group only from the surface side of the ion exchange membrane, The ion exchange group density can be inclined so that the density is high on the front surface and low on the back surface.

  In the ion exchange membrane laminate in the present invention, the interfaces of the first and second conductivity type ion exchange membranes can be integrally joined by hot pressing or the like, thereby improving the handleability of the ion exchange membrane laminate. It is possible to achieve additional effects such as facilitating manufacturing, improving manufacturing yield, and facilitating mass production.

The present invention
A bipolar ion exchange membrane having a front surface and a back surface,
A first film thickness portion where a first conductivity type ion exchange group located on the front side is introduced, and a second film thickness portion where a second conductivity type ion exchange group located on the back side is introduced. And an electrode having the bipolar ion exchange membrane having a third film thickness portion having an ion exchange group density lower than that of the first and second film thickness portions located between the first and second film thickness portions. An iontophoresis device comprising a structure (claim 4), or
A bipolar ion exchange membrane having a front surface and a back surface,
A first film thickness portion where a first conductivity type ion exchange group located on the front side is introduced, and a second film thickness portion where a second conductivity type ion exchange group located on the back side is introduced. And a third film thickness portion having an ion exchange group density lower than that of the first and second film thickness portions located between the first and second film thickness portions. A bipolar ion-exchange membrane for use (claim 8) can also be used.

  The bipolar ion exchange membrane according to claims 4 and 8 includes a first film thickness portion into which a first conductivity type ion exchange group is introduced, and a second film thickness portion into which a second conductivity type ion exchange group is introduced. Therefore, this bipolar ion exchange membrane can serve as an ion exchange membrane laminate in applications 1 and 2.

  Furthermore, since the bipolar ion exchange membrane of claims 4 and 8 has a third film thickness portion with a low ion exchange group density in the middle of the first and second film thickness portions, the first and second film thicknesses when energized. Electrolysis of water that can occur in the middle of the two film thickness portions can be suppressed.

  The bipolar ion exchange membrane according to claims 4 and 8 has the function of the iontophoresis device according to application 1 or 2 by sufficiently increasing the ion exchange group density in the first and second film thickness portions. It can be fully demonstrated.

  That is, with respect to the iontophoresis device of application 1, the ion exchange group density in the film thickness portion where the ion exchange group of the same conductivity type as the drug ion is introduced is sufficiently increased in the first and second film thickness portions. The drug administration efficiency can be improved, and the transfer of drug ions to the electrolyte is suppressed by increasing the ion exchange group density in the film thickness part where the ion exchange groups of the opposite conductivity type to the drug ions are introduced. In addition, decomposition of drug ions due to electrode reaction during energization can be prevented.

  Similarly, with respect to the iontophoresis device of application 2, by increasing the ion exchange group density in the first and second film thickness portions, transfer of drug ions in the working electrode structure to the electrolytic solution and the electrolytic solution are performed. It is possible to prevent migration of ions therein to the chemical solution holding part, or to prevent mixing of two electrolyte solutions in the non-working side electrode structure.

  The bipolar ion exchange membrane of the present invention can be adjusted by an arbitrary method. For example, when introducing an ion exchange group into the ion exchange membrane, the first conductivity type is introduced from the first film thickness portion side. The introduction of the ion exchange group and the introduction of the second conductivity type ion exchange group from the second film thickness portion side result in the introduction of the first conductivity type ion exchange group into the first film thickness portion. And a second film thickness portion in which an ion exchange group of the second conductivity type is introduced, and a third film thickness portion having an ion exchange group density lower than that of the first and second film thickness portions located in the middle. A bipolar ion exchange membrane can be obtained.

  In the bipolar ion exchange membrane of the present invention, the ion exchange group density does not necessarily change step by step between the film thickness parts so that the boundary between the first to third film thickness parts is always clear. The ion exchange group density of the first conductivity type is high on the surface, the ion exchange group density gradually decreases toward the center of the film, and the ion exchange group density of the second conductivity type gradually increases from the center of the film toward the back surface. The ion exchange group density may be continuously changed, for example, as the value of the ion exchange group increases.

  As described above, the iontophoresis device usually has a working electrode structure that holds a drug to be administered to a living body and a non-working electrode structure that serves as a counter electrode. In that case, the iontophoresis device according to claim 1 or 4, wherein at least one of the working electrode structure and the non-working electrode structure comprises the ion exchange membrane laminate or the bipolar ion exchange membrane. It is a cis apparatus, and preferably both of them may include the ion exchange membrane laminate or the bipolar ion exchange membrane. The ion exchange membrane laminate according to claim 7 and the bipolar ion exchange membrane according to claim 8 can be used for the working electrode structure or the non-working electrode structure in the above case, preferably for both. can do.

  Depending on the type of iontophoresis device, the drug to be administered to the living body may be held in both of the two electrode structures connected to both electrodes of the power supply (in this case, both electrode structures are effective). In some cases, a plurality of electrode structures are connected to each pole of the power source. An iontophoresis device comprising at least one of the ion exchange membrane laminate or bipolar ion exchange membrane is the iontophoresis device according to claim 1 or 4, preferably all of the ion exchange membrane laminate or bipolar electrode. An ion exchange membrane can be provided. The ion exchange membrane laminate of claim 7 and the bipolar ion exchange membrane of claim 8 can be used for any one of the electrode structures in the above case, preferably all of them.

  The “drug” in the present specification has a certain medicinal effect or pharmacological action regardless of whether it is prepared or not, and treats, recovers or prevents a disease, promotes or maintains health, diagnoses a medical condition or health condition, etc. Or a substance administered to a living body for the purpose of promoting or maintaining beauty.

  The “drug ion” in the present specification means an ion that is generated by ion dissociation of a drug and is responsible for medicinal effect or pharmacological action.

  In this specification, the “medicine solution” means not only a solution in which a drug is dissolved in a solvent, a stock solution in the case where the drug is in a liquid state, or a mixed solution of the stock solution and the solvent, but at least a part of the drug is dissociated into drug ions. As long as it does, it includes those in various states such as those in which the drug is suspended or emulsified in a solvent or the like, or those prepared in the form of an ointment or paste.

  As used herein, “drug counter ion” means an ion present in a drug solution and having a conductivity type opposite to that of the drug ion.

  “Skin” in the present specification means a biological surface on which a drug can be administered by iontophoresis, and includes, for example, the mucous membrane in the oral cavity. “Biological body” includes humans and animals.

  The “biological counter ion” in the present specification means an ion existing on or in the living body's skin and having a conductivity type opposite to that of the drug ion.

  The “front side” in the present specification means the side close to the living skin on the current path during drug administration.

  In the present invention, “first conductivity type” means positive or negative electric polarity, and “second conductivity type” means a conductivity type (minus or plus) opposite to the first conductivity type.

  The drug ion doped in the first ion exchange membrane or the first film thickness portion in the present invention does not necessarily need to be a single type, and a plurality of types of drug ions may be doped. Similarly, the drug ions and drug counter ions contained in the drug solution holding part of the present invention, or the positive ions and minus ions contained in the electrolyte solution of the electrolyte solution holding part do not necessarily have to be of a single type, respectively. One or both may be of multiple types.

  In the present specification, the “first conductivity type ion exchange group” means an ion exchange group having a first conductivity type ion as a counter ion. Therefore, when the first conductivity type is positive, the “first conductivity type ion exchange group” is a cation exchange group (cation exchange group), and when the first conductivity type is negative, “ The “ion exchange group of the first conductivity type” is an anion exchange group (anion exchange group).

  Similarly, the “second conductivity type ion exchange group” means an ion exchange group having a second conductivity type ion as a counter ion. Therefore, when the second conductivity type is positive, the “second conductivity type ion exchange group” is a cation exchange group (cation exchange group), and when the second conductivity type is negative, “ The “second conductivity type ion exchange group” is an anion exchange group (anion exchange group).

  The “ion exchange group density” in the present specification is the number of ion exchange groups introduced into a unit volume ion exchange membrane. Similarly, “cation exchange group density” and “anion exchange group density” are the number of cation exchange groups and the number of anion exchange groups introduced into a unit volume of cation exchange membrane and anion exchange membrane, respectively.

  The “first conductivity type ion exchange membrane” in the present specification means an ion exchange membrane into which a first conductivity type ion exchange group is introduced. Therefore, when the first conductivity type is positive, the “first conductivity type ion exchange membrane” is a cation exchange membrane, and when the first conductivity type is negative, the “first conductivity type ion exchange membrane”. "Is an anion exchange membrane.

  Similarly, the “second conductivity type ion exchange membrane” means an ion exchange membrane into which a second conductivity type ion exchange group is introduced. Therefore, when the second conductivity type is positive, the “second conductivity type ion exchange membrane” is a cation exchange membrane, and when the second conductivity type is negative, the “second conductivity type ion exchange membrane”. "Is an anion exchange membrane.

  In addition to the ion exchange resin formed into a membrane, the ion exchange membrane includes a heterogeneous ion exchange membrane obtained by dispersing the ion exchange resin in a binder polymer and forming it by heat molding or the like. A composition comprising a monomer capable of introducing an exchange group, a crosslinkable monomer, a polymerization initiator, or a resin having a functional group capable of introducing an ion exchange group dissolved in a solvent is used as a cloth or a mesh. Alternatively, various materials such as a homogeneous ion exchange membrane obtained by impregnating and filling a substrate such as a porous film and carrying out an ion exchange group introduction treatment after polymerization or solvent removal are known.

  More specifically, examples of the cation exchange membrane include ion exchange membranes introduced with cation exchange groups such as Neocepta CM-1, CM-2, CMX, CMS, CMB manufactured by Tokuyama Corporation. Examples of the anion exchange membrane include ion exchange membranes into which anion exchange groups such as Neocepta AM-1, AM-3, AMX, AHA, ACH, ACS, etc. manufactured by Tokuyama Corporation have been introduced.

  Examples of the cation exchange group introduced into the cation exchange membrane include a sulfonic acid group, a carboxylic acid group, and a phosphonic acid group. By using a sulfonic acid group that is a strongly acidic group, the transport number is high. It is possible to control the transport number of the ion exchange membrane depending on the type of cation exchange group to be introduced, such as being able to obtain a cation exchange membrane.

  Examples of the anion exchange group introduced into the anion exchange membrane include a primary to tertiary amino group, a quaternary ammonium group, a pyridyl group, an imidazole group, a quaternary pyridinium group, and a quaternary imidazolium group. By using a quaternary ammonium group or quaternary pyridinium group that is a basic group, an anion exchange membrane having a high transport number can be obtained. It is possible to control.

  Various methods such as sulfonation, chlorosulfonation, phosphoniumation, and hydrolysis can be used as the cation exchange group introduction treatment, and various methods such as amination and alkylation can be used as the anion exchange group introduction treatment. However, it is possible to adjust the transport number and ion exchange group density of the ion exchange membrane by adjusting the conditions of the ion exchange group introduction treatment.

  Also, the transport number and ion exchange group density of the ion exchange membrane can be adjusted by the amount of ion exchange resin in the ion exchange membrane and the pore size of the membrane. For example, in the case of an ion exchange membrane of a type in which a porous film is filled with an ion exchange resin, 0.005 to 5.0 μm, more preferably 0.01 to 2.0 μm, and most preferably 0.00. A large number of small pores having an average pore size of 02 to 0.2 μm (average flow pore size measured in accordance with the bubble point method (JIS K3832-1990)) is 20 to 95%, more preferably 30 to 90%, most Preferably, a porous film having a film thickness of 5 to 140 μm, more preferably 10 to 120 μm, most preferably 15 to 55 μm formed with a porosity of 30 to 60% is used, and more preferably 5 to 95% by mass. Can use an ion exchange membrane filled with an ion exchange resin at a filling rate of 10 to 90% by mass, particularly preferably 20 to 60% by mass. The transport number and ion exchange group density of the ion exchange membrane can be adjusted also by the average pore diameter, the porosity, and the filling rate of the ion exchange resin. The ion exchange membrane of the present invention is particularly preferably a type of ion exchange membrane in which the porous film is filled with an ion exchange resin.

  The “blocking of the passage of ions” described in the present specification for the ion exchange membrane does not necessarily mean that no ions are allowed to pass through. For example, the passage of biological counter ions occurs at a certain speed. However, when the drug ion administration efficiency can be sufficiently increased due to its small degree, the passage speed or the passage amount of the first or second conductivity type ion is sufficiently higher than that of the opposite conductivity type ion. Small cases are included.

  Hereinafter, embodiments of the present invention will be described with reference to the drawings.

  In the following, for convenience of explanation, an iontophoresis device for administering a drug (for example, lidocaine hydrochloride or morphine hydrochloride) whose medicinal component dissociates into positive drug ions will be described as an example. In the case of an iontophoresis device for administering a drug that dissociates into negative drug ions (for example, ascorbic acid, etc.), by reversing the polarity of the power source in the following description and the conductivity type of each ion exchange membrane, An iontophoresis device that can achieve substantially the same effect as the following embodiments can be configured.

  FIG. 1 is an explanatory diagram showing a schematic configuration of an iontophoresis device X according to the present invention.

  As shown in the drawing, the iontophoresis device X is connected by a power supply 30, a working electrode structure 10 connected to the positive electrode of the power supply 30 and the power supply line 31, and a negative electrode of the power supply 30 and the power supply line 32. The non-working side electrode structure 20 is configured.

  The working electrode structure 10 and the non-working electrode structure 20 are provided with containers 16 and 26 in which spaces that can accommodate various structures described below are formed and whose lower surfaces 16b and 26b are opened. The containers 16 and 26 can be made of any material such as plastic, but preferably, a material that can prevent evaporation of moisture from the inside and entry of foreign matter from the outside, movement of the living body, and unevenness of the skin. It can be formed from a flexible material that can follow. In addition, a removable liner made of an appropriate material for preventing evaporation of water and contamination of foreign substances during storage of the iontophoresis device X can be attached to the lower surfaces 16b and 26b of the containers 16 and 26, A pressure-sensitive adhesive layer can be provided on the lower edges 16e and 26e of the containers 16 and 26 in order to enhance adhesion to the skin during drug administration.

  As the power source 30, a battery, a constant voltage device, a constant current device, a constant voltage / constant current device, or the like can be used, but 0.01 to 1.0 mA / cm 2, preferably 0.01 to 0.5 mA. It is preferable to use a constant current device that can adjust the current in the range of / cm 2 and operates under a safe voltage condition of 50 V or less, preferably 30 V or less.

2A to 2C are cross-sectional explanatory views showing configuration examples of working electrode structures 10a to 10c that can be used as the working electrode structure 10 of the iontophoresis device X. FIG.

  The working electrode structure 10 a is disposed on the front side of the electrode 11 connected to the power supply line 31 of the power supply 30, the electrolyte solution holding unit 12 that holds the electrolyte solution that contacts the electrode 11, and the electrolyte solution holding unit 12. The ion exchange membrane laminate 13a is provided.

  By using a conductive material that causes an oxidation reaction when energized, such as silver, the electrode 11 can suppress gas generation and pH change due to the electrode reaction. Gold, platinum, carbon, etc. when the generation of gas or pH change due to electrode reaction can be suppressed by appropriately selecting the composition of the liquid, or when electrode reaction is not a problem due to a small amount of electricity Inactive conductive materials can also be used.

  The electrolytic solution holding unit 12 can hold an electrolytic solution in which an arbitrary electrolyte is dissolved, but uses an electrolyte having an oxidation potential lower than that of water electrolysis or a buffer electrolytic solution in which a plurality of types of electrolytes are dissolved. By doing so, gas generation and pH change during energization can be suppressed.

  Further, when the mobility of positive ions in the electrolyte solution holding unit 12 is larger than the drug ions doped in the cation exchange membrane 13C, the positive ions are transferred to the living body in preference to the drug ions, and the administration efficiency of the drug ions Therefore, it is preferable that the electrolytic solution of the electrolytic solution holding unit 12 has a composition that does not include positive ions having higher mobility than drug ions.

  The electrolyte solution holding unit 12 can hold the electrolyte solution in a liquid form, and can also be held by impregnating an appropriate absorbent carrier such as gauze, filter paper, or aqueous gel.

  The ion exchange membrane laminate 13a is composed of a gradient anion exchange membrane 13A and a cation exchange membrane 13C arranged on the front side thereof.

  The inclined anion exchange membrane 13A has a surface t and a back surface b, and is inclined to an anion exchange group density in the film thickness direction in such a manner that the anion exchange group density is high on the surface t side and the anion exchange group density is low on the back surface b side. Is given. Therefore, a film thickness portion having a high anion exchange group density is formed on the surface t side of the gradient anion exchange membrane 13A, and a film thickness portion having a low anion exchange group density is formed on the back surface b side.

  On the other hand, positive drug ions are doped in the cation exchange membrane 13C. The cation exchange membrane 13C is disposed on the front side of the inclined anion exchange membrane 13A so as to contact the back surface b of the inclined anion exchange membrane 13A.

  FIG. 3 is an explanatory diagram showing an example of a method for introducing an anion exchange group into the gradient anion exchange membrane 13A.

  As shown in the figure, the A tank and the B tank are partitioned by an ion exchange membrane M into which no ion exchange groups have been introduced, and an A-exchange liquid introduction liquid such as a trimethylamine aqueous solution or a methyl iodide aqueous solution is supplied to the A tank. By storing neutral liquid such as water and introducing anion exchange groups only from the tank A side, the ion exchange membrane M is adjusted to the anion exchange membrane 13A in which the anion exchange group density is inclined in the above-described manner. Can do.

  Anion exchange group density on the surface t and back surface b of the inclined anion exchange membrane 13A and an aspect of the gradient of the anion exchange group density (the ion exchange group density is changed in a curve in the film thickness direction of the gradient anion exchange membrane 13A, or linear Whether it is changed in a stepwise manner or in a stepwise manner) can be controlled by the concentration of the anion exchange group introduction solution, the processing temperature, the processing time, and the like.

  In the working electrode structure 10a, as described later, when a positive voltage is applied to the electrode 11, it is necessary that positive ions in the electrolyte solution holding portion 12 can pass through the gradient anion exchange membrane 13A. In the exchange group introduction process, it is preferable to control the transport number of the gradient anion exchange membrane 13A to be a value that is somewhat low, such as 0.7 to 0.98.

  It should be noted that the transport number of the gradient anion exchange membrane 13A is the chemical solution containing the electrolyte solution of the electrolyte solution holding unit 12 and an appropriate concentration of drug ions (for example, a drug solution used for doping drug ions into the cation exchange membrane 13C described below). Among the total charges carried through the gradient anion exchange membrane 13A when the first conductivity type voltage is applied to the electrolyte side with the gradient anion exchange membrane 13A disposed between the negative ions in the chemical solution, It is defined as the ratio of the amount of charge carried by passing through the inclined anion exchange membrane 13A.

  Doping of the cation exchange membrane 13C with drug ions can be performed by immersing the cation exchange membrane 13C in a chemical solution containing drug ions of an appropriate concentration. The amount of drug ions doped into the cation exchange membrane 13C can be controlled by the concentration of drug ions in the chemical solution, the immersion time, the number of immersions, and the like.

  In the iontophoresis device X including the working electrode structure 10a, drug ions are administered by the same mechanism as that of the iontophoresis device disclosed in Application 1.

  That is, the positive ions in the electrolyte solution holding unit 12 are driven by the positive voltage applied to the electrode 11, pass through the inclined anion exchange membrane 13A, and move to the cation exchange membrane 13C. The drug ions doped in the cation exchange membrane 13C are replaced with the positive ions, and are driven by the positive voltage applied to the electrode 11 to move to the living body.

In the iontophoresis device X including the working-side electrode structure 10a, the following effects (1) to (4) are achieved as in the iontophoresis device disclosed in Application 1.
(1) Since migration of drug ions to the electrolyte solution holding unit 12 during storage of the apparatus is blocked by the gradient anion exchange membrane 13A, decomposition of drug ions in the vicinity of the electrode 11 during energization can be prevented. Even when the anion exchange membrane 13A having a low transport number is used as described above, the migration of drug ions during storage (in a non-energized state) to the electrolyte solution holding unit 12 is sufficiently suppressed. it can.
(2) During administration of drug ions, invasion of negatively charged biological counter ions into the device is blocked by the cation exchange membrane 13C, so that drug ion administration efficiency can be increased.
(3) Since drug ions are doped in the cation exchange membrane 13C, which is a member arranged closest to the living skin, the drug ion administration efficiency can be further increased.
(4) Since the drug ions are held in a state of being bonded to the ion exchange groups in the cation exchange membrane 13C, stability against alteration and the like are improved. Accordingly, the storage period of the apparatus can be extended, or stabilizers, antibacterial agents, preservatives, and the like are not required, or the amount of use can be reduced.

  The iontophoresis device X including the working electrode structure 10a further achieves the following effects that cannot be obtained by the iontophoresis devices of the first and second applications.

  That is, since a film thickness portion having a low anion exchange group density is formed on the back surface b of the gradient anion exchange membrane 13A, hydrogen generated by electrolysis of water at the interface between the gradient anion exchange membrane 13A and the cation exchange membrane 13C during energization. Ion generation is suppressed. Therefore, it is possible to suppress a decrease in drug ion administration efficiency and a sudden change in pH value at the living body interface due to the transfer of hydrogen ions to the living body side.

  The working electrode structure 10b has the same configuration as the working electrode structure 10a except that the working electrode structure 10b includes an ion exchange membrane stack 13b instead of the ion exchange membrane stack 13a.

  The ion exchange membrane laminate 13b is composed of an anion exchange membrane 13A and an inclined cation exchange membrane 13C disposed on the front side thereof.

  The inclined cation exchange membrane 13C has a surface t and a back surface b, and is inclined to the cation exchange group density in the film thickness direction in such a manner that the cation exchange group density is high on the surface t side and the cation exchange group density is low on the back surface b side. Is given. Therefore, a film thickness portion having a high cation exchange group density is formed on the surface t side of the inclined cation exchange membrane 13C, and a film thickness portion having a low cation exchange group density is formed on the back surface b side. The inclined cation exchange membrane 13C is disposed on the front side of the anion exchange membrane 13A with its back surface b in contact with the anion exchange membrane 13A, and the inclined cation exchange membrane 13C is doped with positive drug ions.

  The gradient of the cation exchange group density in the inclined cation exchange membrane 13C can be given in a similar manner to the inclined anion exchange membrane 13A in the working electrode structure 10a.

  That is, a cation exchange group introduction solution such as a chlorosulfonic acid solution or a sulfuric acid solution is stored in the A tank of FIG. 3, and a neutral liquid such as water is stored in the B tank. By partitioning with the introduced ion exchange membrane M and introducing cation exchange groups only from the side of tank A, the ion exchange membrane M is adjusted to the inclined exchange membrane 13C in which the cation exchange group density is inclined in the above-described manner. Can do.

  Cation exchange group density on the surface t and the back surface b of the inclined cation exchange membrane 13C and the aspect of the inclination (whether the cation exchange group density is changed in a curve or linearly in the film thickness direction of the inclined cation exchange membrane 13C) Or whether it is changed stepwise) can be controlled by the concentration of the cation exchange group introduction liquid in tank A, the processing temperature, the processing time, and the like.

  In the iontophoresis device X including the working electrode structure 10b, drug ions are administered to the living body in the same manner as the iontophoresis device X including the working electrode structure 10a, and disclosed in Application 1. The same effects (1) to (4) as those of the iontophoresis device to be performed are achieved.

  The iontophoresis device X including the working electrode structure 10b further achieves the following effects that cannot be obtained with the iontophoresis devices of the first and second applications.

  That is, since a film thickness portion having a low cation exchange group density is formed on the back surface b of the inclined cation exchange membrane 13C, hydrogen generated by electrolysis of water at the interface between the anion exchange membrane 13A and the inclined cation exchange membrane 13C during energization. Ion generation is suppressed. Therefore, it is possible to suppress a decrease in drug ion administration efficiency and a sudden change in pH value at the living body interface due to the transfer of hydrogen ions to the living body side.

  The working electrode structure 10c has the same configuration as the working electrode structure 10a except that the working electrode structure 10c is provided with an ambipolar ion exchange membrane 13c instead of the ion exchange membrane stack 13a.

  The bipolar ion exchange membrane 13c includes a first film thickness portion 13 (1) in which a cation exchange group is introduced on the surface t side, and a second film thickness portion 13 (2) in which an anion exchange group is introduced on the back surface b side. The third film thickness portion 13 (3) having an ion exchange group density lower than that of the first and second film thickness portions 13 (1) and 13 (2) in the middle of the second film thickness portion 13 (2) is disposed on the front side of the electrolyte solution holding unit 12 in contact with the electrolyte solution holding unit 12.

  The first film thickness portion 13 (1) of the bipolar ion exchange membrane 13c is doped with positive drug ions.

  The bipolar ion exchange membrane 13c can be formed in a manner similar to the gradient anion exchange membrane 13A in the working electrode structure 10a.

  That is, a liquid for introducing a cation exchange group such as chlorosulfonic acid or sulfuric acid is stored in the tank A in FIG. 3, and a liquid for introducing an anion exchange group such as an aqueous solution of trimethylamine or methyl iodide is stored in the tank B. The cell is partitioned with an ion exchange membrane M into which ion exchange groups have not been introduced, and at the same time as the cation exchange group is introduced from the A side, the anion exchange group is introduced from the B side, thereby making the ion exchange membrane M bipolar. The ion exchange membrane 13c can be adjusted.

  The film thickness and ion exchange group density of the first to third film thickness portions 13 (1) to 13 (3) of the bipolar ion exchange membrane 13c, or the ion exchange group density in the film thickness direction of the bipolar ion exchange membrane 13c. The mode of change (whether it is changed linearly, curvedly or stepwise) is the solution for introducing a cation exchange group in the tank A and the solution for introducing an anion exchange membrane in the tank B. The concentration can be controlled by the concentration, the processing temperature, the processing time, and the like.

  In the working electrode structure 10c, when a positive voltage is applied to the electrode 11, it is necessary that positive ions in the electrolyte solution holding unit 12 can pass through the second film thickness portion 13 (2). In introducing the group, it is preferable to control the transport number of the second film thickness portion 13 (2) to be a value that is somewhat low, for example, 0.7 to 0.98.

  Doping of drug ions to the first film thickness portion 13 (1) of the ambipolar ion exchange membrane 13c is performed by immersing the first film thickness portion 13 (1) in a chemical solution containing drug ions of an appropriate concentration. Can do.

  This process is performed using, for example, the first film thickness portion 13 between the tank A for storing a chemical solution containing an appropriate concentration of drug ions and the tank B for storing a neutral liquid such as water using the apparatus of FIG. This can be done by keeping the state in which the bipolar ion exchange membrane 13c is disposed so that (1) faces the tank A side for a predetermined time. The dope amount of the drug ion to the first film thickness portion 13 (1) can be controlled by the concentration of the drug ion in the chemical solution at this time, the immersion time, and the like.

  In the iontophoresis device X including the working electrode structure 10c, drug ions are administered by the same mechanism as that of the iontophoresis device disclosed in Application 1.

  That is, the positive ions of the electrolyte solution holding unit 12 are driven by the positive voltage to the electrode 11 and pass through the second and third film thickness portions 13 (2) and 13 (3), and the first film thickness portion 13 (1 ). The drug ions doped in the first film thickness portion 13 (1) are replaced with the positive ions, and are driven by the positive voltage applied to the electrode 11 to move to the living body.

  The iontophoresis device including the working electrode structure 10c achieves the effects (1) to (4) similar to those of the iontophoresis device disclosed in the application 1.

  The iontophoresis device X including the working electrode structure 10c further achieves the following effects that cannot be obtained with the iontophoresis device of Application 1.

  That is, since the bipolar ion exchange membrane 13c includes the third film thickness portion 13 (3) having a low ion exchange group density in the middle of the first and second film thickness portions 13 (1) and 13 (2), Generation of hydrogen ions due to electrolysis of water between the first and second film thickness portions 13 (1) and 13 (2) at the time is suppressed. Therefore, it is possible to suppress a decrease in drug ion administration efficiency and a sudden change in pH value at the living body interface due to the transfer of hydrogen ions to the living body side.

  4A to 4C are explanatory diagrams illustrating configuration examples of the working electrode structures 10d to 10f that can be used as the working electrode structure 10 in the iontophoresis device X. FIG.

  The working electrode structure 10 d is disposed on the front side of the electrode 11 connected to the power supply line 31 of the power supply 30, the electrolyte solution holding unit 12 that holds the electrolyte solution that contacts the electrode 11, and the electrolyte solution holding unit 12. The ion exchange membrane laminate 13d, the chemical solution holding portion 14 that is arranged on the front side of the ion exchange membrane laminate 13d and holds a chemical solution containing positive drug ions, and the cation arranged on the front side of the chemical solution holding portion 14 And an exchange membrane 15.

  The electrode 11 and the electrolyte solution holding part 12 of the working electrode structure 10d can have the same configuration as the electrode 11 and the electrolyte solution holding part 12 of the working electrode structure 10a.

  The ion exchange membrane laminate 13d is composed of a gradient anion exchange membrane 13A and a cation exchange membrane 13C arranged on the front side thereof. The inclined anion exchange membrane 13A has a surface t and a back surface b, and is inclined to the ion exchange group density in the film thickness direction in such a manner that the ion exchange group density is high on the surface t side and the ion exchange group density is low on the back surface b side. Is given. Accordingly, a film thickness portion having a high ion exchange group density is formed on the surface t side of the gradient anion exchange membrane 13A, and a film thickness portion having a low ion exchange group density is formed on the back surface b side.

  The gradient anion exchange membrane 13A can be formed by the same method as described above for the gradient anion exchange membrane 13A of the working electrode structure 10a.

  In the working-side electrode structure 10d, in order to ensure energization from the electrolyte solution holding unit 12 to the drug solution holding unit 14, the positive ions of the electrolyte solution holding unit 12 or the drug of the drug solution holding unit 14 is determined by the voltage applied to the electrode 11. It is necessary that the counter ions can pass through the ion exchange membrane laminate 13d. Therefore, a material having a low transport number (for example, 0.7 to 0.98) is used for at least one of the gradient anion exchange membrane 13A and the cation exchange membrane 13C. Here, when the positive ions in the electrolyte solution holding unit 12 move to the chemical solution holding unit 14, the positive ions may become competing ions for the drug ions, which may reduce the administration efficiency of the drug ions. It is particularly preferable to set the transport number as high as possible (for example, 0.95 to 1) and the transport number of the gradient anion exchange membrane 13A to a certain low value (for example, 0.7 to 0.98).

  The drug solution holding unit 14 can hold a drug solution containing positive drug ions in a liquid form, and can also be held by impregnating an appropriate absorbent carrier such as gauze, filter paper, or aqueous gel.

  For the cation exchange membrane 15, it is preferable to use a cation exchange membrane having a transport number as high as possible, for example, 0.95 to 1 in order to suppress the migration of biological counter ions to the drug solution holding unit 14.

In the iontophoresis device X including the working electrode structure 10d, the following effects (5) and (6) can be achieved as in the iontophoresis device disclosed in the application 2.
(5) Since the transfer of negatively charged biological counter ions to the drug solution holding unit 14 during drug ion administration is blocked by the cation exchange membrane 15, the drug ion administration efficiency can be increased.
(6) Since the electrolyte solution holding unit 12 and the chemical solution holding unit 14 are separated by the ion exchange membrane laminate 13d configured by the gradient anion exchange membrane 13A and the cation exchange membrane 13C, the ions in the electrolyte solution holding unit 12 The transfer to the chemical solution holding unit 14 and the transfer of drug ions to the electrolyte solution holding unit 12 are blocked. Therefore, it is possible to prevent the drug ions in the chemical solution holding part 14 from being altered by the ions from the electrolyte solution holding part 12 and the decomposition of the drug ions in the vicinity of the electrode 11 when energized.

  The iontophoresis device X including the working electrode structure 10d further achieves the following effects that cannot be obtained with the iontophoresis device of Application 2.

  That is, since a film thickness portion having a low anion exchange group density is formed on the back surface b of the gradient anion exchange membrane 13A, hydrogen generated by electrolysis of water at the interface between the gradient anion exchange membrane 13A and the cation exchange membrane 13C during energization. Ion generation is suppressed. Therefore, it is possible to suppress a decrease in drug ion administration efficiency and a sudden change in pH value at the living body interface due to the transfer of hydrogen ions to the living body side.

  The working electrode structure 10e has the same configuration as that of the working electrode structure 10d except that the working electrode structure 10e includes an ion exchange membrane stack 13e instead of the ion exchange membrane stack 13d.

  The ion exchange membrane laminate 13e is composed of an anion exchange membrane 13A and a tilted cation exchange membrane 13C arranged on the front side thereof. The inclined cation exchange membrane 13C has a surface t and a back surface b, and is inclined to the cation exchange group density in the film thickness direction in such a manner that the cation exchange group density is high on the surface t side and the cation exchange group density is low on the back surface b side. Is given. Therefore, a film thickness portion having a high cation exchange group density is formed on the surface t side of the inclined cation exchange membrane 13C, and a film thickness portion having a low cation exchange group density is formed on the back surface b side.

  The inclined cation exchange membrane 13C can be formed by the same method as described above for the ion exchange membrane laminate 13b.

  In the working electrode structure 10e, for the same reason as described above for the working electrode structure 10d, the transport number of at least one of the anion exchange membrane 13A and the gradient cation exchange membrane 13C is set to a certain low value. The transport number of the inclined cation exchange membrane 13C is as high as possible, and the transport number of the anion exchange membrane 13A is low to some extent.

  In the iontophoresis device X including the working electrode structure 10e, the same effects (5) and (6) as those of the iontophoresis device disclosed in the application 2 are achieved.

  The iontophoresis device X including the working electrode structure 10e further achieves the following effects that cannot be obtained with the iontophoresis device of Application 2.

  That is, since a film thickness portion having a low cation exchange group density is formed on the back surface b of the inclined cation exchange membrane 13C, hydrogen generated by electrolysis of water at the interface between the anion exchange membrane 13A and the inclined cation exchange membrane 13C during energization. Ion generation is suppressed. Therefore, it is possible to suppress a decrease in drug ion administration efficiency and a sudden change in pH value at the living body interface due to the transfer of hydrogen ions to the living body side.

  The working-side electrode structure 10f has the same configuration as the working-side electrode structure 10d except that a bipolar ion-exchange membrane 13f is provided instead of the ion-exchange membrane laminate 13d.

  The bipolar ion exchange membrane 13f includes a first film thickness portion 13 (1) in which a cation exchange group is introduced on the surface t side, and a second film thickness portion 13 (2) in which an anion exchange group is introduced on the back surface b side. The third film thickness portion 13 (3) having an ion exchange group density lower than that of the first and second film thickness portions 13 (1) and 13 (2) in the middle of the second film thickness portion 13 (2) is brought into contact with the electrolytic solution holding unit 12, and the first film thickness portion 13 (1) is brought into contact with the chemical solution holding unit 14, and is arranged on the front side of the electrolytic solution holding unit 12.

  The bipolar ion exchange membrane 13f can be formed by the same method as described above for the bipolar ion exchange membrane 13c of the working electrode structure 10c.

  In the working electrode structure 10f, for the same reason as described above for the working electrode structure 10d, the transport number of at least one of the first and second film thickness portions 13 (1) and 13 (2) is low to some extent. Particularly preferably, the transport number of the first film thickness portion 13 (1) is set as high as possible, and the transport number of the second film thickness portion 13 (2) is set as low as possible.

  In the iontophoresis device X including the working electrode structure 10f, the same effects (5) and (6) as in the iontophoresis device disclosed in the application 2 are achieved.

  In the iontophoresis device X including the working electrode structure 10f, the following effects that cannot be obtained by the iontophoresis device of Application 2 are further achieved.

  That is, the bipolar ion exchange membrane 13c includes the third film thickness portion 13 (3) having a low ion exchange group density between the first and second film thickness portions 13 (1) and 13 (2). In this case, generation of hydrogen ions due to electrolysis of water between the first and second film thickness portions 13 (1) and 13 (2) is suppressed. Therefore, it is possible to suppress a decrease in drug ion administration efficiency and a sudden change in pH value at the living body interface due to the transfer of hydrogen ions to the living body side.

  It should be noted that the ion exchange membrane laminates 13d and 13e and the bipolar ion exchange membrane 13f in the working electrode structures 10d to 10f are in the opposite directions, that is, the cation exchange membrane 13C, the gradient cation exchange membrane 13C or the first The film thickness portion 13 (1) is in contact with the electrolytic solution holding unit 12, and the gradient anion exchange membrane 13 A, the anion exchange membrane 13 A or the second film thickness portion 13 (2) is arranged in contact with the chemical solution holding unit 14. As a result, the same effect as described above can be achieved for each of the working electrode structures 10d to 10f, and the function of suppressing the electrolysis of water during energization can be achieved. It is possible to further increase the case.

  5 (A) to 5 (C) are explanatory views showing configurations of non-working side electrode structures 20a to 20c that can be used as the non-working side electrode structure 20 of the iontophoresis device.

  The non-working side electrode structure 20a includes an electrode 21 connected to the power supply line 32 of the power source 30, an electrolyte solution holding unit 22 that holds the electrolyte solution that contacts the electrode 21, and an ion exchange membrane disposed on the front side thereof. The laminated body 23a, the electrolyte solution holding part 24 holding the electrolyte solution arranged on the front side thereof, and the anion exchange membrane 25 arranged on the front side thereof are provided.

  By using a conductive material that causes a reduction reaction when energized, such as silver chloride, the electrode 21 can suppress gas generation and pH change due to the electrode reaction. Gold, platinum, carbon, etc. when the generation of gas or pH change due to electrode reaction can be suppressed by appropriately selecting the composition of the electrolyte, or when the electrode reaction is not a problem due to a small amount of electricity. An inert conductive material such as can also be used.

  The electrolytic solution holding units 22 and 24 can hold an electrolytic solution having an arbitrary composition. By holding electrolytic solutions having different compositions in the electrolytic solution holding units 22 and 24, ions having preferable performance can be obtained. A tophoresis device can be provided. For example, the electrolytic solution holding unit 22 uses an electrolyte having a lower reduction potential than the electrolysis of water, or uses a buffer electrolytic solution in which a plurality of types of electrolytes are dissolved. On the other hand, an electrolytic solution excellent in safety to the living body can be used for the electrolytic solution holding part 24 while an electrolytic solution excellent in the function of suppressing pH fluctuation is used.

  The ion exchange membrane laminate 23a has the same configuration as the ion exchange membrane laminate 13d. That is, the ion exchange membrane laminate 23a is composed of a gradient anion exchange membrane 23A and a cation exchange membrane 23C arranged on the front side thereof, and the gradient anion exchange membrane 23A has a surface t and a back surface b, The anion exchange group density in the film thickness direction is inclined in such a manner that the anion exchange group density is high on the t side and the anion exchange group density is low on the back surface b side. The ion exchange membrane laminate 23a is disposed on the front side of the electrolyte solution holding unit 22 with the gradient anion exchange membrane 23A in contact with the electrolyte solution holding unit 22 and the cation exchange membrane 23C in contact with the electrolyte solution holding unit 24. Yes.

  In the iontophoresis device X including the non-working-side electrode structure 20a, when the electrolyte solutions having different compositions are held in the electrolyte solution holding units 22 and 24 as described above, the electrolyte solution holding unit 22 and the electrolytic solution Since the ion exchange membrane laminate 23a composed of the gradient anion exchange membrane 23A and the cation exchange membrane 23C is disposed between the solution holding portions 24, the electrolyte solution in both the electrolyte holding portions 22 and 24 during storage of the apparatus. The effect that it can prevent mixing is achieved.

  Furthermore, in the iontophoresis device X including the non-working-side electrode structure 20a, since the film thickness portion having a low anion exchange group density is formed on the back surface b of the gradient anion exchange membrane 23A, the gradient anion during energization Generation of hydroxyl ions due to electrolysis of water at the interface between the exchange membrane 23A and the cation exchange membrane 23C is suppressed. Therefore, it is possible to suppress a sudden change in pH value at the living body interface due to the hydroxyl ions moving to the living body side.

  The non-working side electrode structure 20b has the same configuration as the non-working side electrode structure 20a except that the non-working side electrode structure 20b includes an ion exchange membrane stack 23b instead of the ion exchange membrane stack 23a.

  The ion exchange membrane laminate 23b has the same configuration as the ion exchange membrane laminate 13e. That is, the ion exchange membrane laminate 23b is composed of the anion exchange membrane 23A and the inclined cation exchange membrane 23C disposed on the front side thereof. The inclined cation exchange membrane 23C has a surface t and a back surface b, and is inclined to the ion exchange group density in the film thickness direction in such a manner that the ion exchange group density is high on the surface t side and the ion exchange group density is low on the back surface b side. Is given. The ion exchange membrane laminate 23b is disposed on the front side of the electrolyte holding unit 22 with the anion exchange membrane 23A in contact with the electrolyte holding unit 22 and the inclined cation exchange membrane 23C in contact with the electrolyte holding unit 24. Yes.

  In the iontophoresis device X including the non-working side electrode structure 20b, the same effect as described above with respect to the iontophoresis device X including the non-working side electrode structure 20a is achieved.

  The non-working side electrode structure 20c has the same configuration as that of the non-working side electrode structure 20a except that the bipolar ion exchange membrane 23c is provided instead of the ion exchange membrane laminate 23a.

  The bipolar ion exchange membrane 23c has the same configuration as the bipolar ion exchange membrane 13f.

  That is, the bipolar ion exchange membrane 23c has a first film thickness portion 23 (1) in which a cation exchange group is introduced on the surface t side and a second film thickness portion 23 (in which an anion exchange group is introduced on the back surface b side. 2) has a third film thickness portion 23 (3) having a lower ion exchange group density than the first and second film thickness portions 23 (1) and 23 (2). The bipolar ion exchange membrane 23c has the second film thickness portion 23 (2) in contact with the electrolyte solution holding portion 22 and the first film thickness portion 23 (1) in contact with the electrolyte solution holding portion 24 to hold the electrolyte solution. It is arranged on the front side of the part 22.

  In the iontophoresis device X including the non-working side electrode structure 20c, the same effect as described above with respect to the iontophoresis device including the non-working side electrode structure 20a is achieved.

  Note that the ion exchange membrane laminates 23a and 23b and the bipolar ion exchange membrane 23c in the non-working side electrode structures 20a to 20c are in the opposite directions, that is, the cation exchange membrane 23C, the gradient cation exchange membrane 23C, or the second The first film thickness portion 23 (1) is in contact with the electrolyte solution holding part 22, and the gradient anion exchange membrane 23 A, the anion exchange membrane 23 A or the second film thickness portion 23 (2) is in contact with the electrolyte solution holding part 24. In this case, the same effects as those of the non-working side electrode structures 20a to 20c are achieved. However, the ion exchange membrane laminates 23a and 23b and the bipolar ion exchange membrane 23c are arranged in the direction of the non-working side electrode structures 20a to 20c, and the function of suppressing the electrolysis of water during energization is superior. preferable.

  As mentioned above, although this invention was demonstrated based on some embodiment, this invention is not limited to these embodiment, A various change is possible within description of a claim.

  For example, in the above-described embodiment, an iontophoresis device including a working electrode structure that holds a drug to be administered to a living body and a non-working electrode structure that serves as a counter electrode has been described as an example. An iontophoresis device in which a drug to be administered to a living body is held in both of two electrode structures connected to both poles of a power supply, and an iontophoresis in which a plurality of electrode structures are connected to each pole of a power supply The present invention can be similarly applied to the lysis apparatus.

  In any of the above cases, at least one of the one or more working-side electrode structures and the one or more non-working-side electrode structures has an ion according to claim 1 or 4 of the present application. Tophoresis device (i.e., an iontophoresis wherein at least one working electrode structure or at least one non-working electrode structure comprises the ion exchange membrane stack of claim 7 or the bipolar ion exchange membrane of claim 8). Cis devices) are included within the scope of the present invention.

  For example, regarding an iontophoresis device of a type comprising a working electrode structure for holding a drug to be administered to a living body and a non-working electrode structure having a role as a counter electrode, the working electrode structure While including the working electrode structure having the ion exchange membrane laminate or bipolar ion exchange membrane of the present invention such as 10a to 10f, the ion exchange membrane of the present invention such as the non-working electrode structure 120 shown in FIG. Even in an iontophoresis device including a non-working side electrode structure that does not have a laminate or an bipolar ion exchange membrane, in addition to the same effects as those of the prior application 1 or the prior application 2, The basic effect of the present invention that the reduction of the drug ion administration rate due to water electrolysis or the pH fluctuation at the skin interface can be eliminated or reduced is achieved. Toforeshisu device is also included in the scope of the present invention.

  Similarly, the non-working side electrode structure including the non-working side electrode structure of the present invention, such as the non-working side electrode structures 20a to 20c, or the bipolar ion exchange membrane, is provided, for example, as shown in FIG. Even in the iontophoresis device including the working electrode structure having no ion exchange membrane laminate or bipolar ion exchange membrane of the present invention such as 110, the same effect as in the prior application 2 is achieved. In addition, the basic effect of the present invention that can eliminate or reduce pH fluctuations at the skin interface caused by water electrolysis is achieved, and such an iontophoresis device is also within the scope of the present invention. included.

  Alternatively, the working electrode structure having the ion exchange membrane laminate or the bipolar ion exchange membrane of the present invention is provided, while the iontophoresis device itself is not provided with the non-working electrode structure, for example, living skin It is also possible to administer a drug by applying a voltage to the working electrode structure in a state where a part of the living body is brought into contact with a grounding member while the working electrode structure is brought into contact with In this case, the basic effect of the present invention is achieved, and such an iontophoresis device is also included in the scope of the present invention.

  Moreover, in the said embodiment, although the case where only any one of the anion exchange membrane or cation exchange membrane which comprises an ion exchange membrane laminated body has an inclination in the ion exchange group density of a film thickness direction was demonstrated, an ion exchange membrane laminated body Both of the anion exchange membrane and the cation exchange membrane constituting s may have an inclination in the ion exchange group density in the film thickness direction. In this case, both the anion exchange membrane and the cation exchange membrane have a low ion exchange group density on the back surface (the surface where the anion exchange membrane and the cation exchange membrane are in contact) and the ion exchange group density on the surface (the opposite surface). It is preferable that the ion exchange group density is inclined so as to be high.

  In the above embodiment, the case where the working electrode structure, the non-working electrode structure, and the power source are configured as separate bodies has been described. However, these elements are incorporated into a single casing, or these are assembled. It is possible to improve the handleability by forming the entire incorporated device into a sheet or patch, and such an iontophoresis device is also included in the scope of the present invention.

Explanatory drawing which shows the iontophoresis apparatus which concerns on this invention. (A)-(C) are sectional explanatory drawings which show the working side electrode structure of the iontophoresis apparatus which concerns on one Embodiment of this invention. BRIEF DESCRIPTION OF THE DRAWINGS FIG. (A)-(C) are sectional explanatory drawings which show the working side electrode structure of the iontophoresis apparatus which concerns on one Embodiment of this invention. (A)-(C) are sectional explanatory drawings which show the non-working side electrode structure of the iontophoresis apparatus which concerns on one Embodiment of this invention. Explanatory drawing which shows the conventional iontophoresis apparatus. (A)-(C) are explanatory drawings which show the working side electrode structure or non-working side electrode structure of the iontophoresis apparatus described in the other application by the present applicant.

Explanation of symbols

X ... iontophoresis device 10, 10a-10f ... working side electrode structure 11 ... electrode 12 ... electrolyte solution holding part 13a, 13b, 13d, 13e ... ion exchange membrane laminate 13c, 13f: Bipolar ion exchange membrane 13A: Anion exchange membrane, inclined anion exchange membrane 13C ... Cation exchange membrane, inclined cation exchange membrane 14 ... Chemical solution holding part 15 ... Cation exchange membrane 16 ... Container 20, 20a-20c ... Non-working side electrode structure 21 ... Electrode 22 ... Electrolyte holding part 23a, 23b ... Ion exchange membrane laminate 23c ... Bipolar ion exchange Membrane 23A ... anion exchange membrane, inclined anion exchange membrane 23C ... cation exchange membrane, inclined cation exchange membrane 24 ... electrolyte holding part 25 ... anion exchange membrane 30 ... power source 31, 32 ... Feed line 110, 210, 310 ... Working side electrode structure 120, 320 ... Non-working side electrode structure 111, 121, 211, 311, 321 ... Electrode 112, 122, 212, 312, 322, 324 ... Electrolyte holding part 113, 115, 123, 125, 213, 215, 313, 313 ', 315, 323, 323', 325 ... Ion exchange membrane 114, 314 ... Chemical liquid holding part 130 ··Power supply

Claims (8)

A first ion exchange membrane of a first conductivity type having a front surface and a back surface;
A second ion exchange membrane of a second conductivity type having a front surface and a back surface,
An iontophoresis provided with an electrode structure having an ion exchange membrane laminate in which the back surface of the first ion exchange membrane is brought into contact with the back surface of the second ion exchange membrane and the first and second ion exchange membranes are laminated. A cis device,
An iontophoresis device, wherein the iontophoresis device is inclined so that an ion exchange group density of at least one of the first and second ion exchange membranes is high on the front surface and low on the back surface. The electrode structure is
A first electrode;
An electrolyte holding unit that holds the electrolyte contacting the first electrode;
The ion exchange membrane laminate is disposed on the front side of the electrolyte solution holding part,
The first ion exchange membrane is disposed on the front side of the second ion exchange membrane;
The iontophoresis device according to claim 1, wherein the first ion exchange membrane is doped with drug ions of a first conductivity type. The electrode structure is
A first electrode;
An electrolytic solution holding unit for holding an electrolytic solution in contact with the first electrode;
A chemical solution holding unit that is disposed on the front side of the electrolyte solution holding unit and holds a chemical solution containing drug ions of the first conductivity type;
The iontophoresis device according to claim 1, wherein the ion exchange membrane laminate is disposed between the electrolyte solution holding unit and the chemical solution holding unit. A bipolar ion exchange membrane having a front surface and a back surface,
A first film thickness portion where a first conductivity type ion exchange group located on the front side is introduced, and a second film thickness portion where a second conductivity type ion exchange group located on the back side is introduced. And an electrode having the bipolar ion exchange membrane having a third film thickness portion having an ion exchange group density lower than that of the first and second film thickness portions located between the first and second film thickness portions. An iontophoresis device comprising a structure. The electrode structure is
A first electrode;
An electrolyte holding unit that holds the electrolyte contacting the first electrode;
The bipolar ion exchange membrane is disposed on the front side of the electrolyte solution holding unit with the back surface in contact with the electrolyte solution holding unit,
The iontophoresis device according to claim 4, wherein the first film thickness portion is doped with a first conductivity type drug ion. The electrode structure is
A first electrode;
An electrolytic solution holding unit for holding an electrolytic solution in contact with the first electrode;
A chemical solution holding unit that is disposed on the front side of the electrolyte solution holding unit and holds a chemical solution containing drug ions of the first conductivity type;
5. The iontophoresis device according to claim 4, wherein the bipolar ion exchange membrane is disposed between the electrolyte solution holding unit and the chemical solution holding unit. A first ion exchange membrane of a first conductivity type having a front surface and a back surface;
A second ion exchange membrane of a second conductivity type having a front surface and a back surface,
An ion exchange membrane laminate in which the first and second ion exchange membranes are laminated by bringing the back surface of the first ion exchange membrane into contact with the back surface of the second ion exchange membrane,
The ion exchange membrane laminate for iontophoresis, wherein the ion exchange group density of at least one of the first and second ion exchange membranes is inclined so as to be high on the front surface and low on the back surface. . A bipolar ion exchange membrane having a front surface and a back surface,
A first film thickness portion where a first conductivity type ion exchange group located on the front side is introduced, and a second film thickness portion where a second conductivity type ion exchange group located on the back side is introduced. And a third film thickness portion having an ion exchange group density lower than that of the first and second film thickness portions located between the first and second film thickness portions. Bipolar ion exchange membrane.

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