JP2007089821A - Iontophoresis apparatus - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide an iontophoresis apparatus capable of receiving a procedural advantage for granting an approval and a registration on the safety and the efficacy executed by government organizations. <P>SOLUTION: This iontophoresis apparatus is provided with a first conductivity type ion exchange membrane doped with first conductivity type medicine ions, and a voltage impressing member for impressing a voltage to the first ion exchange membrane; and the voltage impressing member includes an electrode, an electrolyte retaining section retaining electrolyte coming into contact with the electrode and a detachable impermeable separator disposed in the front face side of the electrolyte retaining section. This iontophoresis apparatus is constituted to dose the medicine ions in such a state that the separator is detached and the first ion exchange membrane is disposed in the front face side of the electrolyte retaining section. <P>COPYRIGHT: (C)2007,JPO&INPIT

Description

  The present invention relates to an iontophoresis device for administering ionically dissociated drug ions to a living body driven by a voltage having the same conductivity type as the drug ions.

  In iontophoresis, drugs dissociated into positive or negative ions in a drug solution are driven by voltage and transcutaneously transferred into the living body. It has the advantage of being excellent in.

  FIG. 6 is an explanatory diagram showing a basic configuration of an iontophoresis device which is a device for performing the iontophoresis.

  As shown in the figure, the iontophoresis device includes an electrode 211 and a working electrode structure 210 having a chemical solution holding part 212 for holding a chemical solution containing positive or negative drug ions, an electrode 221, and an electrolyte solution. A non-working-side electrode structure 220 having an electrolyte solution holding unit 222 to hold, and a power source 230 connected to both ends of the electrodes 211 and 221. The drug solution holding unit 212 and the electrolyte solution holding unit 222 are attached to the living body skin. In the state of contact, a voltage of the same conductivity type as that of the drug ion is applied to the electrode 211 and a voltage of the opposite conductivity type is applied to the electrode 221 so that the drug ion is administered to the living body.

  Patent Document 1 discloses a working electrode structure 310 that is an improvement of the working electrode structure 210, and can increase the administration efficiency of drug ions.

  FIG. 7A is an explanatory diagram showing a configuration of the working electrode structure 310 disclosed in Patent Document 1. FIG.

  As shown in the drawing, the working electrode structure 310 includes an electrode 311 to which a first conductivity type voltage is applied from a power source, a chemical solution holding unit 312 that holds a chemical solution containing a first conductivity type drug ion, and a first conductivity type. A type ion exchange membrane 313 is provided.

  In this working side electrode structure 310, since the first conductivity type ion exchange membrane 313 is interposed between the drug solution holding unit 312 and the living body skin, the transfer of biological counter ions from the living body to the drug solution holding unit 312 is blocked. . Therefore, in the iontophoresis device using the working electrode structure 310, the amount of current consumed by the movement of biological counter ions is reduced, and as a result, the administration efficiency of drug ions is increased.

  The applicant of the present application has devised an iontophoresis device in which the working electrode structure 310 in Patent Document 1 is further improved, and is filed as US Provisional Patent Application No. 60/69668 (hereinafter referred to as “Application 1”). is doing.

  FIG. 7B is an explanatory diagram showing a configuration of the working electrode structure 410 of the iontophoresis device disclosed as one embodiment in the first application.

  As illustrated, the working electrode structure 410 includes an electrode 411 to which a first conductivity type voltage is applied, an electrolyte solution holding unit 412 that holds an electrolyte solution, and a first conductivity type ion exchange membrane 413. The ion exchange membrane 413 is doped with the first conductivity type drug ions.

  In this working side electrode structure 410, a first conductivity type voltage is applied to the electrode 411 in a state where the ion exchange membrane 413 is in contact with the living body skin, so that the first in the electrolyte solution of the electrolyte solution holding unit 412 is obtained. Conduction type ions (hereinafter, the first conductivity type ions in the electrolyte are referred to as “first electrolytic ions”) migrate to the ion exchange membrane 413, and the drug ions doped in the ion exchange membrane 413 are the first electrolytic ions. It is replaced with the living body side.

  Here, in the working electrode structure 410, as in the working electrode structure 310 of Patent Document 1, since the transfer of biological counter ions is blocked by the ion exchange membrane 413, the administration efficiency of drug ions is increased. Can do.

Furthermore, the working electrode structure 410 achieves the following additional effects that cannot be obtained by the working electrode structure 310.
(1) Since the drug ions are held by the first ion exchange membrane, which is a member arranged closest to the living skin, the drug ion administration efficiency can be further increased.
(2) The ion exchange membrane doped with drug ions has better handling than the chemical solution holding unit 312 which is difficult to give wetness and is not self-supporting. Therefore, the assembly work of the electrode structure is facilitated.
(3) Since the drug ions are held in a state of being bound to the ion exchange groups in the first ion exchange membrane, the stability and storage stability of the drug ions are improved. For this reason, stabilizers, antibacterial agents, preservatives, etc. Can be eliminated, or the amount of use can be reduced, or the lifetime of the apparatus can be extended.

  By the way, iontophoresis devices are used as medical devices, health devices, and beauty devices for administering drug ions to living bodies including humans. In many countries and regions, there are restrictions on such devices. It has been. Therefore, in order to manufacture, sell, use, etc. of iontophoresis devices, approvals, registrations, etc. by government agencies, etc. for satisfying certain standards regarding safety and efficacy in each country or region It is necessary to receive.

  In addition, iontophoresis devices can be used to administer a wide variety of drugs that can ionically dissociate medicinal ingredients into living organisms. To use iontophoresis devices for multiple types of drugs, In many cases, it is necessary to obtain approval and registration for each drug.

For this reason, there has been a problem that a lot of time, labor, and cost are required for procedures for obtaining approval and registration in each country and each region.
JP-A-4-297277

  The present invention has been made in view of the above problems, and in addition to achieving the same effect as the iontophoresis device disclosed in Application 1, approval for safety and efficacy by a government agency or the like. It is an object of the present invention to provide an iontophoresis device that can enjoy the advantages of procedures for receiving registration.

  In addition to achieving the same effect as the iontophoresis device disclosed in Application 1, the present invention provides alteration of drug ions in the first ion exchange membrane and drug ions in the electrolyte solution in contact with the electrodes. It is another object of the present invention to provide an iontophoresis device that can prevent the contamination of the material.

The present invention
An iontophoresis device comprising: a first conductivity type ion exchange membrane doped with a first conductivity type drug ion; and a voltage application member for applying a voltage to the first ion exchange membrane,
The voltage applying member is
Electrodes,
An electrolytic solution holding unit for holding an electrolytic solution in contact with the electrode;
It is arranged on the front side of the electrolyte solution holding part, and has a removable non-permeable separator,
The iontophoresis device is characterized in that administration of the drug ion is performed in a state where the separator is removed and the first ion exchange membrane is disposed on the front surface side of the electrolyte solution holding unit (claim). 1).

  In the iontophoresis device of the present invention, the separator is removed prior to the administration of the drug, and then the first ion-exchange membrane is brought into contact with the living skin and a first conductivity type voltage is applied to the electrode, thereby Drug ions doped in one ion exchange membrane are administered to a living body.

  Here, the electrolytic solution in the electrolytic solution holding part has a role of supplying first electrolytic ions for substituting the drug ions doped in the first ion exchange membrane, and the drug in the first ion exchange membrane. The ions can be transferred to the living body by being replaced with the first electrolytic ions from the electrolytic solution holding unit.

  In the present invention, the fact that the first ion exchange membrane is doped with drug ions means that the drug ions are held in a state of being bound to the ion exchange groups of the first ion exchange membrane. Doping of the first ion exchange membrane with drug ions can be performed by immersing the first ion exchange membrane for a predetermined time in a chemical solution containing drug ions of an appropriate concentration. By adjusting the ion exchange capacity, the concentration of drug ions, the immersion time of the first ion exchange membrane in the chemical solution, and the number of times of immersion, it is possible to control the dope amount of the drug ions to the first ion exchange membrane. .

  When the mobility of the first electrolytic ions is larger than the mobility of the drug ions, the transfer of the first electrolytic ions to the living body occurs preferentially to the transfer of the drug ions to the living body. Since the ion administration efficiency may decrease, the electrolyte solution in the electrolyte solution holding part preferably has a composition in which the mobility of the first electrolyte ions is the same as or smaller than the mobility of the drug ions. .

  The separator of the present invention includes a thin film made of any water-impermeable material such as a non-water-permeable resin film such as polyvinyl chloride or polytetrafluoroethylene, a metal film, or a laminate of a metal film and a resin film. Can be used. The film thickness of the separator of the present invention is not particularly limited, and a film having an arbitrary film thickness can be used depending on the strength and flexibility required for handling the apparatus. A release agent can be applied to both or one side of the separator of the present invention in order to facilitate removal during drug administration.

  In the iontophoresis device of the present invention, the first conductivity type doped with drug ions of the first conductivity type is disposed on the front surface side of the voltage application member at the time of drug administration. An effect similar to that described above is achieved.

In addition, the iontophoresis device of the present invention is achieved by the iontophoresis device of Application 1 because the voltage application member and the first ion exchange membrane are separated by a non-permeable separator. The following additional effects (1) to (3) that cannot be achieved are achieved.
(1) It is possible to simplify procedures for obtaining approval and registration in each country or each region regarding safety and efficacy. That is, in the conventional iontophoresis device, the application procedure for approval and registration has to be performed for the entire device loaded with the drug, but in the iontophoresis device of the present invention, the application procedure for the voltage application member is required. Can be expected to be separated from the application procedure for the first ion exchange membrane. Therefore, in the case of receiving approval or registration for a plurality of types of drugs, the application procedure for the first ion exchange membrane needs to be performed for each drug, but in some countries and regions, the voltage application member Once approval or registration is received, it is expected that the application procedure for the voltage application member need not be repeated for each drug. In addition, depending on the country or region, it may be required to perform the application procedure for the voltage application member for each drug, but even in that case, the voltage application member and the first ion exchange membrane are non-permeable separators. It can be expected that simplification of the procedure can be achieved in such a manner that the required test items are reduced because of the separated configuration.
(2) Since the components contained in the voltage application member are blocked from being transferred to the first ion exchange membrane by the non-permeable separator, it is possible to prevent undesired phenomena such as drug alteration due to these components. Is done. Therefore, it is possible to extend the period in which the device can be kept without causing such an undesirable phenomenon.
(3) The migration of drug ions doped in the first ion exchange membrane to the voltage application member is blocked by the impermeable separator. Accordingly, it is possible to prevent inconveniences such as drug ions that have migrated to the electrolyte solution holding part during the device being present are decomposed by an electrode reaction during drug administration.

In the invention of claim 1,
The voltage applying member is
It is preferable that a second ion exchange membrane of a second conductivity type is further provided between the electrolyte solution holding part and the separator.

  As described above, also in the iontophoresis device according to the first aspect, the migration of drug ions from the first ion exchange membrane to the electrolyte solution holding portion during the presence of the device is blocked by the separator.

  However, when the device is left for a certain period of time after the separator is removed and before the administration of the drug, the drug ion moves to the electrolyte holding unit during that time, and the transferred drug ion is caused by the electrode reaction. May be decomposed.

  According to the invention of claim 2, since the migration of the drug ion as described above is blocked by the second ion exchange membrane, even if the time from the removal of the separator to the start of drug administration becomes longer, Decomposition of drug ions due to electrode reaction can be prevented.

  However, when the transport number of the second ion exchange membrane is 1, since the first electrolytic ions cannot be transferred to the first ion exchange membrane to replace the drug ions, the second ion exchange membrane in the present invention. For example, those having a low transport number (for example, a transport number of 0.7 to 0.95) are used. Even when such a second ion exchange membrane having a low transport number is used, drug ions are used. It is possible to sufficiently suppress the transition to the electrolytic solution holding part.

  Note that the transport number here is an electrolyte solution held in the electrolyte solution holding part and a drug solution containing drug ions and drug counter ions at appropriate concentrations (for example, dope drug ions into the first ion exchange membrane). Of the total charge carried through the second ion exchange membrane when a voltage of the first conductivity type is applied to the electrolyte side in a state where the second ion exchange membrane is disposed between the drug ion) Is defined as the proportion of the amount of charge carried by passing through the second ion exchange membrane.

  In the invention of claim 2, instead of the second ion exchange membrane, a semipermeable membrane having molecular weight fractionation characteristics that allows passage of the first electrolytic ions while blocking passage of the drug ions is used. In this case, the same effect as described above can be achieved.

In the invention of claim 2,
The voltage applying member is
Preferably, a third ion exchange membrane of the first conductivity type is further provided between the second ion exchange membrane and the separator.

  As described above, also in the iontophoresis device according to the first and second aspects, the migration of the components contained in the voltage application member during the presence of the device to the first ion exchange membrane is blocked by the separator.

  However, when the device is left for a certain period of time after the separator is removed and before the administration of the drug, the first electrolytic ion or the second conductivity type ion in the electrolytic solution (hereinafter, This may occur when an undesirable phenomenon such as drug ion alteration occurs due to transfer of the “second electrolytic ion”) to the first ion exchange membrane.

  In the iontophoresis device according to claim 3, since the migration of the first electrolytic ions is blocked by the second ion exchange membrane and the migration of the second electrolytic ions is blocked by the third ion exchange membrane, the separator is temporarily removed. Even if the time from the start of drug administration to the start of drug administration becomes longer, it is possible to prevent alteration of drug ions due to the first or second electrolytic ions from the electrolytic solution holding part.

  In the iontophoresis device according to claim 3, water electrolysis occurs at the interface between the second and third ion exchange membranes depending on the transport number and energization conditions of the second and third ion exchange membranes. In some cases, the administration efficiency of drug ions may be reduced by the transfer of hydrogen ions or hydroxyl ions generated by the above to a living body in preference to drug ions. Therefore, when it is necessary to prevent such a phenomenon, a semipermeable membrane not having an ion exchange function capable of allowing at least the passage of the first electrolytic ions is disposed between the second and third ion exchange membranes. It is preferable to do.

In the invention of claim 2,
The voltage applying member is
It is preferable to further have a chemical solution holding unit for holding a chemical solution containing drug ions between the second ion exchange membrane and the separator.

  In such an iontophoresis device, drug ions can be administered to a living body by applying a voltage of the first conductivity type to the electrode with the separator removed and the first ion exchange membrane in contact with the living body skin. Done. That is, energization from the electrolytic solution holding unit to the chemical solution holding unit occurs when the chemical solution counter ion moves to the electrolytic solution holding unit, and the drug solution holding unit is transferred by the drug ions in the chemical solution holding unit to the first ion exchange membrane. The first ion exchange membrane is energized to cause drug ions that have migrated from the chemical solution holding part to the first ion exchange membrane, or drug ions in the first ion exchange membrane that have been replaced by the first ion exchange membrane. It is driven by the voltage of the mold and moves to the living body.

  In the iontophoresis device according to claim 4, a chemical solution containing the same type of drug ion as the drug ion doped in the first ion exchange membrane can be used as the chemical solution in the chemical solution holding unit. Since one electrolytic ion does not cause a problem of transferring to the living body as a competitive ion of the drug ion, the administration efficiency of the drug ion can be further increased.

  In the iontophoresis device according to claim 4, it is also possible to use a chemical solution containing a different type of drug ion from the drug ion doped in the first ion exchange membrane as the chemical solution in the chemical solution holding unit. Adjusts the concentration of drug ions in the drug solution holding portion and / or the amount of drug ions doped into the first ion exchange membrane according to the mobility of each drug ion, thereby allowing each of a plurality of types of drug ions to be desired. An iontophoresis device that can be administered in a ratio can be realized.

In invention of Claims 1-4,
The voltage application member and the first ion exchange membrane are configured separately, and the voltage application member and the first ion exchange membrane can be separated, stored, transported, and handled. (Claim 5).

  In the iontophoresis device according to claim 5, since the voltage application member and the first ion exchange membrane are separate, in order to obtain approval and registration regarding safety and efficacy in more countries and regions. It is considered acceptable to perform the procedure separately between the voltage application member and the first ion exchange membrane. Therefore, it is possible to simplify procedures for obtaining approval and registration for a plurality of drugs in more countries and regions.

  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.

  The “medical solution” in the present specification is not only a solution in which a drug is dissolved in a solvent or a liquid state such as a stock solution in the case where the drug is in a liquid state, as long as at least a part of the drug dissociates into drug ions In various states such as those suspended or emulsified in a solvent or the like, those prepared in the form of an ointment or paste, and the like.

  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 where the positional relationship on the current path during drug administration is close to the skin.

  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.

  In the present invention, the drug ions doped into the first ion exchange membrane do not necessarily need to be a single type, and a plurality of types of drug ions may be doped into the first ion exchange membrane. 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 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.

  The “first-conductivity-type ion exchange membrane” in this specification is an ion-exchange membrane having a function of selectively passing ions of the first-conductivity-type, that is, the first-conductivity-type ions are of the second-conductivity-type. It means an ion exchange membrane that passes more easily than ions. 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” is an ion exchange membrane having a function of selectively passing second conductivity type ions, that is, ions of the second conductivity type are ions of the first conductivity type. It means an ion exchange membrane that passes more easily. 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.

  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 capacity of the ion exchange membrane by adjusting the conditions of the ion exchange group introduction treatment.

  Also, the transport number and ion exchange capacity 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 capacity of the ion exchange membrane can be adjusted also by the average pore diameter, porosity, and filling rate of the 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, there are cases where the passage speed or amount is sufficiently small as compared with ions of the opposite conductivity type, such as when the administration efficiency of drug ions can be sufficiently increased because the degree is small.

  “Allowance of ion passage” described in the present specification for an ion exchange membrane does not mean that there is no restriction on the passage of ions, but even if passage of ions is restricted to some extent, This includes the case of passing at a sufficiently high speed or amount as compared with ions of the opposite conductivity type.

  “Non-permeable” described for the separator in the present specification is the same as above, and procedures for approval and registration of safety and efficacy of the voltage application member and the first ion exchange membrane in any country or region. It is recognized that the moisture permeation can be blocked as long as the effect of the present invention is achieved, and does not necessarily mean that no moisture permeation occurs.

  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 conductivity type of the power source electrode and ion exchange membrane in the following description, An iontophoresis device that can achieve substantially the same effect as that of the embodiment can be configured.

  FIG. 1A is an explanatory diagram showing a configuration of an iontophoresis device X1 according to an embodiment of the present invention.

  As shown in the figure, the iontophoresis device X1 mainly includes a working electrode structure 10, a non-working electrode structure 20, and a power source 30.

  The working electrode structure 10 includes an electrode A1 connected to a positive electrode of a power supply 30 via a power supply line 31, an electrolyte holding part A2 that holds an electrolyte in contact with the electrode A1, and a front side of the electrolyte holding part A2. And a voltage application member A including a separator A6 disposed in the container A7 and a container A7 that accommodates the separator A6, and a cation exchange membrane B disposed on the front side of the separator A6 and doped with positive drug ions.

  As the electrode A1, an electrode made of any conductive material can be used without any particular limitation. However, by using a conductive material that causes an oxidation reaction when energized, such as silver, generation of gas or pH change due to the electrode reaction is suppressed. be able to.

  The electrolytic solution holding unit A2 can hold an electrolytic solution in which an arbitrary electrolyte is dissolved. However, an electrolytic solution 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 is used. By using it, it is possible to suppress the generation of gas and pH change during energization. In that case, an inert conductive material such as gold, platinum, or carbon can be used for the electrode A1.

  When the mobility of the cation in the electrolyte holding part A2 is larger than the drug ion doped in the cation exchange membrane B, the cation is transferred to the living body in preference to the drug ion, and the administration efficiency of the drug ion is increased. Since it may be lowered, it is preferable that the electrolyte solution in the electrolyte solution holding part A2 has a composition that does not contain positive ions having higher mobility than drug ions.

  The electrolytic solution holding unit A2 can hold the electrolytic solution in a liquid form, and can also be held by impregnating an appropriate absorbent carrier such as gauze, filter paper, or aqueous gel.

  As the separator A6, a sheet-like thin film body made of any non-permeable material can be used. The separator A6 is provided over the entire area in the container A7 in order to block the movement of moisture between the electrolyte solution holding unit A2 and the cation exchange membrane B. As shown in the figure, the end e of the separator A6 can be led out of the container A7, thereby facilitating the removal work of the separator A6. Further, it is possible to apply a release agent to one or both sides of the separator A6, and this also facilitates the removal operation of the separator A6.

  The container A7 can be formed of any material such as plastic that can prevent leakage or evaporation of moisture from the inside or contamination of foreign matter from the outside.

  The cation exchange membrane B can be doped with drug ions by immersing the cation exchange membrane B in a chemical solution containing drug ions. The amount of drug ions doped into the cation exchange membrane B can be controlled by the ion exchange capacity of the cation exchange membrane B, the concentration of drug ions in the chemical solution, the immersion time of the cation exchange membrane B in the chemical solution, the number of immersions, and the like. it can. As the cation exchange membrane B, it is preferable to use a cation exchange membrane of a type in which pores of a porous film are filled with a cation exchange resin.

  The non-working-side electrode structure 20 includes an electrode 21 connected to the negative electrode of the power supply 30 via a power supply line 32, an electrolyte solution holding unit 22 that holds an electrolyte solution in contact with the electrode 21, and a container 23 that houses these. And.

  An electrode made of any conductive material can be used as the electrode 21 without any particular limitation, but by using a conductive material that causes a reduction reaction when energized, such as silver chloride, gas generation and pH change due to the electrode reaction are suppressed. can do.

  The electrolytic solution holding unit 22 can hold an electrolytic solution in which an arbitrary electrolyte is dissolved, but uses an electrolyte having a lower reduction potential than the electrolysis of water, or a buffer electrolytic solution in which a plurality of types of electrolytes are dissolved. By doing so, it is possible to suppress the generation of gas and pH change during energization. In that case, an inert conductive material such as gold, platinum, or carbon can be used for the electrode 21.

  The electrolytic solution holding unit 22 can hold the electrolytic 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 electrolyte solution holding unit 22 is an optional element, and the electrolyte solution holding unit 22 is omitted when the skin surface is moist and sufficient conductivity between the non-working side electrode structure 20 and the skin can be secured. It is also possible to do.

  The container 23 can be formed of an arbitrary material such as plastic capable of preventing leakage or evaporation of moisture from the inside or contamination from outside.

The power source 30, battery, voltage regulator, a constant current device, may be used, such as constant current, constant voltage device, 0.01~1.0mA / cm ^2, preferably, from 0.01 to 0. It is preferable to use a constant current device that can adjust the current in the range of 5 mA / cm ² and operates under a safe voltage condition of 50 V or less, preferably 30 V or less.

  When the drug is administered by the iontophoresis device X1, the separator A6 is removed by pulling the end e in the direction of the arrow in FIG.

  FIG. 1B shows the iontophoresis device X1 with the separator A6 removed. As shown in the figure, the electrolyte solution holding part A2 and the cation exchange membrane B are in contact with each other so that electricity can be supplied from the electrode A1 to the cation exchange membrane B. In this state, the cation exchange membrane B and the electrolyte solution holding part 22 The drug ions doped in the cation exchange membrane B are administered to the living body by energizing the skin with the living body.

  Specifically, positive ions in the electrolytic solution are driven by a positive voltage to the electrode A1 and migrate to the cation exchange membrane B, and replace the drug ions doped in the cation exchange membrane B. The drug ion substituted with the positive ion is driven by the positive voltage to the electrode A1 and moves into the living body.

The iontophoresis device X1 achieves the following effects (1) and / or (2) in addition to the same effects as the iontophoresis device disclosed in the first application.
(1) Since the voltage application member A and the cation exchange membrane B are separated by the separator A6, the application procedure for the cation exchange membrane B when receiving approval and registration for safety and efficacy by a government agency, The application procedure for the voltage application member A can be performed separately, or the application procedure for the cation exchange membrane B and the application procedure for the voltage application member A, the non-working side electrode structure 20 and the power source 30 can be separated. Therefore, it is possible to reduce the time, labor, and cost required for the application procedure when receiving approval and registration for a plurality of types of drugs.
(2) Since the voltage application member A and the cation exchange membrane B are separated by the separator A6, the components contained in the electrolyte solution holding part A2 during the presence of the apparatus are transferred to the cation exchange membrane B, or the cation exchange membrane. Migration of drug ions doped into B to the electrolyte solution holding part A2 is blocked by the separator A6. Therefore, it is possible to suppress undesired phenomena such as alteration of drug ions in the cation exchange membrane B caused by components transferred from the electrolyte holding unit A2 and decomposition due to electrode reaction of drug ions transferred to the electrolyte holding unit A2. Can do.

  FIG. 2A is an explanatory view showing, in an enlarged manner, another embodiment of the separator A6 ′ that can be used in the working electrode structure 10 described above.

  As shown in the figure, the separator A6 ′ has one end e1 attached to one side wall of the container A7, an intermediate portion m folded at the other side wall of the container A7, and the other end e2 from the one side wall of the container A7 to the outside. Has been derived.

  In the working electrode structure 10 having the separator A6 ′, the separator A6 ′ can be removed in the manner shown in FIGS. 2B and 2C by pulling the other end e2 in the direction of the arrow. The removal work is easier than the separator A6.

  In addition, also in separator A6 ', the removal operation | work of separator A6' can be further facilitated by apply | coating a mold release agent to the upper surface u or the lower surface b.

  FIGS. 3A to 3C are explanatory views showing configurations of working electrode structures 10 a to 10 c of other modes that can be used in place of the working electrode structure 10.

  The working electrode structure 10a of FIG. 3 (A) includes the same electrode A1, electrolytic solution holding part A2, separator A6, container A7 and cation exchange membrane B as the working electrode structure 10, in addition to the electrolytic solution. An anion exchange membrane A3 is provided between the holding part A2 and the separator A6.

  As in the case of the iontophoresis device X1, the iontophoresis device including the working electrode structure 10a removes the separator A6 and brings the cation exchange membrane B and the electrolyte solution holding unit 22 into contact with the living skin. By conducting electricity in a state, the drug ions in the cation exchange membrane B are administered to the living body.

  In the working electrode structure 10a, in addition to the effects similar to those described above with respect to the working electrode structure 10, the transition of drug ions to the electrolyte solution holding part A2 from the time when the separator A6 is removed until the drug administration is started. Can be blocked by the anion exchange membrane A3, so that even when the time from the removal of the separator A6 to the start of drug administration becomes longer, the additional effect of preventing the decomposition of drug ions due to the electrode reaction is achieved. The

  When the transport number of the anion exchange membrane A3 is 1, positive ions in the electrolyte solution holding part A2 cannot move to the cation exchange membrane B and replace the drug ions. An anion exchange membrane having a low transport number (for example, about 0.7 to 0.95) is used.

  The working electrode structure 10b of FIG. 3 (B) includes an electrode A1, an electrolytic solution holding part A2, an anion exchange membrane A3, a separator A6, a container A7, and a cation exchange membrane B similar to the working electrode structure 10a. In addition, a cation exchange membrane A4 is provided between the anion exchange membrane A3 and the separator A6.

  As in the case of the iontophoresis device X1, the iontophoresis device including the working electrode structure 10b removes the separator A6 and brings the cation exchange membrane B and the electrolyte solution holding unit 22 into contact with the living skin. By conducting electricity in a state, the drug ions in the cation exchange membrane B are administered to the living body.

  In the working electrode structure 10b, in addition to the same effect as that of the working electrode structure 10a, positive ions and negative ions cations in the electrolyte solution holding part A2 from when the separator A6 is removed until drug administration is started. Since the transition to the exchange membrane B can be blocked by the anion exchange membrane A3 and the cation exchange membrane A4, even when the time from the removal of the separator A6 to the start of drug administration becomes longer, the electrolyte from the electrolyte holding part A2 An additional effect is achieved in that alteration of drug ions by positive ions and negative ions can be prevented.

  The working electrode structure 10c of FIG. 3 (C) includes the same electrode A1, electrolyte holding part A2, anion exchange membrane A3, separator A6, container A7, and cation exchange membrane B as the working electrode structure 10a. In addition, a chemical solution holding part A5 for holding a chemical solution containing positive drug ions is provided between the anion exchange membrane A3 and the separator A6.

  The chemical solution in the chemical solution holding unit A5 can include the same or different types of drug ions as the drug ions doped into the cation exchange membrane B.

  The chemical liquid holding unit A5 can hold the chemical liquid in a liquid state, and can also be held by impregnating an appropriate absorbent carrier such as gauze, filter paper, or aqueous gel.

  As in the case of the iontophoresis device X1, the iontophoresis device including the working electrode structure 10c removes the separator A6 and brings the cation exchange membrane B and the electrolyte solution holding unit 22 into contact with the living skin. By conducting electricity in a state, the drug ions in the cation exchange membrane B are administered to the living body.

  At this time, energization from the electrolytic solution holding unit A2 to the chemical solution holding unit A5 is caused by the migration of the drug counter ion in the chemical solution holding unit A5 to the electrolytic solution holding unit A2, and from the chemical solution holding unit A5 to the cation exchange membrane B. The energization occurs when the drug ions in the drug solution holding part A5 move to the cation exchange membrane B, and the energization from the cation exchange membrane B to the living body is the drug ion doped in the cation exchange membrane B or the drug from the drug solution holding part A5 It occurs when ions move to the living body.

  Therefore, when the drug solution holding unit A5 holds a drug solution containing the same type of drug ion as the drug ion doped in the cation exchange membrane B, other types of positive ions from the electrolyte solution holding unit A2 are drug ions. Since it is prevented from transferring to the living body as competitive ions of the drug, it is possible to further increase the drug ion administration efficiency, and the drug solution holding part A5 is a different type of drug from the drug ion doped in the cation exchange membrane B When a drug solution containing ions is held, an iontophoresis device capable of administering a plurality of types of drug ions to a living body at a predetermined ratio can be realized.

  Note that the separator A6 of the working electrode structures 10a to 10c can be replaced with the separator A6 ′ shown in FIG. 2, thereby facilitating the work of removing the separator.

  FIG. 4A is an explanatory diagram showing a configuration of an iontophoresis device X2 according to another embodiment of the present invention.

  As illustrated, the iontophoresis device X2 includes a non-working-side electrode structure 20 and a power source 30 similar to those of the iontophoresis device X1.

  The working electrode structure 110 of the iontophoresis device X2 includes the same components as the working electrode structure 10, but the voltage application member A and the cation exchange membrane B are separate and independent members. This is different from the working electrode structure 10. That is, the working electrode structure 110 includes an electrode A1 connected to the positive electrode of the power supply 30 via the power supply line 31, an electrolyte solution holding unit A2 that holds an electrolyte solution that contacts the electrode A1, and an electrolyte solution holding unit A2. A voltage application member A including a separator A6 disposed on the front surface side and a container A7 that accommodates the separator A6 and a cation exchange membrane B doped with positive drug ions are provided. The voltage application member A and the cation exchange membrane are provided. B is configured as a separate and independent member.

  4 (B) to 4 (D) are explanatory views showing how the iontophoresis device X2 is used during drug administration. First, the separator A6 is removed from the voltage application member A (FIG. 4 (b)). Subsequently, a cation exchange membrane B is affixed to the lower surface of the electrolyte solution holding part A2 (FIG. 4 (c)), and then the cation exchange membrane B and the electrolyte solution holding part 22 are attached in the same manner as the iontophoresis device X1. By energizing from the power supply 30 in contact with the living body skin, the drug ions doped in the cation exchange membrane B are administered to the living body (FIG. 4D).

  Since the iontophoresis device X2 has the same components as the iontophoresis device X1, the same effects as described above for the iontophoresis device X1 can be achieved.

  In addition, in the working electrode structure 110, the voltage application member A and the cation exchange membrane B are separate and independent members. Therefore, when the iontophoresis device X2 is stored and transported, the voltage application member A and the cation exchange membrane B2 are used. In a state where the exchange membrane B is housed in a separate bag (or in a state where the voltage application member A, the power source 30 and the non-working side electrode structure 20 and the cation exchange membrane B are housed in separate bags) The independence of the voltage application member A and the cation exchange membrane B can be enhanced, for example, so that it can be handled.

  Therefore, when receiving approval and registration for safety and efficacy of the iontophoresis device X2, the application procedure for the cation exchange membrane B and the application procedure for the voltage application member A in more countries and regions. It is expected that the application procedure for the cation exchange membrane B and the application procedure for the voltage application member A, the non-working side electrode structure 20 and the power source 30 may be performed separately. it can.

  FIGS. 5A to 5C are explanatory views showing configurations of working side electrode structures 110a to 110c of other modes that can be used in place of the working side electrode structure 110. FIG.

  The working side electrode structures 110a to 110c include the same components as the working side electrode structures 10a to 10c, and the voltage application member A and the cation exchange membrane B are configured as separate and independent members. Only the working side electrode structures 10a to 10c are different.

  Accordingly, the iontophoresis device including the working electrode structures 110a to 110c achieves the same effect as described above for the iontophoresis device X2, and the iontophoresis including the working electrode structures 10a to 10c. An additional effect similar to that of the cis apparatus is achieved.

  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 embodiment, an iontophoresis device comprising a single working electrode structure that holds a drug to be administered to a living body and a single non-working electrode structure that serves as a counter electrode. 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 electrodes of the power supply (that is, the working electrode structure is provided in both electrodes of the power supply). This is similarly applied to iontophoresis devices in which a plurality of working electrode structures or a plurality of non-working electrode structures are connected to one or both poles of a power source. The invention can be applied.

  That is, in any of the above cases, in the iontophoresis device in which at least one of the one or more working electrode structures has the configuration according to any one of claims 1 to 5 of the present application, When receiving approval and registration for properties and efficacy, the application procedure for drug ion-doped cation exchange membranes and voltage application members can be performed separately, or drug ion-doped cation exchange membranes and The application procedures for other parts can be performed separately, and therefore the time, labor, and cost required for the application procedures when receiving approval and registration for multiple types of drugs can be reduced. Such an iontophoresis device is within the scope of the present invention.

  The configuration of the non-working side electrode structure in the iontophoresis device of the present invention is not limited to the mode shown in the above embodiment.

  For example, in Application 1 or Japanese Patent Application Laid-Open No. 2000-229128, an electrode to which a voltage of the same conductivity type as that of drug ions is applied, an electrolyte solution holding unit that holds an electrolyte solution in contact with the electrode, and a front surface side thereof are arranged. Working electrode structure comprising a drug ion and an ion exchange membrane of the opposite conductivity type, or an electrode to which a voltage of the same conductivity type as that of the drug ion is applied, and an electrolyte solution that holds the electrolyte solution in contact with the electrode A holding part, an ion exchange membrane of the same conductivity type as a drug ion arranged on the front side, an electrolyte holding part holding an electrolytic solution arranged on the front side, and a drug ion arranged on the front side A non-working side electrode structure comprising an ion exchange membrane of the opposite conductivity type is disclosed. As the non-working side electrode structure of the iontophoresis device of the present invention, such a working side electrode structure is used. Can also be used An ability, which makes it possible to achieve additional effects, such as non-working electrode of the gas in the structure generation of pH change suppression during energization.

  Alternatively, the iontophoresis device itself of the present invention may not be provided with the non-working side electrode structure. For example, the working side electrode structure is brought into contact with the living body skin, and the living body is attached to a member serving as a ground. It is also possible to administer drug ions by applying a voltage to the working electrode structure in a state where a part of the working electrode structure is in contact, and also in this case, the effect of the present invention is achieved. Such an iontophoresis device is also included in the scope of the present invention.

BRIEF DESCRIPTION OF THE DRAWINGS Explanatory drawing which shows the structure of the iontophoresis apparatus which concerns on one Embodiment of this invention. Explanatory drawing which expands and shows the separator of the other aspect in the iontophoresis apparatus which concerns on one Embodiment of this invention. Explanatory drawing which shows the structure of the working side electrode structure of the other aspect in the iontophoresis apparatus which concerns on one Embodiment of this invention. Explanatory drawing which shows the structure of the iontophoresis apparatus which concerns on other embodiment of this invention. Explanatory drawing which shows the structure of the working side electrode structure of the other aspect in the iontophoresis apparatus which concerns on one Embodiment of this invention. Explanatory drawing which shows the structure of the conventional iontophoresis apparatus. (A) is explanatory drawing which shows the structure of the working side electrode structure disclosed by patent document 1. FIG. (B) is explanatory drawing which shows the structure of the working side electrode structure disclosed by the application 1. FIG.

Explanation of symbols

X1, X2 iontophoresis devices 10, 10a to 10c, 110, 110a to 110c Working electrode structure A Voltage application member A1 Electrode A2 Electrolyte holding part A3 Anion exchange membrane A4 Cation exchange membrane A5 Chemical liquid holding part A6 Separator A7 Container B Cation exchange membrane 20 Non-working side electrode structure 21 Electrode 22 Electrolyte holding part 23 Container 30 Power supply 31, 32 Feeding line 32 Feeding line 210, 310, 410 Working side electrode structure 211, 311, 411 Electrodes 212, 312 Chemical solution holder 412 Electrolyte solution holders 313, 413 Ion exchange membrane 220 Non-working side electrode structure 221 Electrode 222 Electrolyte solution holder 230 Power supply

Claims (5)

An iontophoresis device comprising: a first conductivity type ion exchange membrane doped with a first conductivity type drug ion; and a voltage application member for applying a voltage to the first ion exchange membrane,
The voltage applying member is
Electrodes,
An electrolytic solution holding unit for holding an electrolytic solution in contact with the electrode;
It is arranged on the front side of the electrolyte solution holding part, and has a removable non-permeable separator,
The iontophoresis device is characterized in that the drug ion is administered in a state where the separator is removed and the first ion exchange membrane is disposed on the front surface side of the electrolyte solution holding unit. The voltage applying member is
The iontophoresis device according to claim 1, further comprising a second conductivity type second ion exchange membrane between the electrolyte solution holding unit and the separator. The voltage applying member is
The iontophoresis device according to claim 2, further comprising a third ion exchange membrane of a first conductivity type between the second ion exchange membrane and the separator. The voltage applying member is
The iontophoresis device according to claim 2, further comprising a chemical solution holding unit that holds a chemical solution containing drug ions between the second ion exchange membrane and the separator. The voltage application member and the first ion exchange membrane are configured separately, and the voltage application member and the first ion exchange membrane can be separated, stored, transported, and handled. The iontophoresis device according to any one of claims 1 to 4.

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