JP4606118B2 - Method for producing working electrode structure for iontophoresis device - Google Patents

Description

  The present invention relates to the production of a working electrode structure for use in an iontophoresis device used in iontophoresis (ionosmosis therapy) in which an ionic drug useful for a living body is permeated into the living body using electrophoresis. Regarding the method.

  Iontophoresis, in which an ionic drug useful for the living body is permeated into the living body using electrophoresis, is also called ion osmosis therapy, iontophoresis, and the like. It is widely known as a method of administration.

  Conventionally, in iontophoresis, a drug layer (ionic drug solution holding part) impregnated with an ionic drug is placed on the living body, and a working electrode is disposed on the opposite side of the living body across the drug layer. A counter electrode was placed on a living body separated from the layer, and an ionic drug was infiltrated into the living body by passing an electric current between the working electrode and the counter electrode by a power source. The purpose of this method is to allow only an ionic drug to penetrate into a living body through a living body interface such as skin or mucous membrane. However, in such an electrode, the ionic drug does not necessarily pass through the biological interface, and conversely, sodium cation, potassium cation, chloride anion, etc. penetrate from the biological interface to the drug layer side. Not a few. In particular, an ionic drug that is useful for a living body has a lower mobility than the ions existing in the living body as described above. There was a problem of low efficiency.

  In order to eliminate these drawbacks, a new method of iontophoresis has been proposed in which an ion exchange membrane is placed on the living body interface and medicinal ions permeate the living body through the ion exchange membrane (for example, Patent Documents 1 to 7). reference). In the new system proposed here, an ion exchange membrane that allows only ions having the same sign as the intended medicinal ions to pass through is disposed on the living body interface. For this reason, it is possible to prevent ions having a sign opposite to that of the target drug from exuding from the living body, and higher drug administration efficiency can be obtained as compared with the case where no ion exchange membrane is provided.

Further, at the electrode portion, the ionic drug is decomposed, or water used as a solvent for the ionic drug is electrolyzed to generate H ⁺ ions and OH ⁻ ions, which act on the living body. In order to solve problems such as inflammation, an ion exchange membrane is arranged between the drug-containing layer and the electrode so that the ionic drug contained in the drug-containing layer is not in direct contact with the electrode. A method for preventing the generated H ⁺ ions and OH ⁻ ions from moving toward the living body has also been proposed (see, for example, Patent Documents 3 to 5 and 8).

Furthermore, in order to prevent inflammation due to the H ⁺ ions and OH ⁻ ions, a method of arranging an ion exchange membrane on the counter electrode side has been proposed (see, for example, Patent Documents 6 and 7).

Japanese Patent Laid-Open No. 03-94771 JP-T03-504343 Japanese Patent Laid-Open No. 04-297277 JP 2004-188188 A JP 2004-202057 A JP 2000-229128 A International Publication No. 03/037425 Pamphlet JP-T 63-502404

  In iontophoresis using an ion exchange membrane as described above, in order to improve drug administration efficiency, the contact efficiency between the ion exchange membrane and the living body interface, that is, adhesion must be good.

  However, according to the study by the present inventors, when a dried ion exchange membrane is fixed and an ionic drug solution holding portion is laminated thereon, wrinkles or strains ( Hereinafter, it became clear that deformation) occurred. When such deformation occurs in the ion exchange membrane, the adhesion with the living body interface decreases, and the drug administration efficiency decreases. In addition, there arises a problem that the ion exchange membrane is easily broken due to such deformation.

  Therefore, an object of the present invention is to provide a working electrode structure for an iontophoresis device that does not cause the above-described deformation, and thus has a high drug administration efficiency and excellent reliability.

  The present inventors have conducted intensive research to solve the above problems. As a result, the ion exchange membrane is preliminarily moistened with the drug solution, and then the working electrode structure is manufactured in the order in which the ion exchange membrane is brought into contact with the substance containing the drug solution, thereby preventing the occurrence of deformation during the energization. The present invention was completed as a result of the heading and further examination.

That is, in the present invention, an electrode, an ionic drug solution holding part, and an ion exchange membrane having a thickness of 5 to 150 μm are laminated in this order, and medicinal ions contained in the ionic drug solution holding part are passed through the ion exchange membrane. In the method for producing a working electrode structure for an iontophoresis device used for administration to a living body by electrophoresis, the ion exchange membrane has a structure prior to stacking the ionic drug solution holding part and the ion exchange membrane. A method for producing a working electrode structure for an iontophoresis device, comprising a step of replacing a counter ion of an ion exchange group with the medicinal ions.

  Another invention is a method for manufacturing an iontophoresis device using the method for manufacturing a working electrode structure.

  The iontophoresis device using the working electrode structure for an iontophoresis device obtained by the production method of the present invention can prevent a decrease in administration efficiency due to deformation of the ion exchange membrane during energization. This makes it possible to stably administer the target drug and is an extremely useful iontophoresis device with excellent reliability.

  The present invention will be described below with reference to the drawings. As shown in FIG. 1, the iontophoresis device according to the present invention typically includes a working electrode structure 1, a counter electrode structure 2, and a power supply unit 3 electrically connected to these structures. Is done.

  The working electrode structure 1 is a structure including an electrode 4 serving as a working electrode, an ionic drug solution holding unit 5 containing an ionic drug, and an ion exchange membrane 6. The ion exchange membrane 6 is administered. It is an ion exchange membrane that selectively transmits ions having the same sign as medicinal ions. As shown in the figure, the electrodes, the ionic drug solution holding part, and the ion exchange membrane are arranged in this order. Usually, these are laminated in one exterior material (not shown), and are used in the orientation in which the ion exchange membrane is arranged on the living body interface. Moreover, in order to prevent decomposition | disassembly of the chemical | medical agent to administer and to prevent that the pH of a chemical | medical agent containing layer changes by an electrode reaction, the ion exchange membrane 8 may be arrange | positioned further between an electrode and a chemical | medical agent containing layer. In this case, as the ion exchange membrane 8, generally used is an ion exchange membrane that selectively transmits ions having the opposite sign to the medicinal ions.

  In the method for producing a working electrode structure according to the present invention, prior to stacking the ion exchange membrane 6 and the ionic drug solution holding unit 5, the ion exchange group counterion of the ion exchange membrane 6 is ionized. Replacement with medicinal ions contained in the drug solution holding part 5 is performed.

In the present invention, the reason why the ion exchange membrane can be prevented from being deformed through the steps as described above is that the counter ion of the ion exchange group in the ion exchange membrane (for example, H ⁺ , Na ⁺ , or OH ⁻ , Cl ^−, etc.) is much larger in size than medicinal ions, and when energized, the membrane expands due to ion exchange, whereas by performing ion exchange in advance, the membrane expands. This is presumed to be suppressed.

  The method for substituting the counter ion of the ion exchange group of the ion exchange membrane 6 with a medicinal ion is not particularly limited, but a method of immersing the ion exchange membrane in a solution containing the medicinal ion is preferable. It is done. The counter ion of the medicinal ion in the solution containing the medicinal ion is not particularly limited as long as it is an ion that is not harmful to the living body, but is the same kind as the counter ion in the ionic drug contained in the ionic drug solution holding part. It is preferable that The solvent is not particularly limited as long as it is not harmful to the living body and can obtain a solution containing medicinal ions. Usually, water, ethanol or the like is used.

  As described above, when substitution of counter ions is performed by immersion, the substitution is faster and more reliably as the medicinal ion concentration is higher. Although it varies depending on the thickness of the ion exchange membrane, the kind of the ionic agent, etc., it is usually immersed in a solution of about 0.1 to 300 mmol / L, preferably about 1 to 100 mmol / L for about 10 minutes to 24 hours. Is enough. In addition, the amount of the solution used is calculated from the absolute amount of medicinal ions (concentration × solution amount) from the amount of ion-exchange groups of the ion-exchange membrane to be immersed, that is, the mass of the ion-exchange membrane soaked × ion-exchange capacity The value may be set to be 2 times or more, preferably 5 times or more, more preferably 10 times or more.

  The exchange rate of counter ions is determined by measuring the amount of medicinal ions re-eluted with a strong acid or strong base from the membrane ion-exchanged under the predetermined conditions as described above, and the amount of ion-exchange groups possessed by the ion-exchange membrane. Can be obtained by comparing Although the exchange rate of the counter ion is preferably higher, it is not always necessary to exchange 100%. In order to prevent deformation during energization under the average use condition, it should be about 70% or more. It is preferably 80% or more, particularly preferably 90% or more. If the exchange rate of the counter ion is low, a higher concentration solution may be used, or the immersion conditions may be changed so as to be immersed for a longer time.

  In addition to the above immersion, a solution containing medicinal ions may be applied by brushing or spraying, or dropped on an ion exchange membrane.

  In the production method of the present invention, the ion exchange membrane in which counter ions are substituted with medicinal ions obtained as described above is laminated in contact with the ionic drug solution holding part. The ion exchange membrane may be used after being dried once after substitution of the counter ion, but is preferably subjected to a step of laminating with the ionic drug solution holding portion in a wet state without being dried.

  The ionic drug in the present invention is not particularly limited as long as it can be administered by iontophoresis. Specific examples of such drugs include ionic drugs with positively charged medicinal ions such as anesthetic agents such as procaine hydrochloride, lidocaine hydrochloride and dibucaine hydrochloride, antineoplastic agents such as mitomycin and bleomycin hydrochloride, and morphine hydrochloride. Steroids such as medroxyprogesterone acetate, histamine and the like, while negatively charged ionic drugs include vitamin B2, vitamin B12, vitamin C, vitamin E, vitamins such as folic acid, aspirin, Anti-inflammatory agents such as ibuprofen, corticosteroids such as dexamethasone-based water-soluble preparations, and antibiotics such as benzylpenicillin potassium.

  Since such an ionic drug is a solid, it must be dissolved in a solvent in which the drug can be dissolved in order to enable administration to a living body. The solvent is typically water, but an organic solvent such as ethanol may be used as necessary.

  As a method for producing the ionic drug solution holding part containing the ionic drug solution, any known method can be employed without any limitation as the method for iontophoresis. For example, a method of adding a non-ionizing hydrophilic polymer such as polyethylene glycol, polypropylene glycol, polyvinyl alcohol, polyvinyl pyrrolidone, gelatin or the like and a fine particle filler such as colloidal silica to the drug solution to form a paste or gel Is mentioned. Further, as another method, a method in which an ionic drug solution is soaked into a hydrophilic sheet-like or film-like substance such as paper or cotton cloth can be suitably employed.

  The method of laminating the ion exchange membrane in which the counter ion is replaced with the medicinal ion with the ionic drug holding part is not particularly limited. For example, the ionic drug solution as described above is placed on the ion exchange membrane fixed in a planar shape. Examples of the method include arranging a soaked sheet or a gel formed in a plate shape, or applying a paste containing an ionic drug solution. The laminated body of the ion exchange membrane and the ionic drug solution holding part thus obtained is further provided with an ion exchange membrane having a reverse polarity on it to seal and fix the peripheral part, or to arrange an electrode or the like. What is necessary is just to laminate | stack with the provided exterior material and to fix to this exterior material.

  In addition, the paste or gel containing the ionic drug solution is filled in the exterior material or the like in which the electrodes are disposed, and the ion exchange membrane is placed on the gel or paste so as to adhere to the gel or paste. A fixing method is also suitable.

  The working electrode structure thus obtained can be used in the same manner as a working electrode structure for ordinary iontophoresis. Typically, the iontophoresis device as shown in FIG. 1 is used. Can be used as part of

  The effect of the production method of the present invention increases as the ion exchange membrane in which the counter ion is replaced by the medicinal ions is thinner. That is, an ion exchange membrane having a small film thickness has low membrane resistance and excellent medicinal ion permeability, but on the other hand, it is thin and easily deforms.

  As such an ion exchange membrane having a thin film thickness and thus low membrane resistance and excellent medicinal ion permeability, a porous film as a base material is particularly preferable because of its excellent mechanical strength. Useful. Such ion exchange membranes based on a porous film are disclosed in Japanese Patent Application Laid-Open Nos. 2004-188188 and 2004-202057.

That is, an ion exchange membrane having a structure in which a void portion of a porous film made of a thermoplastic resin having a thickness of 5 to 150 μm, preferably 10 to 120 μm, more preferably 10 to 70 μm, is filled with a cross-linked ion exchange resin. is there. As said thermoplastic resin, polyolefin resin, such as polyethylene, a polypropylene, polybutene, is preferable. In addition, the porous film preferably has an average pore diameter measured in accordance with the bubble point method (JIS K 3832-1990) in that it is thin and excellent in strength and easy to form an ion exchange membrane with low electrical resistance. The thickness should be 0.005 to 5.0 μm, more preferably 0.01 to 2.0 μm, and most preferably 0.02 to 0.2 μm. Similarly, the porosity of the porous film is preferably 20 to 95%, more preferably 30 to 90%, and most preferably 30 to 60%. Ions based on such a porous film Briefly describing the method for producing the exchange membrane, styrene, α-methylstyrene, 3-methylstyrene, 4-methylstyrene, 2,4-dimethylstyrene, p-tert-butylstyrene, α-halogenated styrene, vinylnaphthalene A monomer capable of introducing a cation exchange group such as styrene, vinyl toluene, chloromethyl styrene, vinyl pyridine, vinyl imidazole, α-methyl styrene, vinyl naphthalene and the like. A monomer having divinylbenzene, divinylsulfone, butadiene, chloroprene, divinylbiphenyl, Cross-linking agents such as trivinylbenzene, and octanoyl peroxide, lauroyl peroxide, t-butylperoxy-2-ethylhexanoate, benzoyl peroxide, t-butylperoxyisobutyrate, t-butylperoxylaur Preparing a polymerizable composition comprising a mixture with a polymerization initiator such as rate, t-hexylperoxybenzoate, di-t-butyl peroxide, and soaking the porous film in the polymerizable composition; The polymerizable composition is allowed to enter the voids of the porous film, and then polymerized by heating or the like with both surfaces covered with a smooth film such as a polyester film. The ion exchange membrane thus obtained has both sufficient strength and flexibility and high drug administration efficiency.

  Of course, the production method of the present invention is not limited to the ion exchange membrane obtained by the method as described above, and a production method of an ioton foresis device using any ion exchange membrane that can be used for other iontophoresis. You may apply to.

The production method of the present invention is more effective when the area of the ion exchange membrane is larger, and is preferably applied when a membrane having an effective area for drug administration of 3 cm ² or more is used, and a membrane of 4 cm ² or more. It is more preferable to apply to a film of 5 cm ² or more.

  In order to describe the present invention more specifically, examples and comparative examples will be described below, but the present invention is not limited to these examples.

  First, ion exchange membranes 1 to 7 used in the test were produced by the following method.

Production Example 1
Preparation of ion exchange membrane 1 A monomer composition comprising 380 g of chloromethylstyrene, 20 g of divinylbenzene, and 20 g of t-butylperoxyethylhexanoate was prepared, and 420 g of this monomer composition was placed in a 500 ml glass container. In this, a porous film of 20 cm × 20 cm (made of polyethylene having a weight average molecular weight of 250,000, a film thickness of 25 μm, an average pore size of 0.03 μm, a porosity of 37%) is immersed at 25 ° C. for 10 minutes under atmospheric pressure, This porous film was impregnated with the monomer composition. Subsequently, the porous film was taken out from the monomer composition, and both sides of the porous film were covered with a 100 μm polyester film, and then heated and polymerized at 80 ° C. for 5 hours under a nitrogen pressure of 3 kg / cm ² . . Next, the obtained membrane was reacted at room temperature for 5 hours in an amination bath consisting of 10 parts by weight of 30% by weight trimethylamine, 5 parts by weight of water and 5 parts by weight of acetone to obtain a quaternary ammonium type anion exchange membrane. . The obtained ion exchange membrane was cut into a size of 3 cm × 4 cm (dry weight: about 0.03 g) and immersed in physiological saline until just before use to prevent drying.

Production Examples 2-5
Production of Ion Exchange Membranes 2-5 Anion exchange membranes were produced in the same manner as in Production Example 1 except that the monomer composition and the porous film were replaced with the compositions shown in Table 1.

Production Example 6
Preparation of Ion Exchange Membrane 6 A monomer composition comprising 244 g of N, N-dimethylaminoethyl methacrylate / methyl chloride salt, 28 g of nonaethylene glycol dimethacrylate, 128 g of hydroxyethyl methacrylate, and 12 g of t-butylperoxyethyl hexanoate 400 g of this monomer composition was placed in a 500 ml glass container, and each 12 cm × 13 cm porous film (made of polyethylene having a weight average molecular weight of 250,000, film thickness of 25 μm, average pore diameter of 0.03 μm, porosity) 37%) was immersed at 25 ° C. for 10 minutes under atmospheric pressure, and the porous film was impregnated with the monomer composition. Subsequently, the porous film was taken out of the monomer composition, and both sides of the porous film were covered with a 100 μm polyester film, and then nitrogen pressure of 3 kg / cm ^{2 was applied} at 70 ° C. for 2 hours, and then 90 A quaternary ammonium type anion exchange membrane was obtained by heat polymerization at 0 ° C. for 3 hours.

  The ion exchange capacity, water content, membrane resistance, and film thickness of the obtained anion exchange membrane were measured. The results are shown in Table 1.

Production Example 7
Preparation of ion exchange membrane 7 A monomer composition comprising 360 g of styrene, 40 g of divinylbenzene, and 20 g of t-butyl peroxyethyl hexanoate was prepared, and impregnated into the porous film in the same manner as in the case of the ion exchange membrane 1. It was. Subsequently, the porous film was taken out from the monomer composition, and both sides of the porous film were covered with a 100 μm polyester film, and then heated and polymerized at 80 ° C. for 5 hours under a nitrogen pressure of 3 kg / cm ² . Next, the obtained membrane was immersed in a 1: 1 mixture of 98% concentrated sulfuric acid and chlorosulfonic acid having a purity of 90% or more at 40 ° C. for 45 minutes to obtain a sulfonic acid type cation exchange membrane.

Production Example 8
Production of Ion Exchange Membrane 8 A cation exchange membrane was produced in the same manner as the ion exchange membrane 7 except that the monomer composition was changed to the composition shown in Table 1.

  The membrane physical properties of the obtained ion exchange membrane were measured by the following method. The results are shown in Table 1.

(1) ion exchange capacity and moisture content;
The ion exchange membrane is immersed in a 1 mol / L HCl aqueous solution for 10 hours or more.

Thereafter, in the case of a cation exchange membrane, the hydrogen ion type is replaced with a sodium ion type with a 1 mol / L NaCl aqueous solution, and the liberated hydrogen ions are converted into a potentiometric titrator (COMMITE-900, Hiranuma using a sodium hydroxide aqueous solution). (Amol). On the other hand, in the case of an anion exchange membrane, a chloride ion type is replaced with a nitrate ion type with 1 mol / L NaNO ₃ aqueous solution, and the liberated chloride ion is converted into a potentiometric titrator (COMMITITE-900, (Amol).

  Next, the same ion exchange membrane is immersed in a 1 mol / L HCl aqueous solution for 4 hours or more, washed thoroughly with ion exchange water, and then the membrane is taken out. The surface moisture is wiped off with a tissue paper or the like (Wg). Was measured. Next, the membrane was dried under reduced pressure at 60 ° C. for 5 hours, and its weight was measured (Dg). Based on the measured value, the ion exchange capacity was determined by the following equation.

Ion exchange capacity = A × 1000 / W [mmol / g-dry weight]
Moisture content = 100 × (WD) / D [%]
(2) membrane resistance;
An ion exchange membrane is sandwiched in a two-chamber cell equipped with a platinum black electrode, 3 mol / L sulfuric acid aqueous solution is filled on both sides of the ion exchange membrane, and the resistance between the electrodes at 25 ° C. is measured by an AC bridge (frequency 1000 cycles / second). The difference between the resistance between the electrodes and the resistance between the electrodes when no ion exchange membrane was installed was obtained. The membrane used for the above measurement was previously equilibrated in a 3 mol / L sulfuric acid aqueous solution.

Example 1
The surface of the 3 cm × 4 cm ion exchange membrane 1 taken out from the physiological saline was wiped with a tissue paper to lightly remove moisture. This was immersed in 25 ml of a 100 mmol / L aqueous solution of ascorbic acid phosphate magnesium salt at 25 ° C. for 24 hours, and the ion exchange membrane was impregnated with drug ions (ascorbic acid phosphate ions). A working electrode structure shown in FIG. 2 was prepared using this membrane and an ion exchange membrane (ion exchange membrane 7) that prevents the drug from reaching the electrode. The contact area between the skin and the ion exchange membrane was specified to be 6 cm ² (2 cm × 3 cm). The chemical chamber was filled with a 10 mmol / L aqueous solution of magnesium ascorbate phosphate, and the electrode chamber was filled with a 0.1 mol / L sodium lactate aqueous solution. The working electrode structure, the power source and the counter electrode structure were connected as shown in FIG. 2 and fixed to the back skin of a minipig (Yucatan Micropig, 5 months old, female). The virtual skin chamber was filled with 0.9% by weight sodium chloride aqueous solution. Next, while stirring the virtual skin chamber, it was energized for 1 hour at a constant current density of 0.5 mA / cm ² at 25 ° C. After the energization was completed, the liquid in the virtual skin chamber was immediately removed and the drug amount was measured by liquid chromatography. It was measured. The same operation was performed without energization, the blank value was measured, and the difference from the amount of drug when energized was calculated as the drug permeation amount. Further, after the energization was completed, the working electrode structure was removed from the mini-pig skin, and the state of deformation of the ion exchange membrane was visually evaluated. The results are shown in Table 2.

Comparative Example 1
In Example 1, evaluation was performed by performing the same operations except that the step of immersing the ion exchange membrane 1 in an aqueous solution of magnesium ascorbate phosphate for 24 hours to impregnate the drug ions was not performed. The results are shown in Table 2.

Example 2
In the same manner as in Example 1, an ion exchange membrane 1 impregnated with ascorbic acid phosphate ester ions) was obtained.

A cell as shown in FIG. 3 was assembled using this membrane, the back skin of a minipig, and a protective ion exchange membrane (ion exchange membrane 7). The effective area of the ion exchange membrane was specified to be 6 cm ² (2 cm × 3 cm). The chemical chamber is filled with 10 mmol / L aqueous solution of ascorbic acid phosphate magnesium salt, the virtual skin chamber is filled with 0.9 wt% sodium chloride aqueous solution, and the two electrode chambers are filled with 0.1 mol / L sodium lactate aqueous solution. Satisfied. Next, while stirring the chemical chamber and the virtual skin chamber, energization was performed for 1 hour at a constant current density of 0.5 mA / cm ² at 25 ° C. After the energization was completed, the liquid in the virtual skin chamber was immediately extracted and subjected to liquid chromatography. The amount of drug was measured. The same operation was performed without energization, the blank value was measured, and the difference from the amount of drug when energized was calculated as the drug permeation amount. Further, the state of contact between the membrane at the end of energization and the minipig skin was visually evaluated. The results are shown in Table 3.

Comparative Example 2
In Example 2, the same operation was performed and evaluated except that the step of immersing the ion exchange membrane 1 in an aqueous solution of ascorbic acid phosphate magnesium salt for 24 hours and impregnating the drug ions was not performed. The results are shown in Table 3.

Examples 3-7
Except that the ion exchange membranes 2 to 6 were used in place of the ion exchange membrane 1, the amount of drug permeation was measured in the same manner as in Example 2, and the state of contact between the membrane and the minipig skin was evaluated. The results are shown in Table 3.

Comparative Examples 3-7
The amount of drug permeation was measured in the same manner as in Comparative Example 2 except that ion exchange membranes 2 to 6 were used in place of the ion exchange membrane 1, and the state of contact between the membrane and minipig skin was evaluated. The results are shown in Table 3.

Example 8
As the ion exchange membrane to be brought into contact with the skin, the ion exchange membrane 7 is used instead of the ion exchange membrane 1, the lidocaine hydrochloride aqueous solution is used instead of the ascorbic acid phosphate magnesium aqueous solution, and the ion exchange membrane is further used as a protective ion exchange membrane. Except for using 1, the amount of drug permeation was measured in the same manner as in Example 2, and the state of contact between the membrane and the minipig skin was evaluated. The results are shown in Table 4. The concentration of the lidocaine hydrochloride aqueous solution is 100 mmol / L at the time of immersion in the ion exchange membrane before assembling the cell and 10 mmol / L at the time of the drug permeation test, as in Example 2.

Example 9
The amount of drug permeation was measured in the same manner as in Example 8 except that an ion exchange membrane 8 was used instead of the ion exchange membrane 7 as the ion exchange membrane to be brought into contact with the skin, and the amount of drug permeation was measured in the same manner. Was evaluated. The results are shown in Table 4.

Comparative Example 8
In Example 8, evaluation was performed by performing the same operations except that the step of immersing the ion exchange membrane 7 in a 100 mmol / L aqueous solution of lidocaine hydrochloride for 24 hours and impregnating the drug ions was not performed. The results are shown in Table 4.

Comparative Example 9
Except for using the ion exchange membrane 8 in place of the ion exchange membrane 7, the amount of drug permeation was measured in the same manner as in Comparative Example 8, and the state of contact between the membrane and the minipig skin was evaluated. The results are shown in Table 4.

Examples 10-12, Comparative Examples 10-12
Evaluation was performed in the same manner as in Example 2 (each example) or Comparative example 2 (each comparative example) except that the ionic chemicals shown in Table 5 were used instead of the ascorbic acid phosphate magnesium salt. The results are also shown in Table 5.

  As described above, in iontophoresis in which the ion exchange membrane to be brought into contact with the skin is preliminarily immersed in the drug solution and ion exchange is not performed, deformation occurs such as wrinkles on the membrane during energization, and the drug permeation amount is On the other hand, when manufactured by the method of the present invention, there is no deformation during energization and a high drug permeation amount can be obtained.

The schematic diagram which shows the typical structure of the apparatus for iontophoresis of this invention. The schematic diagram of the apparatus used in Example 1 and the comparative example 1 in order to evaluate the deformation | transformation of the ion exchange membrane of a working electrode structure, and chemical | medical agent permeation amount. In Examples 2-12 and Comparative Examples 2-12, the schematic diagram of the other apparatus used in order to evaluate the deformation | transformation and chemical | medical agent permeation amount of an ion exchange membrane.

Explanation of symbols

1: Working electrode structure 2: Counter electrode structure 3: Power supply unit 4, 4 ′: Electrode 5: Ionic drug solution holding unit 6: Ion exchange membrane 7: Living body surface (interface)
8: Ion exchange membrane 9: Electrolyte containing part 10: Ion exchange membrane

Claims (2)

An electrode, an ionic drug solution holding part, and an ion exchange membrane having a thickness of 5 to 150 μm are laminated in this order, and the medicinal ions contained in the ionic drug solution holding part are biologically dispersed by electrophoresis through the ion exchange membrane. In the method for producing a working electrode structure for an iontophoresis device used for administration to an iontophoresis device, prior to laminating the ionic drug solution holding part and the ion exchange membrane, a pair of ion exchange groups possessed by the ion exchange membrane The manufacturing method of the working electrode structure for iontophoresis apparatuses characterized by including the process of replacing ion with the said medicinal ion.   The manufacturing method of the iontophoresis apparatus which includes the manufacturing method of the working electrode structure for iontophoresis apparatuses of Claim 1 in the process.

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