WO2006101146A1

WO2006101146A1 - Iontophoresis device

Info

Publication number: WO2006101146A1
Application number: PCT/JP2006/305747
Authority: WO
Inventors: Akihiko Matsumura; Takehiko Matsumura; Mizuo Nakayama; Hidero Akiyama; Tsutomu Shibata; Akihiko Tanioka
Original assignee: Transcutaneous Technologies Inc.
Priority date: 2005-03-22
Filing date: 2006-03-22
Publication date: 2006-09-28

Abstract

An iontophoresis device capable of administering of first drug ions resulting from dissociation in conductive form through a skin contact member having multiple needlelike items for skin puncturing, wherein an element capable of selective permeation of first conductive ions is disposed between a drug retention part for retaining of drug ions and the skin of living body as recipient of the drug ions. Thus, there is provided an iontophoresis device that can not only enhance the rate of drug administration and the efficiency thereof but also realize administration of drugs of high molecular weight, such as proteins and peptides.

Description

Specification

Iontophoresis device

Technical field

[0001] The present invention relates to an iontophoresis device for driving a drug dissociated into positive or negative ions in a solution by an electric field and transcutaneously transferring it into a living body. Background art

[0002] Iontophoresis is a method in which a drug dissociated into positive or negative ions in a solution is driven by an electric field and transcutaneously transferred into the living body, and the burden on the patient is reduced. It is considered that this is an administration method with excellent controllability of the dose, and various drugs are currently administered by iontophoresis.

[0003] However, the mobility of ions due to an electric field tends to decrease in inverse proportion to the molecular weight of the ions, and ions having a higher molecular weight tend to have lower permeability to the skin (especially the stratum corneum). It has been considered difficult to administer drugs with a molecular weight higher than a certain level, especially drugs with a large molecular force such as proteins and peptides, by iontophoresis.

Patent Document 1 discloses an iontophoresis device shown in FIG. 6 as a device for enabling administration of a drug having such a large molecular force.

As shown in the figure, in this apparatus, a plurality of needle-like bodies for puncturing the skin 240 on the surface of the base (support layer) 251 between the drug holding part (storage layer) 214 and the skin 240. (Microneedles) A skin contact member (conveying means) on which 252 is formed is arranged, and drug ions in the drug holding part 214 are formed inside the needle-like body 252 by a voltage applied from the electrode 211. It is to be administered into the skin 240 through the pore (flow path) 253.

[0006] According to Patent Document 1, the length of the needle-like body 252 penetrates the stratum corneum 241 completely or partially, but has little or no effect on the underlying epidermal layer 242. In particular, the length (L) of the gold † -like body 252 is set to 1000 μm at the maximum, especially 1 μm to 5

N

By setting it to 00 / zm, it is possible to prevent pain during patient administration, and more specifically, by setting the porosity of the skin contact member 215 to a maximum of 30%, ,needle 252 to about 2500 holes are provided at a density of Zcm ² and the length (L) of the holes 253 is 1 m.

K

~ 3000 μm, especially 10 μm to 1000 μm, and air diameter of 253 is 0.03 μm to 300 μm, especially 0.1 μπι to 100 / ζ m. It is supposed to be possible to administer a quantity of drug.

However, due to the studies by the present inventors, even with the apparatus disclosed in Patent Document 1, the administration rate of high molecular weight drugs such as proteins and peptides is extremely insufficient. Under conditions of current or voltage that do not damage the skin, it is impossible to administer the amount of drug necessary to obtain a medicinal effect within a time that is acceptable as the administration time of the drug. It became clear that they had such problems.

[0008] Patent Document 1: Japanese Patent Publication No. 10-510175

Patent Document 2: US Pat. No. 6,256,533

Patent Document 3: Japanese Translation of Special Publication 2005-503194

Disclosure of the invention

Problems to be solved by the invention

[0009] The present invention has been made in view of the above problems, and a high molecular weight ionic drug such as a protein or peptide (a drug whose medicinal component dissociates into positive or negative ions when dissolved) is obtained. It is an object of the present invention to provide an iontophoresis device that can be administered to a living body at a higher rate or efficiency.

[0010] The present invention also provides an iontophoresis device capable of efficiently administering a high molecular weight ionizable drug such as a protein or peptide to a living body under a lower current condition or voltage condition. Let it be an issue.

[0011] In addition, the present invention, including the one described in Patent Document 1, regardless of the molecular weight of the ionic drug, has a significantly higher efficiency or speed than the conventional iontophoresis device. Another object of the present invention is to provide an iontophoresis device capable of administering an ionizable drug.

[0012] In addition, the present invention, including those described in Patent Document 1, regardless of the molecular weight of the ionic drug, is lower than the conventional iontophoresis device under current conditions or voltage conditions. Providing an iontophoresis device that can efficiently administer ionic drugs It is also an issue to provide.

Means for solving the problem

[0013] The present invention is an iontophoresis device that administers drug ions dissociated into the first conductivity type via a skin contact member having a plurality of needle-like bodies that are punctured into the skin. An iontophoresis device in which an element having a function of selectively passing ions of the first conductivity type is disposed between a drug holding unit holding the drug and the skin of a living body receiving the drug ion The above-mentioned problems are solved by the invention. Specifically, the above-mentioned problems are solved by the inventions of the following first to fifth aspects.

[0014] That is, in the first aspect of the present invention,

A first electrode;

A skin contact member having a base body having a front surface and a back surface, and a plurality of needle-like bodies capable of skin puncture protruding from the surface of the base body;

A drug holding unit disposed on the back side of the substrate and adapted to be energized by the first electrode force, the drug holding unit holding a drug solution containing drug ions charged in a first conductivity type; An iontophoresis device comprising a working electrode structure having a hole inside the needle-like body that communicates the tip of the needle-like body and the back surface of the base.

According to an iontophoresis device, wherein the vacancies of the needle-like body are filled with an ion exchange resin into which an exchange group having a first conductivity type ion as a counter ion is introduced. The above problem is solved.

[0015] In the present invention of the first aspect, as in Patent Document 1, by applying a voltage of the first conductivity type to the first electrode, the drug ions in the drug holding portion pass through the cornea layer. The exchange group with the first conductivity type ion filled in the hole as a counter ion is introduced into the living body through the hole in the needle-like body punctured by the skin. Due to the action of the introduced ion exchange resin, ions (biological counterions) charged to the second conductivity type (conductivity type opposite to the drug ions) are prevented from flowing back to the drug holding part from the living body side. It has become so.

[0016] Therefore, most of the current applied to the first electrode is iontophoresis of biological counter ions (especially, biological counter ions with high molecular weight such as Na + and C1— which have low molecular weight). It is possible to avoid consumption due to the transfer into the device, and to contribute a larger part of the current applied to the first electrode to the transfer of drug ions to the living body. A dramatic improvement in speed can be achieved.

[0017] In the iontophoresis device of the present invention, in order to achieve the above-described effects, the drug ion administration efficiency and administration speed can be improved regardless of the molecular weight of the drug ion, or the drug administration can be performed. Current and voltage conditions can be made more gradual, and even drug ions with a large molecular force such as proteins and peptides can be made higher with lower current and voltage conditions. Drug ions can be administered at a rate or efficiency.

[0018] In the present invention, an ion exchange resin introduced with an exchange group having a first conductivity type ion as a counter ion may be a hydrocarbon resin such as polystyrene resin or acrylic acid resin. Cation exchange groups such as sulfonic acid groups, carboxylic acid groups, and phosphonic acid groups (exchange groups whose counter ion is a cation), etc., in high molecules with a three-dimensional network structure such as fluorocarbon resin having a fluorocarbon skeleton, Alternatively, anion exchange groups such as primary to tertiary amino groups, quaternary ammonium groups, pyridyl groups, imidazole groups, quaternary pyridinium groups, and quaternary imidazolium groups (exchange in which the counter ion is an anion) Conventionally known ion exchange resins such as those having a group introduced therein can be used.

[0019] Further, the filling of the ion-exchange resin into the needle-like vacancies in the present invention can be performed by any method, for example, a compound comprising a crosslinking agent in the monomer constituting the hydrocarbon-based resin. Infiltrate or impregnate the needles into the pores of the needle-like body to cause a crosslinking reaction, or a powdered ion exchange resin blended with an appropriate binder polymer penetrates into the pores of the needle-like body. It can be impregnated and filled, for example, by curing the binder polymer if necessary.

[0020] It is preferable that the needle-like body of the present invention has a base force protruding such that it can penetrate all or most of the stratum corneum, which is a main barrier in the transdermal administration of drugs. The inner diameter of the holes formed in the needle-like body whose length is preferably 1000 μm or less, particularly preferably 1 μm to 300 μm, is, for example, 0.03 μm to 300 μm. In particular, it is preferable that the substrate back surface force is 0.1 μm to l 00 m. The hole length to the needle tip is, for example, 1 Preferable to be μm to 3000 μm, especially 10 μm to 500 μm! / ヽ.

The needle-like body or skin contact member in the present invention can be manufactured by a known technique such as lithography technique, molding technique, laser processing using an organic material such as hard plastic or an inorganic material such as silicon. .

[0022] In the second aspect of the present invention,

A first electrode;

The skin contact member further includes a first ion exchange membrane that is disposed between the drug holding portion and the base and selectively allows the first conductivity type ion to pass therethrough. The above-mentioned problem is solved by an electrophoresis device.

[0023] In the second aspect of the present invention, by applying a voltage of the first conductivity type to the first electrode, the drug ions in the drug holding part pass through the holes provided in the needle-shaped body. On the other hand, the biological counter ions cannot pass through the first ion exchange membrane due to the action of the first ion exchange membrane, and the inside of the needle hole or the skin contact member cannot be passed. Since it stays in the space of the first ion exchange membrane, the movement of biological counter ions will be substantially blocked. Therefore, the efficiency or speed is the same as or similar to the first embodiment. Administration of drug ions is realized.

[0024] The needle-like body or skin contact member in the second aspect that works is the same as that described in the first aspect.

[0025] Further, the first ion exchange membrane in the second aspect is an arbitrary one having a function of selectively passing ions of the first conductivity type and blocking or suppressing the passage of ions of the second conductivity type. However, it is particularly preferable to use a part of the pores of the porous film. Alternatively, an ion exchange membrane of a type filled with an ion exchange resin into which all of the exchange groups having the first conductivity type ion as a counter ion are introduced can be used particularly suitably.

[0026] It should be noted that the second aspect of the present invention provides an iontophoresis device by a simple process in which an ion-exchange membrane that is easily available in the market or the like is disposed between a drug holding part and a skin contact member. Since it can be manufactured, there is an advantage that the manufacturing cost can be reduced.

[0027] In the third aspect of the present invention,

A first electrode;

A skin contact member comprising: a base body having a front surface and a back surface; and a plurality of columnar bodies made of an ion exchange resin embedded in the base body and introduced with an ion exchange group having a first conductivity type ion as a counter ion;

A drug holding unit disposed on the back side of the substrate and adapted to be energized by the first electrode force, the drug holding unit holding a drug solution containing drug ions charged in a first conductivity type; An iontophoresis device comprising a working electrode structure having one end, wherein one end of the columnar body is exposed on the back surface of the base, and the other end of the columnar body protrudes a predetermined length of the surface force of the base. The above problem is solved by an iontophoresis device characterized by forming a needle-like body that can be punctured through the skin.

[0028] In the third aspect, the columnar body made of an ion exchange resin has both a function as a needle-like body that punctures the skin and a function as a member that selectively allows the first ions to pass through. Thus, the same effects as those of the first and second aspects are achieved.

That is, by applying a voltage of the first conductivity type to the first electrode, the drug ion of the drug holding part is guided into the living body through the columnar body, while the columnar body is the first electrode. Since it is formed by an ion exchange resin in which an exchange group having a conductive ion as a counter ion is introduced, it prevents the biological counter ion from flowing back to the drug holding part side through the columnar body. As a result, as in the first and second embodiments, it is possible to improve the administration efficiency and administration speed of drug ions, or to make the current conditions or voltage conditions during drug administration more gradual. Even drug ions having a large molecular force such as proteins and peptides can be administered at a higher rate and efficiency under a lower current condition or voltage condition. [0030] The ion exchange resin (the ion exchange resin introduced with an exchange group having the first conductivity type ion as a counter ion) forming the columnar body according to the third embodiment is a first example. The same method as described above can be used, and as a method for imparting a columnar shape to the ion exchange resin, for example, a hydrocarbon-based resin or a fluorine-based resin constituting the ion-exchange resin is used. It is possible to adopt a method such as forming into a linear shape by an extrusion method or the like and then cutting to a predetermined dimension.

[0031] The cross-sectional shape of the columnar body may be any shape such as a circle or a rectangle, and the longitudinal dimension of the columnar body is, for example, 1 μm to 3000 μm, particularly 10 μm to 500 μm. m, preferably S, the diameter of the columnar body is ί or ί, and is preferably 0.03 μm to 300 μm, particularly preferably 0.1 μm to 100 μm. The acicular body formed by the body (the length of the columnar body protruding from the surface of the substrate) is preferably 1000 μm or less, particularly preferably 1 μm to 300 μm.

[0032] In the fourth aspect of the present invention,

A first electrode;

A plurality of needle-like protrusions made of a base having a front surface and a back surface, and a plurality of needle-like protrusions made of an ion-exchange resin embedded in the base and introduced with an ion-exchange group having a first conductivity type ion as a counter ion A skin contact member having a multi-needle body;

A drug holding unit disposed on the back side of the substrate and adapted to be energized by the first electrode force, the drug holding unit holding a drug solution containing drug ions charged in a first conductivity type; An iontophoresis device comprising a working electrode structure having: a surface of at least a part of the multi-needle body is exposed on the back surface of the base body, and the needle-like protrusion of any of the multi-needle bodies The above problem is solved by an iontophoresis device characterized in that a needle-like body that protrudes a predetermined length from the surface of the substrate to form a skin puncture is formed.

[0033] In the fourth aspect, similarly to the third aspect, a multi-needle body made of an ion exchange resin has a function as a needle-like body that punctures the skin, and allows the first ions to pass selectively. By having both functions as members, the same effects as the first to third aspects are achieved.

That is, by applying a voltage of the first conductivity type to the first electrode, On is guided to the living body through a multi-needle body, and this multi-needle body is formed by an ion exchange resin introduced with an exchange group having a first conductivity type ion as a counter ion. Therefore, the biological counter ions are prevented from flowing back to the drug holding part side through the multi-needle body. As a result, the administration efficiency and the administration speed of the drug ions are improved, or the drug is administered at the time of drug administration. Current and voltage conditions can be made more gradual, and even a drug ion having a large molecular force such as a protein peptide has a higher speed or efficiency under a lower current or voltage condition. With this, it becomes possible to administer drug ions.

[0035] The ion-exchange resin (the ion-exchange resin into which an exchange group having the first conductivity type ion as a counter ion) that forms a multi-needle body in the powerful fourth embodiment is used. Those similar to those described in the first embodiment can be used.

[0036] The needle-like projections of the multi-needle body according to the fourth aspect of the present invention may be formed to a length of 1000 / zm or less, particularly from 111 1 to 300 111, for example, by micromachining or the like.

[0037] In the fifth aspect of the present invention,

A first electrode;

An skin contact member having a base body having a front surface and a back surface and a plurality of skin-piercing needle-like bodies protruding from the front surface of the base body, wherein ions that selectively pass ions of the first conductivity type A skin contact member formed by an exchange membrane;

A drug holding unit that is disposed on the back side of the skin contact member and is energized by the first electrode force, and holds a drug solution containing drug ions charged in the first conductivity type. The above problem is solved by an iontophoresis device comprising a working electrode structure having a portion.

[0038] In the fifth aspect, as in the third and fourth aspects, by applying a voltage of the first conductivity type to the first electrode, the drug ions in the drug holding portion pass through the needle-shaped body. On the other hand, since the skin contact member is formed of an ion exchange membrane that selectively allows ions of the first conductivity type to pass through, the inflow of biological counter ions to the drug holding portion is prevented. As a result of inhibition or suppression, as in the first to fourth aspects, the drug ion administration efficiency and administration rate are improved, or the current and voltage conditions during drug administration are more gradual. Even drug ions that have macromolecular power, such as proteins and peptides, It becomes possible to administer drug ions at a higher rate or efficiency under lower current conditions or voltage conditions.

[0039] As the ion exchange membrane in the fifth aspect, an ion exchange membrane made of the same material as described above for the second aspect can be used, and the needle-like body on the surface of the ion exchange membrane can be used. The formation of can be performed, for example, by molding and pressing a base material constituting the ion exchange membrane.

In the third to fifth aspects of the present invention, a hole or a recess that communicates with the opening on the back surface of the substrate is formed inside the columnar body, multi-needle body or needle-like body. This makes it possible to further increase the drug ion administration rate or administration efficiency.

[0041] Further, in the iontophoresis device according to the first to fifth aspects of the present invention, the working electrode structure holds a first electrolyte solution that keeps contact with the first electrode. An electrolyte holding unit; and a second ion exchange membrane that is disposed between the first electrolyte holding unit and the drug holding unit and selectively allows ions of the second conductivity type to pass therethrough. This can prevent the decomposition of drug ions in the vicinity of the first electrode, transfer the H + ions and OH- ions generated at the first electrode to the drug holding part, or this drug Changes in pH value at the interface between the holding part and the skin contact member and the skin, or inflammation that may occur on the skin surface in contact with the skin contact member, are prevented, and the stability and safety of drug administration are prevented. Can be improved.

[0042] Further, the iontophoresis device according to the first to fifth aspects of the present invention includes a second electrolyte solution holding unit for holding a second electrode and an electrolyte solution kept in contact with the second electrode. A third ion exchange membrane that is disposed on the front side of the second electrolyte solution holding section and selectively allows ions of the first conductivity type to pass through, and an electrolyte that is disposed on the front side of the third ion exchange membrane. A non-operating having a third electrolyte holding part for holding the liquid, and a fourth ion exchange membrane which is disposed on the front side of the third ion exchange membrane and selectively passes the second conductivity type ion It is possible to further include a polar structure, and this may cause a change in pH value at the interface between the non-working electrode structure and the skin, or if it occurs on the skin surface in contact with the non-working electrode structure. Inflammation is prevented and the stability and safety of drug administration can be improved. Kill. Brief Description of Drawings FIG. 1 is an explanatory diagram showing a configuration of an iontophoresis device according to an embodiment of the present invention.

FIG. 2 (a) is an explanatory view showing the configuration of a skin contact member used in the iontophoresis device according to the present invention. (B) is explanatory drawing which shows the aspect of the movement of the ion in the iontophoresis apparatus which concerns on this invention.

FIG. 3 (a) to (f) are explanatory views showing other embodiments of the skin contact member.

圆 4] An explanatory view showing an example of a method for manufacturing a skin contact member.

FIG. 5 is an explanatory diagram showing a configuration of an iontophoresis device according to another embodiment of the present invention.

FIG. 6 is an explanatory view showing an example of a conventional iontophoresis device.

BEST MODE FOR CARRYING OUT THE INVENTION

Hereinafter, embodiments of the present invention will be described.

[0045] For convenience of explanation, a drug whose medicinal component dissociates into positive drug ions (for example, lidocaine hydrochloride as an anesthetic, salty calchun as a gastrointestinal disease treatment, bromide as a skeletal muscle relaxant) An example of an iontophoresis device for administering a bank mouth, an anesthetic morphine hydrochloride, etc. will be described as an example, but a drug (for example, a vitamin drug) that releases a medicinal component into a negative drug ion. In the case of an iontophoresis device for administering certain ascorbic acid or lipid A used as an adjuvant for vaccines, it is introduced into the power supply and ion exchange membrane or ion exchange resin in the following embodiments. It can be constructed by switching the polarity (plus and minus) of the exchange group. In addition, proteins and peptides are ampholytes and can be dissociated into either positive or negative ions depending on the pH of the drug solution. Select which type of iontophoresis device to use depending on the pH. become.

FIG. 1 is a schematic cross-sectional view showing a basic configuration of an iontophoresis device 1 according to the present invention.

As shown in the figure, the iontophoresis device 1 of the present invention includes a working electrode structure 10, a non-working electrode structure 20, and a power supply 30 as large components (members).

[0048] The working electrode structure 10 includes an electrode member 11 connected to the positive electrode of the power supply 30, a drug holding unit 14 that holds a drug solution that is energized from the electrode member 11 by contacting the electrode member 11, The skin contact member 15 disposed on the front surface of the medicine holding portion 14 and the force for accommodating them It consists of a bar or container 16.

On the other hand, the non-working electrode structure 20 includes an electrode member 21 connected to the negative electrode of the power supply 30 and an electrolyte that holds the electrolyte that is energized from the electrode member 21 by contacting the electrode member 21. The liquid holding unit 22 and a cover or container 26 for storing them are configured.

[0050] As the electrode members 11, 21, electrodes made of any conductive material can be used without limitation.

In particular, an active electrode such as a silver-z salt-silver-coupled electrode that can suppress the generation of H + ions and OH- ions due to electrolysis of water can be preferably used.

[0051] The drug holding unit 14 is a drug in which the medicinal component dissociates into positive ions when dissolved as a drug solution (for example, a protein or peptide having a positive total charge, or lidocaine, salt solution). Aqueous solutions of calchunes, bromide bank mouthwater, morphine hydrochloride) are retained.

[0052] The electrolytic solution holding unit 22 holds an electrolytic solution for ensuring electric conductivity, and as this electrolytic solution, it is possible to use phosphate buffered saline or physiological saline, Alternatively, electrolytes that are more susceptible to oxidation or reduction than the water electrolysis (oxidation at the positive electrode and reduction at the negative electrode), such as inorganic compounds such as ferrous sulfate and ferric sulfate, ascorbic acid ( Vitamin C) By using a pharmaceutical agent such as sodium ascorbate, an organic acid such as lactic acid, oxalic acid, malic acid, succinic acid, fumaric acid and Z or a salt thereof or a mixture thereof, the pH due to the electrolytic reaction of water It is also possible to prevent the fluctuation of the value or the generation of gas and the increase of the conductive resistance due to this.

[0053] The drug holding unit 14 and the electrolyte solution holding unit 22 may hold the drug solution or the electrolyte solution in a liquid state, but may be a fibrous sheet such as gauze or filter paper, or an talyl type. By impregnating and holding a drug solution or electrolyte solution as described above in a carrier made of any material having water retention properties such as a hydrogel of acrylic resin (acrylic hydrogel), a high molecular gel sheet such as a segmented polyurethane gel, It is possible to improve the handling properties.

[0054] In this case, the impregnation ratio of the drug solution or the electrolyte solution to the carrier should be set to an appropriate value that can obtain a sufficient conductivity and transport rate. By setting the liquid impregnation rate to 20-60%, a high transport rate (high drug delivery), for example, 70 ~ 80% can be obtained.

[0055] Here, the impregnation ratio is% by weight, and the weight at the time of drying is D, and the weight after impregnation is W. 100 X (W—D) ZD [%] Is the ratio of the current that contributes to the migration of drug ions out of the total current fed to the working electrode structure.

FIG. 2 (a) is a conceptual explanatory diagram showing details of the configuration of the skin contact member 15 in the iontophoresis device 1.

As shown in the figure, the skin contact member 15 includes a base body 51 having a front surface 51a and a back surface 51b, and a needle-like body 52 having a size, shape, and strength enough to project skin on the surface 51a. Each needle-like body 52 is formed with a hole 53 extending from the opening 53a at the tip of the needle-like body to the opening 53b on the back surface of the substrate.

[0058] Various methods for manufacturing such a skin contact member 15 are known. For example, by molding an organic material such as plastic according to the method disclosed in US Pat. No. 6,256,533, or It can be manufactured by etching an inorganic material such as silicon according to the method disclosed in Table 2005-503194.

[0059] Here, the length (L) of the needle-like body 52 of the skin contact member 15 is 1000 μm or less, preferably 1 μm to

N

By setting the length to 300 m, the pain given to the patient during drug administration can be reduced. The length (L) of the hole 53 from the opening 53a at the tip of the needle-like body to the opening 53b at the back of the substrate is 1 m.

K

To 3000 μm, preferably 10 μm to 500 μm, and by setting the inner diameter of the air gap 53 to 0.03 μm to 300 μm, preferably 0.1 μπι to 100 / ζ m, A sufficient flow path for smoothly administering drug ions can be secured. The density of the needle-like bodies 52 to the holes 53 on the skin contact member 15 can be, for example, several to 5000 Zcm ² .

[0060] The cross-sectional shape of the needle-like body 52 and the Z or hole 53 may be any shape such as a circle, an ellipse, and a rectangle. Also, as shown in FIG. It is possible to have a uniform cross-sectional area in the longitudinal direction of the shape 52, and it is also possible to improve the puncture property to the skin by adopting a tapered shape as shown in FIG.

In addition, the cavities 53 of the needle-like body 52 are filled with a cation exchange resin (ion exchange resin in which an exchange group having a positive ion as a counter ion is introduced) 54.

[0062] Examples of such cation exchange resin 54 include polystyrene resin and acrylic acid resin. Hydrocarbon resin such as fluorinated resin having a perfluorocarbon skeleton and a polymer substrate with a three-dimensional network structure, and cation such as sulfonic acid group, carboxylic acid group, and phosphonic acid group What introduced the exchange group can be used.

[0063] The pores 53 of the cation exchange resin 54 can be filled by any method. For example, the polymer base material such as styrene-divinylbenzene, chloromethylstyrene-dibutenebenzene, etc. is formed. The tip of the needle-like body 52 or the entire skin contact member 15 is immersed in a solution in which a polymerization initiator is blended with a crosslinkable monomer, or the solution of the substrate 51 is made using a spatula member or the like. The above-mentioned solution is permeated into the pores 53 by pouring the back side 51b side force, etc., and this is polymerized and then introduced into the solution as described above by introducing the cation exchange group as described above. Instead, a cation-exchange resin fine powder dispersed in a binder polymer such as phenol resin or methyl methacrylate was permeated or impregnated into the pores 53 in the same manner as described above, and then the Cure the molecule You can line Ukoto by.

[0064] The cation exchange resin 54 can be filled over the entire length of the hole 53 as shown in FIG. 2 (a). It is also possible to fill only a part of the holes 53 with the cation exchange resin 54, such as filling only the vicinity of the 53a portion.

[0065] Fig. 2 (b) shows the state of ions in the drug holding part 14 and the skin 40 when the skin contact member 15 is brought into contact with the skin 40 and electricity is applied from the electrode member 11 (and the electrode member 21). It is an explanatory diagram schematically showing the mode of movement, in which D + is a positively charged drug ion, D− is its counter ion (drug counter ion), and it exists in the living body (or on the skin 40) It shows negative ions. Reference numeral 41 denotes a stratum corneum covering the skin surface, and reference numeral 42 denotes a subcutaneous tissue below the stratum corneum.

The drug ion D + in the drug holding part 14 is driven by a positive voltage applied to the electrode member 11 and is administered into the skin 40 through the hole 53. At this time, since the drug ion D + has a brass polarity, it can pass through the cation exchange resin 54 filled in the hole 53.

[0067] Further, the needle-like body 52 penetrates through the stratum corneum 41 serving as a barrier against the movement of the drug ion D +. Since the puncture is performed, the drug ion D + guided to the opening 53a can move to the subcutaneous tissue 42 without receiving the resistance of the stratum corneum 41. It is most preferable that all the needle-like bodies 52 completely penetrate the stratum corneum 41 as shown in the illustrated example, but all or part of the needle-like bodies 52 are stratum corneum 41. In this case, the drug may be administered while being punctured partway through.In this case, depending on the degree to which the stratum corneum 41 existing from the opening 53a to the subcutaneous tissue 42 is thin, Administration efficiency can be increased.

On the other hand, biological counter ions present in the living body (or on the skin) are driven toward the drug holding unit 14 side by a positive voltage applied to the electrode member 11, Since the cation exchange resin 54 is filled, the migration of the biological counter ion B— to the drug holding part 14 is completely prevented or suppressed to a sufficient extent.

[0069] Accordingly, the ratio of the current consumed for the transfer of the biological counter ion B- to the drug holding unit 14 out of the total current supplied to the electrode member 11 is reduced or substantially zero, and the drug As a result, the rate of current that contributes to the transfer of D + to the living body increases, and as a result, the administration rate or administration efficiency of the drug ion D + is improved, or it is efficiently performed under a lower current condition or voltage condition. Drug ion D + can be administered.

[0070] Since the mobility of ions tends to decrease in inverse proportion to the molecular weight, when the cation exchange resin 54 is not present in the pore 53, the molecule of the drug ion D + to be administered is The larger the amount, the larger the ratio of the current consumed by the transfer of the biological counter ion B— to the drug holder 14, so the molecular weight was difficult to administer with conventional iontophoresis devices! / Vaginal drug ions can be observed when the rate of increase in drug ion administration rate or administration efficiency according to the present invention becomes significant.

[0071] As the power source 30 in the iontophoresis device of the present invention, a battery, a constant voltage device, a constant current device, a constant voltage 'constant current device, or the like can be used. Use a safe voltage condition that allows arbitrary current adjustment in the range of cm ² , preferably 0.01-0.5mAZcm ² , specifically, a constant current device that operates at 50V or less, preferably 30V or less. It is preferable to do.

[0072] In the iontophoresis device, the skin holding member 15 and the Z or the electrolyte solution holding unit 22 on the front side of the drug holding unit 14, the electrolyte solution holding unit 22 drying or the skin contact member 15, the electrolyte solution holding unit It is possible to affix a liner to prevent foreign matter from entering 22 and the working electrode structure 10, the non-working electrode structure 20 and the skin on the bottom b of the force bar or container 16 and Z or 26. It is also possible to provide a pressure-sensitive adhesive layer for improving the adhesiveness.

FIGS. 3 (a) to 3 (g) are explanatory views showing configurations of the skin contact members 15a to 15g of other modes that can be used in place of the skin contact member 15. FIG.

The skin contact member 15a in FIG. 3 (a) has the same base 51, needle-like body 52 and holes 53 as the skin contact member 15, but the cation exchange resin is inside the holes 53. Instead of being filled with 54, a cation exchange membrane (ion exchange membrane that selectively allows cations to pass through) 55 is disposed at a position on the back side of the base 51 and on the front side of the drug holding part 14.

In the iontophoresis device using such a skin contact member 15a, as in the case of the iontophoresis device 1, the drug ion D + is cationized by the action of the voltage applied to the electrode member 11. The opening force at the tip of the needle-like body 52 through the exchange membrane 55 and the hole 53 is also administered into the living body.

On the other hand, the transfer of the biological counter ion B— to the drug holding part 14 is blocked or suppressed by the cation exchange membrane 55, so that the biological counter ion B— stays in the hole 53. The movement of the living body versus ion B— will be substantially prevented.

[0077] Therefore, it becomes possible to contribute a larger part of the energized current to the transfer of the drug ion D + to the living body, improve the administration rate or administration efficiency of the drug ion D +, It becomes possible to perform drug administration under voltage conditions.

[0078] As the cation exchange membrane 55 used here, for example, a cation such as NEOSEPTA CM-1, CM-2, CMX, CMS ゝ CMB manufactured by Tokuyama Corporation is selectively used. Arbitrary cation exchange membranes that can pass through can be used, but some of the pores of the porous film can also be used such as polyolefin resin, salt resin resin, fluorine resin, polyamide resin, polyimide resin, etc. Alternatively, a cation exchange membrane of the type filled with a cation exchange resin can be used particularly preferably. For example, cation exchange resin can be filled with styrene-dibutylbenzene or chloromethylstyrene-dibulenebenzene. A solution in which a polymerization initiator is mixed with a crosslinkable monomer such as the above is impregnated into the pores of the porous film and then polymerized, and the polymer is polymerized with a sulfonic acid group, a carboxylic acid group, a phosphoric acid group. Such as phonic acid group This can be done by introducing a cation exchange group.

[0079] In addition, it is preferable to bond the interface between the cation exchange membrane 55 and the substrate 51 by an appropriate method such as bonding using an adhesive or ultrasonic bonding, thereby creating a gap at this interface. This can prevent problems such as an increase in the amount of movement of ion B— or a decrease in electrical conductivity due to the generation of bubbles.

The skin contact member 15b in FIG. 3 (b) includes a base 51 similar to the skin contact 15 and a large number of columnar bodies 56 made of a cation exchange resin embedded in the base 51. Each columnar body 56 has one end exposed on the back surface of the base 51 and the other end protruding a predetermined length from the surface of the base 51 to form a needle-like body 52.

In the iontophoresis device using such a skin contact member 15b, as in the case of the iontophoresis device 1, the drug ion D + is columnar due to the positive voltage applied to the electrode member 11. While passing through the body 56 and being administered into the living body, the transfer of the biological counter ion B— to the drug holding part 14 is prevented or suppressed by the action of the cation exchange resin constituting the columnar body 56, so More part of the generated current can contribute to the transfer of the drug ion D + to the living body, improve the administration rate or administration efficiency of the drug ion D +, and administer the drug under a lower current condition or voltage condition. Can be done.

[0082] As the cation exchange resin constituting the columnar body 56, the same cation exchange resin 54 as described above for the cation exchange resin 54 of the skin contact member 15 can be used, and the columnar shape thereof is a matrix. It is cut into a predetermined size after being formed into a linear shape by extruding the hydrocarbon-based resin or fluorine-based resin constituting the cation-exchanged resin, such as by machining with chromatin. It can be formed by a method such as introducing a cation exchange group before or after.

[0083] The length of the columnar body 56 (L) is, for example, 1 μm to 3000 μm, preferably 10 μm.

κ

If the cross-sectional shape of the columnar body 56 is circular, the diameter thereof is, for example, 0.03 μm to 300 μm, preferably 0.1 μm to 100 μm. Also, when embedding in the substrate 51, the protruding length (L) force from the surface of the substrate 51, eg 1000 m

N

In the following, it is preferable to set it to 1 μm to 300 μm! /.

Note that the cross-sectional shape of the columnar body 56 is not limited to a circle, and may be an arbitrary shape such as an ellipse or a rectangle. In addition, it is possible to enhance the puncture ability to the skin by forming a taper on the tip.

The skin contact member 15c in FIG. 3 (c) has a recess 56a that opens on the back surface side of the base 51 in the columnar body 56, except that the skin contact member 15b It has the same configuration.

Therefore, in the iontophoresis device using the skin contact member 15c, the drug ion D + is administered in the same manner as when the skin contact member 15b is used. Since this drug solution can penetrate into the recessed portion 56a, it is possible to administer drug ions with higher efficiency than when the skin contact member 15b is used.

[0087] The recessed portion 56a can be formed by subjecting the columnar body 56 formed by the above-described method to processing by micromachining or the like.

[0088] The skin contact member 15d of Fig. 3 (d) includes a base body 51 similar to the skin contact member 15, and a multi-needle body 57 made of a cation exchange resin embedded in the base body 51. Has been. As shown in the drawing, the multi-needle body 57 has a shape in which a plurality of needle-like protrusions protrude radially, and any one of the needle-like protrusions protrudes from the surface of the base 51 to form the needle-like body 52. Further, at least a part of the multi-needle body 57 is embedded in the base body 51 so as to be exposed on the back surface of the base body 51.

[0089] As the cation exchange resin of the multi-needle body 57, the same one as the columnar body 56 can be used, and the shape thereof can be formed by a technique such as micromachining.

[0090] In the iontophoresis device using such a skin contact member 15d, as in the case of the iontophoresis device 1, the drug ion D + is increased due to the positive voltage applied to the electrode member 11. While passing through the needle body 57 and being administered into the living body, the migration of the biological counter ion B— to the drug holding unit 14 is prevented or suppressed by the cation exchange resin constituting the multi-needle body 57. A larger part of the energized current can contribute to the transfer of drug ion D + to the living body, improve the administration rate or administration efficiency of drug ion D +, and administer the drug under a lower current condition or voltage condition. Can be performed.

[0091] In the skin contact member 15d, the multi-needle body 57 having an appropriate length and number of needle-like protrusions is used, so that the direction of the multi-needle body 57 (orientation) is not considered. Even when embedded in the needle, one of the needle-like protrusions protrudes toward the surface 51a of the base 51, and at least the multi-needle body 57 However, since part of the substrate 51 can be exposed on the back surface 51b of the substrate 51, there is an advantage that the manufacturing process can be simplified as compared with the skin contact member 15b.

The skin contact member 15e of FIG. 3 (e) is the above skin contact member except that the base 51 and the multi-needle body 57 are provided with a recessed portion 57a that opens toward the back surface 51b of the base 51. It has the same configuration as 15d.

[0093] Therefore, in the iontophoresis device using the skin contact member 15e, drug ions are administered in the same manner as when the skin contact member 15d is used. Since the drug solution can permeate into the recessed portion 57a, drug ions can be administered with higher efficiency than when the skin contact member 15d is used.

[0094] Note that the recessed portion 57a can be processed by a method such as micromachining.

The skin contact member 15f shown in FIG. 3 (f) has a base 51 and a needle-like body 52 protruding from the surface of the base 51, and the whole is formed of a cation exchange membrane.

[0096] Such a skin contact member 15f can be formed, for example, by molding using molds 61a and 62a having a shape as shown in Fig. 4 (a).

[0097] Specifically, a porous film 63 made of a thermoplastic resin such as polyolefin resin, salt vinyl resin, fluorine resin, polyamide resin, polyimide resin or the like is molded 61a, 62a is then press-molded, and then the cation exchange membrane 55 is filled with cation exchange groups in the same manner as described above for the cation exchange membrane 55, or in advance, the cation exchange in the pores. The skin contact member 15f can be formed by press-molding the porous film 63 filled with the resin with the molds 61a and 62a.

Alternatively, a film obtained by dispersing fine powder of a cation exchange resin in a binder polymer such as polyethylene, polystyrene, phenol resin, methyl methacrylate or the like between molds 6 la and 62 a is formed. Therefore, the skin contact member 15f as described above can be formed.

[0099] In the iontophoresis device using such a skin contact member 15f, as in the case of the iontophoresis device 1, the drug ion D + is peeled off by the positive voltage applied to the electrode member 11. While passing through the contact member 15f and being administered into the living body from the tip of the needle-like body 52 Since the transfer of the biological counter ion B— to the drug holding part 14 is inhibited by the skin contact member 15f, which is a cation exchange membrane, a larger part of the energized current is transferred to the drug ion D + organism. It is possible to contribute to the transition, improve the administration rate or administration efficiency of the drug ion D +, and administer the drug under a lower current condition or voltage condition.

[0100] Furthermore, in this iontophoresis device, the drug ion D + moves from the portion other than the needle-like body 52 of the base body 51 in contact with the skin 40 into the living body through the stratum corneum 41. Therefore, in particular, when the molecular weight of the drug ion is low to some extent, a significant amount is administered through the stratum corneum 41, and in the case of a possible drug ion, the drug administration rate or the administration efficiency is high. It will be further enhanced.

[0101] The skin contact member 15g of Fig. 3 (g) is the same as that described above except that a recess 58 extending from the back surface of the base 51 to the inside of the needle-like body 52 is formed in the skin contact member 15g. It has the same configuration as the contact member 15f.

[0102] Such a skin contact member 15g can be formed by the same method as described above for the skin contact member 15f by using molds 6 lb and 62b having a shape as shown in FIG. 4 (b). It is.

[0103] In the iontophoresis device using the skin contact member 15g, drug ions are administered in the same manner as in the case of using the skin contact member 15f, but the drug from the drug holding unit 14 is used. Since the liquid can permeate into the recess 58, drug ions can be administered with higher efficiency than when the skin contact member 15g is used.

FIG. 5 is an explanatory diagram showing the configuration of an iontophoresis device 101 according to another aspect of the present invention.

Similar to the iontophoresis device 1, the iontophoresis device 101 includes a working electrode structure 110, a non-working electrode structure 120, and a power supply 130.

The working electrode structure 110 holds the electrode member 111 connected to the positive electrode of the power supply 130, and the electrolyte solution that is configured to receive power from the electrode member 111 by maintaining contact with the electrode member 111. The electrolyte holding unit 112, the ion exchange membrane 113 disposed in front of the electrolyte holding unit 112, and the electrolyte holding unit 112 and the ion exchange membrane 113 disposed in front of the key exchange membrane 113. And a skin contact member 115 disposed on the front surface of the medicine holding portion 114, and the overall force S cover It is contained in the solstice container 116.

On the other hand, the non-working electrode structure 120 is composed of an electrode member 121 connected to the negative electrode of the power source 130 and an electrolyte solution that is energized from the electrode member 121 by keeping contact with the electrode member 121. Electrolyte holding part 122, cation exchange membrane 123 arranged in front of the electrolyte holding part 122, and arranged in front of the cation exchange membrane 123 via the electrolyte holding part 122 and cation exchange membrane 123. An electrolyte holding part 124 that is energized from the electrode member 121 and a key-on exchange membrane 125 disposed on the front surface of the electrolyte holding part 124 are provided, and the whole is housed in a cover or container 126.

Here, for the electrode members 111 and 121, the drug holding unit 114 and the electrolyte solution holding unit 112, 122 and 124, the electrode members 11 and 21, the drug holding unit 14 and the electrolyte solution holding unit 22 are respectively described above. The cation exchange membrane 123 can be the same as that described above for the cation exchange membrane 55.

[0109] In addition, as the ion exchange membranes 113 and 125, for example, anion ions such as Neosepta AM-1, AM-3, AMX, AHA, ACH, ACS, manufactured by Tokuyama Co., Ltd. are selectively used. Any anion exchange membrane that has a function of passing through can be used, and preferably an anion exchange membrane of the same type as the cation exchange membrane 55, in which the anion exchange resin is filled in the pores of the porous film. In this case, for example, the anion exchange resin can be filled by adding a solution in which a polymerization initiator is mixed with a crosslinkable monomer such as styrene-dibutylbenzene or chloromethylstyrene-dibulenebenzene. Polymerization after impregnation in the pores of the porous film and introduction of anion exchange groups into this polymer can be carried out.

[0110] The skin contact member 115 may be the same as the skin contact member 15 or 15a to f.

[0111] In the iontophoresis device 101, the iontophoresis device 1 or the device in which the skin contact member 15 of the iontophoresis device 1 is replaced with the skin contact members 15a to 15f has the same effect as described above. In addition to achieving the following, the following additional effects can be achieved.

[0112] Due to the action of the ion exchange membrane 113 or the cation exchange membrane 123, the electrode members 111 and 121 H + and OH− generated in this step is prevented or suppressed from being driven by the voltage from the electrode members 111 and 121 and transferred to the drug holding unit 114 and the electrolyte solution holding unit 124. Therefore, the fluctuation of the pH value on the skin contact surface of the drug holding part 114, the electrolyte holding part 124, and eventually the working electrode structure 110 and the non-working electrode structure 120 is suppressed, and damage to the skin is reduced. The safety of drug administration can be increased.

[0113] Further, as described above, since the transfer of H + and OH- to the drug holding unit 114 and the electrolyte holding unit 124 is prevented or suppressed, the electrode members 111 and 121 are not silver / silver chloride couple electrodes. It is possible to use a carbon electrode, which is an inert electrode, instead of any active electrode. Therefore, there is no concern that the metal ions that elute the electrode force migrate to the living body and cause health damage. An iontophoresis device can be realized.

[0114] Further, since the drug holding part 114 is separated from the electrode member 111 by the key-on exchange membrane 113, the drug ions are decomposed in the vicinity of the electrode member 111, and harmful substances are generated. Can be prevented.

[0115] Although the present invention has been described based on some embodiments, the present invention is not limited to these embodiments, and the constituent elements in the above embodiments are within the scope of the claims. Can be added, changed, or deleted.

Claims

The scope of the claims

[1] a first electrode;

An iontophoresis device, wherein the vacancy of the needle-like body is filled with an ion exchange resin into which an exchange group having a first conductivity type ion as a counter ion is introduced.

[2] a first electrode;

The skin contact member further includes a first ion exchange membrane that is disposed between the drug holding portion and the base and selectively allows the first conductivity type ion to pass therethrough. Endophoresis device.

[3] a first electrode;

A drug holding unit disposed on the back side of the substrate and adapted to receive an electric current from the first electrode force, the drug holding a drug solution containing drug ions charged in the first conductivity type An iontophoresis device comprising a working electrode structure having a holding part, wherein one end of the columnar body is exposed on the back surface of the base, and the other end of the columnar body is the surface force of the base. An iontophoresis device characterized by forming a needle-like body that protrudes long and can puncture the skin.

[4] The iontophoresis according to [3], wherein holes are formed in the columnar body, and the holes communicate with an opening formed in the back surface of the base body. Equipment.

[5] a first electrode;

A drug holding unit disposed on the back side of the substrate and adapted to be energized by the first electrode force, the drug holding unit holding a drug solution containing drug ions charged in a first conductivity type; An iontophoresis device comprising a working electrode structure having: a surface of at least a part of the multi-needle body is exposed on the back surface of the base body, and the needle-like protrusion of any of the multi-needle bodies An iontophoresis device characterized in that a needle-like body capable of skin puncture is formed by protruding from the surface of the base body by a predetermined length.

[6] The iontophoresis according to [5], wherein a hole is formed inside the multi-needle body, and the hole communicates with an opening formed in the back surface of the base body. Race equipment.

[7] a first electrode;

A drug holding unit that is disposed on the back side of the skin contact member and is energized by the first electrode force, and holds a drug solution containing drug ions charged in the first conductivity type. An iontophoresis device comprising a working electrode structure having a portion.

[8] The iontophoresis according to [7], wherein the skin contact member is formed with a hole extending from the inside of the plurality of needle-like bodies to the opening on the back surface of the base body. Equipment.

[9] The working electrode structure is

A first electrolyte holding part for holding an electrolyte solution kept in contact with the first electrode; and a second conductivity type ion disposed between the first electrolyte holding part and the drug holding part. 9. A second ion exchange membrane that selectively allows a gas to pass therethrough is further provided. The iontophoresis device according to claim 1.

[10] a second electrode;

A second electrolyte holding unit for holding an electrolyte solution in contact with the second electrode; and disposed on the front side of the second electrolyte holding unit to selectively select ions of the first conductivity type. A third ion exchange membrane to pass through;

A third electrolytic solution holding unit for holding an electrolytic solution disposed on the front side of the third ion exchange membrane;

The non-working electrode structure further comprising a fourth ion exchange membrane disposed on the front side of the third ion exchange membrane and selectively allowing ions of the second conductivity type to pass therethrough. The iontophoresis device according to any one of 1 to 9.