JPH07185016A - Living body application device for iontophoresis - Google Patents

Abstract

PURPOSE:To provide an application device for iontophoresis for efficiently deliver medicine into a living body by reducing leakage of current on a surface of skin. CONSTITUTION:In a living body application device for iontophoresis in which a medicinal electrode compartment 4 and a counter electrode compartment 5 are arranged in the same plane with an insulator 6 between them, a skin contact part 7 is formed on a skin fitting surface or the insulator 6.

Description

Detailed Description of the Invention

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a biomedical device for iontophoresis in which a drug electrode compartment and a counter electrode compartment are integrated, and more specifically, it can be easily used like an adhesive patch while being easily used. TECHNICAL FIELD The present invention relates to a biomedical application device for iontophoresis, which has good dose efficiency.

[0002]

2. Description of the Related Art Iontophoresis has attracted attention as one of transdermal therapeutic systems (TTS), and various specific systems such as a medical device type in which a drug electrode device and a counter electrode device are separately configured. Have already been put to practical use. In recent years, instead of such a conventional medical device type, a micro device type of which the entire system is smaller and both electrodes are configured in the same plane and which can be easily used is put into practical use. Are being considered.

For example, JP-A-3-133464 discloses an ion transmitter (drug electrode compartment) and a receiver (counter electrode compartment) of a specific shape.
There is described an electrode device for iontophoresis in which and are alternately arranged on the same plane with an insulator interposed therebetween. Further, Japanese Patent Laid-Open No. 4-208116 describes an iontophoresis microdevice capable of programming the release of an active ingredient by electric control.
In this device, a plurality of electrodes are arranged so as to be insulated on the same plane. For example, in the electrodes, the drug electrode compartment and the counter electrode compartment are arranged concentrically with an insulating material spaced from each other. Since such a microdevice is extremely compact with an overall size of several cm to several tens of cm, it is more portable than a conventional medical device type and should be used as easily as a patch. You can

[0004]

However, in the above-mentioned microdevice, the bipolar compartments have to be arranged in close proximity due to the morphological limitation, and the arrangement interval between the drug electrode compartment and the counter electrode compartment is extremely large. narrow. On the other hand, the electric resistance of human skin tissue to which iontophoresis is applied is as high as several 100 kΩ, and water is always present on the skin surface due to a sweating action.

When iontophoresis is actually performed on such human skin using a microdevice, the electric current generated from the drug electrode compartment has less water content than that passing through the skin having a high electric resistance and has a low electric resistance. Leaks easily on the skin surface. Therefore, even if a voltage required for the bipolar compartments is applied, a current line reaching the lower layer of the stratum corneum cannot be obtained, and so-called electricity quantity efficiency is significantly reduced. Since the amount of drug delivered to the body decreases when the distribution of current lines inside the skin tissue decreases, compared to the so-called medical device type system in which the bipolar compartments are separated and independent, it is necessary for therapeutic purposes. The drug will not be fully administered in vivo. The above-mentioned problems in the case of performing iontophoresis using a microdevice have not been pointed out so far, and therefore, a method for solving this problem has not been studied at all.

The present invention solves the above-mentioned drawbacks of the microdevice for iontophoresis and has high electric energy efficiency, that is, the leakage of current on the skin surface is minimized to efficiently deliver the drug into the body. The present invention provides a biocompatible device for iontophoresis that can be used. The present invention also provides a biomedical device for iontophoresis in which the bipolar compartments of the device are in good contact with the skin.

[0007]

The invention according to claim 1 is
A biomedical device for iontophoresis in which a drug electrode compartment and a counter electrode compartment are arranged on the same plane with an insulator interposed therebetween, characterized by having a skin adhesive portion on the skin-mounting surface of the insulator. By providing such a configuration, the device of the present invention can improve its electrical quantity efficiency, and in turn, can deliver a sufficient amount of drug into the body by applying a low voltage.

Further, the invention according to claim 2 is an iontophoresis biocompatible device in which a drug electrode compartment and a counter electrode compartment are arranged in the same plane with an insulator interposed therebetween, and covers the skin-mounting surface of the device. A) made of a material having low conductivity, and b) having a drug-permeable membrane having pores penetrating in the electrode-skin direction, and corresponding to the surface shape of the insulator on the drug-permeable membrane. It is characterized by having a skin adhesive part. By providing such a configuration, not only to further improve the electric quantity efficiency of the device, but also to achieve the excellent effect of the present invention, even when a liquid component such as an electrolyte solution is used as the matrix component of the bipolar compartment. can do.

Further, the invention according to claim 3 is characterized in that an adhesive buffer portion is provided between the drug permeable membrane and the insulator of the device according to claim 2. By providing such a configuration, the electrical efficiency of the device can be remarkably improved in combination with the effect of the pores provided in the outer drug permeable membrane and the skin adhesive portion.

[0010]

In other words, the biomedical device for iontophoresis according to the present invention has an insulator disposed between the drug electrode compartment and the counter electrode compartment, which is attached to the skin by a skin adhesive portion having a surface shape corresponding to that of the insulator. The close contact can reduce the current leakage on the skin surface, which is seen in the conventional microdevice type. Further, even if a liquid type is used as the matrix component of the bipolar compartment, the electrode-is provided with a low-conductivity drug-permeable membrane having pores penetrating only in the skin direction so as to cover the skin-contacting surface of the device. Similarly, leakage of current on the skin surface can be suppressed. Furthermore, by providing an adhesive buffer between the drug permeable membrane and the insulator,
A drug permeable membrane covering the bipolar compartments of the device when worn on the skin can be adhered to the skin. As described above, the present invention has various characteristic structures for overcoming the drawbacks of microdevices, which structurally tend to cause a decrease in electrical efficiency, and as a result, absorption of drugs by iontophoresis. The promotion effect is remarkable. Therefore, the device of the present invention not only can withstand actual use in the medical field, but also has a wide range of applications.

[0011]

EXAMPLE FIG. 1 is a schematic cross-sectional view of the device of an example of the present invention with the skin-mounting surface facing upward.
It is composed of a substrate 1, an electrode (a) 2, an electrode (b) 3, a drug electrode compartment 4, a counter electrode compartment 5, an insulator 6, a skin adhesive portion 7, a lead wire 8 and a power source portion 9.

The insulator 6 of FIG. 1 is arranged between the drug electrode compartment 4 and the counter electrode compartment 5 in order to electrically shield them. The height and width of the insulator 6 are not strictly limited, and can be selected within a range necessary for making the drug electrode compartment 4 and the counter electrode compartment 5 have a desired volume. However, since the skin adhesive portion 7 described below needs to be arranged on the insulator surface on the skin attachment surface side (indicated by the arrow AA), the width of the insulator on the skin attachment surface is
For example, it is preferably about 0.1 to 4 mm, and more preferably about 0.5 to 2 mm. The material is not particularly limited as long as it is a member (for example, a photoresist agent such as methacrylate) generally used as an insulator in the field of electronics, but a material that is not irritating to the skin is preferable.

The skin adhering portion 7 is for adhering the insulator 6 to the surface of the skin of the living body to suppress the leakage of current on the skin surface. The skin adhesive portion 7 does not necessarily have to be arranged so as to completely cover the entire surface of the insulator, but in order to sufficiently suppress the leakage of current on the skin surface, at least the surface shape of the insulator (for example, , The device pattern to be described later (the portion shown by the inner thick line in FIGS. 5 to 10)
It is preferable that they are continuously arranged corresponding to the above. The material of the skin adhesive portion 7 is preferably one having low conductivity, and for example, a rubber-based adhesive such as silicone rubber, natural rubber, isoprene-based rubber, isobutylene-based rubber, or diene-based rubber is used. The thickness of the skin adhesive portion 7 is not strictly limited, and prevents the skin-attached surfaces of the drug electrode compartment 4 and the counter electrode compartment 5 from contacting the skin surface when the device of the present invention is applied to the skin. It is not necessary to have such a level, but specifically, for example, it is preferably about 1 to 50 μm, and more preferably about 10 to 20 μm.

The drug electrode compartment 4 comprises the drug to be administered, a solution of the drug and a matrix holding the drug. The material of the matrix is not particularly limited as long as it is a gel or solid material generally used in the field of iontophoresis, and rubbers such as tragacanth rubber: alkyl cellulose, hydroxyalkyl cellulose, cellulose ether, cellulose ester. Polysaccharides such as dextrin, carrageenan, soluble starch and agar: Polypeptides such as gelatin and collagen: Sodium polyacrylate, synthetic water-soluble polymers such as polyvinyl alcohol, etc., alone or as required. However, among these, those that do not cause a volume change due to an electric field are preferable.

The drug is not particularly limited as long as it is a drug whose skin permeability can be improved at least by applying a voltage, but preferred examples include antitussive and expectorant such as sodium cromoglycate, ketotifen: formoterol, etc. Bronchodilators: morphine, nalbuphine, pentazocine, diclofenac sodium, etc. analgesics: dopamine, etc. cardiotonics: perphenazine, phenothiazine, etc. psycholeptics: cefotetanni sodium, dibekacin,
Antibiotics such as amikacin, netilmycin, sisomycin, minocycline: anti-neoplastic agents such as adriamycin, mitomycin C, bleomycin hydrochloride, lentinan, picibanil, vincristine, cisplatin, methotrexate: nitricate citrate, meclofenoxate, lisuride, calcium fopatenate Circulatory function improving agents such as: Gout remedies such as allopurinol: LHR
H, enkephalin, endorphin, interferon, interleukin, insulin, calcitonin,
TRH, oxytocin, lypressin, vasopressin, glucagon, pituitary hormone (HGH, HMG, HC
G, desmopressin acetate), peptides such as luteinizing hormone, and pharmacologically acceptable salts of these or these drugs can be used alone or in combination.

The drug is mixed in the matrix as a solution, and as the solution, a substance capable of dissolving the drug and stably held in the matrix, such as water, is preferable. A mild electrolyte may be dissolved.

The counter electrode compartment 5 is a component selected from rubbers, polysaccharides, polypeptides, synthetic water-soluble polymers and the like exemplified as the matrix constituting the drug electrode compartment 4, and an electrolyte which is mild to skin. It is composed of a solution of.

If necessary, the drug electrode compartment 4 and the counter electrode compartment 5 may further contain an additive. As the additive, a pH adjusting agent or an antiseptic agent usually used in the field of iontophoresis may be used. Examples include agents, antioxidants, plasticizers, surfactants, skin permeation enhancers, moisturizers and the like.

The shapes of both compartments described above are not particularly limited, and as the plane pattern of the skin-mounting surface composed of both compartments and an insulator, for example, a square type (see FIG. 5), a microarray type (see FIG. 6), a concentric circle is used. A shape such as a mold can be arbitrarily selected. In the case of the square shape, the compartment may be further divided into sub-shapes (see FIGS. 7 to 10). However,
Since it is necessary to transfer a weak current between both compartments sandwiching the insulator, if the distance between arbitrary points on both compartments is too large, the electric quantity efficiency (described later) tends to decrease. Therefore, the length of the minor axis on the skin-mounting surface of each compartment is preferably in the range of about 1-5 mm, more preferably in the range of about 2-4 mm.

The electrode (a) 2 and the electrode (b) 3 are connected to a power source section 9 by a lead wire 8 described later, and a positive voltage or a negative voltage is applied to each of them. The material of the electrode is not particularly limited as long as it is a material generally used as an electrode member in the field of iontophoresis, for example, a positive electrode is silver, and a negative electrode is a combination of copper and platinum black plated. Particularly preferred is a combination of a positive electrode plated with platinum or platinum black having a large oxygen overvoltage and a negative electrode plated with copper having a large hydrogen overvoltage and plated with platinum black. The latter combination is excellent because it has the additional effect of suppressing the generation of gas due to the electrolysis of the aqueous electrolyte solution.

The substrate 1 supports the above-mentioned components and is made of a material generally used as a substrate in the field of iontophoresis, but it can be easily applied like a patch. In the device, it is preferable to use a material such as polyimide, which is heat-resistant and capable of photoetching and is flexible enough to cope with the curved surface of the skin.

The power supply unit 9 supplies a voltage or a current to the electrodes (a) 2 and (b) 3, but in the microdevice of the present invention which can be simply applied like a patch. For example, a sheet-shaped battery can be used.

Although there is no strict limitation on the overall size of the device of the present invention constituted by such a member, considering that it is used in the same manner as a patch, the length of one side of the skin-mounting surface is For example, it has a planar structure of about 5 to 40 mm, and the thickness is about 0.1 to 5 mm excluding the power supply unit 9.
Can be a degree. Further, when a plurality of the above devices are arranged vertically and horizontally as a unit to form a device assembly, a planar structure of about 20 to 200 mm can be obtained, which allows administration of a larger amount of drug. is there.

FIG. 2 is a schematic cross-sectional view of the application example of the present invention shown in FIG. 1 with the skin-mounting surface facing upward. The substrate 1, the electrodes (a) 2 and the electrodes (b) are shown. 3, drug electrode compartment 4, counter electrode compartment 5, insulator 6,
It is composed of a skin adhesive layer 7, lead wires 8, a power supply unit 9 and a porous membrane 10.

The porous membrane 10 is arranged in one or both of the polar compartments 4 and 5 so as to cover only the skin-mounting surface thereof, and is made of an ion-permeable polymer membrane. By including such a porous membrane 10, not only the gel-like or solid-state components such as the above-mentioned rubbers, polysaccharides, polypeptides, and synthetic water-soluble polymers as the matrix component of the compartment but also the liquid components such as the electrolyte solution Things can also be used.

Although arranging the porous membrane 10 only on the skin-mounting surface of the compartment can be easily carried out if the pattern shape of the compartment is simple, the shape is complicated (for example, as shown in FIGS. 1
When it becomes 0), it becomes technically difficult. Therefore, when using a liquid one as the matrix component of the compartment, a device having a constitution shown in the embodiment of FIG. 3 below is preferable.

The other components are the same as those in the embodiment shown in FIG. 1, and the description thereof will be omitted.

FIG. 3 is a schematic cross-sectional view showing the skin-mounting surface of an embodiment of the present invention having a drug permeable membrane having pores penetrating in the direction of the electrode-skin. A substrate 1, an electrode (a) 2, an electrode (b) 3, a drug electrode compartment 4, a counter electrode compartment 5, an insulator 6, a skin adhesive part 7, a lead wire 8, a power source part 9 and a drug permeable membrane 11. .

The drug permeable membrane 11 is made of a material having low conductivity and has pores 12 penetrating in the electrode-skin direction so as to cover the entire skin contact surface including the insulator surface of the device. Can be placed. The drug permeable membrane 11 allows the flow of the drug caused by the current line to pass through the electrode.
Although it is intended to regulate only in the skin direction, by providing this drug permeable membrane 11, the above rubbers, polysaccharides, as the matrix component of the compartments 4 and 5,
Not only gel-like components such as polypeptides and synthetic water-soluble polymers, but also liquid ones such as electrolyte solutions can be used.

The porous membrane 1 used in the embodiment of FIG.
When 0 is arranged on the entire surface in this manner, even if the skin adhesion portion 7 corresponding to the surface shape of the insulator is provided, the current leaks inside the film. However, the drug permeable membrane 11 of the present invention
With, the electric current flows only in the electrode-skin direction, and such leak does not occur. Further, since it is not necessary to arrange the device in a shape that matches the surface shape of the compartment, it is possible to easily manufacture the device of the present invention even with a complicated pattern shape.

The size of the pores 12 of the drug permeable membrane 11 is not strictly limited and may be any size as long as the matrix component constituting the bipolar compartment does not leak out. About 4 μm, preferably about 0.1
The inner diameter may be about 0.2 μm. Moreover, the thickness of the drug permeable membrane 11 is not particularly limited. As the material, any material having low conductivity may be used, and it is possible to use a material that is recognized to be safe even if it is in contact with a living body for a long time in the field of patches, such as polycarbonate. it can. Nucleipore (Cost) which is easily available as the drug permeable membrane 11 satisfying the above conditions is available.
(manufactured by ar Co., Ltd.), etc., for example, by directly irradiating the film made of the above-mentioned polycarbonate with α-rays vertically on the film surface by a method usually used in the technical field of radiation, It is also possible to use the one provided with the pores 12. The drug permeable film 11 is adhered to the surface of the insulator 6 with a low conductive adhesive such as an epoxy adhesive.

The skin adhesive portion 7 is arranged not on the surface of the insulator 6 but on the surface of the drug permeable membrane 11 corresponding to the shape of the insulator surface.

The other components are the same as those of the embodiment shown in FIG. 1, and the description thereof will be omitted.

FIG. 4 is a schematic cross-sectional view showing the skin-mounting surface of an embodiment of the present invention having an adhesive buffer portion between the drug permeable membrane and the insulator of the embodiment shown in FIG. The substrate 1, the electrode (a) 2, the electrode (b) 3, the drug electrode compartment 4, the counter electrode compartment 5, the insulator 6, the skin adhesive portion 7, the lead wire 8, the power source portion 9, and the drug. It is composed of the permeable membrane 11 and the adhesive buffer portion 13.

The adhesive cushioning portion 13 is made of a member having a large elasticity and a low electric conductivity and which does not leak out the matrix component of the bipolar compartment. Examples of such a member include silicone rubber, natural rubber and isoprene. Examples thereof include rubber-based adhesives such as rubber-based rubber, isobutylene-based rubber, and diene-based rubber. The adhesive cushioning portion 13 does not necessarily have to be arranged so as to completely cover the entire surface of the insulator, but it is arranged continuously corresponding to at least the surface shape of the insulator, and as a result, the insulator 6 is formed. A closed compartment is formed with the side surface of each of the electrodes, each electrode 2 and 3, and the drug permeable membrane 11. The thickness of the adhesive buffer portion 13 is not strictly limited and is, for example, about 50 to 400 μm.
The thickness is preferably about m, more preferably about 100 to 200 μm.

By inserting and arranging such an adhesive buffer portion 13 between the insulator 6 and the drug permeable membrane 11, when the device of the present invention is attached to the skin, the drug permeable membrane on the bipolar compartments is further improved. It can be brought into close contact with the skin, which can promote percutaneous absorption of the drug.

The other components are the same as those in the embodiment shown in FIG. 1, and the description thereof will be omitted.

The present invention will be described in more detail below with reference to production examples and pharmacological tests, but it goes without saying that such description does not limit the present invention.

[Manufacturing Example] Manufacturing Example 1 : (1) Two negative resist sheets having a thickness of 75 μm are stacked on a glass epoxy substrate having a length of 120 mm, a width of 180 mm and a thickness of 1 mm, and thermocompression-bonded. (2) On the resist sheet of the member obtained above, a mask in which three patterns shown in FIG. 5 are arranged vertically and four patterns are horizontally arranged and black and white are reversed, and after irradiating with ultraviolet light and exposing,
This is developed and etched. (3) Electrolessly plating copper on the bottom of the etched recess,
After forming a lead wire hole and a gel injection hole so as to penetrate the substrate, connect the lead wire, and further, silver is plated on the positive electrode and platinum black is plated on the negative electrode to form an electrode. . (4) Nuclepore (made by Costar) with silicone rubber coated on the part corresponding to the insulator of the pattern shown in FIG.
Is adhered to the device obtained in (3) above with an epoxy adhesive so that the surface on which the silicon rubber is adhered is on the outside. (5) From the back side of the substrate, place 6- in the drug electrode compartment 4.
About 20 μl of agar gel containing 6% (W / V) of carboxyfluorescein is injected. Similarly, about 20 μl of agar gel containing 0.9% NaCl solution was injected into the counter electrode compartment 5 and then separated for each pattern,
Device 1 of the present invention (drug electrode compartment surface area:
0.730 cm ² / counter electrode surface area: 1.
12 pieces of 507 cm ² / insulator width: 692 μm) were obtained.

Production Example 2 : In accordance with the method described in Production Example 1 above, the device 2 of the present invention having a bipolar pattern shown in FIG. 6 (drug electrode compartment surface area: 0.880 cm ^2).
/ Counter electrode surface area: 0.880 cm ² / insulator width: 692 μm) and FIG. 7 shows device 3 of the present invention (drug electrode surface area: 0.790 cm ^2).
/ Counter electrode surface area: 1.933 cm ² / insulator width: 500 μm) was obtained.

Production Example 3 : In accordance with the method described in Production Example 1 above, the patterns of the two poles are shown in FIGS. 5, 7, 8, 9, and 10.
Each device of the present invention 4 (drug electrode compartment surface area: 0.730 cm ² / counter electrode surface area: 1.507 cm ² / insulator width: 692 μm), 5
(Drug electrode compartment surface area: 0.790 cm ² /
Counter electrode compartment surface area: 1.933 cm ² / insulator width: 500 μm), 6 (drug electrode compartment surface area: 0.730 cm ² / counter electrode compartment surface area:
1.507 cm ² / insulator width: 692 μm), 7 (drug electrode compartment surface area: 0.728 cm ² / counter electrode surface area: 1.492 cm ² / insulator width:
692 μm) and 8 (drug electrode compartment surface area:
0.740 cm ² / counter electrode surface area: 1.
413 cm ² / insulator width: 692 μm) was obtained. However,
In these devices, the drug permeable membrane and the surface of the insulator were adhered with silicone rubber instead of the epoxy adhesive.

[Pharmacological Test] Model Test 1 : The following skin permeation model experiments were conducted using the biomedical devices 1 and 2 for iontophoresis of the present invention obtained in the above Production Examples.

The abdominal total extirpated skin of an ICR nude mouse (male, 5 weeks old) was hydrated in a HEPES buffer solution of pH 7.4 for about 2 hours and then mounted on a vertical diffusion cell. The device of the present invention of type 1 or type 2 was attached on this skin.
A constant voltage of 2 V was applied between both electrodes of each device to sample from the receptor phase of the cell (pH 7.4 HEPES buffer), and the permeation amount of 6-carboxyfluorescein and the current value were measured. As a control, a device having no skin adhesive portion, that is, a device in which the skin-mounting surface of the device was not coated with silicone rubber was used.

The results are shown in Table 1 below. The values in the left column of each table below have the following meanings. J value: drug permeation rate in steady state EF value: ratio of J value per unit area to passive diffusion q _t value: total amount of electricity flowing between both electrodes q _i X10 ³ value: transport of 6-carboxyfluorescein Total amount of electricity flowing by CE value: electricity efficiency, that is, q _i / q _t X100

[0045]

[Table 1]

As is apparent from Table 1, the device of the present invention showed extremely good electrical efficiency as compared to the control device having no skin adhesive.

Model test 2 : In the same manner as in the model test 1, a skin permeation model experiment using the device 3 of the present invention (16-division square type shown in FIG. 3) was conducted. The results are shown in Table 2 below.

[0048]

[Table 2]

As is clear from Table 2, the device 3 of the present invention showed extremely good electricity efficiency. It was found that the electrical efficiency of the device used in this test was much better than the electrical efficiency of the undivided square type device 1 (Table 1).

Model test 3 : In the same manner as in the model test 1, a skin permeation model experiment using the devices 4 to 8 of the present invention was conducted. However, in this test, the constant voltage applied between both electrodes of each device was set to 1V. As a control, 6% 6-carboxyfluorescein agar gel was applied to the surface of the test skin. The results are shown in Table 3 below. In the values in the left column of the table below, the LT value means a so-called lag time until the transmission of 6-carboxyfluorescein begins to be detected, and other values have the same meanings as described above.

[0051]

[Table 3]

From the data in Table 3, it was found that the electrical efficiency of the device is greatly influenced by the pattern on the skin-mounting surface of the device.

In Vivo Test with Hyperglycemic Rats : (1) Method Wistar male 7-week-old rats (body weight: 18
(0-230 g), streptozotocin was administered under anesthesia and urine was collected about 24 hours later, and the urine glucose content was 250
Hyperglycemic rats with mg / dl or more are selected and used. In the experiment, the one that has been passed about 48 to 72 hours after the administration of streptozotocin is used.

0.05M in the drug compartment
2 ml of HEPES buffer (pH 7.4) to 0.0 agar
Agar solution prepared by adding 3 g and dissolving the same amount of Humarine R
Pour a mixture of Note (100 U) in a 50 ° C. water bath. The counter compartment is filled with only the above agar solution. The device 6 obtained in Production Example 3 is used as the test device, and a constant voltage of 1 V or 1.5 V is applied.

A test rat that had been fasted for about 24 hours was fixed in a dorsal position under anesthesia with Nembutal (92.5 mg / kg, ip), and abdominal hair removal treatment was performed. About 4 after administration of Nembutal
After 0 minutes, two devices of the present invention are mounted on the abdominal skin membrane using a protector film, and electric conduction is started. With 0 minute immediately before the start of energization, 0.4 ml of blood is collected from the jugular vein at 30 minute intervals for 120 minutes, and the blood glucose level and serum insulin concentration are measured according to the usual method. For the measurement of insulin concentration, only the human insulin concentration was quantified by using the enzyme immunoassay method using the sandwich method, and the endogenous insulin concentration was excluded. As a control, the blood glucose level of each rat, which was equipped with a device injected with an agar gel containing no insulin and was energized at 1.5 V, and a rat intravenously injected with Humarine R injection (5 U / kg), were measured and compared. did.

(2) Results FIG. 11 shows the result of measuring the blood insulin concentration, and FIG. 12 shows the change of the blood glucose level. As is clear from the figure, the device of the present invention showed a very good absorption promoting effect of insulin. In particular, under the condition of 1.5 V energization, the maximum blood glucose effect (decrease of 33%) was obtained about 90 minutes after the start of energization, which was comparable to the intravenous injection of Humarine R injection.

[0057]

EFFECT OF THE INVENTION The biomedical device for iontophoresis of the present invention can be used as easily as a patch, but has extremely good electricity efficiency. Therefore, it is expected that the occurrence of damage due to electric current burns will be suppressed as an unavoidable effect.

By using a drug permeable membrane having pores, the device of the present invention having a drug electrode and / or counter electrode compartment having a complicated shape can be easily produced. Therefore, the present invention can exert the above effects in microdevices of various patterns.

[Brief description of drawings]

FIG. 1 is a schematic cross-sectional view of a biomedical device for iontophoresis having a skin adhesive portion, which is an embodiment of the present invention.

FIG. 2 is a schematic cross-sectional view of a biomedical application device for iontophoresis, which is an embodiment of the present invention and includes a drug permeable membrane (porous membrane) only on a compartment.

FIG. 3 is a schematic cross-sectional view of a biomedical device for iontophoresis, which is an embodiment of the present invention and is provided with a drug permeable membrane having pores on the entire surface.

FIG. 4 is a schematic cross-sectional view of a biomedical application device for iontophoresis, which is an embodiment of the present invention and includes an adhesive buffer portion between a drug permeable membrane and an insulator.

FIG. 5 shows the skin-contacting surface pattern of a device of the invention in which the compartments are square.

FIG. 6 shows a skin-contacting surface pattern of a device of the invention in which the compartments are of the microarray type.

FIG. 7 shows a skin-contacting surface pattern of a device of the present invention in which the compartment is a 16-division square type.

FIG. 8 shows a skin-contacting surface pattern of a device of the present invention in which the compartment is a two-division square type.

FIG. 9 shows a skin-contacting surface pattern of a device of the present invention in which the compartment is a quadrant.

FIG. 10 shows a skin-contacting surface pattern of a device of the present invention in which the compartment is a 9-division square type.

FIG. 11 shows changes in serum insulin concentration when iontophoresis was performed in hyperglycemic rats using the device of the present invention.

FIG. 12 shows changes in blood glucose level in hyperglycemic rats subjected to iontophoresis using the device of the present invention.

[Explanation of symbols]

 AA Skin-mounting surface side 1 Substrate 2 Electrode (a) 3 Electrode (b) 4 Drug electrode compartment 5 Counter electrode compartment 6 Insulator 7 Skin adhesion part 8 Lead wire 9 Power supply part 10 Drug permeable membrane (porous membrane) 11 Drug permeable membrane (With pores) 12 pores 13 adhesive buffer section

Claims (3)

[Claims] 1. A biomedical device for iontophoresis in which a drug electrode compartment and a counter electrode compartment are arranged in the same plane with an insulator interposed therebetween, and a skin adhesion part is provided on the skin-mounting surface of the insulator. A bio-applicable device for iontophoresis. 2. A biomedical device for iontophoresis in which a drug electrode compartment and a counter electrode compartment are arranged in the same plane with an insulator sandwiched therebetween so as to cover the skin-mounting surface of the device. A) Low conductivity B) Electrode-having pores penetrating in the skin direction, having a drug permeable film, and having a skin adhesive part on the drug permeable film corresponding to the surface shape of the insulator A biocompatible device for iontophoresis. 3. The bioapplicable device for iontophoresis according to claim 2, which has an adhesive buffer portion between the drug permeable membrane and the insulator.