JP2845490B2 - Bioelectrode for skin treatment - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a device for injuring skin or mainly the stratum corneum thereof to the extent that there is substantially no irritation such as micropores or microcracks during transdermal administration.

The administration of drugs by transdermal administration is expected to be a means of sufficiently exerting the medicinal effect without causing side effects such as gastrointestinal disorders as compared with oral administration, and further enhances percutaneous respiration by adding electric means. Iontophoresis has recently been receiving increasing attention. ((Glass James et al., International Journal of Dermatology
s JM et al., Int. J, Dermatol.) 19 519 (1980); Russo J., American Journal of Hospital Pharmacy (Russo J., Am. J. Hosp. Pharm,) 3784.
3 (1980); Gangalosa LP, et al., Journal of Pharmacological Experiment and Therapy (Grangarosa LP et al., J. Pharmacol. Exp. The
r.) 212 377 (1980); Kwanbyes et al., Journal of Infectious Dessies (Kwon BS et a
l., J. Infect. Dis.) 140 1014 (1979); Hill JM et al., Annual of Tuyoke Academia of Science (Hill JM et al., Ann. NY. Acad, Sci.) 2
4 604 (1977) and Tannebaum M., Physical
Therapy (Tannebaum M., Phys. Ther.) 60 792 (1980)
And so on)). However, in the transdermal administration method of the passive diffusion method, the percutaneous absorbability of the medicinal component has not yet been sufficiently elucidated, and also for iontophoresis, drugs capable of sufficiently expressing the medicinal effect are limited. The range of application for transdermal administration of drugs was extremely limited.

Therefore, the present invention provides not only a simple transdermal drug delivery system of passive diffusion type but also a suitable skin pretreatment for iontophoresis. Since the impedance or barrier layer has a keratin layer composed of hard proteins having a thickness of about several tens of microns, the electrode having a plurality of micro solid electrode portions capable of substantially making point contact with the skin surface is used as a skin layer. Abut,
By conducting electricity, microcracks and micropores can be generated substantially painlessly and without irritation. As a result, administration of a drug having a large molecular weight such as a peptide such as insulin or carmitonin can be effectively achieved. The inventors have found that the present invention can be obtained, and have reached the present invention.

 The outline of the present invention is as follows.

The micropores formed in the horny layer of the skin the site by the local high concentration of NaOH and O ₂ or the like produced in the point contact portion between fine solid electrode portion and the skin, as it allowed to increase the transdermal administration efficiency of a drug Te following is there. That is, to achieve local electrolysis of the keratin. (Electrical experiment method, written by Honkawa Hikiichi) The point contact area is 1 μm to 1 mm, preferably 10 μm.
Although it is sufficient that the thickness is about 100 μm, the numerical value is not limited.

The term “substantially point contact” as used in the present invention indicates not only a state where the micro solid electrode portion and the skin surface are in contact but also a state where they are close to each other.

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

In FIG. 1, (11) is a conductive member. The material is aluminum, carbon, titanium or the like, but is not specified, and may be any of rigidity and flexibility. In addition, the conductive member (11) has a convex portion (12) as a minute solid electrode portion.

The conductive member (11) is provided with a conductive connect portion (14) for making an electrical connection with an electric lead wire (13) extending from an external electric output device (not shown). .

 The operation will be described with reference to FIG.

The electrode (10) shown in FIG. 1 is brought into contact with the skin surface (00). Attach the counter electrode (02) at the same time. A minute DC is applied from the external electric output device (01) (current: about several μA).

Electrolysis occurs at the contact portion between the protrusion (12) and the stratum corneum (03) based on the above-described outline of the present invention for a predetermined time after the application. At the same time, the stratum corneum (03) is decomposed and electrolysis occurs. At the same time, the stratum corneum (03) decomposes,
A through hole is formed between the projection (12) and the skin surface (04).

The counter electrode (02) is not specified, and examples include a laminate of a conductive adhesive gel made of karaya gum material and a conductive sheet.

 FIG. 2 shows another embodiment.

FIG. 2 shows a state where conductive fine particles (22) are sprinkled on a flat conductive member (21) and fixed by an adhesive (23).

Other than the above, the conductive connecting part (14) and the lead wire (13) are provided in FIG. 2 as in the embodiment shown in FIG.

In addition, since the example of use is performed in the same manner as the example of use in FIG. 1, the description thereof will be omitted.

In the above embodiment, in order to fix the conductive fine particles (22),
Adhesives or pressure-sensitive adhesives such as epoxy resins, silicone resins, polyvinyl alcohol, polyvinyl acetate emulsions, and sorbite mixtures are used, but may be omitted.

That is, when using the present invention, the conductive fine particles (22) are sprinkled on the skin surface, and then the conductive member (21) is sprinkled on the skin surface from above the conductive fine particles (22). That is all that is required.

The conductive fine particles, as described above, it is not necessary to use a specific material, iron, gold, silver, aluminum, titanium, and the like, as long as it has conductivity regardless of metal, non-metal, Carbon and platinum are preferred materials because of their good compatibility with living organisms and good conductivity.

Further, the density of the conductive fine particles on the conductive member depends on what is to be used after the perforation, but it is sufficient to provide several tens of holes in units of several microns, large and small.

 Still another embodiment will be described with reference to FIG.

FIG. 3 shows an embodiment in which a conductive adhesive gel (31) is further laminated on the embodiment shown in FIG.

The conductive adhesive gel (31) thinly covers the apex of the projection (12).

 This operation will be described with reference to FIG.

The electrode (30) shown in FIG. 3 is attached to the skin selling surface (00). At the same time, attach the counter electrode (02).

A micro electric output is applied to the electrode (30) from the external electric output device (01).

When an electric output is performed from the external electric output device, electrolysis occurs in the conductive adhesive gel (31) near the apex of the projection (12), and micropores are formed in the conductive adhesive gel (31).

If this electrical output is maintained, the stratum corneum is finally perforated.

Also, if the conductive adhesive gel (31) is impregnated with a chemical solution, it can be electrically transdermally administered.

 This embodiment is shown in FIG.

In FIG. 4, (41) is a conductive adhesive gel impregnated with a chemical solution.

The apex of the projection (12) slightly protrudes from the conductive adhesive gel (41).

 The operation will be described with reference to FIG.

After the electric output is performed by the electric output means (01) and holes are formed in the stratum corneum (03), the electric output for iontophoresis is performed from the electric output means (01).

The chemical solution impregnated in the conductive adhesive gel (41)
The chemical reaches the epidermis through the hole provided in 3), and as a result, the chemical solution penetrates the electrically conductive epidermis.

 Another embodiment is shown in FIG.

In the embodiment shown in FIG. 5, a conductive adhesive gel (51) impregnated with a chemical solution is further mixed with conductive fine particles (52).

The conductive fine particles (52) serve as the fine solid electrodes shown in the present invention. This mixing is performed by adding and mixing at the time of producing the conductive adhesive gel (51).

The conductive fine particles (52) are exposed on the surface of the conductive adhesive gel (51) formed in a sheet shape.

Since the amount of expression is controlled by mixing, it is not necessary to intentionally install a fine solid electrode on the electrode surface,
The embodiment shown in FIG. 5 is extremely practical.

 FIG. 6 shows still another embodiment.

(64) is a chemical solution (6) with a conductive member (66)
3) Reservoir for storing, under the reservoir (64), a semi-permeable membrane (65) for the chemical to flow in one direction
Is arranged.

Reference numeral (61) denotes a porous member, which is made of porous ceramics or a conductive adhesive gel material or the like, and has conductive fine particles (62) arranged only at the interface with the skin tissue.
The operation is the same as that of the above-described embodiment, and the description is omitted.

As described above, the embodiment of the present invention when used for iontophoresis has been described with reference to FIGS. 4 to 6, but the present invention is not limited to these structures.

 Examples of the conductive adhesive gel include the following materials.

A hydrophilic resin or a polymer compound is mainly used, and as the hydrophilic resin, for example, an acrylic resin such as polyacrylamide, polyacrylic acid or an alkali metal salt or an ester thereof, polyvinylpyrrolidone, polyvinyl alcohol, polyvinyl ethyl ether and Examples thereof include vinyl resins such as copolymers and natural polysaccharides such as tragacanth gum and karaya gum. Examples of high molecular compounds include methylcellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose, hyaluronic acid and alkali metal salts thereof.

Further, various known hydrophilic polymer materials as so-called electrode materials for living bodies and the like can be optionally used. For example, Japanese Unexamined Patent Publication Nos. 1958/9585, 54977/77489, 1980/555272/55/55/81635/55/55/12935/56/56, 15728/56/36939/56/36940. No. 60534, No. 56534, No. 89270, No. 56, 143141, No. 57, 28505, No. 57, 49431, No. 57, 52463, No. 57, 55132, No. 57, 132428, No. No. 160439, No. 164064, No. 166142, No. 167675, No. 168675, No. 4569, No. 1569, No. 10066, No. 1980, No. 80689, No. 1980, No. 135706, The various hydrophilic polymer materials disclosed in 138603, 1957, 93305, 1957 179413, 1975 185309, etc. can be prepared by appropriately adjusting the water content, etc. of the conductive polymer of the present invention. It can be used as a gel base material for a gel layer.

As described above, the gel base material of the conductive gel layer of the present invention is a hydrophilic polymer, which is softened and plasticized with water and / or alcohol, and preferably gives a skin-adhesive viscoelastic gel. It is not limited to a specific material, and the base material composition is determined in consideration of compatibility with a drug to be used, skin compatibility, conductivity, and the like. Further, these gel layers can be disposable or exchanged with another husband.

In addition, the form of the electric output used in the present invention is not particularly limited as long as the voltage and current are set according to the state of the adaptive skin, such as the thickness of the stratum corneum. An electric output of about 5 (V) or several (μA) is exemplified.

It should be noted that a direct current causes an irritation such as a burn to the skin of a living body, and therefore it is often unsuitable to use it. Therefore, it is preferable to use a depolarized pulse or an alternating wave instead of the direct current. Also in this case, as described above,
The voltage and current values are appropriately selected and are not particularly limited.

Also, as described above, the surroundings of the power source using the depolarized pulse or the alternating wave and the micro solid electrode are also conductive, and at the time of skin contact,
The combination with the embodiment in which both are in contact with the skin is a practically excellent embodiment of the present invention.

As described in detail above, the present invention makes it possible to realize perforation of the stratum corneum effective for transdermal drug administration by means of easily controllable electric means. Since it is a perforation in the stratum corneum of a micron, it has effects such as not giving pain to a patient.

BRIEF DESCRIPTION OF THE DRAWINGS FIGS. 1 to 6 show an embodiment of the present invention.
FIGS. 8A and 8B are explanatory diagrams in the case where one embodiment of FIGS. 1 to 6 is used. 11 ... conductive member, 12 ... convex part, 13 ... lead wire, 14 ... conductive connect part, 22 ... conductive fine particles, 31 ... conductive adhesive gel.

──────────────────────────────────────────────────続 き Continued on the front page (58) Fields surveyed (Int.Cl. ⁶ , DB name) A61N 1/30 A61N 1/04

Claims (2)

(57) [Claims] 1. A conductive member having a plurality of protrusions constituting a micro solid electrode formed on a surface thereof, and a conductive adhesive gel formed in a layer so as to cover the surfaces of the plurality of protrusions of the conductive member. And a biological electrode for skin treatment, wherein the biological electrode is in contact with the biological skin via the conductive adhesive gel. 2. A conductive member comprising: a conductive member; and a conductive adhesive gel formed in a layer so as to cover the surface of the conductive member, and a plurality of conductive fine particles constituting a minute solid electrode are scattered inside or on the surface. A bioelectrode for skin treatment, which is in contact with living skin via the conductive adhesive gel.