JPH0217187B2 - - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to an iontophoresis device, and particularly to an extremely easy-to-operate and lightweight plaster structure for iontophoresis that can be directly attached to human skin.

Iontophoresis has recently received increasing attention as an effective topical administration method that promotes transdermal absorption of ionic drugs (Glass JM et al., Int.J.
Dermatol.19 519 (1980); Russo J., Am.J.
Hosp.Pharm.37 843 (1980); Gangarosa LP et
al., J.Pharmacol.Exp.Ther.212 377 (1980;
Kwon BS et al., J.Infect.Dis.140 1014
(1979); Hill JM et al., Ann.NY.Acad.Sci.284
604 (1977) and Tannebaum M.Phys.Ther.60
792 (1980), etc.).

Iontophoresis in these prior art is usually made by connecting the output terminal of a continuous current generator or an intermittent current generator to a conductor such as a metal plate, which is made by covering a conductor such as a metal plate with cotton wool impregnated with a chemical solution, or a similar structure. Because it is performed by connecting the drug to a nonconforming inductor, its implementation is quite complicated, and although it is extremely effective as a medication method, its widespread use has been limited. . In addition, these conductors are generally fixed to the treatment area with rubber bands, etc. to apply transdermal electricity, so burns are likely to occur due to poor contact between the skin and the conductor, so constant contact with the conductor is required during the treatment. Since it required monitoring with an ammeter, there was no hope that it would become popular as a general home treatment, even if it was only used by doctors.

Therefore, the main object of the present invention is to provide a novel plaster structure for iontophoresis that overcomes the difficulties of these known techniques and is extremely easy to operate and lightweight, and can be used by directly adhering to the human skin.

Hereinafter, a first embodiment of the present invention will be described in detail with reference to FIGS. 1 to 3 of the drawings. In the figure 1
1 is a plaster structure for iontophoresis, which has a separator 2 and a separator 3. The conductor 2 is an ionic material made of paper material such as water-absorbing paper, cloth material such as gauze, fiber material such as cotton wool, sponge or porous material such as open synthetic resin foam or water-absorbing resin, etc. The water-absorbing material layer 4 for holding the chemical impregnation and the current dispersing conductive material layer 5 formed of metal foil such as aluminum foil, conductive rubber or resin film, etc. are bonded together using a conductive adhesive such as Dotite (registered trademark). It is integrally formed by laminating layers with a compound or the like. In addition, the insensitivity conductor 3 is made by laminating a skin-adhesive conductive gel layer 6 formed in the form of a flexible sheet or film, and a current dispersion conductive member layer 7 formed of aluminum foil or the like as described above. It is integrally formed. A lightweight battery is located approximately at the center of the upper surface of the conductor 2.
For example, a so-called button-shaped battery 8 is installed such that one of its poles, for example, the (-) pole, is in contact with the current dispersion conductive member layer 5. Further, the (+) pole of this button-shaped battery 8 is connected to the current dispersion conductive material layer 7 of the indifferent conductor 3 by a lead wire 9 made of aluminum foil, for example, whose lower surface except near both ends is coated with an insulator. has been done. 10 is an insulating backing layer. This insulating backing layer 10
is made of, for example, a non-conductive synthetic resin in the form of a flexible sheet or film, and the conductor 2 and the conductor 3 are spaced apart and fixed to this insulating backing layer 10. That is, the inductor 2, the inductor 3, and the button-shaped battery 8 are connected to the insulating backing layer 1.
They are integrally supported and connected by 0.

Next, the function and usage of the plaster structure for iontophoresis of the present invention constructed as described above will be explained. First, the water-absorbing material layer 4 of the separator 2 is impregnated with a desired ionic chemical solution, and then the separator 2 is attached to a desired position on the human body so as to come into contact with it. At the same time, Seki conductor 2 and Insen conductor 3 form a closed circuit,
Transdermal permeation of the ionic drug in the water-absorbing member layer 4 for impregnation with the ionic drug liquid of the seki-doshi 2 is accelerated.

Each component of the plaster structure of this example will be explained in more detail as follows.

Skin-Adhesive Conductive Gel Layer This layer is preferably made of natural resin polysaccharides such as karaya gum, tragacanth gum, xanthan gum, or vinyl such as polyvinyl alcohol partially saponified products, polyvinyl formal, polyvinyl methyl ether and its copolymers, polyvinyl pyrrolidone, polyvinyl methacrylate, etc. system resin, polyacrylic acid and its sodium salt, polyacrylamide and its partially hydrolyzed product, partially saponified polyacrylic ester, poly(acrylic acid-acrylamide)
Various hydrophilic natural or synthetic resins, such as acrylic resins, are softened and plasticized with water and/or alcohols such as ethylene glycol and glycerin to produce flexible films or sheets that have self-shape retention and skin adhesion. Supplied as a gel.

On the other hand, electrolytes such as sodium chloride, sodium carbonate, potassium citrate, etc. are added in required amounts (usually about 1 to 15%) to impart sufficient electrical conductivity. The conductive gel layer suitable for the present invention obtained in this way is in the form of a flexible film or sheet and can be closely attached to the skin, so it has low skin contact resistance and is effective for transdermal penetration of drug ions. In addition, it also has the advantage of being able to adhere and support the entire structure to the skin without requiring other skin adhesion means such as adhesive tape. In particular, when a natural resin polysaccharide such as the aforementioned Karaya gum is used as the base material of the gel layer, its natural polymeric acid structure provides PH buffering properties, skin protection properties, extremely high water retention capacity, moderate adhesion to the skin, etc. This not only provides a gel with good electrochemical conductivity, but also provides suitable skin compatibility.

In addition, when formulating the composition of these gel layers, it goes without saying that electrochemical considerations should be made in much the same way as in the case of so-called electrophoresis gels, but the main consideration is the type of drug used and the required dosage (dose). ), the duration of use of the adhesive, the output of the battery used, the skin contact area, etc., are carried out as appropriate so that the ion mobility or conductivity reaches the required value.

Here, some of the preferable conductive gel layers in this example are as follows: 1. The average molecular weight is 440,000 and the degree of saponification is about 60 using a conventional method.
Prepare 30g of % polyvinyl alcohol powder,
To this, 40 g of distilled water containing 10% NaCl and 30 g of glycerin, which had been preheated to 80°C, were added and stirred, and then the resulting mixture was heated to 80°C using a hot press machine at a pressure of 0.6 kg/cm ² for about 20 minutes. A flexible sheet with a thickness of 3 mm was obtained by heating and pressing. This flexible sheet-like material had sufficient skin adhesion and had a specific resistance of 0.8 KΩ·cm.

2 A flexible sheet-like conductive gel layer was manufactured using the following composition in the same manner as in 1 above.

(Composition Example A) Polyvinylpyrrolidone (PVP- manufactured by GAF)
K90; average molecular weight 360,000)...20g Distilled water containing 10% NaCl...40g Glycerin...40g The obtained sheet had strong skin adhesion and its specific resistance was 0.2KΩ·cm.

(Composition example B) Polyvinyl formal (average molecular weight 1.6 million, degree of formalization 15%; degree of saponification of raw material polyvinyl alcohol 60%) ...15g Distilled water containing 5% NaCl ...70g Propylene glycol ...15g The obtained sheet has a sufficient amount of Has skin adhesive properties,
Its specific resistance was 1.0KΩ·cm.

(Composition example C) Polyvinyl acetoacetal (average molecular weight 44
(degree of acetalization: 30%; degree of saponification of starting polyvinyl alcohol: 70%)...40g Distilled water containing 15% NaCl...50g Ethylene glycol...10g Has sufficient skin adhesion and has a specific resistance of 0.75KΩ.
cm.

3 Sodium polyacrylate (Aronbis SS manufactured by Nippon Pure Chemical Industries, Ltd.; average molecular weight 3 million to 5 million) 20 g at 5%
12g of distilled water containing NaCl and 68g of glycerin solution
The mixture was mixed uniformly with the mixture and heated and pressed at 80°C for 10 minutes to obtain a flexible sheet. This sheet has moderate skin adhesion and its specific resistance after being left for one day and night.
It was 0.5KΩ・cm.

4 30g of Karaya gum and 30g of distilled water containing 5% NaCl
and 40 g of glycerin were mixed and heated and pressed to prepare a sheet in the same manner. Specific resistance 0.65KΩ・cm.

5 Sodium polyacrylate (Aronbis S manufactured by Nippon Pure Chemical Industries, Ltd.; average molecular weight 3 million to 5 million) 20 g 7%
A sheet was prepared in the same manner by mixing with 80 g of distilled water containing NaCl and applying heat and pressure. Specific resistance 0.47KΩ・cm.

As is clear from the above, the gel base material composition or range of the conductive gel layer of the present invention is not limited to a specific one, and a wide range of hydrophilic polymers can be softened and plasticized with water and/or alcohols. Generally, in order to have shape retention properties, the composition is selected within the range of 10 to 70% by weight of the hydrophilic polymer and the balance water and/or alcohol. Each of the above-mentioned conductive gel layers has sufficient skin adhesion by itself, but if desired, a pressure-sensitive adhesive component such as an acrylic adhesive or a vinyl acetate emulsion adhesive may be added. It's okay.

Ionic drugs All ion dissociative drugs can be used, but
Some examples of those already widely used in the field of iontophoresis are as follows: iodopotassium, procaine hydrochloride, melicol, various skin vitamins such as vitamin B ₁ , B ₂ , B ₆ , C, and histamine. , sodium salicylate, dexamethasone, epinephrine, hydrocortisone, idoxolidine, undecylenate, etc.

Lightweight battery and output Any type of battery may be used as long as it is lightweight and can be used for adhesion to the skin, such as a button-shaped battery or a sheet-shaped battery, but the above two types are usually preferably used due to their small size and flexibility.

On the other hand, the current value required to perform iontophoresis is usually about several μA to several 100 μA/cm ² , and the contact resistance between the conductor and the skin is from several KΩ to several tens of K.
Since the voltage is approximately Ω, the output of the battery is approximately 0.5 to 10 V, depending on the contact area between the skin and the conductor.
Therefore, if necessary, several of these lightweight batteries may be arranged or stacked. Further, if necessary, a constant current element or a light emitting element to indicate energization may be added.

Water-absorbing member Any material can be used as long as it can impregnate and retain an aqueous ionic drug solution, such as water-absorbing paper, cloth,
Suitable examples include sponge materials, porous materials, and the like.

Example of Use One example of the use of the structure shown in the attached FIGS. 1 to 3 will be described in more detail as follows. That is, the conductive gel layer is made of 20% by weight of the aforementioned sodium polyacrylate (Alonbis S), 15% by weight of distilled water containing 20% NaCl, and 65% by weight of glycerin, and has a thickness of 1.5 mm and an area of approximately 12 cm ² and is skin adhesive. It is a viscoelastic gel with a thickness of about 1.7 mm.
It is made of gauze material or polyvinyl formal sponge material with an area of about 6 cm ² .

On the other hand, the conductive members 5 and 7 for current distribution use aluminum foil in this case, and connect the cathode of the button-shaped battery 8 (output voltage 1.5 V) directly to the conductor 2, and the anode to the conductor 2 through the lead wire 9. 3 conductors are connected, and the whole is made of polyethylene film 1.
0, the plaster structure 1 is provided by integrally laminating the plaster structure 1 using a heat sealing method.

In use, 1 to several ml of a 3% vitamin C-containing aqueous solution (stored in ampoules) is dripped into the water-absorbing member layer 4, and the entire structure is then adhered to the affected area to begin the treatment.

As is well known, vitamin C (ascorbic acid) or its derivatives (sodium ascorbate, etc.)
It is effective for pigmentation such as so-called melasma, sparrow spots, and various melasma, and iontophoresis treatment is already known to be useful in beauty and dermatology. However, as mentioned above, it is not widely used due to the complicated operation. However, this example allows the treatment to be performed with extremely simple operations, and can be said to be revolutionary as a therapeutic or cosmetic plaster.

In addition, when using the configuration of this example on the face, the amount of current is normally 10 to 80 μA/cm ² , and vitamin C
It takes about 20 to 60 minutes for it to reach the melanocyte-containing epidermal basal cell layer.

In addition, the plaster structure in this usage example is applied as an anti-inflammatory plaster when sodium salicylate is used, but in this case, so-called galvanization, which has a vasodilatory effect, is also used. Therefore, it can be understood that the drug exhibits a synergistic effect on diseases such as nerve passage, joint passage, and rheumatoid arthritis.

Other gel base materials Some preferred examples of the gel base material for the conductive gel layer of the present invention are as described above, but various hydrophilic polymer materials known as so-called biological electrode materials may also be selected at will. It is once again pointed out that it can be used. For example, JP-A-52-95895, JP-A-56-
Various hydrophilic polymer materials disclosed in Japanese Patent No. 15728, No. 56-36939, No. 56-36940, etc. can be used as the gel base material of the conductive gel layer of the present invention by appropriately adjusting their water content etc. .

As described above, it is sufficient that the gel base material of the conductive gel layer of the present invention is a hydrophilic polymer that can be softened and plasticized with water and/or alcohol to give a skin-adhesive viscoelastic gel. The composition of the base material is not limited to the material used, but the composition of the base material is determined in consideration of compatibility with the drug used, compatibility with the skin, electrical conductivity, etc. Furthermore, these gel layers can be disposable or replaced with other materials.

Incidentally, a polarity switching means may be added to the structure so that the yin and yang of the conductor can be freely changed depending on the yin and yang of the effective drug ion species.

Next, a second embodiment of the plaster structure for iontophoresis according to the present invention will be described in detail with reference to FIG. 4 of the drawings. In this embodiment, a sheet-shaped battery 15 is used as a lightweight battery. . On one side of this sheet-like battery 15, conductive member layers 16 and 17 for current dispersion made of copper foil, carbon fiber nonwoven fabric, etc. are disposed, and one pole thereof is impregnated with an aqueous solution of an ionic drug and held therein. A water-absorbing member layer 4 is laminated thereon, and a conductive gel layer 6 is laminated on the other pole.

According to the configuration of this embodiment, since the sheet-like battery is extremely thin at 0.5 mm to 2 mm, the thickness of the entire plaster structure 1 is also extremely thin, and a smart plaster structure without any convex portions can be obtained.

Note that the output terminal of the sheet-like battery may be formed into a planar shape, and this output terminal may be used as each current dispersion conductive member layer.

In this way, by arranging the skin-adhesive and conductive gel layer around the periphery or end of the structure, the entire structure can be attached to the skin without the need for any other fixing means such as adhesive tape. It is held fixed.

If necessary, the water-retaining member layer may be made removable, and the member impregnated with a chemical solution may be placed at a predetermined position in the structure at the time of use and used for treatment. Furthermore, it is clear that in place of the water-absorbing member, non-adhesive hydrogels commonly used in the field of electrophoresis, such as agar gel and gelatin gel, may be used. An example of an agar water gel composition is as follows.

Agar powder 4.0 parts by weight Purified water 100.0 Vitamin C (ascorbic acid: its Na salt ~ 1:
1) 5.0 This kind of hydrogel pieces may be arranged in advance in a structural manner, or they may be arranged in use as described above.

As is clear from the above, the plaster structure of the present invention allows iontophoresis, which is an effective method for promoting drug administration, to be performed with a significantly simple operation, does not require complicated and large equipment, and can be performed safely and reliably. It has a remarkable effect of obtaining.

[Brief explanation of drawings]

1 to 3 show a first embodiment of the plaster structure for iontophoresis of the present invention.
The figure shows a plan view, FIG. 2 a sectional view taken along the line - in FIG. 1, and FIG. 3 a bottom view. FIG. 4 is a sectional view showing the second embodiment. DESCRIPTION OF SYMBOLS 1...Plaster structure for iontophoresis, 2...Seki conductor, 3...Seki conductor, 4...Water absorbent material layer for impregnation with ionic chemical solution, 5, 16... Current dispersion of Seki conductor 6... Skin-adhesive conductive gel layer, 7, 17... Conductive material layer for current dispersion of indifferent conductors, 8... Button-shaped battery (lightweight battery), 15... Sheet Type battery (lightweight battery).

Claims (1)

[Claims] 1. A conductor formed by integrally laminating a water-absorbing material layer for impregnation with an ionic chemical solution and a conductive material layer for current dispersion, and a flexible sheet or film-like conductive material having both self-shape retention and skin adhesion properties. It consists of a combination structure of an indifferent conductor formed by integrally laminating a conductive gel layer and a conductive material layer for current dispersion, and an iontophoresis device driven by a lightweight battery, and the combination structure An iontophoresis device characterized in that each of the conductors and the iontophoresis device are integrally supported and connected so that the conductors can be integrally attached to the skin due to their skin-adhesive properties. Plaster structure for Reese.