Interface for iontophoresis

Abstract: An interface composed of an aqueous solution (2) supply portion capable of providing a fine hole (7) for supplying an aqueous solution (2), a water-permeable electrode (3), and a water-absorbable or water-permeable film-like membrane (5), laminated integrally, wherein the fine hole (7) for supplying the solution (2) is made in the aqueous solution supply portion at the time of use, the aqueous solution (2) is supplied through the water-permeable electrode (3) and water-absorbable or water-permeable film-like membrane (5), and, when the aqueous solution (2) reaches them, the drug or the drug-containing water-soluble layer dissolve and a locally high concentration solution of the drug is formed.

Description: BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to an interface (or a skin contact structure) for iontophoresis. 2. Description of the Related Art An interface for iontophoresis has a structure comprised of an assembly of a reservoir for holding a drug solution and an electrode for current dispersion. The structure of the above-mentioned reservoir must be one which allows a predetermined amount of the drug solution to reliably reach the interface with the skin of the living body along with the elapse of time, but the reservoir itself is steric and further contains water as the medium and thus there is dilution of the drug and, further, leakage of the drug solution, water etc. to outside the interface, including the reservoir, causing leaks across the electrodes. A satisfactory structure has not yet been proposed. EP-A-417 290 discloses an interface for an electrical percutaneous drug administration comprising a non-electroconductive membrane having a porous or capillary structure. The disclosed structure uses penetration of a hollow needle for transporting the conveying liquid within the interface. SUMMARY OF THE INVENTION Accordingly, the objects of the present invention are to eliminate disadvantages of the conventional interfaces and to provide an interface having a structure capable of accurately administering a drug, suitable for iontophoresis. Other objects and advantages of the present invention will be apparent from the following description. In accordance with the present invention, there is provided an interface for iontophoresis according to claim 1. A preferred feature is set out in claim 2. BRIEF DESCRIPTION OF THE DRAWINGS The present invention will be better understood from the description set forth below with reference to the accompanying drawings, wherein: Fig. 1(a), (b) and (c) are views for explaining an embodiment of the present invention. DESCRIPTION OF THE PREFERRED EMBODIMENTS The characteristics of the present invention will now be explained. As defined above, the present invention comprises an aqueous solution reservoir providing a fine hole for supplying an aqueous solution at least when used, a water-absorbable or water-permeable electrode, and a water-permeable film-like membrane laminated integrally. When the fine hole for supplying the solution is unblocked in the aqueous solution reservoir at the time of use and the aqueous solution is supplied through the water-permeable electrode and water-absorbable or water-permeable film-like membrane and reaches them, the drug or the drug-containing water-soluble layer is dissolved and a locally high concentration solution of the drug is formed. Therefore, when an electric current is passed, the transdermic or transmucosal administration of the drug is promoted, while keeping the drug at a high concentration without diffusion or dilution of the drug solution. Further, the aqueous solution passes from the reservoir through the fine hole and gradually permeates to the water-absorbing or water-permeable film-like membrane to just fill the same, so that the solution does not leak outside. In the present invention, it is possible to keep the drug in a solid form, that is, a dried form, before use, so that the drug is suitably stored for a long-term intact on the shelf. Further, the drug need only be deposited on the water-absorbable or water-permeable film-like membrane in a suitable amount at a suitable time, so that effective administration of the drug becomes possible. The aqueous solution reservoir means a combination of a sheet composed of a plastic resin (e.g., PET (polyethylene telephthalate), EVA (ethylene vinyl acetate), PE (Polyethylene), VC (vinylchloride) etc., having both softness and hardness and a reservoir composed of an ampule, container, pouch, bag, etc. in which an aqueous solution is sealed. As the sheet and the reservoir, mention may be made of ones which are formed integrally in advance or ones which are joined at the time of use. The aqueous solution may be any one which is capable of dissolving a drug. As a water-permeable electrode, mention may be made of a sheet or film formed partially or entirely in a meshed or porous form and having conductivity. As the raw material therefor, mention may be made of a sheet composed of carbon, silver, silver chloride, titanium, etc., a composite sheet composed of a nonwoven fabric on which carbon, silver, silver chloride, or titanium paste is printed, etc. Further, the water permeability need only be manifested at the time of use and it is not necessarily required that the above-mentioned shape be provided. As the water-absorbable or water-permeable film-like membrane it is possible to use a layer composed of a water-permeable fiber such as a laminated membrane filter, paper, nonwoven fabric, porous film (made of, for example, nylon membrane Biodyne A®, Biodyne Plus®, cellulose ester membrane or cellulose acetate membrane etc. or the like, a water-soluble polymer (e.g., PVA (polyvinyl alcohol), soluble starch CMC (carboxymethyl cellulose), MC (methyl cellulose), hydroxypropyl cellulose etc.) holding, adhering, or containing a predetermined drug, a PVP film, or other water-absorbing (aqueous) film. Usually, it is formed into a thin film. The aqueous solution supplying hole is a fine hole made in the reservoir of the aqueous solution. The hole suitably has a diameter of about 0.5 mm to 2 mm. It is suitably selected in accordance with the time by which the aqueous solution inside the aqueous solution supply unit is supposed to reach the drug or the shape and materials of the water-permeable electrode and the water-absorbable or water-permeable film etc. A plurality of the holes may be formed. EMBODIMENTS An embodiment of the present invention will now be explained in detail with reference to Fig. 1. In Fig. 1, (1) is an aqueous solution supply member, which has a bag-like reservoir connected in an integrally formed manner at the approximate center. The material is a resin or plastic having flexibility and an electrical insulation property. The reservoir is made of a similar material. The reservoir is connected to only part of the end surface of the aqueous solution supply member (1). Reference numeral (2) represents an aqueous solution, which is filled in the reservoir of the aqueous solution supply member (1). Reference numeral (3) is a water-permeable electrode, which is formed by printing or branding a conductive ink of carbon, silver, silver chloride, titanium, etc. on the rear surface of the aqueous solution supply member (1). Reference numeral (4) is an external connecting terminal, which has conductivity and which is for connection with an external iontophoresis output unit. The external connecting terminal (4) is connected with the water-permeable electrode (3) and projects partially out at the surface of the aqueous solution supply member (1). Reference numeral (5) is a film-like membrane, which consists of said material having water-absorbency or water-permeability. At the periphery of the film-like membrane (5) is formed an adhesive layer, which is connected with the aqueous solution supply member (1). Reference numeral (6) is a drug, which is deposited on a part of the film-like membrane (5). Reference numeral (8) is a peel-off membrane, which is formed by a paper, resin, etc. coated with silicone. Reference numeral (10) is a projection, which is formed integrally with the peel-off member (8) and further passes through the film-like membrane (5) and is connected to a part of the reservoir of the aqueous solution supply member (1). The method of use and operation will now be explained. Before use, as shown in Fig. 1(a), the projection (10) of the peel-off membrane (8) and part of the reservoir of the aqueous solution supply member (1) are in a connected state. The drug (6) exists in the closed space sandwiched between the peel-off membrane (8) and the film-like membrane (5). Upon use, as shown in Fig. 1(b), the peel-off membrane (8) is peeled off. When it is peeled off, the projection (10) is pulled so as to break the connection between the reservoir of the aqueous solution supplying member (1) and the projection (10), whereby the fine hole (7) is formed. After the peel-off member (8) is peeled off, the interface is adhered to the surface of the body (MM). The state of attachment is shown in Fig. 1(c). The aqueous solution (2) inside the reservoir of the aqueous solution supplying member (1) passes through the fine hole (7) and reaches the surface of the living body (MM). At the same time, it diffuses and permeates inside the film-like membrane (5) and reaches the portion where the drug (6) is deposited. The conductive terminal (4) and the external iontophoresis output unit are connected by the electric lead line (11) and the conductive metal fitting connected to the same. The drug (6) dissolved in the aqueous solution (2) is placed under an electrical transdermal administration state while keeping a high concentration locally. Further, the film-like membrane (5) and the surface of the body (MM) are joined by providing an adhesive layer on the film-like membrane (5) or applying plaster from above. The above-mentioned embodiment shows the case where the main electrode and the counter electrode were separate and an iontophoresis electrical output unit was provided exteriorly, but it is also possible to have an integral construction by placing the main electrode and counter electrode on the same electrically insulating member and attaching an iontophoresis electrical output unit to the same. The above-mentioned drug is not limited in terms of its molecular weight or other physical quantities, but the interface of the present invention is particularly useful for insulin and other peptide type drugs which, despite being used in small quantities, have to be held at as high a concentration as possible and be sufficiently moist for the efficiency of the iontophoresis. Examples of the drugs are given below: Local anesthetics : Lidocaine hydrochloride; Antitussive expectorants : Sodium cromoglicate, ketotifen fumarate; Bronchial vasodilators : Formoterol fumarate; Analgesics : Nalbuphine hydrochloride, pentazocine lactate, Diclofenac sodium ; Cardiacs ; Dopamine hydrochloride; Psychoneurotic stabilizers : Perphenazine, phenothiazine; Antibiotics : Cefotetan disodium, dibekacin sulfate, amikacin sulfate, netilmicin sulfate, sisomicin sulfate; Anti-malignant tumor agents . Adriamycin, mitomycin C, bleomycin hydrochloride, lentinan , picibanil , vincristine sulfate, cisplatin ; Circulatory function ameliorators : Nicametate citrate, meclofenoxate hydrochloride, lisuride maleate, calcium hopantenate ; Gout therapeutic agents : Allopurinol Other peptides : LHRH, enkephalin , endorphin, interferon, insulin, calcitonin, TRH, oxytocin, lypressin vasopressin, glucagon, pituitary hormones (HGH, HMG, HCG, desmopressin acetate), follicular luteinizing hormones, growth hormone releasing factors and analogues. As mentioned in detail above, the present invention enables sufficient moisture to be supplied, without the drug solution being diluted and enables long-term storage without deteolization, decomposition, etc. since the drug is in a dried state before use. Further, since the drug is only present at the contact surface with the skin once dissolved, very highly efficient drug utilization can be achieved under electric current field with minimum leakage from the application site. Thus, this invention is particularly suitable for administration of drugs which are highly potent and very expensive.

Claims: An interface for iontophoresis, comprising a water-permeable electrode (3) having a first and a second side opposite the first side, a reservoir (1) of an aqueous solution (2) laminated to the first side of the electrode and having a second fine hole, a water absorbable or water permeable film-like membrane (5) laminated to the second side of the electrode (3), a medication in dry form (6) positioned on the film-like membrane (5), and a peel-off membrane (8) covering over the film-like membrane (5) and sandwiching the medication (6) between the peel-off membrane (8) and the film-like membrane (5), characterized in that the electrode (3) has a first hole; the second fine hole is aligned with the first hole in the electrode (3); the film-like membrane (5) has a third hole aligned with the first and second holes; wherein the peel-off membrane (8) has a projection (10) blocking at least the second fine hole to contain the solution in the reservoir (1); the aqueous solution (2) in the reservoir (1) is supplied to the film-like membrane (5), which solution dissolves the medication (6) upon removal of the peel-off membrane (8) from the film-like membrane (5). The interface as claimed in claim 2, wherein the second hole has a diameter of about 0.5 mm to about 2 mm.

Inventors: OKABE KEIICHIRO, OKABE, KEIICHIRO
Applicants: HISAMITSU PHARMACEUTICAL CO, HISAMITSU PHARMACEUTICAL CO. INC.
Application year: 1993
Main classification: A61N1
IPC codes: A61N1