JPH01224312A - Treating tool - Google Patents

Abstract

PURPOSE:To obtain a treating tool for percutaneous administration, having a small amount of drug vaporized free from change of property by drug, by sealing a drug-containing layer between a tacky member having a tacky agent layer on the periphery and a release member and forming a releasable seal part at the inner peripheral side of the tacky agent layer. CONSTITUTION:A drug-containing layer 2 supporting a percutaneously absorbable drug on a carrier such as a gelatinized substance, viscous substance, porous material, fibrous material or foam rubber is laid between a nontacky part of a tacky member 1 having a tacky agent layer 3 at the periphery and a release member 4, sealed 5 at the inner peripheral side of the tacky agent layer and hermetically closed. In order to form a sealing part having excellent releasability, opposing faces of the tacky member and the release member consist of materials having different melting points and the sealing part is preferably sealed by heat sealing method. Use of impermeable outer bag is eliminated by making the tacky member and the release member made of impermeable materials, operation time is shortened and the aimed treating tool can be provided at low cost.

Description

DETAILED DESCRIPTION OF THE INVENTION Field of Industrial Application The present invention relates to pharmaceutical formulations for transdermal absorption, and more specifically, transdermal drugs are encapsulated between impermeable members, and thus can be stored for a long period of time. The present invention relates to a therapeutic device which allows the user to easily open the enclosing seal and perform treatment immediately.

BACKGROUND OF THE INVENTION In recent years, the use of transdermal preparations in particular has increased, and many forms have been proposed or implemented, such as gel preparations, tape preparations, batch preparations, etc., and it is not necessary to list them all. Typical techniques for batch formulations are listed below: (1) Practical use 132728-1982; (2) Japanese Patent Application Laid-Open No. 62-1983.
212321, (3) JP-A-61-50914, (4)
JP-A No. 61-43113, (5) JP-A No. 62-1261
23, (6) Japanese Patent Laid-Open No. 153214/1983.

Problems to be Solved by the Invention Among the above-mentioned conventional techniques, other techniques other than JP-A No. 62-212321 do not include measures to prevent the dissipation of drug components in the therapeutic device or preparation itself. Therefore, after preparing the drug in the form of a gel, tape, or batch, it must be sealed with a material that is at least impervious to the medicinal ingredients in order to prevent the medicinal ingredients from escaping.

In particular, gel-like or batch-like preparations that are housed in a container or case have the disadvantage that the packaging has a double structure of the container or case and the exterior.

Furthermore, including JP-A No. 62-212321, preparations that are housed in a container or case (hereinafter collectively referred to as batch preparations) contain an adhesive layer for the purpose of sticking to the skin and a drug-containing layer. If the layers are directly or indirectly fused, there is a sufficient risk that the drug in the drug-containing layer or the solvent contained therein will migrate to the adhesive layer, softening the adhesive or reducing its viscosity. Contains. In order to preserve the formulation for a long time using conventional techniques, the dissolution segment may be reduced by using a special adhesive that is not affected by drugs or solvents, etc., or by using some method or means. This method has a major disadvantage in that it requires the use of adhesives and the like.

Means for Solving the Problems The present invention eliminates the drawbacks of the prior art and provides a treatment device of simple construction and low cost, in which the drug-containing layer is sealed between the members of the impermeable electrode. This eliminates the double structure of the packaging, and furthermore, by providing an adhesive layer on the circumferentially outer side of the adhesive part for sealing (hereinafter referred to as the sealing part), the adhesive layer caused by the drug can be prevented. This treatment device is designed to prevent deterioration and also to allow easy peeling of the seal portion, and includes a treatment device that includes a central non-adhesive portion of an adhesive member having an adhesive layer on the periphery and a peeling member; A therapeutic device that encapsulates a drug-containing layer, and further has a seal portion for encapsulating the drug-containing layer that is removable, and the adhesive member and/or the peeling member include at least A material is used that is impermeable to the drug encapsulated in the therapeutic device.

Further, when the surface of the drug-containing layer is brought into contact with the skin for treatment, the seal portion must be easily peeled off.

Hereinafter, referring to the drawings of embodiments of the present invention, 1 is an adhesive member, 2 is a drug-containing layer, 3 is an adhesive layer, and 4 is a peeling member.

The adhesive member 1 serves as a support for the drug-containing layer 2, and is required to have physical and mechanical properties such that it will not be damaged during storage or treatment and can withstand sufficient use. It is.

Materials selected while taking into account the physical properties, characteristics, and feeling of use during treatment include synthetic resin films and/or sheets with opaque treatment, metal foils,
Mention may be made of metal foil and synthetic resin composites, metallized films and/or sheets. The drug-containing layer 2 is made of a drug and a carrier for the drug, and the drug will not be scattered during the manufacturing process of the therapeutic device, during treatment, when the package is opened, etc. For example, a drug is absorbed into a gelling substance to form a gelled drug (hereinafter referred to as a gelled agent). The drug is kneaded into a viscous substance to form a drug paste (referred to below as a paste). This is because techniques such as a drug (hereinafter referred to as an adsorbed drug) in which a drug is absorbed/adsorbed into a porous body and/or a fibrous body are used.

Examples of drug carriers in the present invention include acrylic polymers, carboxyvinyl polymers, Karaya gum, polyacrylamide, polyvinyl alcohol, methylcellulose, carboxymethylcellulose, and chitosan as gelling substances, and as viscous substances. Examples of rubber adhesives, porous bodies and/or fibrous bodies include silica gel, activated carbon, activated ceramics, activated earth, sponges, shells, and foamed synthetic resins (open-cell polyethylene, polystyrene, and polyurethane). , foam rubber, etc. powder, granule, solid. Further examples include cotton, cotton cloth, synthetic fiber cotton, nonwoven fabric, paper (natural paper, synthetic paper), etc., but the above description does not preclude the use of other materials.

In the therapeutic device of the present invention, if the therapeutic method requires slow action and a long time, it is appropriate to use a gelatinous agent or paste using a gelatinous substance as the drug carrier. In some cases, it is desirable to use an adsorbent agent in which the drug is present in liquid form.

Regarding the adhesive used in the adhesive layer 3, the scope, characteristics, and type of its use are not limited in any way, and the use of any conventionally practiced technology or newly implemented technology is not prohibited. do not have. Like the adhesive member 1, the peeling member 4 is a technique that requires an impermeable composition and sufficient strength to withstand tearing force during peeling.

Next, a sealing portion 5 formed to seal the drug-containing layer 2
Regarding this, the seal portion 5 in the present invention is required to have high airtightness and at the same time, good releasability, and in the present invention, in order to obtain good releasability, In the case of sealing by the heat sealing method, materials having different melting points are used on the opposing surfaces of the adhesive member 1 and the peeling member 4, for example, polyester and polyethylene, polyester and E. V. Contains polyethylene, polyester and low-temperature melting resin (trade name: hotmelt, hereinafter simply referred to as hotmelt). Nylon and polyethylene, nylon and E. V. A mixed polyethylene, nylon and hot melt, aluminum foil and polyethylene, aluminum foil and E. V. When the treatment device is made of mixed polyethylene, aluminum foil, hot melt, etc., and the shape of the treatment device is relatively large, the facing surface of the adhesive member 1 (hereinafter referred to as the "facing surface") is made of flexible material such as nylon. It is desirable to use a material having a melting point lower than that of polyethylene for the opposing surface of the peeling member 4, and any material having a melting point lower than that of polyethylene can be used.

On the other hand, if the shape of the treatment tool is relatively small, polyester or aluminum foil may be used on the opposing surface of the adhesive member 1.

Next, to explain in detail the shape and order of construction of the therapeutic device of the present invention, the drug carrier of the drug-containing layer 2 (hereinafter referred to as carrier) is soft and flexible, and can be used even under small pressure. If the volume increases or decreases easily and there is a risk that the adsorbed drug may leak to the outside, a recess of an appropriate size is formed in advance in the central non-adhesive part of the adhesive member 1, and the recess is removed. It is preferable to embed the carrier in the container, and if the carrier is made of steel and has a relatively thin thickness, it is not necessary to form a recess. Even when the drug-containing layer 2 is a gel-like agent, it is desirable to form a recess, and the shape of the entire treatment device is a circular flat shape or a rectangular flat shape.

The drug used in the present invention is not particularly limited as long as it is a physiologically active substance and can be absorbed transdermally.
To mention a few examples below, (1) corticosteroids, such as hydrocortisone, prednisolone, peclomethasone brobionate, flumethasone,
Triamcinolone, triamcinolone acetonide, fluocinolone, fluominolone acetonide, fluocinolone acetonide acetate, clobetasol propionate, etc.

(2) Analgesic anti-inflammatory agents, such as acetaminophen, mefenamic acid, flufenamic acid, indomethacin, diclofenac, diclohenac sodium, alclofenac, oxyphenbutazone, phenylbutazone, ibuprofen, arulpiprofen, salicylic acid ,
Methyl salicylate, l-menthol, camphor, sulindac, trimethine sodium, naproxen, fenbufen, etc. (3) Hypnosedatives, such as phenobarbital, amobarbital, cyclobarbital, triazolam, nitrazebam, lorazebam, haloberidol, etc. (4) Psychotropic agents Stabilizers include, for example, fluphenazine, theoritazine, diazepem, fludiazepam, flunitrazepem, haloperidol, chlorpromazine, etc. (5) Antihypertensive agents include, for example, clonidine, clonidine hydrochloride, pindolol, propranol, propranol hydrochloride, pufranolol, indenolol, nivedipine , nimodipine, lofedixin, nitrendipine, nipradilol, pukumolol, etc. (6) Antihypertensive diuretics, such as hydrothiazide, pendroflunathiazide, cyclobenziazide, etc. (7) Antibiotics, such as penicillin, tetracycline, oxydetracycline, Sulfuric acid, fradiomycin, erythromycin, chloramphenicol, etc. (8) Anesthetics such as lidocaine, dypcaine hydrochloride, penzocaine, ethyl aminobenzoate, etc. (9) Antifungal substances such as pentamycin, amphotericin B, pyrrolnitrin , clotrimazole, etc. (10) Antibacterial substances such as penzalkonium hydrochloride, nitrofurazone, nystatin, acetosulfamine, clotrimazole, etc. (11) Vitamins such as vitamin A, ergocalciferol, cholecalciferol, octothiacin, riboflavin Butyrate esters, etc. (12) Antiepileptic agents, such as nitrazepam, mepropamate, clonazepam, etc. (13) Coronary vasodilators, such as nitroglycerin, nitroglycol, isosorbide dinitrate, erythritol tetranitrate, propetyl nitrate, nifedipine. (14) As an antihistamine,
For example, diphenbitramine hydrochloride, diphenylimidazole, etc. (15) Antitussives, such as dextromethorphan, dextromethorphan hydrobromide, telbutasone sulfate, ephethrine, ephedrine hydrochloride, salptanol, salptamol sulfate, isoproterenolol, isoproterenolol hydrochloride , isoproterenolol sulfate, etc. (16) Sex hormones, such as progesterone, estradiol, etc. (17) Cerebral circulation improving agents, such as ergot alkaloids, ifenprodil, etc. (18) Antiemetics and antiulcer agents, such as metoclopramide, crepo Pride, Domperidone, Espolamine,
Scopolamine hydrobromide, 5-fluorouracil, mercabutobrine, etc. (19) As biomedicines, for example, polypeptides (TR
H, LHRH derivatives), prostaglandins, etc. (20) Others include fentanyl, digoxin, desmopressin, dihydroergotamine methanesulfonic acid, dihydroergotamine tartrate, etc.
If necessary, two or more types can be used in combination.

These drugs mentioned above are preferably used in the range of 1.3% to 45% of the total drugs impregnated or contained in the drug-containing layer 2, and if it is less than 1.3%, the therapeutic effect is poor.
A low ratio of 45% or more may result in waste.

In addition, the solvent or dispersion medium used in the invention is not particularly new and has been used in the past, but examples include lower alcohols such as ethanol, ethylene glycol, triethylene glycol, polyethylene glycol, and propylene. Glycol, etc., dimethyl sulfoxide, dimethyldecyl phosphooxide, methyl octyl sulfoxide, dimethyl acetamide, dimethyl formamide, dimethyl sepecate, N-methyl-2-pyrrolidone, isosorpitol, liquid parahine, surfactant, mineral oil, lanolin, acetic acid Transdermal absorption enhancers include ethyl, toluene, chloroform, benzine alcohol, etc.
For example, diethylene glycol, propylene glycol,
polyethylene glycol, polypropylene glycol,
Olive oil, squalene, lanolin, urea, allantoin, dimethyldecyl phosphozoxide, methyloctyl sulfoxide, dimethyl sulfoxide, dimethylfolimamide, dimethylacetamide, dimethyllaurylamide,
dodecylpyrrolidone, isosorbitol, salicylic acid,
Examples include amino acids, benzine nicotinic acid ester, sodium lauryl sulfate, Salocol, phthalate ester, diethyl sepacate, ethoxylated stearyl alcohol, glycerin ester, isopropyl myristate, ethyl laurate, N-methylpyrrolidone, etc. .

When forming the drug-containing layer 2 by using one or more of the above drugs, if there is a drug that may be denatured or compositionally altered by the temperature during heat sealing, rubber-based, It is necessary to form the seal portion 5 by selecting an appropriate adhesive from starch-based synthetic resin adhesives.

Example 1 The material composition of the first example is a film consisting of nylon 30 microns (hereinafter referred to as μ)/vinylidene chloride 2-5 μm/polyethylene 30 μm. An adhesive layer 3 is provided so that the diameter is 6 cm to form an adhesive member 1, and an adhesive layer 3 with a diameter of 5 cm is placed approximately in the center of the adhesive member 1 so that the nylon side surface is on the inside.
m, a recess with a depth of 2.5 mm was formed, and in the recess, a foam with a diameter of 5 cm, a thickness of 3 mm, and a foaming ratio of 3 was formed.
0 to 35 times (porosity is 30 to 35%) and is made of a support made by embedding continuously foamed urethane resin, and furthermore, 80% of N-methylpyrrolidone is added to the support. The drug-containing layer 2 is formed by impregnating 1.5 cc of a drug-containing liquid containing 20% nifedipine, a coronary vasodilator.

Next, polypropylene 30μ/vinylidene chloride 2-5μ
/70% polyethylene, E. A film consisting of V30%40μ is cut to a diameter of 80 m to form a peeling member 4, with the polyethylene side of the peeling member 4 facing the adhesive member 1 (hereinafter referred to as the inside), and the drug-containing layer 2 The treatment device of the present application was implemented by covering the tube with an average diameter of 5.5 cm and a width of 1.5 mm and sealing it by heat sealing.

2nd Example, carried out in the same manner as in the 1st Example except that an image paper 6 with an outer diameter of 8 cm and an inner diameter of 6 cm was attached to the outside of the adhesive layer 3 of the treatment tool in the 1st Example. It is.

The third example is the second example except that the carrier is a molded silica gel powder, the porosity is 25%, the drug-containing liquid is 60% N-methylpyrodrine and 40% nifedipi, and the impregnated amount is 1 cc. It was carried out in the same manner as the implementation.

Fourth example, polyester 15μ/aluminum vapor deposition 3
A film consisting of ~5μ was cut to a diameter of 5cm, an adhesive layer 3 was placed on the polyester side surface so that the inner diameter was 3.5cm, and the outer diameter was 5cm and the inner diameter was 3.5cm.
A release paper 6 of m is attached to form the adhesive member 1, and a nylon nonwoven fabric cut to a diameter of 2.5 cm is laminated approximately in the center of the adhesive member 1 so as to have a thickness of 1.5 mm. This was partially bonded using an ultrasonic bonding method, and further impregnated with 0.8 cc of a drug-containing liquid consisting of 60% liquid paraphen and 40% nitroglycerin to form a drug-containing layer 2. This is what I did. Next, the drug-containing layer 2 was covered with a peeling member 4 having the same composition as in the first embodiment, and the average diameter was 3 cm.
A seal portion 5 having a width of 1.5 mm was heat-sealed using a high-frequency current.

The present invention can be carried out as described above, and the effects of the present invention are listed below. As a result, the impermeable outer bag that was conventionally used is no longer necessary, reducing working time and making it possible to provide a low-cost treatment tool.

(2) Since the drug-containing layer is sealed between the adhesive member and the release member that have been subjected to opaque treatment, no matter what packaging form you choose (using materials such as paper for the exterior), The drug does not dissipate, and there is no risk of the drug (especially the solvent) migrating to the adhesive layer, so there is no need for a special adhesive and it can be achieved using conventional techniques. The adhesive used is sufficient.

(3) Since the volume space formed by the sealed adhesive member and peeling member and the volume of the adhesive layer are approximately the same, the amount of drug volatilization is extremely small, making this invention the most suitable for long-term storage. be.

(4) Since materials with different melting points are used for the opposing surfaces of the adhesive member and the peeling member, this technology allows for sealing and at the same time allows for very easy peeling.

(5) Since the drug is in liquid form, its viscosity is low, and as a result,
Excellent drug release over a long period of time.

(6) Transdermal drugs made based on conventional technology, especially tape formulations (techniques in which drugs are mixed into an adhesive layer), tablet-type preparations (techniques in which drugs are mixed with other substances, and this is made into tablets). However, in the treatment device of the present invention, the adhesive member is impermeable, and the treatment device cannot be attached to the skin. When it comes into contact with
This is an excellent technology that prevents drug devices from leaking to the outside for the two reasons mentioned above: the drug is sealed by the adhesive.

[Brief explanation of the drawing]

FIG. 1 is an enlarged sectional view of the first embodiment, FIG. 2 is an enlarged sectional view of the second to third embodiments, and FIG. 3 is an enlarged sectional view of the fourth embodiment. DESCRIPTION OF SYMBOLS 1... Adhesive member, 2... Drug-containing layer, 3... Adhesive layer, 4... Peeling member, 5... Seal part, 6... Release paper.

Claims (3)

[Claims] (1) In a therapeutic device in which a drug-containing layer is enclosed between an adhesive member having an adhesive layer on the periphery and a peeling member, it is important to note that the melting points of the materials on both sides where the adhesive member and the peeling member come into contact are different. Featured therapeutic tools. (2) The treatment device according to claim 1, wherein the enclosing seal portion is made removable. (3) The treatment device according to claim 1, wherein the adhesive member and the peeling member are impermeable.