JPH02149514A - Material for medicine - Google Patents

Abstract

PURPOSE:To obtain a medical material which can effect percutaneous absorption of medicines continuously by inserting a medicine-holding layer between the backing layer and the medicine release-controlling layer, sealing them, and setting a medicine-containing pressure-sensitive polymer layer on the other side of the release-controlling layer. CONSTITUTION:A medicine-holding layer 4 which is composed of a solution, dispersion or gel containing medicines and medicine absorption auxiliary is inserted between an impermeable backing material 2 and a medicine release- controlling layer 5 such as a porous membrane of ethylene-vinyl acetate copolymer, and a pressure-sensitive polymer layer 3 (such as an acrylic composition or rubber sticky composition) containing the same medicine as in the holding layer 4 is laminated on the other surface of the release-controlling layer 5. The migration of the medicine from the holding layer to the skin side and the opposite side is inhibited and the migration from the holding layer to the polymer layer is controlled by the controlling layer and the migration and release of the medicine from the polymer layer to the living body is well balanced.

Description

DETAILED DESCRIPTION OF THE INVENTION (a) Field of Industrial Application The present invention relates to a pharmaceutical component for continuously absorbing a drug through the skin.

(b) Prior art In recent years, the following have been proposed for this type of medicinal component in order to reliably obtain pharmacological action.

■Pressure-sensitive adhesive polymer material containing supersaturated active ingredient drug.

■A drug containing an absorption aid in a pressure-sensitive adhesive polymer material to increase transdermal absorption.

■Through the release control membrane, the required amount is effectively absorbed transdermally from the resibor layer containing absorption aids and drugs (U, S
, P, 4,379,454).

■The absorption aid holding layer and the drug-containing adhesive layer are separated by a substrate layer,
The drug is effectively transdermally absorbed by diffusing the absorption aid from the absorption aid holding layer through the substrate layer into the drug-containing adhesive layer (Japanese Patent Publication No. 62-54283).

(c) Problems to be Solved by the Invention However, in the case of (2) above, the pressure-sensitive adhesion is severely degraded due to the drug crystals deposited on the surface of the adhesive polymeric material layer, resulting in poor contact with the skin. The adhesion of the drug is markedly reduced, and as a result, the transdermal absorption of the drug is often extremely reduced.In the case of (■) above, the safety of the absorption aid becomes a problem, and for this reason, the amount of the drug to be blended is However, there is a limit to the amount of absorption aid that can be added, or because it reduces the cohesive force of the pressure-sensitive adhesive polymer, there is a limit to the amount of absorption aid that can be added, and as a result, sufficient effects cannot be obtained.

In addition, in the case of (■) above, for drugs that are relatively easily absorbed through the skin, the amount of drug released by the control membrane is
Although highly effective and innovative, most of the drugs desired to be formulated into transdermal absorbable formulations are relatively difficult to absorb transdermally, so this method of administration has not always been effective. Therefore, as mentioned in (■) above, by containing all the necessary drugs in the pressure-sensitive polymer layer that comes into direct contact with the skin and diffusing the adjuvants from the absorption adjuvant layer, many drugs can be effectively absorbed. Attempts have been made to absorb it through the skin. However, in this case, migration of the drug from the pressure-sensitive adhesive polymer layer to the absorption aid layer occurs, resulting in a decrease in the drug content in the pressure-sensitive adhesive polymer layer, and depending on the type of absorption aid and drug. Since the pressure-sensitive adhesive polymer layer is explicitly plasticized, it may cause cohesive failure, resulting in not only a decrease in drug release properties but also a decrease in the performance of the preparation, such as a poor feeling of use.

(d) Means for Solving the Problems The inventors of the present invention have made extensive studies to solve the above problems, and have obtained the following knowledge.

That is, not only is the drug contained in the pressure-sensitive adhesive polymer layer that is directly attached to the skin, but also the drug is contained between the drug release control layer laminated on one side of the polymer layer and the impermeable backing support. When a drug-retaining layer is interposed and encapsulated in the skin, and the drug in the polymer layer and the drug in the drug release control layer are the same, the drug in the polymer layer is absorbed on the side opposite to the skin surface, that is, when the drug in the polymer layer is the same as the drug in the drug release control layer. In addition to being able to prevent the drug (and absorption aid) from migrating to the retention layer, the drug (and absorption aid) can be prevented from migrating from the drug retention layer into the polymer layer.
The drug control layer can control the migration of the drug (and the drug absorption aid) and maintain a balance between the migration of the drug (and the drug absorption aid) and the release of the drug (and the drug absorption aid) from the polymer layer into the body. Furthermore, it was found that by changing the type and composition of the absorption aid, better transdermal administration over a long period of time is possible.

In addition, for drugs with poor percutaneous absorption, it is necessary to add a considerable amount of drug absorption aid, but with this structure, the drug absorption aid can be stored in the drug-retaining layer. It is no longer necessary to increase the concentration of the drug absorption aid in the adhesive polymer layer, and cohesive failure of the polymer layer can be prevented as much as possible, and when this medical component is applied to the human body,
It was also found that both the drug and the drug absorption aid migrate into the polymer layer, resulting in good transdermal administration.

The present invention was completed based on the above-mentioned findings.

The present invention will be explained in detail below.

The pharmaceutical component of the present invention comprises a solution containing a drug and a drug absorption aid between an impermeable backing support and a drug release controlling layer;
A drug-retaining layer made of a dispersion or gel is interposed and encapsulated,
The present invention is characterized in that a pressure-sensitive adhesive polymer layer containing the same drug as the drug-retaining layer and adhesive at room temperature is provided on the other surface of the drug-release controlling layer.

The backing support used in the present invention is not particularly limited as long as it is essentially impermeable in order to prevent loss of the drug or drug absorption aid, but examples include polyester, Single films such as nylon, saran, polyethylene, polypropylene, ethylene-vinyl acetate copolymer, polyvinyl chloride, ethylene-ethyl acrylate copolymer, Surlyn, etc., or thermoplastic inert polyethylene, polyester, nylon, saran, etc. Examples include films laminated with polypropylene, ethylene-vinyl acetate co-electric composite, Surlyn, etc.
In order to improve the appearance and light-shielding properties, examples include films made of polyester, nylon, and Saran coated with aluminum vapor deposition or printing. Preferably, aluminum vapor deposition or printing is applied to a 6 to 25 μm polyester film, and The film has a total thickness of 30 to 140 .mu.m and is laminated with polyethylene or Surlyn to a thickness of 5 to 100 .mu.m, preferably 20 to 80 .mu.m, on the opposite side to the vapor-deposited and printed surface.

The drug release control layer used in the present invention controls the migration of the drug (and drug absorption aid) from the drug-retaining layer into the pressure-sensitive adhesive polymer layer. It has the function of maintaining the balance of release of drugs, etc. from the layer into the living body, and changing the release properties of drugs, etc. from the drug-retaining layer.

Examples of the drug release control layer include acetyl cellulose, polyurethane, polyacrylonitrile, polyvinyl chloride, polyethylene, ethylene-vinyl alcohol copolymer, ethylene-vinyl acetate copolymer, ethylene-methacrylic acid copolymer, ethylene- It is composed of a porous film made of ethyl acrylate copolymer, polypropylene, silicone rubber, hydrophilic acrylic polymer polyvinyl alcohol, gelatin, polyvinyl acetate, sulfonated polystyrene, or polyethylene, polypropylene, etc., but preferably ethylene-acetic acid. It is a porous membrane made of vinyl copolymer and polyethylene.

Furthermore, in this ethylene-vinyl acetate copolymer, the vinyl acetate content is 8 to 55% by weight, and by varying the vinyl acetate content within this range, the drug (and drug absorption aid) can be removed from the drug-retaining layer. However, if the vinyl acetate content is less than 8% by weight,
Release of the drug (and drug absorption aid) is too small, and on the other hand, if it exceeds 55% by weight, the mechanical strength will drop significantly, which is not preferable. In addition, porous membranes do not necessarily have to be homogeneous, and may be partially porous, but their air permeability is 900 as measured by the Ishitsu method.
0 seconds/100cc or less is desirable.

In addition, by changing the type and thickness of the drug release control layer and changing its properties by mechanical perforation, the drug release property can be changed, and the drug can be released from the drug-containing pressure-sensitive adhesive polymer layer. It is possible to change the release properties of

A feature of the present invention is that a drug-retaining layer is interposed and encapsulated between the backing support and the drug-release controlling layer, and the same drug as the drug-retaining layer is provided on the other surface of the drug-releasing layer. The point is that a pressure-sensitive adhesive polymer layer containing adhesive at room temperature is provided.

In other words, it is characterized in that the drug-containing pressure-sensitive adhesive polymer layer and the drug-retaining layer each contain a drug, and both contain the same drug, thereby producing the desired effect.

This drug-retaining layer may be made of a solution, dispersion, or gel containing a drug and a drug absorption aid.

In addition, in the drug-retaining layer, the gel agent for forming the drug-containing gel may be one that stably retains the drug used and has appropriate sustained release properties for the drug and drug absorption aid. Examples include cellulose acetate, methylcellulose, hydroxyethylcellulose, hydroxyphyllobylcellulose, polyvinyl alcohol, polyvinylpyrrolidone, acrylic acid,
Examples include gels such as polyethylene glycol, polypeptide gels made of gelatin, collagen, alginic acid polymers, etc., silicone-based or rubber-based gels, and oily gels made of fatty acid esters.

Incidentally, a drug absorption aid may be added to the drug-retaining layer, if desired. In particular, the viscosity of the solution or dispersion containing the absorption aid at this time is determined from the viewpoint of drug migration, retention, etc. , 10 to 120 voices, more preferably 20 to 80 voices. Furthermore, the filling amount of this solution or dispersion is suitably 2 to 80 μg/cJ, and more preferably 4 to 60 μg/c in view of effectiveness and economical efficiency.
+n2.

The pressure-sensitive adhesive polymer layer used in the present invention is not particularly limited as long as it is a layer formed of a pressure-sensitive adhesive polymer that is sticky at room temperature.

In addition, this pressure-sensitive adhesive polymer layer contains the same drug as the drug-retaining layer described later, but the blending ratio of the drug is the f! Although it varies depending on the amount of the drug to be supplied to the skin, it is preferable that the mixture contains 0.1 to 40% by weight of the drug, and if the content of the drug is less than 0.1% by weight, On the other hand, if the amount exceeds 40% by weight, there will be a limit to the therapeutic effect and it will be economically disadvantageous.

In this case, it is possible to also contain a drug absorption aid, and the blending ratio in this case is preferably 0.5 to 20% by weight of the entire drug-containing adhesive polymer layer. If the content is less than 0.5% by weight, the effect will be poor and there is no point in adding it. On the other hand, if the content exceeds 201% by weight, it will plasticize the pressure-sensitive adhesive polymer layer, causing cohesive failure and drug release. This is undesirable because it may lead to a decrease in the performance of the preparation, such as a poor feeling of use, as well as a decrease in performance.

Examples of this pressure-sensitive adhesive polymer include 1-butyl (meth)acrylate, hexyl (meth)acrylate, 2-ditylbutyl (meth)acrylate, inoctyl (meth)acrylate, and (meth)acrylate. 2-ethylhexyl acrylate,
(meth)acrylic acid esters such as decyl (meth)acrylate, dodecyl (ivy)acrylate, and tridecyl (meth)acrylate; (meth)acrylic acid, itaconic acid, and maleic acid that can be copolymerized with the esters; Functional monomers such as maleic anhydride, hydroquinethyl (meth)acrylate, hydroxypropyl (meth)acrylate, (meth)acrylamide, trimethylacrylamide, methylaminoethyl methacrylate, methoxyethyl (meth)acrylate and/or or acrylonitrile, vinyl acetate,
Examples include acrylic compositions that are copolymers with vinyl monomers such as vinyl propionate and vinyl pyrrolidone.

Examples of rubber include rubber-based viscous materials mainly composed of rubber, such as silicone rubber, polyisoprene rubber, polyisobutylene rubber, styrene-butanoene (or isoprene)-styrene block copolymer rubber, acrylic rubber, natural rubber, etc. Examples include vinyl polymers, such as vinyl viscous materials containing polyvinyl ether, polyvinyl alcohol, polyvinyl acetate, etc. as main components.

By the way, by using a pressure-sensitive adhesive polymer layer with a crosslinked structure, even if the drug absorption aid 1 or drug causes the pressure-sensitive adhesive polymer layer to become plasticized excessively, this can be prevented. This makes it possible to prevent cohesive failure.

In this case, for this crosslinking, a vulcanizing agent (if the main ingredient is rubber), a polyisocyanate compound, an organic peroxide,
Examples of methods include disposing a crosslinking component such as an organic metal salt, a metal compound, or a polyfunctional compound, and causing a heat reaction to chemically crosslink the crosslinking component. The rubber-based polymer contains 0.01 to 2.0 parts by weight of a vulcanizing agent represented by sulfur and sulfur-containing compounds per 100 parts by weight of the rubber component, and the acrylic polymer contains a polyisocyanate-based compound, organic 3
A crosslinking component such as an oxide, an organic metal salt, a metal chelate compound, or a polyfunctional compound is blended in an amount of 0.01 to 2.0 parts by weight per 100 parts by weight of the pressure-sensitive adhesive polymer.

The drug absorption aids include water, lower alcohols such as ethanol, glycols* (mainly drug solubilizers) such as ethylene glycol, diethylene glycol, triethylene glycol, flopylene glycol, polyethylene glycol, and polypropylene glycol; Fats and oils such as olive oil, castor oil, squalene, and lanolin (
(mainly improves drug diffusivity), urea, urea derivatives such as 7-lane (mainly improves water retention in the stratum corneum), ethyl acetate, ethanol, dimethyldecyl sulfoxide, methyloctylsulfoxide, trimethylsulfoxide, dimethylformamide, dimethyl Organic solvents such as acetamide, trimethyllaurylamide, dodecylpyrrolidone, and insorbitol (mainly improves keratin permeability), salicylic acid (mainly improves keratin softening property), amino acids (mainly improves keratin permeability), sodium lauryl sulfate, and sorbitan. Various surfactants such as moacaprylate, sorbitan monooleate, glyceryl monooleate, glyceryl monostearate, and polyethylene glycol fatty acid esters (mainly to change the surface condition of the skin), Salocol (combined with drugs that have good transdermal absorption) Examples include. Other diisopropyl acybate, 7
Examples include plasticizers such as tarric acid esters and noethyl sebacate, hydrocarbons such as liquid paraffin, ethoxylated stearyl alcohol, glycerin esters, isopropyl mystylate, ethyl laurate, and N-methylpyrrolidone. In addition to being used alone or in combination, these materials may be mixed with components such as cellulose acetate, methylcellulose, hydroxyethylcellulose, hydroxypropylcellulose, polyvinyl alcohol, polyvinylpyrrolidone, and acrylic acid to improve handling and manufacturability. is desirable.

The transdermal absorption of drugs can be controlled by the above-mentioned release control layer, but the f! Category 1,
It is possible to make large changes depending on the combination, mixture composition, etc. Therefore, it is preferable to achieve the optimal amount of drug absorption by combining the release control layer and the absorption aid composition.

The drug used in the present invention is not particularly limited as long as it is a physiologically active substance and has percutaneous absorption.

Examples of such drugs include those shown below.

b) Flutifosteroids: For example, hydrofutison, prednisolone, beclomethasone probionate, flumethacin, triamcimerone, triamcinolone acetonide, fluocinolone, fluocinolone acetonide,
Fluocinolone acetonide acetate, clobetasol propionate, etc.) Chain anti-inflammatory agents: e.g. acetamino-7ene, mefenamic acid, flufenamic acid, indomethacin, Nocro7enac, Nocro7enac sodium, Alcro7enac, Oxy7 Embutazone, phenylftasone, iffuro-7ene, flurbipro-7ene, salicylic acid, methyl salicylate,! - Menthol, camphu T-sulindac, tolmetin sodium, naproxen, fuenbufuene, ketopro7ene, etc. c) Hypnotic tA silencing: e.g. 7e7 barbital, amobarbital, cyfrobarbital, triazolam, nitrazebam, lorazepam, halobe17) 2) Tranquilizers: e.g. flu 7 enanone, teolitazine, diazepam, fludiazepam, fludiazepam, haloperidol, chlorpromazine e) Antihypertensive agents: e.g. clonidine, clonidine hydrochloride,
pindolol, propranolol, propranolol hydrochloride, bucumolol, indenolol, nianidipine, nivadipine, nimodipine, roanidixin, nidorenzvin, nipradilol, bucumolol, etc. f) Antihypertensive diuretics: e.g. hydrothiazide, pendroarnathiazide, cyclobenziazide, etc. g) Antibiotics Substances: e.g. penicillin, tetracycline,
Oxytetracycline, 7-radiomycin sulfate, erythromycin, chloramphenicol, etc.; 1) Anesthetics: e.g. lidocaine, dibucaine hydrochloride, pensicaine, ethyl ami-7 benzoate, etc.; razon, nyscutin, acetosulfamine, clotrimazole, etc.) Antifungal substances: e.g. pentamycin, amphotericin B1 vialnitrin, clotrimazole, etc. l) Vitamins: e.g. vitamin A1 ergocalciferol, cholecalciferol , octothiazine, riboflavin butyrate, etc., 2) Anti-epileptic drugs: e.g. nitrazepam, mepropamate, clonazepam, etc. 4) Coronary vasodilators: e.g. nitroglycerin, nitroglycol, insorbidoniitrate, urithritol tetranitrate, penta Erythritol tetranitrate, propyl nitrate, nianidipine, etc.) Antihistamines: e.g. noaenhydramine hydrochloride,
Chlorpheniramine, diphenylimiguzole, etc. El)vA cough medicines: e.g. dextromethorphan, dextromethorphan hydrobromide, telbutasone sulfate, ephedrine, ephedrine hydrochloride, salbutamol, salbutamol sulfate, isobroterenolol, isoproterenolol hydrochloride , isobrotylenolol sulfate, etc., 1) Sex hormones: e.g., propsterone, estradiol, etc.; Emetics, anti-tumor agents: e.g. metoclopramide, clebopride, tonperiton, sufboramine, sufvoramine hydrobromide, 5-fluorouracil, mercaptopurine, etc.) Biomedicines: e.g. polypeptide M (TRH, LHR)
H derivatives), brostaglandins, etc.; n) Others: Examples include 7-entanyl, digoxin, desmobrecin, nohydroergotamine methanesulfonic acid, dihydroergotamine tartrate, etc., and two types of these drugs may be used as necessary. The above can be used together.

In addition, in the pharmaceutical component of the present invention, it is preferable that the drug is hydrophobic, because hydrophilic drugs generally form salts and have a higher melting point, and are more easily absorbed through the skin than hydrophobic drugs. In addition to poor solubility in the pressure-sensitive adhesive polymer layer, drug crystals easily precipitate in the pressure-sensitive adhesive polymer layer, reducing adhesion to the skin. This is because transdermal absorbability decreases.

In the present invention, a hydrophobic drug refers to water 1 of the above-mentioned drugs.
The amount of dissolution per 00 mN is 0.4° or less at room temperature.

In addition, by using isosorbide dinitrate or glyceryl trinitrate as the above drug, it is possible to obtain higher blood concentration and longer duration than conventional tape-type preparations, allowing for more effective treatment. It becomes.

In the pharmaceutical member of the present invention, when the drug in the drug-retaining layer has a saturated solubility, it is possible not only to retain the drug to the maximum extent (but also to effectively transfer the drug to the drug-containing pressure-sensitive adhesive polymer layer). In addition to being able to transfer the drug from the pressure-sensitive adhesive polymer layer to the drug-retaining layer, the drug can be used effectively and is extremely economical.

(e) Effect The medical member of the present invention has the above structure, and not only contains a drug in the pressure-sensitive adhesive polymer layer that is directly attached to the skin, but also contains a drug that is laminated on one side of the polymer layer. When a drug-retaining layer is interposed and encapsulated between the drug-release controlling layer and the impermeable backing support, and the drug in the polymer layer and the drug in the drug-release controlling layer are the same, the above-mentioned Not only can it prevent the drug in the polymer layer from migrating to the side opposite to the skin surface, that is, the drug (and absorption aid) retaining layer, but also the drug (and absorption aid) from the drug retaining layer can be prevented from migrating into the polymer layer. The drug control layer controls the migration of the drug (and drug absorption aid) and maintains a balance between the migration of the drug (and drug absorption aid) and the release of the drug (and drug absorption aid) from this polymer layer into the body. In addition, by changing the type and composition of the absorption aid, it has the effect of enabling better transdermal administration over a long period of time. In addition, drugs and drug absorption aids (
Even if the concentration of the drug (if necessary) is reduced, the drug and drug absorption aid (if necessary) are replenished from the drug-retaining layer.
Therefore, the concentration of drugs and drug absorption aids (if necessary) can be lowered, thereby preventing cohesive failure of the pressure-sensitive adhesive polymer layer and increasing the safety of pharmaceutical components. .

In addition, for drugs with poor percutaneous absorption, it is necessary to add a considerable amount of drug absorption aid to the pressure-sensitive adhesive polymer layer, but with this structure, the drug absorption aid can be added to the drug-retaining layer. Therefore, it is no longer necessary to increase the concentration of the drug absorption aid in the pressure-sensitive adhesive polymer layer, and cohesive failure of the polymer layer can be prevented as much as possible. When applied to the human body, both the drug and the drug absorption aid migrate into the polymer layer, resulting in better transdermal administration.

Furthermore, in this way, not only the drug is contained in the pressure-sensitive adhesive polymer layer that is directly attached to the skin, but also the same drug as the above drug is contained and retained in the drug (and absorption aid) retention layer. As a result, drug replenishment is sufficient even if the drug concentration in the pressure-sensitive adhesive polymer layer is lowered, and crystallization of the drug on the surface of the layer is prevented, resulting in good adhesion to the skin. It has the following effect.

Cf') Examples The present invention will be explained in detail based on Examples below, but the present invention is not limited thereto.

In addition, in the following, parts or % mean parts by weight or weight %.

Example of groove made from Ming Dynasty Next, the present invention will be specifically explained based on the drawings.

In FIG. 1, the pharmaceutical component (1) of the present invention includes a drug-retaining layer (4) between an impermeable backing support (2) and a pressure-sensitive adhesive polymer MC3) that is adhesive at room temperature. Intermediate and enclosed.

The drug-retaining layer (4) is made of a solution containing a drug and a drug absorption aid, a drug dispersion, or a gel containing a drug, and the pressure-sensitive adhesive polymer N (
3) contains the same drug as the drug-retaining layer (4).

Furthermore, a drug release control layer (5) is provided between the drug-containing pressure-sensitive adhesive polymer layer (3) and the drug-retaining layer (4), thereby controlling the amount of drug administered into the body. drugs (and absorption aids)
This makes it possible to change the release properties of the drug from the retention layer.

Note that (6) is a peeled body.

Example 1 95 parts of 2-ethylhexyl acrylate and 5 parts of acrylic acid were placed in a flask under an inert gas atmosphere, and 0.3 parts of azobisisobutyronitrile was added as a polymerization initiator. While maintaining the temperature at 60℃, polymerization is performed to form an acrylic pressure-sensitive adhesive polymer solution (solid content 34.9%).
) was obtained.

To 80 parts of the solid content of this solution, 19.9 parts of insorbidonitrate and 1 part of Coronate HL were added, and ethyl acetate was added to obtain a solution with a total solid content of 22%.

This solution was applied onto a polyester release body with a thickness of 75 μm so that the thickness after drying would be 100 μm, and this was dried at a temperature of 100°C for 3 minutes.
% ethylene-vinyl acetate copolymer film (thickness 50
μIII) and knee-song at room temperature for 48 hours, thereby forming the drug-containing pressure-sensitive adhesive polymer layer (3).
and drug release control/i! ! A laminate film (5) was obtained.

Next, it is printed in flesh color and aluminum is vapor deposited to a thickness of 12
An impermeable backing support (2 μm thick polyester film laminated with polyethylene to a thickness of 30 μIo)
) and the above laminated film with a height of 71+am and a width of 71am.
Heat sealing was performed so that the size of the arm and the seal width were 4+nw. Add this to insorbide dinitrate 2.0
2 parts of hydroxypropyl cellulose, 3 parts of diethylene glycol. (1. A drug-containing (retention) solution with a viscosity of approximately 50 voids consisting of 62 parts of ethanol and 31 parts of water is
Inject into the g-seal, heat seal the injection port, and then vertically? The pharmaceutical member (1) of the present invention is punched out to a size of 71 mm in width, and the drug holding layer (4) is sealed in a laminated manner between the backing support (2) and the drug release control 11 layer (5). ) was obtained.

After 20 days had passed since the preparation of this medical component (1), the test drive described below was carried out.

The results are shown in Table 1.

Example 2 The pharmaceutical member of the present invention ( 1) was obtained.

After 20 days had passed since the preparation of this medical component (1), the test described below was conducted.

The results are shown in Table 1.

Example 3 The pharmaceutical component (1) of the present invention was prepared in the same manner as in Example 1, except that the drug release control NJ (5) in Example 1 was changed to one with a vinyl acetate content of 33% and a thickness of 50 μIfi. Obtained.

After 20 days had passed since the preparation of this medical component (1), the test described below was conducted.

The results are shown in Table 1.

Example 4 In Example 1, drug-containing pressure-sensitive adhesive polymer layer (3)
During the preparation of Example 1, 2 parts of hydroxypropyl cellulose, 3.5 parts of diethylene glycol, 63 parts of ethanol, and 31.5 parts of water were used instead of the drug-retaining layer (4). The method was repeated in the same manner as in Example 1, except that a solution consisting of
1) was obtained.

After 20 days had passed since the preparation of this medical component (1), the test described below was conducted.

The results are shown in Table 1.

Example 5 In Example 1, drug-containing pressure-sensitive adhesive polymer layer (3)
The medical component (1) of the present invention was obtained in the same manner as in Example 1, except that HL (Coronet) was not added during the preparation.

After 20 days had passed since the preparation of this medical component (1), the test described below was conducted.

The results are shown in Table 1.

Example 6 Using the acrylic pressure-sensitive adhesive polymer solution obtained in Example 1, 29.8 parts of glyceryl trinitrate and 0.2 parts of Coronate HL were added to 70 parts of the solid content of this solution to completely dissolve the solution. A solution with a solids content of 22% was obtained. This drug-containing pressure-sensitive adhesive polymer solution, 10 parts of glyceryl trinitrate,
A pharmaceutical component (1) of the present invention was obtained in the same manner as in Example 1 using a drug-containing (retention) solution consisting of 2 parts of hydroxypropyl cellulose, 59 parts of ethanol, and 29 parts of water.

Example 7 The same procedure as in Example 6 was carried out, except that when creating the drug-containing pressure-sensitive adhesive polymer layer, 0.1 part of ML and 29.9 parts of glyceryl trinitrate were used. Thus, a medical component (1) of the present invention was obtained.

After 20 days had passed since the preparation of this medical component (1), the test described below was conducted.

The results are shown in Table 1.

Example 8 In Example 1, the drug release control layer was made of a vinyl acetate-containing layer.
114%, thickness 30 μm, and further changed the composition of the drug-containing solution to 2.0 parts of HPC, 3.0 parts of diethylene glycol, 0.6 parts of isosorbide dinitrate, 37.8 parts of ethanol, and 56.6 parts of water. A medical component (1) of the present invention was obtained in the same manner as in Example 1 except that the ingredients were changed.

Twenty days after the preparation of this medical component (1), the test described below was conducted.

The results are shown in the Pt41 table.

Example 9 In Example 8, the composition of the drug-containing solution was changed to NPO2,
0 parts, diethylene glycol 3.0 parts, insorbide nonitrate 1.4 parts, ethanol 56.2 parts, water 37
．． A medical component (1) of the present invention was obtained in the same manner as in Example 8 except that the amount was changed to 4 parts.

After 20 days had passed since the preparation of this medical component (1), the test described below was conducted.

The results are shown in Table 1.

Example 10 In Example 8, the composition of the drug-containing solution was changed to HPC2.0.
parts, diethylene glycol 3.0 parts, isonrubidononitrate 2.79 parts, ethanol 73.8 parts, water 18.
A medical component (1) of the present invention was obtained in the same manner as in Example 8 except that the amount was changed to 5 parts.

After 20 days had passed since the preparation of this medical component (1), the test described below was conducted.

The results are shown in Table 1.

Example 11 In Example 8, the drug-containing solution ILe, [IP
The pharmaceutical component of the present invention (
1) was obtained.

After 20 days had passed since the preparation of this medical component (1), the test described below was conducted.

The results are shown in Table 1.

Example 12 With respect to 86 parts of the solid content of the pressure-sensitive adhesive polymer solution used in Example 1, 19.
9i, 0.1 part of aluminum triisopropylate dissolved in 10 parts of 7-cetylacetone was added, and ethyl acetate was further added to obtain a solution with a total solid content of 22%. This was coated in the same manner as in Example 1, and after drying, a polyethylene porous membrane (air permeability 300 seconds/100 cc, thickness 50 μL) was applied.
11) was laminated to obtain a laminate film of a drug-containing pressure-sensitive adhesive polymer layer and a drug release control layer. This laminated film has a composition of 2.0 parts of HFO, 3.0 parts of diethylene glycol, and 0.6 parts of insorbide dinitrate.
A medicinal component (1) of the present invention was obtained in the same manner as in Example 1 using a drug-containing solution consisting of 1 part, 37.8 parts of ethanol, and 56.6 g of water.

20 days after creating this medical component (1)! After one period of time, the test described below was conducted.

The results are shown in Table 1.

Example 13 Example except that the composition of the drug-containing solution is 2.0 parts of HFO, 3.0 parts of diethyleneglyfur, 1.4 parts of insorbidonitrate, 56.2 parts of ethanol, and 37.4 parts of water. The medical component (1) of the present invention was obtained in the same manner as in Example 12.

After 20 days had passed since the preparation of this medical component (1), the test described below was conducted.

The results are shown in Table 1.

Example 14 Same as Example 12 except that the composition of the drug-containing solution was 2.0 parts of HFO, 3.0 parts of diethylene glycol, 2.7 parts of insorbidonitrate, 73.8 parts of ethanol, and 18.5 parts of water. The medical component (1) of the present invention was obtained in the same manner.

Twenty days after the preparation of this medical component (1), the test described below was conducted.

The results are shown in Table 1.

Example 15 The method of the present invention was carried out in the same manner as in Example 12, except that the composition of the drug-containing solution was 2.0 parts of HFO, 3.0 parts of diethylene glycol, 4.1 parts of insorbide dinitrate, and 90.9 parts of ethanol. A medical component (1) was obtained.

After 20 days had passed since the preparation of this medical component (1), the test described below was conducted.

The results are shown in Table 1.

Example 16 Using the pressure-sensitive adhesive polymer solution obtained in Example 1, 9.9 parts of ketopro7ene, 0.1 part of Coronate HL, and ethyl acetate were added to 90 parts of the solid content of this solution to give a total solution. A solution with a solids content of 22% was obtained. This solution and vinyl acetate content 1
4%, ethylene-vinyl acetate copolymer film with a thickness of 30/j+n, and 5.0 parts of RFe, 3.0 parts of diethylene glycol, 3.7 parts of ketopro7ene, and 36 parts of ethanol.
, 5p, and 54.8 parts of water in the same manner as in Example 1 to obtain a medical component (1) of the present invention.

After 20 days had passed since the preparation of this medical component (1), the test described below was conducted.

The results are shown in Table 141.

Comparative Example 1 In Example 1, when creating the drug-containing pressure-sensitive adhesive polymer layer, Coronae) 1-(L was not added, and a 9 μm thick polyester film was laminated to the polymer layer as a support. Then, it was punched out to a length of 71 mm and width of 7 inches+m to obtain a tape-like preparation without a drug-retaining layer.

Comparative Example 2 In Example 6, Coronae 1-IL was not added when creating the drug-containing pressure-sensitive adhesive polymer layer, and a 9 μm thick polyester film was laminated to this polymer layer as a support, A tape-like preparation without a drug-retaining layer was obtained by punching out a tape having a radius of 71 mm and an IF of 271 mm.

Comparative Example 3 In Example 16, the composition of the drug-containing solution was RPO2.0.
All the same as Example 16 except for IIS, 3.07 g of diethylene glycol, 38.0 parts of ethanol, and 57.0 parts of water.
A medical member similar to the present invention was obtained in the same manner.

After 20 days had passed since the preparation of this medical member, the test described below was conducted.

The results are shown in Table 1.

Comparative Example 4 When creating the drug-containing pressure-sensitive adhesive polymer layer in Example 16, Coronae) HL was not added, and this polymer layer was laminated with a 9 μm thick polyester film as a support, W171 m+n, horizontal. 71a+m was punched out to obtain a tape-like preparation without a drug-containing bath WL layer.

(Hereinafter, the margin χ 72L GI 1 FALSE and "k 2") The samples of each Example and each Comparative Example were pasted on the back of a rabbit whose hair had been removed in advance, and 0.5.1.21.t, 6.8.24 Two [n1] blood samples were taken at each lapse of time, and the drug concentration in the blood was measured using a gas chromatography device.

Furthermore, the adhesion during application and the peeling state at the end of the test were visually evaluated.

The results are shown in FIGS. 2 to 6 and Table 1.

From the results shown in FIGS. 2 to 6, the drugs of each Example had a 7 degree better transdermal administration property than the Comparative Example.
Moreover, from the results shown in Table 151, the products of each Example had no cohesive failure and no adhesive residue was left after use.

(g) Effects of the Invention The pharmaceutical component of the present invention has a drug-retaining layer consisting of a solution, dispersion, or del containing a drug and a drug absorption aid between the impermeable backing support and the drug release control layer. A pressure-sensitive adhesive polymer layer containing the same drug as the drug-retaining layer and adhesive at room temperature is provided on the other surface of the drug-release controlling layer. By culturing, the pressure-sensitive adhesive polymer layer has good adhesion to the skin and good sustained release of the drug in the pressure-sensitive adhesive polymer layer.
This prevents accidental destruction and maintains a balance between the transfer of the drug from the drug-retaining layer into the polymer layer and the release of the drug from this polymer layer into the body, allowing the drug to be maintained for a long period of time. Both can be efficiently administered through the skin and have the same effects.

Therefore, the medical device of the present invention has a significantly higher transdermal administration effect than conventional tape preparations.

Furthermore, in the pharmaceutical member of the present invention, a drug release control layer is provided between the drug (and absorption aid) holding layer and the pressure-sensitive adhesive polymer layer, and the characteristics and absorption aid of this drug release control layer are By changing the type and composition of drug 1 depending on the disease situation, in other words, by changing the release properties of the drug from the drug (and absorption aid) retaining layer, we can change the percutaneous absorption pattern of the drug and make it safe and effective. A therapeutic effect can be achieved. In the pharmaceutical member of the present invention, when the drug in the drug-retaining layer has a saturated solubility, not only can the drug be retained to the maximum extent, but also
The drug can be effectively transferred to the drug-containing pressure-sensitive adhesive polymer layer, and it is also possible to prevent the drug from transferring from the pressure-sensitive adhesive polymer layer to the drug-retaining layer, allowing effective use of the drug. Therefore, it is possible to achieve effects such as being extremely economical.

[Brief explanation of the drawing]

FIG. 1 is a sectional view showing an example of the present invention, and FIGS. 2 to 6 are characteristic diagrams showing changes over time in the blood concentration of a drug in each example and each comparative example. (1)...Medical component, (2)...Backing support, (3
)...value drug-containing) pressure-sensitive adhesive polymer layer, (4)...
Drug retention layer, (5)...Drug release control layer, (6)...
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Claims (2)

[Claims] (1) A drug-retaining layer made of a solution, dispersion, or gel containing a drug and a drug absorption aid is interposed and enclosed between the impermeable backing support and the drug-release controlling layer to control the drug release. A pharmaceutical member characterized in that a pressure-sensitive adhesive polymer layer containing the same drug as the drug-retaining layer and adhesive at room temperature is provided on the other side of the layer. (2) The pharmaceutical member according to claim 1, wherein the drug concentration in the drug-retaining layer is a saturated solubility.