JPH1192361A - Percutaneous absorption preparation - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain a percutaneous absorption preparation excellent in skin following properties, appearance of preparation, medicine absorption, etc. SOLUTION: This percutaneous absorption preparation comprises (1) a supporting substrate composed of a polyester ether block copolymer consisting of a hard segment made of an aromatic dicarboxylic acid and an aliphatic diol as main constituent components and a soft segment made of a polyoxytetramethylene glycol as a main component, (2) a mixture layer composed of a water-soluble polymer and a water-soluble tackifier and (3) a tacky agent layer containing a higher fatty acid ester compound and a medicine. The mixture layer is laid between the supporting substrate and the tacky agent layer.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a percutaneous absorption preparation, and more particularly, to a percutaneous absorption preparation excellent in, for example, skin followability, good appearance of the preparation, and drug absorption.

[0002]

2. Description of the Related Art Percutaneous absorption preparations intended for administering a drug to the body through the skin by applying it to the skin include various forms such as cataplasms and plasters. Is being developed. Percutaneous absorption preparations are formed by laminating a pressure-sensitive adhesive layer containing a drug on a support, and include a variety of drugs such as local-acting drugs such as anti-inflammatory analgesics and systemic drugs such as vasodilators. It is diverse. Because the percutaneous absorption preparation is applied to the skin surface,
It is necessary that the material does not have a sense of incongruity when applied, and that it follows the movement of the skin, and a flexible material such as a plastic film, a nonwoven fabric, or a woven fabric is used as the support base material. . In addition, a material having elasticity as well as flexibility is used for a portion where the attachment portion is a bent portion such as an elbow and knee joint portion. As a material satisfying the above conditions, JP-A-7-165565 discloses a polytetramethylene glycol component as a hard segment component,
A polyester / ether block copolymer containing polyoxytetramethylene glycol as a soft segment component is used.

[0003] This polyester ether block copolymer is excellent because it contains no harmful substances, is flexible and does not exude a plasticizer or the like. However, this copolymer is
The transfer of higher fatty acid ester compounds, which are generally used to promote the transdermal absorption of drugs, cannot be prevented, and the support base material swells and wrinkles occur with the transfer. There are problems such as the above problems and a decrease in drug absorption. In order to prevent this, a method of laminating PET (polyethylene terephthalate) on a soft plastic film and a method of laminating a fluororesin (JP-A-2-237)
915) and a method of laminating a metal thin film such as an aluminum foil. However, these methods have problems such as lack of flexibility of the supporting substrate, lack of elasticity, and easy formation of the formed layer.

[0004] That is, an object of the present invention is to provide a transdermal absorption preparation having skin follow-up properties. It is a further object of the present invention to provide a transdermal absorption preparation that has skin-tracking properties and is excellent in drug absorption and the like. Another object of the present invention is to provide a percutaneous absorption preparation having skin following properties, for example, having less wrinkles and having excellent appearance of the preparation. Still another object of the present invention is to provide a percutaneous absorption preparation having skin following properties, for example, having less wrinkles, excellent in appearance of the preparation, and further excellent in drug absorption and the like. I do.

[0005]

Means for Solving the Problems The inventors of the present invention have conducted intensive studies to solve the above-mentioned problems, and as a result, have found that a support base made of a polyester ether block copolymer, a water-soluble polymer and a water-soluble tackifier are used. It has been found that a desired percutaneous absorption preparation can be obtained by using such a mixture. That is, the present invention provides a polyester ether block copolymer comprising (1) a hard segment mainly containing an aromatic dicarboxylic acid and an aliphatic diol and a soft segment mainly containing polyoxytetramethylene glycol. A support substrate comprising: (2) a mixture layer comprising a water-soluble polymer and a water-soluble tackifier; and (3) an adhesive layer comprising a higher fatty acid ester compound and a drug, wherein the mixture layer comprises It is a transdermal absorption preparation provided between a substrate and the pressure-sensitive adhesive layer.

[0006]

BEST MODE FOR CARRYING OUT THE INVENTION The polyester ether block copolymer used in the present invention comprises a hard segment mainly composed of an aromatic dicarboxylic acid and an aliphatic diol and a soft segment mainly composed of polyoxytetramethylene glycol. And segments. Such a polyester ether block copolymer usually has properties as an elastomer, but the polyester ether block copolymer is preferably a polyester elastomer because of its use as a support base material for the transdermal absorption preparation of the present invention. preferable. Such a hard segment is usually preferably a crystalline polyester, but as the aromatic dicarboxylic acid, for example, terephthalic acid, isophthalic acid, naphthalenedicarboxylic acid, diphenyldicarboxylic acid, diphenylsulfondicarboxylic acid, diphenoxyethanedicarboxylic acid, Examples thereof include diphenyl ether dicarboxylic acid, methyl terephthalic acid, and methyl isophthalic acid. Of these, terephthalic acid and 2,6-naphthalenedicarboxylic acid are preferred. In addition, for example, an aliphatic dicarboxylic acid such as succinic acid, adipic acid, sebacic acid, decanedicarboxylic acid, or dodecanedicarboxylic acid may be partially used in a range that does not impair the crystallinity of the polymer (for example, 20 mol% or less); It may be replaced by an alicyclic dicarboxylic acid such as cyclohexanedicarboxylic acid. As the dicarboxylic acid component, only one kind may be used, or two or more kinds may be used in combination.

As the aliphatic diol component constituting the hard segment, for example, ethylene glycol,
Trimethylene glycol, tetramethylene glycol,
Hexamethylene glycol and cyclohexane dimethanol can be mentioned. Of these, tetramethylene glycol is particularly preferred as the diol component. Two or more diol components may be used in combination.
In addition, the hard segment is in a range that does not impair the crystallinity of the polymer (eg, 20 mol% or less, preferably
Mol% or less), some of them may be replaced with a polyester composed of other carboxylic acids such as oxycarboxylic acids such as ε-oxycaproic acid, oxybenzoic acid and hydroxyethoxybenzoic acid. The average molecular weight of the polyoxytetramethylene glycol constituting the soft segment is preferably from 500 to 20,000, and particularly preferably from 600 to 4,000. The polyester ether block copolymer used in the present invention is, for example, the above-mentioned aromatic dicarboxylic acid or an ester-forming derivative thereof constituting a crystalline polyester, and a diol or an ester-forming derivative thereof, and polyoxytetramethylene glycol or the same. It can be produced by a conventionally known polymerization method using an ester-forming derivative. The content of the hard segment in the polyester ether block copolymer is desirably 10 to 50% by weight based on the total amount of the hard segment and the soft segment. When the content of the hard segment is less than 10% by weight, the heat resistance of the obtained polyester ether block copolymer is insufficient, and when the content is more than 50% by weight, the elastic properties as a supporting base material are deteriorated, and the skin followability is poor. It is not preferable because it becomes sufficient. The preferred content of the hard segment is 20 to 40% by weight.

The intrinsic viscosity of the polyester ether block copolymer in the present invention is phenol / 1,1,2,2
When measured in a mixed solvent of 2-tetrachloroethane (weight ratio: 4/6, temperature: 35 ° C.), it is preferably from 0.5 to 6.0. In particular, when the intrinsic viscosity is less than 0.5, practical strength may be insufficient, or elastic properties as an elastomer may not be sufficiently exhibited. As a support base material made of the polyester ether block copolymer, a woven fabric,
Non-woven fabrics, knits, films and the like can be mentioned, and non-woven fabrics and films are particularly preferred. The thickness of the supporting substrate is not particularly limited, but is preferably 5 to 5000 μm, more preferably 1 to 5000 μm.
0 to 2000 μm. Examples of the water-soluble polymer in the present invention include polyacrylic acid and salts thereof, polyacrylamide, polyvinyl alcohol and derivatives thereof, polyvinyl compounds such as polyvinyl methyl ether and polyvinyl pyrrolidone; polyethers such as polyethylene oxide and polypropylene oxide; And polysaccharides such as carboxymethylcellulose, methylcellulose, ethylcellulose, hydroxymethylcellulose, alginic acid, acetylated starch, hydroxyethylated starch, dialdehyde starch, and dextrin; and polypeptides such as glue, gelatin, and casein. Among them, polyvinyl compounds; polysaccharides are preferable, and polyacrylic acid and salts thereof, gum arabic, and alginic acid are particularly preferable. One of these water-soluble polymers may be used alone, or two or more thereof may be used. The water-soluble tackifier in the present invention may be any as long as it forms a pressure-sensitive adhesive by mixing with the above water-soluble polymer. Examples thereof include polyhydric alcohols such as glycerin, sorbit, polyethylene glycol and pentaerythritol; Polyhydric alcohol derivatives such as triacetin, polyether polyol and polyoxyethylene phenol ether; polyethylene glycol surfactants such as polyoxyethylene alkyl phenol ether and polyoxyethylene alkyl ether; polyethylene imine and its derivatives; water-soluble salts of rosin Is mentioned. The optimal water-soluble tackifier differs depending on the water-soluble polymer,
For example, when sodium polyacrylate is used as the water-soluble polymer, a polyethylene glycol-based surfactant is preferable as the water-soluble tackifier, and when a gum arabic is used, polyethyleneimine and its derivatives are preferable.

The weight ratio of the water-soluble polymer to the water-soluble tackifier in the mixture is not particularly limited as long as the flexibility and the cohesive force of the obtained mixture layer are satisfied.
3 is preferred. When the ratio of the water-soluble polymer is less than 3%, the cohesive force of the mixture layer is too small, which is not preferable. Also,
When the ratio of the water-soluble polymer is more than 97%, the flexibility of the mixture layer is lacking, which is not preferable. The weight ratio of the water-soluble polymer to the water-soluble tackifier is more preferably from 5/95 to 95/5. For example, when polyacrylic acid is used as the water-soluble polymer and polyethylene glycol is used as the water-soluble tackifier, the weight ratio of polyacrylic acid to polyethylene glycol is preferably 10/90 to 70/30,
15 / 85-60 / 40 is more preferred. The mixture layer of the present invention, for example, by applying a mixed solution of the water-soluble polymer and a water-soluble tackifier on a release film, by drying, or by directly coating on the support substrate, It can be obtained by drying. In the mixture layer comprising the water-soluble polymer of the present invention and a water-soluble tackifier, a compounding agent such as a plasticizer, a filler and an antioxidant can be contained as required. The thickness of the mixture layer can be appropriately selected according to the support base material and the pressure-sensitive adhesive layer described later. Generally, the thickness of such a mixture layer is from 1 to 1000
μm, preferably 5 to 500 μm. Examples of the higher fatty acid ester compound of the present invention include isopropyl myristate, isooctyl palmitate, ethyl oleate, diethyl sebacate and the like. Such a higher fatty acid ester compound is contained in the pressure-sensitive adhesive layer in an amount of 0.1 to 0.1%.
It is preferable to contain 50% by weight. If the amount is less than 0.1% by weight, it is difficult to improve the transdermal absorbability of the drug. If the amount is more than 50% by weight, the self-aggregation ability of the pressure-sensitive adhesive layer becomes inferior. Will remain.

The drug of the present invention may be any drug as long as it is absorbed transdermally into the living body, and examples thereof include the following drugs. 1) Corticosteroids: for example, hydrocortisone, prednisolone, paramethasone, beclomethasone propionate, flumethasone, betamethasone, betamethasone valerate, dexamethasone, triamcinolone,
Triamcinolone acetonide, fluocinolone, fluocinolone acetonide, fluocinolone acetonide acetate, clobetasol propionate, etc. 2) Anti-inflammatory analgesics: for example, indomethacin, ketoprofen, acetaminophenone, mefenamic acid, flufenamic acid, diclofenac, diclofenac sodium , Alclofenac, oxyphenbutazone, phenylbutazone, ibuprofen, flurbiprofen,
Salicylic acid, methyl salicylate, 1-menthol, camphor, sulindac, tolmetin sodium, naproxen, fenbufen, etc. 3) Hypnotic sedatives: for example, phenobarbital, amobarbital, cyclobarbital, triazolam, nitrazepam, flunitrazepam, lorazepam, haloperidol, etc. 4) tranquilizers: for example, fluphenazine, theorytazine, diazepam, fludiazepam, flunitrazepam,
5) Antihypertensive agents: for example, clonidine, clonidine hydrochloride, pindolol, propranolol, propranolol hydrochloride, bufuranol, indenolol, nivadipine,
Nimodipine, lofedixine, nitrendipine, nipradilol, bucmorol, nifedipine, etc.

6) Antihypertensive diuretics: for example, hydrothiazide, bendroflumesiazide, cyclobenchazide, etc. 7) Antibiotics: for example, penicillin, tetracycline, oxytetracycline, fradiomycin sulfate,
Erythromycin, chloramphenicol, etc. 8) Anesthetic: for example, lidocaine, dibucaine hydrochloride, benzocaine, ethyl aminobenzoate, etc. 9) Antibacterial substances: for example, benzalkonium chloride, nitrofurazone, nystatin, acetosulfamine, clotrima Sol, etc. 10) Antifungal agents: for example, pentamycin, amphotericin B, pyrrolnitrin, clotrimazole, etc. 11) Vitamin agents: for example, vitamin A, vitamin E,
Vitamin K, ergocalciferol, cholecalciferol, octothiacin, riboflavin butyrate, etc. 12) Antiepileptic agents: for example, nitrazepam, meprobamate, clonazepam, etc.

13) Coronary vasodilators: for example, nitroglycerin, nitroglycol, isosorbide dinitrate, erythritol tetranylate, propachyl nitrate, dipyridamole, molycidamine, etc. 14) Antihistamines: for example, diphenhydramine hydrochloride, chlorpheniramine , Diphenylimidazole, etc. 15) Antitussives: for example, dextromethorphan hydrobromide, dextromethorphan, terbutaline, terbutason sulfate, ephedrine, ephedrine hydrochloride, salbutamol sulfate, salbutamol, isoproterenol hydrochloride, isoproterenol sulfate, isoproterenol sulfate 16) Sex hormones: for example, progesterone, estradiol, etc. 17) Antidepressants: for example, doxepin 18) Brain circulation improver For example, Hydergine, ergot alkaloids, such as ifenprodil, 19) anti-emetics, anti-ulcer agents: for example, metoclopramide,
Crevopride, domperidone, scopolamine, scopolamine hydrobromide, etc. 20) Biopharmaceuticals: for example, polypeptides, etc. 21) Others: for example, fentanyl, desmopressin, digoxin, 5-fluorouracil, mercaptopurine, etc.

[0013] Such a drug is contained in the pressure-sensitive adhesive layer in an amount of from 0.05 to 0.05.
The drug is contained in the range of 40% by weight, but two or more of these drugs can be used in combination depending on the purpose, action and the like of the treatment. The pressure-sensitive adhesive used in the pressure-sensitive adhesive layer of the present invention is not particularly limited as long as the drug to be contained can be released to the skin surface by diffusion movement, and a natural polymer or a synthetic polymer can be used. . Examples of such an adhesive include (meth) acrylic acid butyl ester, (meth) acrylic acid pentyl ester, (meth) acrylic acid hexyl ester, (meth) acrylic acid heptyl ester, (meth) acrylic acid octyl ester,
Nonyl (meth) acrylate, decyl (meth) acrylate, undecyl (meth) acrylate, dodecyl (meth) acrylate, (meth)
Examples include a polymer comprising at least one of alkyl (meth) acrylates such as tridecyl acrylate, and an acrylic pressure-sensitive adhesive comprising a copolymer of a monomer copolymerizable with the ester. Can be

Examples of the copolymerizable monomer include, for example,
Carboxyl group-containing monomers such as (meth) acrylic acid, itaconic acid, crotonic acid, maleic acid, maleic anhydride, and fumaric acid; styrene sulfonic acid, allyl sulfonic acid, sulfopropyl acrylate, (meth) acryloyloxynaphthalene Sulfoxyl group-containing monomers such as sulfonic acid, acrylamidomethylpropanesulfonic acid, and acroyloxybenzenesulfonic acid; hydroxyl group-containing monomers such as hydroxyethyl (meth) acrylate and hydroxypropyl (meth) acrylate Body; (meth) acrylamide, dimethyl (meth)
Amide group-containing acrylic monomers such as acrylamide, N-butylacrylamide, tetramethylbutylacrylamide, N-methylol (meth) acrylamide;
Alkyl monomers containing alkylaminoalkyl groups such as aminoethyl (meth) acrylate, dimethylaminoethyl (meth) acrylate, diethylaminoethyl (meth) acrylate, and tert-butyl (meth) acrylate Methoxyethyl (meth) acrylate, ethoxyethyl (meth) acrylate, butoxyethyl (meth) acrylate, tetrahydrofurfuryl (meth) acrylate, methoxyethylene glycol (meth) acrylate, (meth) acrylate ) Alkoxy groups such as methoxydiethylene glycol acrylate, methoxypolyethylene glycol (meth) acrylate, and methoxypolypropylene glycol (meth) acrylate; (Monomer bond) -containing monomers; vinyl monomers such as N- (meth) acryloylamino acid; acrylic monomers such as urethane, urea and isocyanate of acrylic acid; and (meth) acrylonitrile and vinyl acetate , Vinyl propionate, vinyl pyrrolidone, vinyl pyridine, vinyl pyrazine, vinyl piperazine, vinyl piperidone, vinyl pyrimidine, vinyl pyrrole, vinyl imidazole, vinyl caprolactam, vinyl oxazole, vinyl thiazole, vinyl morpholine, styrene, α-methyl styrene, bis (N , N-dimethylaminoethyl) maleate and the like.
0% by weight, preferably in the range of 5 to 50% by weight,
It can be polymerized. Outside of these ranges, sufficient tackiness and internal cohesion may not be obtained, which is not preferred.

Other usable pressure-sensitive adhesives include, for example, acrylic rubber, natural rubber, polyisoprene rubber, polyisobutylene rubber, polybutadiene, styrene-butadiene (or isoprene) -styrene block copolymer rubber, and silicone rubber. Rubber-based adhesive substance; polyvinyl alkyl ether, polyvinyl acetate, partially saponified polyvinyl acetate, and vinyl-based adhesive substance mainly composed of polyvinyl alcohol, depending on the type of drug to be contained, the desired adhesive strength, etc. The type can be appropriately selected. In addition, when using the above-mentioned pressure-sensitive adhesive, when the pressure-sensitive adhesive layer is liable to cause cohesive failure or adhesive residue on the skin surface due to lack of internal cohesive force after application to the skin surface, it is usually used. The crosslinking agent may be blended with a known crosslinking agent, a crosslinking monomer may be blended as a copolymer component to improve cohesive strength, or crosslinking may be performed by irradiation with an electron beam, ultraviolet light, or the like. The pressure-sensitive adhesive used in the present invention must be variously selected depending on the kind of the drug used in order to decompose the contained drug as much as possible, but generally, a carboxyl group, an amino group, and an acid amide which are considered to have high reactivity. When a monomer having a reactive site such as a group is used, the reactivity can be reduced by reducing the amount of the monomer or by masking the site. The pressure-sensitive adhesive layer of the present invention includes, for example, a mixed solution obtained by adding a solution containing a higher fatty acid ester compound and a drug to the pressure-sensitive adhesive solution, on a release film, and the like. As long as it does not violate the physical and chemical properties such as the stability of the drug, it can be obtained using a conventionally known method for producing a drug-containing pressure-sensitive adhesive layer. The thickness of the pressure-sensitive adhesive layer is not particularly limited, but is 5 to 1000 μm, preferably 10 to 500 μm.
By setting it to μm, it can be stuck well.

In the present invention, a higher fatty acid ester compound is used to improve the transdermal absorbability of a drug.
When an effective amount of absorption is not expected, an auxiliary for promoting percutaneous absorption, for example, glycols and their alkyl esters; alkyl ethers; oils and fats; urea derivatives; Can be contained within a range that does not impair the skin adhesion properties and the stability of the drug to improve drug absorption. The transdermally absorbable preparation of the present invention comprises a support substrate comprising the above polyester ether block copolymer, a mixture layer, and an adhesive layer, and the mixture layer comprises
It is provided between the supporting substrate and the pressure-sensitive adhesive layer. As the structure of such a preparation, a percutaneous absorption preparation comprising a support substrate, a mixture layer, and then the pressure-sensitive adhesive layer laminated in this order can be mentioned as a preferable example. Of course, for example, an additional layer can be provided as needed between the mixture layer and the pressure-sensitive adhesive layer. For example, as a method for producing a preparation having such a preferable structure, a mixture layer composed of a water-soluble polymer and a water-soluble tackifier is laminated on one surface of a supporting substrate. Specifically, for example, an aqueous solution containing a water-soluble polymer and a water-soluble tackifier is prepared, applied to one surface of a support substrate, and dried to be laminated. Also,
It is also possible to adopt a method in which a mixture layer composed of a water-soluble polymer and a water-soluble tackifier is previously formed on release paper, and this is superimposed on a supporting substrate and transferred. Further, for example, by applying a pressure-sensitive adhesive layer containing a higher fatty acid ester compound and a drug to the mixture surface side, the transdermal absorption preparation of the present invention can be obtained.

[0017]

According to the present invention, since a supporting substrate of a polyester ether block copolymer can be used, it is soft and stretchable, has a good skin sensation, has good skin following properties, and is provided with a mixture layer to provide higher fatty acids. It is possible to use a higher fatty acid ester compound which can prevent the generation of wrinkles of the supporting substrate caused by the permeation of the ester compound into the base material, thereby improving the appearance of the preparation and further promoting the absorption of the drug. It is possible to provide a percutaneous absorption preparation excellent in sex and drug efficacy.

[0018]

The present invention will be described in more detail with reference to the following examples, but the present invention is not limited to the examples. (1) The intrinsic viscosity of the polyester elastomer was measured in a phenol / 1,1,2,2-tetrachloroethane mixed solvent (weight ratio 4/6, temperature 35 ° C.). (2) The 50% modulus of a test piece of 12 mm × 60 mm was stretched by 20 mm using a tensile tester at a test length of 40 mm and a pulling speed of 40 mm / min (5).
0% elongation), and the load (g) at this time is defined as a 50% modulus. (3) The elongation at break of a test piece of 12 mm × 60 mm was measured using a tensile tester at a test length of 40 mm and a tensile speed of 40 mm.
The test piece is stretched at mm / min, and the load (g) when the test piece breaks is defined as the breaking elongation. (4) The occurrence of wrinkles was left for one hour after the preparation of the patch, and visually determined. (5) The feeling of discomfort when affixed to the elbows of five adult males was judged by a score according to the following criteria. 0 point: no discomfort 2 points: slight discomfort 4 points: discomfort There was an evaluation based on the average score of five people. (6) The drug permeation amount was determined as follows. The snake skin is set between the donor and acceptor of the vertical diffusion cell. A test piece punched to 16.5 mmφ was attached to the donor side. PH 7 on the acceptor side.
20 ml of the phosphate buffer solution No. 2 was filled. 37 diffusion cells
Was set in a constant temperature bath and stirred with a magnetic stirrer. Six hours later, the liquid on the acceptor side was sampled, the drug concentration was analyzed by liquid chromatography, and the amount of permeation of the drug was measured. The experiment was repeated four times with the same sample, and the average value was defined as the transmission amount of the sample.

[Example 1] Dimethyl terephthalate 310
Parts, tetramethylene glycol 29 parts, average molecular weight 20
Polymerization of 65 parts of polytetramethylene glycol with titanium tetrabutoxide catalyst, 0.5 part of dibutylhydroxytoluene as a stabilizer was added 10 minutes before ejection, and the polyester ether block copolymer was taken out and formed into chips. Raw materials. The melting point of this chip is 19
At 0 ° C., the intrinsic viscosity was 1.53. The chip thus obtained was extruded into a sheet at 240 ° C. by an extruder equipped with a T-die, and cooled by a cooling drum cooled to 10 ° C. to obtain a thickness of 30 μm
m (supporting substrate) was obtained. 50 of this film
The% modulus was 200 g / 12 mm, and the breaking elongation was 1500%. A solution obtained by mixing 20 parts of a 10% aqueous solution of polyacrylic acid (average molecular weight: 450,000) and 8 parts of polyethylene glycol (average molecular weight: 400) on one surface of the supporting base material is applied so as to be 19 g / m ² after drying. After drying, a support substrate on which the mixture layer was laminated was obtained. 96 g of an ethyl acetate solution of 7.3 wt% of a copolymer composed of 7.5 wt% of methyl methacrylate, 90 wt% of 2-ethylhexyl acrylate and 2.5 wt% of acrylic acid, 2 g of isopropyl myristate, and 10 g of a chloroform solution of 10 wt% of ketoprofen were added. Thereafter, this mixed solution was applied onto a silicone-coated release film so that the thickness of the dried pressure-sensitive adhesive layer was 30 μm, and dried at 60 ° C. for 30 minutes to obtain a drug-containing pressure-sensitive adhesive. The pressure-sensitive adhesive layer thus obtained was transferred to the mixture layer side of the above-mentioned support substrate, and a transdermal absorption preparation (paste) was obtained. The performance of the patch thus obtained was examined for the items shown in Table 1. Table 1 shows the obtained results.

Example 2 The same polyester ether block copolymer film as in Example 1 was coated on one side with 20 parts of a 10% aqueous solution of gum arabic powder (Kanto Chemical) and a 30% aqueous solution of polyethyleneimine (average molecular weight 70,000, Wako Pure Chemical)
A patch was prepared in the same manner as in Example 1 except that a solution obtained by mixing 27 parts was dried and applied so as to have a weight of 14 g / m2, and then dried. Table 1 shows the evaluation results.

Example 3 Polyester ether block copolymer (hereinafter referred to as EL-1; hard segment; polybutylene-2,6-naphthalate 30% by weight,
Soft segment; polyoxytetramethylene glycol 70% by weight, intrinsic viscosity 1.73, melting point 180 ° C.) 5 g
Was dissolved in 15 g of NMP at 130 ° C. 30 ℃
The mixture was cast on a glass plate heated by a 2 mil doctor blade and allowed to cool at room temperature for 30 minutes. After confirming that the entire film became cloudy, the film together with the glass plate was immersed in water at 50 ° C. Thirty minutes later, the film was peeled off from the glass plate, and the film was taken out and dried to obtain a porous film (support base material) composed of a polyester ether block copolymer having white and good surface properties. The film thickness was 42 μm, the 50% modulus was 30 g / 12 mm, and the breaking elongation was 430%. A mixture layer was laminated on one surface of the supporting substrate in the same manner as in Example 1, and then the pressure-sensitive adhesive layer was transferred thereon in the same manner as in Example 1 to prepare a patch. Table 1 shows the evaluation results.

Example 4 A nonwoven fabric (average fiber diameter: 7 μm, basis weight: 40) was prepared from the same polyester ether block copolymer as in Example 1 by a melt blow method.
g) was obtained. The 50% modulus of this nonwoven fabric (support substrate) was 113 g / 12 mm, and the breaking elongation was 450%. A mixture layer was laminated on one surface of the supporting substrate in the same manner as in Example 1, and then the pressure-sensitive adhesive layer was transferred thereon in the same manner as in Example 1 to prepare a patch. Table 1 shows the evaluation results.

Comparative Example 1 A patch was prepared in the same manner as in Example 1 except that a mixture layer of polyacrylic acid and polyethylene glycol was not used. Table 1 shows the evaluation results.

Comparative Example 2 A patch was prepared in the same manner as in Example 1 except that the pressure-sensitive adhesive layer did not contain isopropyl myristate. Table 1 shows the evaluation results.

Comparative Example 3 A biaxially stretched polyethylene terephthalate film (thickness: 3 μm) was formed on one surface of the same polyester ether block copolymer film as in Example 1.
Was laminated. An adhesive layer was transferred to the polyethylene terephthalate film side in the same manner as in Example 1,
A patch was prepared. Table 1 shows the evaluation results.

[0026]

[Table 1]

As can be seen from Table 1, it is recognized that the patches (transdermal preparations) of the examples show excellent effects in any of the items.

 ──────────────────────────────────────────────────続 き Continued on the front page (72) Inventor Takeyuki Kawaguchi 2-1 Hinodecho, Iwakuni-shi, Yamaguchi Prefecture Teijin Limited Iwakuni Research Center

Claims (4)

[Claims] 1. A polyester ether block copolymer comprising a hard segment mainly composed of an aromatic dicarboxylic acid and an aliphatic diol and a soft segment mainly composed of polyoxytetramethylene glycol. A support substrate, (2) a mixture layer comprising a water-soluble polymer and a water-soluble tackifier, and (3) an adhesive layer containing a higher fatty acid ester compound and a drug, wherein the mixture layer comprises A percutaneous absorption preparation provided between a material and the pressure-sensitive adhesive layer. 2. A percutaneous absorption preparation comprising the support substrate, the mixture layer, and the pressure-sensitive adhesive layer laminated in the order of the support substrate, the mixture layer, and the pressure-sensitive adhesive layer. 3. The water-soluble tackifier is a polyhydric alcohol and a derivative thereof; a polyethylene glycol-based surfactant;
The percutaneous absorption preparation according to claim 1 or 2, which is one or more selected from the group consisting of polyethyleneimine and derivatives thereof; and a water-soluble salt of rosin. 4. The process according to claim 1, wherein the water-soluble polymer is one or more selected from the group consisting of a polyvinyl compound; a polyether; a polysaccharide; and a polypeptide. Skin absorption preparation.