WO2008075665A1 - Transdermally absorbable preparation and adhesive sheet for application to the skin - Google Patents

Abstract

Disclosed is a transdermally absorbable preparation comprising an adhesive skin patch characterized in that the adhesive skin patch comprises a substrate and an adhesive composition layer formed on the substrate, wherein the adhesive composition layer comprises a polyether polymer having a siloxane bond and at least one of the layers constituting the adhesive composition layer contains a physiologically active substance. Specifically, the adhesive composition layer in the transdermally absorbable preparation is produced by curing an adhesive composition comprising: (A) a polyether polymer having at least one alkenyl group at the terminus; (B) a compound having 1 to 10 hydroxyl groups in the molecule; and (C) a hydroxylation catalyst. The transdermally absorbable preparation has less irritation to the skin compared to a conventional one, has good wettability on the skin, good conformability to the skin and a satisfactory level of adhesion to the skin, can contain a satisfactory amount of a physiologically active substance, and can release the physiologically active substance satisfactorily.

Description

 Specification

 Transdermal absorption preparation and adhesive sheet for skin application

 Technical field

 [0001] The present invention relates to a treatment for a diseased part of the body or a transdermal absorption preparation for administering a physiologically active substance to the circulatory system or skin, and an adhesive sheet applied to the skin surface to protect or treat the skin surface. About. More specifically, the present invention relates to a transdermally absorbable preparation excellent in solubility, skin adhesive properties and skin fixability of a physiologically active substance regardless of the type of the physiologically active substance.

 Background art

 [0002] In recent years, percutaneous absorption preparations aimed not only at the skin disease part but also for systemic action have been remarkably developed based on the concept of a drug deliner system, and are particularly useful as sustained-release preparations. Has been recognized. Conventionally, as this type of transdermally absorbable preparation, a bioactive substance-impermeable support layer provided with an adhesive polymer layer containing a bioactive substance is known. By attaching it, a physiologically active substance is administered to the diseased part or circulatory system of the body.

 [0003] As an adhesive base for this transdermally absorbable preparation, a highly safe and well-balanced adhesive property and a good release of a physiologically active substance are required. It is known that the release of a physiologically active substance from a carrier for holding a physiologically active substance is an important factor particularly in a percutaneous absorption preparation intended for systemic action. As an adhesive composition layer of a transdermal absorption preparation, an acrylic adhesive is used and a transdermal absorption accelerator is added, or the skeleton is modified! (Patent Document 1). There is a problem with safety such as lowering or strong skin irritation. As a base for transdermally absorbable preparations, silicone elastomers are known to be effective as bases for implantable and transdermally absorbable preparations that are particularly safe! (Patent Document) 2). However, silicone adhesives have the following problems: the bioactive substances have low solubility and cannot maintain the necessary concentration of bioactive substances! /, And! /.

[0004] On the other hand, in addition to the above-mentioned percutaneously absorbable preparations, as an adhesive sheet including dressings used for the protection and treatment of skin damaged parts, first of all, in order to prevent the skin from falling off, , Requires a certain level of skin adhesion, but the greater the skin adhesion, When peeling and removing from the skin surface, physical irritation becomes stronger, causing pain and peeling of the stratum corneum at the time of peeling, which may cause unnecessary irritation and damage to the skin surface and cause pain to the user.

 [0005] Thus, the pressure-sensitive adhesive sheet for application to the skin is required to maintain a balance between skin adhesive force and skin irritation.

 [0006] Therefore, for the purpose of reducing the skin adhesive force, a method of incorporating an oily liquid component having high compatibility into the pressure-sensitive adhesive layer has been proposed (for example, Patent Documents 3 and 4). This pressure-sensitive adhesive sheet gives a soft feeling to the pressure-sensitive adhesive layer, and improves the adhesion to the skin surface and the solubility of the physiologically active substance. Skin irritation can be reduced, and when removing after use, it can be removed smoothly without causing keratin damage. However, since it is necessary to contain a relatively large amount of liquid component in order to give a soft feeling, blooming of the liquid component in the adhesive sometimes causes an increase in skin irritation.

 [0007] In addition, for administration of physiologically active substances to the skin such as epidermis and dermis, tarem, ointment and the like have been used as dosage forms (Patent Documents 5 and 6), but the skin compared to transdermal absorption preparations. It has good wettability and familiarity with the skin, but it has good contact efficiency with the skin. However, the content of bioactive substances and the amount of application on the skin (application thickness) are limited, so it is often necessary to bring about sufficient effects. There were problems such as smearing, stickiness due to large amount of smearing, sticking to clothing and other things and not showing medicinal effects.

 Patent Document 1: JP 2004-97730

 Patent Document 2: JP-A-60-169414

 Patent Document 3: JP-A-3-220120

 Patent Document 4: JP 2000-44904 A

 Patent Document 5: Japanese Patent Laid-Open No. 56-150007

 Patent Document 6: Japanese Patent Laid-Open No. 58-103311

 Disclosure of the invention

 Problems to be solved by the invention

[0008] The object of the present invention is to provide skin with less skin irritation than conventional transdermal absorption preparations. A percutaneous absorption preparation that has good wettability and familiarity to skin, has sufficient adhesive strength to the skin, can contain a sufficient amount of a physiologically active substance, and has a good release of the physiologically active substance. It is to provide. Another object of the present invention is to provide an adhesive sheet that reduces the amount of liquid components mixed, suppresses the blooming of organic liquid components, and reduces the skin irritation associated with peeling and exfoliation of the skin.

 Means for solving the problem

 As a result of intensive studies in view of such problems, the present invention has been completed. That is, the present invention is as follows.

 [1] In a skin patch having a pressure-sensitive adhesive composition layer formed on a support, the pressure-sensitive adhesive composition layer is made of a polyether polymer having a siloxane bond, A transdermally absorbable preparation, wherein at least one layer of the agent composition layer contains a physiologically active substance.

 [2] In a percutaneous absorption preparation having a pressure-sensitive adhesive composition layer formed on a support, the pressure-sensitive adhesive composition layer comprises

 (A) a polyether polymer having at least one alkenyl group at its end;

 (B) a compound having 10 to 10 hydrosilyl groups in the molecule;

 (C) Hydrosilylation catalyst

 A transdermally absorbable preparation characterized by curing a pressure-sensitive adhesive composition, and containing a physiologically active substance in at least one layer of the pressure-sensitive adhesive composition layer.

[0012] The skin-absorbing preparation according to [1] or [2], wherein the pressure-sensitive adhesive composition layer contains (D) an organic liquid component.

 [4] The transdermal absorption preparation according to any one of [1] to [3], wherein the pressure-sensitive adhesive composition layer contains a transdermal absorption enhancer.

 [5] The transdermally absorbable preparation according to any one of [1] to [4], wherein the polyether polymer of the polymer (A) is polyoxypropylene.

[0015] [6] The bioactive substance is dissolved in the polymer (A), mixed with the compound (B) and the catalyst (C), and then cured, [1] to [5] ] /, How to make any transdermal preparation.

[7] [7] After dissolving the physiologically active substance in the organic liquid component (D), the polymer (A) and the compound ( A method for producing a transdermally absorbable preparation according to any one of [3] to [5], which is obtained by mixing B) and catalyst (C) and curing the mixture.

[8] A pressure-sensitive adhesive sheet for skin application, wherein a pressure-sensitive adhesive composition layer is formed on a support, the pressure-sensitive adhesive composition layer comprising

 (A) a polyether polymer having at least one alkenyl group at its terminal

 (B) a compound having in the molecule;! -10 hydrosilyl groups

 (C) Hydrosilylation catalyst

 (D) Organic liquid component

 A pressure-sensitive adhesive sheet for application to the skin, which is obtained by curing a mixture of force.

[9] [9] In a pressure-sensitive adhesive sheet for skin application in which a pressure-sensitive adhesive composition layer is formed on a support, the total amount of hydroxyl groups of compound (B) is 1 mol of total alkenyl groups of polymer (A). [6] The pressure-sensitive adhesive sheet according to [8], characterized by having 0.4 to 4 moles of hydrosilyl group.

[10] The pressure-sensitive adhesive sheet according to [8] or [9], wherein the polyether polymer of the polymer (A) is polyoxypropylene.

[0020] [11] The hydrosilylation catalyst (C) is a platinum monobutylsiloxane complex

 [8] to [; 10]!

[0021] [12] The pressure-sensitive adhesive sheet according to any one of [8] to “; 11”, wherein the organic liquid component (D) is a fatty acid ester.

 [0022] [13] The content ratio of the polymer (A) and the organic liquid component (D) is 1.0: 0.001; 1.0: 1.5, [8] [; 12], the slippery adhesive sheet.

 The invention's effect

 [0023] According to the transdermally absorbable preparation and the pressure-sensitive adhesive sheet of the present invention, the skin irritation is small compared with the conventional ones, the wettability to the skin, the familiarity is good, and the adhesive strength is sufficient. Good long-term fixation to the skin. Further, according to the transdermally absorbable preparation of the present invention, a sufficient amount of a physiologically active substance can be contained, and good release properties can be obtained. BEST MODE FOR CARRYING OUT THE INVENTION

[0024] The present invention is described in detail below.

[0025] In the present invention, at least one pressure-sensitive adhesive composition layer is provided on a support. [0026] The support used in the transdermally absorbable preparation of the present invention is not particularly limited as long as it can hold the pressure-sensitive adhesive composition before being cured, but a physiologically active substance contained in the pressure-sensitive adhesive composition, etc. Is preferably lost from the back through the support and does not cause a decrease in content. Specifically, urethane polymers such as polyether urethane, amide polymers such as polyether amide, acrylic polymers such as polyacrylate, polyethylene, polypropylene, ethylene polymers such as olefin copolymer, Examples thereof include ester polymers such as ether polyester. In addition, fluorine-based polymers such as polytetrafluoroethylene, silicon-based polymers such as polydimethylsiloxane and polydiphenylsiloxane, finalenes such as polychlorinated butyl, polyvinylidene chloride, and polybutyl alcohol, or the above polymer materials Examples include foam sheets, non-woven fabrics, and metal foils.

 [0027] When the support is a single layer or a laminate including a plurality of layers, each layer may be made of the same material or different types of materials. For example, a non-woven fabric that has moisture permeability is preferably used. The thickness of the substrate is not particularly limited and can be appropriately selected depending on the purpose and application, and 10 to 5000 111 is exemplified. If the thickness of the support is greater than 5000 am, the followability to the skin is reduced and the skin becomes easy to peel off, which is not preferable because the physical irritation to the skin becomes stronger. The thickness of the support is as thin as 10 m! /, Which is preferable from the viewpoint of durability! /. From the viewpoint of irritation to the skin and durability, 10 to 2000 111 force << preferably, more preferably (between 10 and; 1000 m.

 [0028] The pressure-sensitive adhesive composition laminated on the support comprises (A) a polyether polymer having at least one alkenyl group at the terminal, (B) in the molecule;! -10 hydrosilyl groups. It is obtained by curing a pressure-sensitive adhesive composition comprising a compound having (C) a hydrosilylation catalyst.

[0029] The polymer (A) is a polyether polymer having at least one alkenyl group at the terminal. The alkenyl group is not particularly limited as long as it is a group containing a carbon-carbon double bond active for hydrosilylation reaction. The alkenyl group is preferably an aliphatic unsaturated hydrocarbon group having 2 to 20 carbon atoms, more preferably 2 to 6 carbon atoms (for example, a vinylol group, an arinole group, a methyl butyl group, a propenyl group, a butyr group). Group, pentyl group, hexenyl group, etc.), preferably a cyclic unsaturated carbon having 3 to 20 carbon atoms, more preferably 3 to 6 carbon atoms. Hydrogenated group (eg, cyclopropenyl group, cyclobutyl group, cyclopentyl group, cyclohexenyl group, etc.) Methacryl group and the like can be mentioned.

[0030] Preferable alkenyl groups include those represented by the following formulas (1) and (2) from the viewpoint of easy synthesis reaction. In the following formula, R ¹ and R ² are a hydrogen atom or a hydrocarbon group having 1 to 10 carbon atoms, preferably a hydrogen atom or a methyl group:

 H 0 = 0 (^)-(1)

HC (R ² ) = CH-(2).

 [0031] The polymer (A) has an average of at least 1, preferably 15, more preferably ;! to 3, more preferably 12 alkenyl groups in one molecule. Polymer (A) l If the average number of alkenyl groups in the molecule is less than 1, the curability is insufficient, and if the number of alkenyl groups in the molecule is too large, the network structure becomes dense. For this reason, the adhesive properties tend to deteriorate.

 [0032] As a typical example of the polyether polymer as the basic skeleton of the polymer (A), a general formula:

(One R ³ -O-)

The polyoxyalkylene type polymer which consists of a repeating unit represented by these is mentioned. Here, R ³ is a divalent alkylene group. The main chain of the preferred polymer (A) is polyoxypropylene (that is, the above R ³ — is —CH 2 CH ³ (CH 2) —) because of its adhesive properties, skin irritation and wettability to the skin. Moreover, it is preferable also from the point of workability | operativity on acquisition. The polyether polymer may be composed of one type of repeating unit or may be composed of a plurality of repeating units. The polyether polymer may be a linear polymer or a branched polymer.

 [0033] It is preferable that all of the polymer (A) other than the alkenyl group is composed of a polyether skeleton, but may contain other structural units. In that case, the total of the polyether skeletons in the polymer (A) is preferably 80% by weight or more, and more preferably 90% by weight or more.

[0034] The molecular weight of the polymer (A) (from a number average of 3000 50,000 is preferred <, 6000 is preferred over 50,000 000 <, 10000) because good adhesive properties with good workability at room temperature are obtained. —3 0000 force S Particularly preferred, when the number average molecular weight is less than 3000, the resulting cured product is brittle. Conversely, if the number average molecular weight exceeds 50,000, the viscosity tends to increase and workability tends to decrease. The molecular weight is a polystyrene-equivalent number average molecular weight measured by GPC. The bonding mode of the alkenyl group to the polyether polymer is not particularly limited, and examples thereof include a direct bond of an alkenyl group, an ether bond, an ester bond, a carbonate bond, a urethane bond, and a urea bond.

[0035] The production method of the polymer (A) is not particularly limited, and examples thereof include a method of introducing an alkenyl group after obtaining a polyether polymer. In this case, various known production methods can be applied to the polyether polymer, and a commercially available polyether polymer may be used. In addition, a method for introducing an alkenyl group into a polyether polymer is also known. For example, a monomer having an alkenyl group (eg, allylglycidyl ether) and a monomer for synthesizing a polyether polymer are used. A method of copolymerization or a functional group (eg, hydroxyl group, alkoxide group) is previously introduced into a desired portion (end of main chain, etc.)! Examples thereof include a method of reacting a compound having both a reactive functional group and an alkenyl group (eg, acrylic acid, methacrylic acid, butyl acetate, acrylic acid chloride, etc.).

The compound (B) is a compound having an average of two or more hydrosilyl groups in one molecule. A hydrosilyl group means a group having a Si—H bond. In the present invention, when two hydrogen atoms (H) are bonded to the same silicon atom (Si)! /, It is calculated as two hydrosilyl groups. The chemical structure of the compound (B) other than the hydrosilyl group is not particularly limited. The number average molecular weight of the compound (B) calculated from the SiH group value obtained by titration is preferably 400 to 3000, more preferably 500 to 1000. This is because if the number average molecular weight is too low, it tends to be difficult to obtain a cured product that easily volatilizes during heat-curing, and if it is too high, the curing rate tends to be slow.

[0037] The number of hydrosilyl groups contained in one molecule of the compound (B) is 1 to 10 and preferably 2 to 8. If the average number of hydrosilyl groups is 2 or more, a plurality of polymer (A) molecules can be cross-linked during curing, exhibiting a cohesive force preferable as a percutaneous absorption preparation, and affixed to the skin. When peeled off, adhesive residue or the like hardly occurs. However, if the number of hydrosilyl groups is too large, the cross-linking becomes too dense, resulting in a transdermal absorption preparation such as skin adhesive strength and tackiness. Kimono properties tend to decrease. The density of the cross-linking affects the density between the polymer parts as the main chain of the polymer (A), and also affects the moisture permeability of the entire transdermally absorbable preparation. Therefore, the number of hydrosilyl groups in compound (B) should be selected in consideration of the balance with adhesive properties. Compound (B) may be used alone or in combination of two or more.

 [0038] The compound (B) is preferably compatible with the polymer (A). From the viewpoint of easy availability of raw materials and compatibility with the polymer (A), examples of suitable compounds (B) include organohydrogensiloxanes modified with organic groups. A typical example of the organohydrogensiloxane is a compound represented by the following formula (3).

 [0039] [Chemical 1]

[0040] The value of a in the above formula (3) matches the number of hydrosilyl groups in the molecule. The value of a + b is not particularly limited but is preferably 2-50. R is a hydrocarbon group having 2 to 20 carbon atoms in the main chain. The compound of the above formula (3) can be obtained by modifying R of unmodified methylnodrosilicone and introducing R. Unmodified methylnodogen silicone corresponds to the compound in which R is all H in the above (3). “Silicon market prospect” published by CMC Co., Ltd. As described in "I", it is used as a raw material for various modified silicones. Organic compounds for the introduction of R include α-olefin, styrene, α-methylstyrene, allylalkyl ethereol, arinoleanoleno quinenole estenole, arino refeno enole ethenore, arino refino eno estenore. Etc. The number of hydrosilyl groups in the molecule after modification can be adjusted by the amount of the organic compound added for modification.

[0041] The ratio of the amount of the polymer (Α) to the compound (Β) in the pressure-sensitive adhesive composition for forming the pressure-sensitive adhesive composition layer is such that the compound ( Β) Expressed by the total amount of derived hydrosilyl groups. The total amount of alkenyl groups in the pressure-sensitive adhesive composition depends on the size of the total amount of hydrosilyl groups per mole. Considering the balance between imparting appropriate tackiness and reducing the adhesive residue, etc., the total amount of hydrosilyl groups per mol of alkenyl groups is preferably 0.;! To 5.0 mol, more preferably (It is mono 0.4-4.

[0042] The hydrosilylation catalyst that is the catalyst (C) is not particularly limited, and any catalyst that promotes the hydrosilylation reaction can be used. Specifically, chloroplatinic acid, platinum-vinylsiloxane complexes (for example, platinum-1,3, divinyl-1,1,3,3, -tetramethyldisiloxane complexes are platinum 1,3,5,7 tetravinyl 1 , 3, 5, 7 tetramethylcyclotetrasiloxane complexes), platinum-olefin complexes (e.g.

 Pt (ViMe SiOSiMe Vi), Pt [(MeViSiO)] (where x, y, and z are positive integers))

 2 2 4

 Etc. are exemplified. Among these, from the viewpoint of the activity of the catalyst, platinum 1,3-divinyl-1,1,2 which is more preferable than platinum bullysiloxane complex which is preferable platinum complex catalyst which does not contain a conjugate base of strong acid as a ligand. A 3, 3, —tetramethyldisiloxane complex or a white gold 1,3,5,7-tetravinyl-1,3,5,7-tetramethylcyclotetrasiloxane complex is particularly preferred.

The amount of the catalyst (C) is not particularly limited, but is preferably 10—sio— ¹ mol, more preferably 10—with respect to ¹ mol of the total amount of alkenyl groups of the polymer (A). ⁶ ~; a ^10-2 mol. Within the above range, it is easy to achieve an appropriate curing rate, stable curability, and necessary pot life.

 [0044] In the present invention, the organic liquid component (D) is preferably contained in the pressure-sensitive adhesive composition layer. Addition of organic liquid components reduces pain and skin irritation when peeling adhesive tape for skin application and transdermal absorption preparation from the skin surface, and improves diffusion of bioactive substances by plasticizing the adhesive. In some cases, it may contribute to improving the release of physiologically active substances on the skin surface.

 [0045] The organic liquid component used in the present invention is not particularly limited, but is preferably a component having compatibility with each component and capable of being uniformly dissolved and dispersed in the pressure-sensitive adhesive composition layer.

[0046] As such an organic liquid component, _a ) Polyhydric alcohols such as ethylene glycol, diethylene glycol, dipropylene glycol, propylene glycol, polyethylene glycol, polypropylene glycol, butanediol, triethylene glycol, glycerol;

 b) Oils such as olive oil, camellia oil, soybean oil, castor oil, lanolin;

 c) fatty acids such as oleic acid;

 d) Polyoxyethylene castor oil, polyoxyethylene hydrogenated castor oil, polyoxyethylene sorbitan monolaurate, polyoxyethylene sorbitan monopalmitate, polyoxypolyoxyethylene lauryl ether, polyoxyethylene laurate, sorbitan monooleate, sorbitan Liquid surfactants such as trioleate, sorbitan sesquioleate;

 e) Strength methyl pronate, methyl caprylate, methyl caprate, methyl laurate, methyl myristate, methyl stearate, methyl oleate, ethyl laurate, ethyl myristate, ethyl oleate, isopropyl myristate, palmitic Isopropyl acid, butyl noremitate, isostearyl laurate, isostearyl palmitate, octyl palmitate, octyl stearate, octyldodecyl myristate, isotridecyl myristate, diisopropyl adipate, octyl palmitate, octyl stearate , Other fatty acid esters such as decyl sebacate, caprylic glyceride, pelargonic glyceride, capric glyceride, triethyl taenoate, tributyl acetyl citrate; Hydrocarbons such as fins, squalene, squalene;

 g) Organic solvents such as ethanol, ethyl acetate, dimethyl sulfoxide, isosorbitol, dimethyldecyl sulfoxide, methyloctyl sulfoxide, dimethylformamide, dimethylacetamide, N-methinorepyrrolidone, dodecinorepyrrolidone;

 Etc. These organic liquid components can be used by mixing one or more kinds as required.

 [0047] Among the above organic liquid components, preferred! / Organic liquid components include fatty acid esters because of excellent diffusibility of physiologically active substances.

[0048] The content of these organic liquid components is not particularly limited. For example, a polymer (A ) For a weight of 1 is 0.001-1.5, preferably <is 0.001-1.0. When the content of the liquid component is outside this weight ratio, practical skin adhesion and low skin irritation cannot be obtained, and the release of the physiologically active substance is not sufficient.

 [0049] The percutaneous absorption enhancer used in the present invention improves the solubility of the physiologically active substance in the pressure-sensitive adhesive, or acts on the skin surface to cause keratin softening, keratin penetration, pore opening. By fulfilling functions such as porosity, the transdermal absorbability of physiologically active substances can be improved.

 [0050] The percutaneous absorption enhancer used in the present invention is not particularly limited, but is preferably one that can be uniformly dispersed in the pressure-sensitive adhesive layer. In addition, among the above organic liquid components, those that act as a transdermal absorption enhancer may be used alone or mixed with other transdermal absorption enhancers to exhibit both characteristics. Even if you use it, it ’s powerful and fun.

 [0051] Examples of such a transdermal absorption enhancer include, for example, monovalent or polyhydric alcohols, monovalent or divalent carboxylic acids, hydroxycarboxylic acids, esters, pyrrolidone derivatives, surfactants, Hydrocarbons, monocyclic monoterpenes, urea derivatives, specific compounds, etc. are used

Yes

 [0052] The monohydric alcohol is preferably an alcohol having 18 or less carbon atoms from the viewpoint of promoting transdermal absorption. For example, methyl alcohol, ethyl alcohol, n-propyl alcohol, isopropyl alcohol, n butyl alcohol, isobutyl alcohol, sec butyl alcohol, tert butyl alcohol, pentyl alcohol, hexyl alcohol, heptino rare alcohol, otachinole alcohol Nore, noninoreanoreconole, isononinoreanoreconole, laurinoreanoreconole, oleinoreanoreconole, cetinoreanoreconole.

 [0053] Examples of the polyhydric alcohol include ethylene glycol, diethylene glycol, dipropylene glycol, propylene glycol, polyethylene glycol, polypropylene glycol, butanediol, triethylene glycol, and glycerin.

[0054] The monovalent carboxylic acid is preferably a carboxylic acid having 20 or less carbon atoms from the viewpoint of promoting transdermal absorption. For example, strength purine acid, nonanoic acid, strength prillic acid, lauric acid, myristic acid, pentadecylic acid, palmitic acid, margaric acid, stearic acid, oleic acid, linoleic acid Aliphatic monocarboxylic acids such as formic acid and linolenic acid can be mentioned.

[0055] Examples of the divalent carboxylic acid include oxalic acid, malonic acid, succinic acid, dartaric acid, pimelic acid, suberic acid, adipic acid, sebacic acid, phthalic acid, isophthalic acid, terephthalic acid, and the like.

 [0056] Examples of the hydroxycarboxylic acid include malic acid and tartaric acid.

[0057] As the esters, esters composed of the monovalent and polyhydric alcohols and monovalent and divalent carboxylic acids or hydroxycarboxylic acids are preferably used. For example, methyl caprate, methyl nonanoate, methyl caprylate, methyl laurate, methyl myristate, methyl pentadecylate, methyl palmitate, methyl margarate, methyl stearate, methyl oleate, methyl linoleate, methyl linolenate , Ethyl caprylate, ethyl ethyl nonanoate, ethyl ethyl caprylate, ethyl laurate, ethyl ethyl myristate, pentaethyl ethyl oleate, ethyl ethyl palmitate, ethyl gallate, ethyl stearate, ethyl oleate, ethyl linoleate, linolenic acid Ethyl, propyl purinate, propyl nonanoate, propyl prillate, propyl laurate, propyl myristate, propyl pentadecylate, propyl palmitate, propyl margarate, propyl stearate, olein Propyl, propyl linoleate, propyl linolenate, isopropyl nonpurate, isopropyl nonanoate, isopropyl prillate, isopropyl laurate, isopropyl myristate, isopropyl pentadecylate, isopropyl palmitate, isopropyl margarate, isopropyl stearate, Isopropyl oleate, isopropyl linoleate, isopropyl linolenate, butyl caprate, butyl nonanoate, butyl caprylate, butyl laurate, butyl myristate, butyl pentadecylate, butyl palmitate, butyl margarate, butyl stearate, olein Acid butyl, butyl linoleate, butyl linolenate and the like.

[0058] Examples of the pyrrolidone derivatives include 1-dedecylazacycloheptane-2-one, 1-geranylazacycloheptane 2-one, 1-arnesylazacycloheptane 2-one 2 pyrrolidone, 1-methyl 2 Pyrrolidone, 5 Methyl 2 Pyrrolidone, 1,5 Methyl-2 Pyrrolidone, 1-Ethyl 2 Pyrrolidone, 2 Pyrrolidone 1-5 Carboxylic acid. [0059] As the above surfactant, a noionic surfactant, a cationic surfactant, a cationic surfactant, or an amphoteric surfactant is used.

 [0060] Examples of the nonionic surfactant include polyoxyethylene sorbitan monolaurate, polyoxyethylene sorbitan monopalmitate, sorbitan monolaurate, sorbitan alkyl esters such as sorbitan monopalmitate; polyoxyethylene lauryl ether nore, Poly oxyethylene hexenoredecinoleateolate, etc. Poly oxyethylene alcohol quinoleic tere; Fatty acid amides such as lauric acid diethanolamide, tetraoleic acid polyoxyethylene sorbite, polyoxyethylene fatty acid Examples thereof include amides and alkylaminoxides.

 [0061] Examples of the anionic surfactant include those having at least one of a carboxylic acid group, a sulfonic acid group, a sulfate ester group and a phosphate ester group in the molecule.

 [0062] Examples of those having a carboxylic acid group include, for example, fatty acid sarcophagus, ether carboxylic acid (salt), carboxylates such as condensates of amino acids and fatty acids, and the like; For example, alkyl sulfonate, sulfosuccinic acid, ester sulfonate, alkyl allyl and alkyl naphthalene sulfonate, N-acyl sulfonate, etc .; those having a sulfate ester group include, for example, sulfated oil, ester sulfate, ether Sulfates, alkylaryl ether sulfates, amide sulfates, etc .; those having a phosphate ester group include, for example, alkyl phosphates, amide phosphates, ether phosphates, alkyl phosphates, Each is listed.

 [0063] Examples of the cationic surfactant include fatty acid amines, alkyl quaternary ammonium salts, aromatic quaternary ammonium salts, pyridinium salts, imidazolium salts and the like.

[0064] Examples of the amphoteric surfactants include sulfobetaine, aminocarboxylate, imidazoline derivatives, etc., in addition to force lupoxybetaine such as lauryldimethylaminoacetic acid betaine.

 [0065] Examples of the hydrocarbon include liquid paraffin, squalane, squalene, and the like.

[0066] Examples of the monocyclic monoterpenes include P-menthane, limonene, α-terbinene, and terpino. Len 1-menthol, 1-strength nore-p-onole, α-terhineol 1-mentholone, d-carbon, cineol, and urea derivatives include urea, allantoin and the like.

[0067] Examples of the specific compound include panthenol, tocopherol, tocopheryl acetate, tocopheryl linoleate, crotamiton, pyrothiodecane, polybylpyrrolidone, and EDTA.

 [0068] One or more of these transdermal absorption enhancers can be mixed and used as necessary.

 Moreover, although it is preferable to use the said transdermal absorption promoter, use of a compound other than the above is not denied.

 [0069] The content of the percutaneous absorption enhancer is not particularly limited. For example, the content of the percutaneous absorption enhancer is 0.0001-1.5, preferably <is 0. 001-1. 0. If the content of the percutaneous absorption accelerator is outside this weight ratio, practical skin adhesion and low skin irritation may not be obtained, and the release of bioactive substances may not be achieved. But it may not be enough.

 [0070] The pressure-sensitive adhesive composition layer in the transdermally absorbable preparation and the adhesive sheet for skin application of the present invention is obtained by curing the above-mentioned pressure-sensitive adhesive composition. Here, curing refers to heating the pressure-sensitive adhesive composition mixed with the polymer material to cause the polymer (A) and the compound (B) to undergo a hydrosilylation reaction by heating. Examples of the curing condition include leaving it to stand at 40 to 180 ° C.-ei for 60 minutes. If you want to cure more completely, you can leave it at 40-80 ° C for several days.

 [0071] The viscosity upon curing is preferably 10-; lOOOPa's. This viscosity can be controlled by the ratio of the amounts of components (A) to (C) and the type and amount of storage stabilizer for compound (B) described above.

Yes

 [0072] The pressure-sensitive adhesive composition for forming the pressure-sensitive adhesive composition layer may contain components other than the above (A) to (D) and the percutaneous absorption enhancer. These components include tackifiers, storage stabilizers for compound (B), and other components.

[0073] Examples of the tackifier include phenol resin, modified phenol resin, terpene phenol resin, xylene phenol resin, cyclopentagen monophenol resin, xylene resin, petroleum resin, phenol-modified petroleum resin, rosin ester resin, low molecular weight polystyrene. Resin, terpene resin and the like. When these are used in order to improve the adhesive properties, they may be used alone or in combination of two or more. When these tackifiers are used, the amount used is preferably 10 to 100 parts by weight, more preferably 15 to 50 parts by weight with respect to 100 parts by weight of the total amount of the polymer (A) and the compound (B). Part. If the amount used is too large, the moisture permeability of the pressure-sensitive adhesive composition layer decreases, which is preferable! /.

[0074] Examples of the storage stabilizer for the compound (B) include compounds containing an aliphatic unsaturated bond, organophosphorus compounds, organosulfur compounds, nitrogen-containing compounds, tin compounds, and organic peroxides. The Specifically, 2-benzothiazolyl sulfide, benzothiazocarboxylate, 2,6 di-tert-butyl-4-methylphenol, butylhydroxyanisole, vitamin E, 2- (4-morphodinyldithio) benzothiazole, 3 Methylol 1-butene-3-ol, acetylenically unsaturated group-containing organosiloxane, acetylenic alcohol, 3 methyl-1-butyne 3 honore, 2 methyl-3-butyne 2 ol, gallinole fumarate, gallinole fumarate, jetino The power S that can include refumarate, jetinoremalate, dimethyl maleate, 2-pentenenitrile, 2,3 dichroic propene, etc. is not limited to these. Storage stabilizer suppresses conversion of hydrosilyl group (Si H group) to Si OH group in compound (B) (due to standing for a long time or mixing of moisture), improving the pot life of coating Can be made. The amount of storage stabilizer, relative to the total amount to 1 mol of the hydrosilyl group contained in the compound (B) and the adhesive composition due to compound (C), preferably from 10 ⁶ to; 10- ¹ mole is there.

 [0075] In addition, the pressure-sensitive adhesive composition for forming the pressure-sensitive adhesive composition layer includes a water-soluble organic polymer and a water-absorbent for improving the water resistance, sweat resistance, water absorption and the like of the pressure-sensitive adhesive composition layer. Polymers may be added, and other plasticizers, softeners, fillers, pigments, surfactants, ultraviolet absorbers, antioxidants, antibacterial agents, and the like may also be added. At this time, it is preferable not to use organic solvents, but it is not to deny their use!

 [0076] The physiologically active substance in the present invention is not particularly limited and can be used. Specific examples of the physiologically active substance include the following compounds.

[0077] 1. β-adrenergic agonists such as albuterol, bumpterol, vitorte Ronole, Carbuteronole, Clenbuteronole, Chlorprenalin, Denonomine, Dioxededrine, Dopexamine, Ephedrine, Epinephrine, Etafedrine, Ethylnorepinephrine, Fuenoteronole, Formoteronole, Hexoprenaline, Evotrenaline, Provoline Monore, Mabuteronorole, Metaproterenol, Methoxyphenamine, Oxipheudrin, Pinole Buteronorenore, Pre-Nanoterero Norre, Pro Power Teronol, Protokironole, Reproterol, Limitero Noreno, Litodolin, Soterenore, Terbuterol and Xamoterol

Yes

 [0078] 2. / 3—Adrenergic blocking agents such as acebutolol, alprenolol, ammos laronore, arochinoronore, atenololinore, befnoronore, betaxolonore, benontronore, bisoproronole, bopindronore, f, cumolono Behuetoronore, Fu, Furoronole, Pu, Nitroronore, Buplanolo Monore, Butidoline Hydrochloride, Butofiroro Norole, Carazolol, Force Noor Theoronole, Force Nole Bejiro Nore, Serif. Rollo Nore, Setamoronore, Chlorano Ronore, Gileno Ronore, Eno Rono Norole, Esmolono, Indeno Ronore, Labeta Ronore, Levov, Noro Nonore, Mepindronore, Metiplano Roole, Meproro Ronore, Mopro Rono Leo Oxyprenololeno, penbutronole, pindronore, practolo nore, pronetaro nore, propranolo nore, sotaronore, snorffinaronore, talino ronore, tenoreta ronore, timolo ronore, and triprolonore.

[0079] 3. Analgesics such as chlorobutanol; narcotic analgesics such as alfentanil, allylprozin, alphaprozin, anileridine, benzylmorphine, benzitolamide, buprenorphine, butorphanol, cloutazen, codine, methylcodine bromide, Codin phosphate, codin sulfate, desomorphin, dextromoramide, dezocine, dianpromide, dihydrocodine, dihydrocodine enol acetate, dihydromorphine, dimenoxadol, dimethylepheptanol, dimethylthianbutene, dioxaphethyl butyrate, dipipanone utazene , Fentanyl, hydrocodone, hydromorphone, hydroxypentidine, isomethadone, ketobemidone, levorfano monole, oral fentanyl, meperidine, meptazinol , Methazosin, methadone hydrochloride, methopone, morphine, morphine derivatives, milophine, nalbuphine, narcein, nicomorphine, norlevorfanonore, normethadone, normorphine, Norepipanone, opium, oxycodone, oxymorphone, papaveratum, pentazocine, phenadoxone, phenazosin, pheoperidine, pimidine, pyritramide, proheptazine, promedol, properidine, proviram, propoxyphene, sufentanil and thyridine, non-narcotic analgesics, For example, acetaminophen, acetylsalicylic salicylic acid and anolecrofenac.

 [0080] 4. Anti-anginal drugs, such as acebutolol, alprenolol, amaminodarone, amlodipine, alotinoronole, atenololenore, beprizinore, benotronolore, bukumoronore, buetoronore, pu, fulleronole, pu, nitroronole, , Pranolo nore, carozolo nore, canolete chin nore, force nore veiro ronore, seriprolonore, cineno zet maleate, dinorethiazem, enonolol, ferrodipine, galopamil, imolamine, indenolol, isosorbide ristromepine reprodine , Nadro Ichinole, Nikanorepine, 2 Fedipine, 2 Fenaronore, Ninorevadipine, Niplageronore, Disordipine, Nitroglycerin, Kishipurenororu, Okishifuedorin, Ozadareru, Bae Nbutororu, pentaerythritol tetranitrate, pindolol, pro neta roll, Puropurano Ronore, Sotaronore, terodiline, Chimoronore, Toripuroronore and Berano Minore.

 [0081] 5. Antiarrhythmic drugs, for example, acebutol, asecaine, adenosine, ajmarin, alpenolone, amiodarone, amoproxan, apuridine, arochinoronore, atenololone, bevantolol, bretyrimole tosylate, bubumolonore, bufetrolol, bunaphtholol, bunaphtholol , Butidoline hydrochloride, butobenzine, capobenic acid, carazolone, carteololole, cifenline, chloranolore, disopyramide, encainide, esmolol, flecainide, galopamil, hydroquinidine, indecainide, indenolol, ipirato bromide, cadmium bromine Metibra Noro-no-re, Mexiletine, Moricidin, Nadoxolonore, Niphenaro Norre, Oxipreno Monore, Pembutoro Norre, Pindronore, Pinole Menore, Practoronore, Pradimarin, Hydrochloric Pro-Inamide, Pronetalol, Propafenone, Propranolol, Pyrinoline, Quinidine Sulfate, Quinidine, Sotaronore, Talinoro Norre, More Minore, Biquizinore and Kisinololenore

6.Antidepressants: bicyclic systems such as vinedarin, caloxazone, citalopram, dimetazan, i Ndalpine, fencamine, indeloxazine hydrochloride, nefobum, nomifensine, oxytributane, oxypertin, paroxetine, sertraline, thiazesim, trazodone and zometapine; And phenelzine; pyrrolidone series such as cotinine, oral lysiprin and rolipram; tetracyclic systems such as maprotiline, metralindole, mianserin and oxaprotilin. Tricyclic systems such as azinazolam, amitoliptyline, amitriptyline, amoxapine, buttriptyline, clomipramine, dexipitrine, desipramine, dibenzepine, dimetracrine, docepine, doxepin, fluacidin, imipramine, imipramine N-oxide, iprin Oral fepramine, melitracene, metapramine, nonoretriptyline, noxiptylline, obipramol, pizotirin, puvisepine, protriptyline, quinupramine, tianeptine and trimipramine; and others such as adrafiel, benactidine, bupropion, butacetin, danol , Acedarmic acid deanol, acetoamide benzoic acid dianol, dioxadrole, etoperidone, pheno-remamate, Xetine, fenpentadionole, funole-aged xetine, fluvoxamine, hematoporphyrin, hypersinin, levofacetoperan, medifoxamine, minaprine, mokuguchibemid, oxafurozan, piberaline, prolintane, pyriscideanol, rubidium chloride, snolepiride , Snoretov. Lido, teniloxazine, tozalinone, tofenacin, troxatone, tranylcypromine, L-tryptophan, risperidone, viloxazine and dimenoresin.

 [0082] 7. Antiestrogens such as dermadinone acetate, ethamoxytriphetol, tamoxifen and toremifene.

[0083] 8. Anti-gonadotropins, such as danazol, gestrinone and paroxypropion.

[0084] 9. Antihypertensive agents: allylethanolamine derivatives, such as amothralol, bufura ronore, gireno ronore, labetaro nore, pronetaronore, sotaroronole and snorefinarol; allylooxypropanolamine derivatives such as acebutolol, alprenolol Nore, Arachino Ronore, Ateno Ro Nore, Betaxo Ronole, Benon Thoro Nore, Bisopro Roh Nore, Boppin Roh Nore, Pu, Nitro Ro Nore, Pu, Plano Roan Nore, Pu, Tofiro Ronore, Carazo Ronore, Canole Tesoro Lore, Power Nore Loro Nore, Seta Moronore, Eno Noro Nore, Nendoro Monore, Mepindronore, Metibranolo Norre, Metoprolonore, Moprolonore, Nadro Norole, Niprazinorole, Oxipreno Norenore, Penbutronole, Pindronore, Propranolo Nore, Talinolorenore, Timoro Dore Mouth flumethiazide benzthiazide, benzil hydrochrome thiazide, butiazide, black mouth thiazide, chlorthalidone, cyclopentia azide, cyclothiazide, diazoxide, epithiazide, ethiazide, fenquizone, hydrotarothiazide, hydroflumethiazide, methylcrothiazide, methiclan , Polythiazide, tetrachloromethiazide and N-carboxylalkyl (peptide / latatam) derivatives such as aracapril, captopril, cilazapril, delapril, enalapril, enalabril rat, fosinopril, lisinopril, mobiletipril, perindopril, quinapril and ramipril, eg dihydropyridine , Amlodipine, ferrodipine, isradipine, dicanorespine, diphedipine, dirubapine, disoldipine and nitrendipine; guanidine derivatives such as betazidine, debrisoquine, guanabens, guanacrine, guanadrel, guanazodine, guanfacine, guanfacine, guanfacine, Guanoxabenz and guanoxane; hydrazine and lid

Derivatives such as clodidine, lofexidine, phentolamine, thiamenidine and tronidine; quaternary ammonium compounds, azamethonium bromide, chlorisondamine chloride, hexamethonium, bis (methyl sulfate) pentacinium, pentamethonium bromide, Pentritium tartrate, phenactodium chloride and trimethydinum methosulfate; quinazoline derivatives such as alfuzosin, bunazosin, doxazosin, prazosin, terazosin and trimazosin; reserpine derivatives, vietaserpine, deservidin, resinpine, resorpine and cincin sulfonamide derivatives, e.g., ambuside, clopamide, furosemide, in Dapamido, quinethazone, tripamide and xipamide; and others such as, ajmaline, Amino butyric , Bufue two Ord, chlorthalidone, Shikuretain, ciclosidomine, tannin thunk Riputenamin, Fuenorudobamu, Furosekuinan, indoramin, ketanserin, Metobutameto, Mekaminoreamin, Mechirudono X methyl 4-pyridyl ketone Chio semicarbazide Luzon, Metra Zon, minoxidil, muzolimin, nordiline, penvidin, pinacidil, piperoxane, primaperone, protoberatrines, rubacin, recimethonole, rilmenidene, salalacin, ditroprusside sodium, ticrinaphene, trimetaphane, force mucillate, tyrosinase and Urapidil.

10. Anti-inflammatory (non-steroidal) agents: aminoaryl carboxylic acid derivatives such as fenfenamic acid, ethoenamate, flufenamic acid, isonyxin, meclofenamic acid, mefanamic acid, diflumic acid, tanolenifnoremate, telophenamate and tolfenam Acid; allylic acetic acid derivatives such as acemetacin, alclofenac, amphenac, bufae exac, synmethacin, clopilac, diclofenac sodium, etodolac, felubinac, fenclofenac, fenclolac, fenclozic acid, fenthiazac, gnorecamecin , Ibufenac, Indomethacin, Isofezolac, Isoxepak, Ronazolac, Methiazine acid, Oxamethasine, Progourmet Tacin, Sulindac, Tiarami Arleyl butyric acid derivatives such as bumadizone, butybufen, fenbufen and xembucin; allylcarboxylic acid derivatives such as cridanac, ketorolac and tinolidine; allylpropionic acid derivatives such as aluminoprofen, venoxy Saprofen, Bucloxylic acid, Canoleprofen, Fenoprofen, Funoloxaprofen, Flurbiprofen, Ibuprofen, Ibuproxam, Indoprofen, Ketoprofen, Loxoprofen, Miroprofen, Naproxen, Taixaprozin, Picoteprofen, Pirprofen, Pranoprofen , Protidic acid, suprofen and thiaprofenic acid; pyrazoles such as diphenamizole and epyrizole; pyrazolone , E.g., anozone, benzpiperilone, pheprazone, mofebutazone, morazon, gifted xifenbutazone, phenibutazone, pipebuzon, propifenazone, lamifenazone, sukibuzone, and thiazolinobutazone; salicylic acid derivatives, such as acetaminosalol, aspirin, Benolylate, bromosaligenin, acetinoresalitinoleic acid canolecium, difunolenisanol, ethersalate, fendosa, gentisic acid, glycol salicylate, imidazolic acid imidazole, acetyl salicylic acid ricin, mesalamine, salicylic acid morpholine, salicylic acid Acetyl salicylate phenyl, salicylic acid phenyl, salacetamide, salicylamine o acetic acid, salicyl sulfate, salsalate and Rufasalazine; thiazine carboxamides such as droxicam, isoxicam, piroxicam and tenoxicam; and others such as ε-acetamidocaproic acid, S-adenosylmethionine, 3-amino-1-hydroxybutyric acid, amixetrine, vendor Zac, benzydamine, bucolome, difenpyramide, ditazole, emorfazone, guajazulene, nabumetone, nimesulide, olgotin, oxaseprol, paradiline, perisoxal, pifoxime, proquazone, valdecoxib, ketorolata, proxazole and tenidap.

11. Antitumor agents: 2 Aminolevulinic acid and alkylating agents: alkyl sulfonates such as busulfan, improsulfan and piperosulfan; aziridines such as benzodeva, carboquan, meledepa and uredeno; ethyleneimine and methylmelamines such as , Altretamine, triethylenemelamine, triethylenephosphoramide, triethylenphosphoramide and trimethylolomelamine; nitrogen mustard systems such as chlorambucil, chlornafazine, cyclophosphamide, estramustine, ifosfamide, Mechlorethamine, mechlorethamine hydrochloride, melphalan, nobenbiquine, phenesterin, prednisotin, trophosphamide and uracil mustard; nitrosourea For example, force noremustine, chlorozotocin, hotemustine, mouth mucin, dimustine and ranimustine; and others, such as dacarbazine, mannomustine, mitopronithonole, mitractol and pipbloman; antibiotics such as aclacinomycin, actinomycin mycin Fl, anthromycin , Azaserine, bleomycin, cactinomycin, canolevicin, cardinophyrin, chromomycin, dactinomycin, daunorubicin, 6-diazo 5-norxoleucine, norleucine, doxorubicin, epilubicin, mitomycin, mycofenenorenoic acid, nogaramicin, olivomycin, Pepromycin, Pricamycin, Ponolephromycin, Puromycin, Streptonigrin, Streptozocin, Tubenoresidin, Ube Nimettas, Dinostatin and Zorubicin; Antimetabolites: Folic acid analogs such as denopterin, methotrexate, pteropterin and trimetrexate; Purine analogs such as fludarabine, 6-mercaptopurine, thiapurine and thiguanine; and pyrimidine analogs For example, ancitabine, azacitidine, 6-azauridine, carmofur, cytarabine, Enzymes such as L-asparaginase; and others such as acegraton, ansatalin, vestlabsyl, bisantrene, carpoplatin, cisplatin, dehofamide, demecholcine, diaziquan, erfornitine, ellipticum acetate, etoglucid, Etoposide, gallium isotate, hydroxyurea, interferon alpha, interferon / 3, interferon gamma, interleukin 2, lentinan, nidamine, mitguazone, mitoxantrone, mopidamomore, nitracrine, pentostatin, phenamet, pyranolevicin, pod Phyllic acid, 2-ethidrazide, procanolevateniposide, tenuazonic acid, triadic acid, 2,2 ', 2 "—trichlorotriethylamine, urethane, vinblastine, vincristine and Vindesine; antitumor (hormonal) agents: androgens, such as carsterone, drmostanolone propionate, epiciostanol, mepitiostan and test lactones; anti-adrenal systems, such as aminoglutethimide, mitotane and trilostane; E.g. flutamide and dilutamide; and antiestrogens such as tamoxifen and toremifene

 [0087] 12. Antiparkinson agents such as amantadine, benserazide, bietanautin, biperidene, bromocriptine, budipine, carbidono, deprenyl, dexetimide, dietadine, droxidopa, etopropazine, ethylbenzhydramine, lepodopa, naxagolide, Noregolide, pyroheptin, pridinol, prodipine, tenoledaride, tigloidin, and trihexyphenidyl hydrochloride.

[0088] 13. Antiprostatic hypertrophy agents, for example, guestnolone caproate, mepaltricin.

[0089] 14. Antipsychotics: butyrophenones, eg, benperidol, bromperidol, oral peridonole, funoreanisone, neuroperidonole, menoleperone, moperon, pinonperone, superon, timiperone and trifluperidol; phenothiazines For example, acetophenazine, butaperazine, force norefenadine, chronoreproetadine, chronorepromazine, crospydazine, methoxypromazine, metofenazet, oxaflumazine, perazine, pericazine, permethazine, penolefenadine, piperacetazine, pipothiazine, Perazine, promazine, sulforidazine, thiopropazate, thioridazine, trifluoperazine and triflupromazine; thioxanthene series such as chlorprothixene Kuropenchi Xanthore, funolepentixorole and thiothixene; other tricyclic systems such as benzquinamide, carpipramine, clocapramine, chromaclan, clothiapine, clozapine, obipramol, protipendil, tetrabenazine and zotepine; and others such as alizaprid, Ammisolepride, Bramate, Full Spirylene, Morindon, Penfunoreridorole, Pimo

 [0090] 15. Antispasmodic drugs such as alibendol, ambusetamide, aminopromazine, apoat mouthpin, methylbebonium sulfate, vietamiberin, butavelin, butohoutu bromide, N-butylscopolammonium bromide, caro Verin, symtropium bromide, cinnamedrine, talepopride, fluoric acid quine, hydrochloric acid quine, cycloiodide iodide, difumeline, diisopromine, dioxafethyl butyrate, diponium bromide, drofenine, bromide mepronium, ethaverin, fetalamine, fenalamide, Berin, fenpiplan, fenpiberin bromide, fentonium bromide, flavoxate, furopropion, darconic acid, guaiacamine, hydramidazine, himecromon, leiovirol, mebeberine, moxaverine, nafibe Phosphorus, Octamiramin, Octaverine, Pentapiperide, Phenamaside hydrochloride, Phloroglucinol, Pinaberium bromide, Piperylate, Pipoxolan hydrochloride, Pramiberin, Prifinium bromide, Oral peridine, Propinokun, Propiromazine, Prozapine, Racefamine, Rosivelin , Spas molytonol, styronium iodide, snoretroponium, chemonium iodide, thixium bromide, tiropramide, trevibutone, trichrominole, triphorium, trimebutine, N, N—1-trimethyl 3,3-diphenylpropylamine , Tropendil, trospium chloride and nitropium bromide.

[0091] 16. Anti-anxiety drugs: arylpiperazines such as buspirone, gepirone and ipsapirone; benzodiazepine derivatives such as alprazolam, bromazepam, force mazepam, clonoresidazepoxide, clobazam, chlorazepate, cothiazebam, cloxazolam , Diazenome, ethinole oral frazepate, etizolam, funoreidazepam, funoretazolam, funoretopram zepam, halazebam, ketazolam, lorazepam, loxapine, medazepam, metaclazebam, mexazolam, zezepamopam, zezepamopam, zezepamopam For example, cyclalbamate, emyl strength, hydroxyphenamate, meprobamate, fenprobamate and cibamate; and others If, Alpidene, benzocamine, captodiamine, chlormezzanone, etifoxin, fluoresson, glutamic acid, hydroxyzine, mechloralurea, mefenoxalone, oxanamide, phenaglycol, and slyclone.

 [0092] 17. Calcium regulators such as calciphediol, calcitonin, calcitrione, clodronic acid, dihydrotaxosterol, elcatonin, etidronic acid, ipriflavone

, Pamidronic acid, parathyroid hormone and teriparatide acetate.

 [0093] 18. Cardiotonic agents such as acephylline, acetyl digititoxin, 2-amino-4-picoline, anrinone, benfurosyl semisuccinate, bucladecin, selvage mouth, camphoramide, conbalatoxin, simarin, denopamine , Deslanoside, ditalin, digitalis, digitoxin, digoxin, dobutamine, dopamine, dopexamine, enoximone, erythrofrein, phenalkamine, guitarine, gitoxin, glycosamine, heptaminol, hydrastinine, ibopamine, lantodinoline, lantodisino, rietholine Vine, Oxifedrine, Prenalterol, Prosilaridin, Reciprochogenin, Silarene, Silarenin, Stroke Fantin, Sulmazonole, Theobromine and Samoteroru.

 [0094] 19. Chelating agents such as defelodimine, dithiocarb sodium, calcium sodium edetate, disodium edetate, sodium edetate, trisodium edetate, penicillamine, trisodium calcium pentenoate, pentectic acid , Sushi mail and trientin.

 [0095] 20. Dopamine receptor agonists such as bromocriptine, dopexamine, fenoldopam, ibopamine, lisuride, naxagolide and pergolide.

[0096] 21. Enzyme inducer (liver), for example, flumesinol.

[0097] 22. Estrogens: Non-steroidal estrogens such as benzestrone, bropalo estrone, chlorotrianicene, genestrone, getinorestino lestrone, dipropionate getinorestino lestrone, dimestrone, phosfe Stranole, hexestroleol, metallestritol and metestrone, and steroidal estrogens such as colpolmon, conjugated estrogen hormone, ethylenin, equilin, estradiol, estradiol benzoate, 17 / 3-estradiol cypionate, estrio 1 Norest Estrone, Ettinorest Radio 1 Norst, Mestranol, Mexestrone, Mitatorie Diol, clobetasone butyrate, quinestradiol and quinestrol.

[0098] 23. Darcocorticoids, such as 21-acetoxyprefunenolone, alclomethasone, algestone, amicinonide, beclomethasone, betamethasone, budesonide, chloroprednisone, clobetasole, pu, oral betazone, croconoletron, Cloprednenole, Conoleticosterone, Cortisone, Cortivazole, Deflazacort, Desonide, Desoxymethazone, Dexamethasone, Diflorazone, Diflucortron, Diflupredonate, Enoxolone, Fluazaconoleto, Fluchlorosonide, Flumethonolide, Flunosolito Nido, fluocortin butyl, fluoreoconoretron, fluorometron, fluperolone acetate, fluprednidene acetate, fluprednisolone, fluland lenoli , Formocortal, no, noresinonide, halomethasone, halopredone acetate, hydrocortamate, hydrocortisone, hydroconorethone acetate, hydroconorethone phosphate, 21-hydroconorethone sodium succinate, hydrocortisone tebutate, madridone, medridone, meso Prednisone, methionol prednisolone, mometasone furoate, parameterzone, prednisocarbate, prednisolone, prednisolone 21-deethylaminoacetate, sodium prednisolone phosphate, prednisolone sodium succinate, prednisolone sodium 21-m-sulfobenzoate, 21-stearoyl gnolecolate prednisolone, tebutonic acid prednisolone, 21-trimethylacetate prednisolone, prednisone, prednival, predonidene, 21 Jechiruamino acetate Puredoniri Den, thixotropic Col tar, Torianshinoron, tri Ann Shino Ron § Seto acetonide, to Torianshinoron Benetonido and Torianshinoron Kisasetonido.

[0099] 24. Mineralcorticoids such as aldosterone, deoxycorticosterone, deoxycorticosterone acetate, and flucortisone.

[0100] 25. Monoamine oxidase inhibitors such as deprenyl, iproclozide, ipronid azide, isocarboxazide, mokuguchibemid, octomoxine, noregilin, phenelzine, phenoxypropazine, bivalylbenzhydrazine, prodipine, Troxaton and tranylcypromine.

[0101] 26. Muscle relaxants (skeletal), such as afroqualone, alchlorium, atracacrylic besylate, noclofen, benzocamine, benzoquinone chloride, C-carepsin, calisop oral doll, chlormezanone, strength Chlorphenesin rubamate, chlorproetadine, clozo Oxazone, clare, cyclalbamate, cyclobenzaprine, dantrolene, decamethonium bromide, diazepam, eperisone, fazadinium bromide, flumetramide, triethogallium iodide, hexacarbaline bromide, hexafluorenium bromide, idrosilamide, Methyl lauexium, leptodactylin, memantine, mefenesin, mefenoxalone, methaxalone, metcarbamol, methocrine iodide, dimetazebum, orphenadrine, punk ronumum bromide, fenprobamate, phenylamidole, pipetarium bromide , Promoxolan, sulphonate, styramate, succinylcholine bromide, succinylcholine chloride, succinylcholine iodide, sukisetonium bromide, tetrazebam, thiocorkicoside, tizanidine, Luperisone, popocurarine chloride, beclodium bromide, pridinol mesylate and zoxolamine.

[0102] 27. Narcotic antagonists such as amifenazole, cyclazocine, levalorphan, nazide, nalmuphen, nalorphine, narolphine dinicotinate, naloxone and naltrexone.

 [0103] 28. Progestogens such as, for example, arlinolestrenole, anastrone, chlormadinone acetate, dermadinone acetate, demegestone, desogestrel, dimethisterone, diddrogesterone, ethisterone, ethinodiol, full mouth gestone, guest den, caproic acid Guest Nolone, haloprogesterone, 17 hydroxy 16 methylene progesterone, 17 α-hydroxyprogesterone, caproic acid 17 α hydroxygesterone, linestrenol, medlogestone, medroxyprogesterone, megestrol acetate, melengestrol, noregetindrone, Norethinodrel, Norgesterone, Norgestimate, Norgestrel, Noregestrienone, Norevinisterone, Pentagestrone, Progesterone, Promeg Ton,

[0104] 29. Vasodilators (coronary arteries), such as amotrifen, bendazole, hemisuccinate benflozinore, benziodalone, cloacidin, chromonaninole, clobenflownore, clonitolate, dirazep, dipyridamonore, dropreniramine, efritoxone, erythritol Erythritinole tetrasuccinate, etafenone, fendiline, florezinole, gangleven, hexestrol bis (/ 3-jetylaminoethyl ether), hexobenzine, itramin tosylate, kellin, ridofurazine, mannitol hexanitrate, medibazine, nicorandil, Nitroglycerin, tetralithic oxalate pentauri linole, pen line linole, penole hexillin, pimefilin, pre Reniramine, propatyl nitrate, pyridophylline, travidyl, trichromyl, trimetazidine, trolnitrate phosphate and bisnadine and peripheral vasodilators, such as aluminum nicotinate, nomethane, bencyclane, betahistine, bradykinin, brovincamine, buhonide, buflumedinore , Butalamine, sechezinole, cyclonicate, cinepazide, cinnarizine, cyclandrate, diisopropylamine dichloroacetate, eledoisin, phenoxydil, flunaricin, heronicate, yfenprodil, inositol niacinate, isixispurine, kallidin, kallikrein, moxycilite , Nicergoline, nicofuranose, nicotinino reanoreconole, dilidrin, pentifylline Pentoxifylline, Piribe Jill, pro Tag orchid gin El, Surokuchijiru and Naiashin acid Kisanchinaru.

[0105] 30. Benzodiazepine antagonists, such as flumazenil.

 [0106] 31. Bronchodilators: Ephedrine derivatives, such as albuterol, bumpterol, vitonoletero nore, canolebutero nore, clenbuteronole, clonoleprenalin, dioxededrine, ephedrine, epinifrin, eprodinole, etafedrin, etyl Pinephrine, fenoterone, hexoprenalin, isoetarine, isoproterenol, mabuteronorenore, metaproterenorole, N-methylephedrine, pyrbuteronole, protellonore, protokironole, lef. Oral terror, limiterenore, soterenore, tenolef, 'talin and llop' terol; quaternary ammonium compounds such as methylbebonium sulphate, kurt mouth pium bromide, iprato mouth pium bromide and oxytropium bromide; Xanthine derivatives such as acephylline, acefiline piperazine, ambuphylline, aminophylline, nomiphylline, corinte offylinate, doxophilin, daphylline, enprofylline, etamifilin, ethophylline, guaytylin, proxyphylline, theobromine acetic acid and theobromine acetic acid and theobromine acetic acid; And others, such as fence pyrido, medivadin, methoxyphenamine and tretoquinol.

 [0107] 32. Other incontinence treatments such as oxiputinine, osteoporosis treatments such as risedronate, antihistamine treatments such as ketofetin acetate, diabetes treatments such as tolptamide, and ventilation treatments such as colchicine.

 [0108] These may be used in combination of two or more as required.

[0109] If there is at least one pressure-sensitive adhesive composition layer containing these physiologically active substances, plural You can also stack the adhesive composition layer!

 [0110] The method for mixing these physiologically active substances into the pressure-sensitive adhesive composition is not particularly limited, but usually the physiologically active substance is dissolved in the polymer (A) and then mixed with the compound (B) and the catalyst (C). However, in order to further improve the solubility of the physiologically active substance, the polymer (A) and the compound (A) and the compound (A) are dissolved after the physiologically active substance is dissolved in the organic liquid component. B) and the catalyst (C) are more preferred to be produced by mixing and curing this! /.

 [0111] The method of laminating the pressure-sensitive adhesive composition layer on the support is not particularly limited. For example, a method in which the pressure-sensitive adhesive composition is applied to one surface of the support and then cured under the above conditions, An example is a method in which the support is bonded after the adhesive composition is coated on a sheet (release sheet) previously provided with a release agent and cured. Various release agents such as silicones, olefins, and fluorines are known as release agents, and can be used appropriately. Of these, olefin-based and solvent-free addition-curable silicone-based release agents are preferred from the standpoints of cost and ensuring releasability.

 [0112] The thickness of the pressure-sensitive adhesive composition layer is not particularly limited, and may be, for example, 10 to 5000 Hm.

 Example

 [0113] Hereinafter, the present invention will be described more specifically with reference to examples. However, the present invention is not limited thereto, and various applications can be made without departing from the technical idea of the present invention. Is possible.

 [0114] (Synthesis of polymer (A))

 An oxypropylene polymer glycol having a number average molecular weight of 3000 was obtained by a polymerization method using caustic alkali. In accordance with the method of Synthesis Example 1 of JP-A-5-117521, propylene oxide was prepared using a double metal cyanide complex catalyst (zinc hexanocobaltate) using the oxypropylene polymer glycol as an initiator. Polymerization was performed to obtain a polymer having a number average molecular weight of 28000. This polymer is converted into a allyl group using 28% methanol solution of sodium methylate and allylic chloride, and then desalted and purified to have approximately two allylic terminus in one molecule. A polyoxyalkylene polymer (polymer (A)) was obtained. The amount of the aryl terminal group of the obtained polymer was 0.12 mmol / g.

[0115] (Synthesis of Compound (B)) In the presence of a platinum catalyst, 0.6 equivalent of α-methylstyrene of the total amount of hydrosilyl groups is added to a methylnodogen silicone represented by the following formula (4) (wherein X is an average of 5), A compound (compound (Β)) having an average of 2.5 hydrosilyl groups in one molecule was obtained. The hydrosilyl group content of this compound was 3.2 mmol / g.

 [0116] [Chemical 2]

[0117] (Example 1)

Polymer (A) 100 parts by weight of compound (B) 2.3 parts by weight and 0.03 parts by weight of ubiquinone (ubidecarenone) as a physiologically active substance are added to platinum 1, 3— Divinyl-1,1,3,3-tetramethyldisiloxane complex (3 wt% platinum isopropanol solution) 0.1 part by weight and 0.03 part by weight of dimethyl maleate were mixed thoroughly to obtain an adhesive composition It was. This pressure-sensitive adhesive composition was applied to a treated surface of a release paper that had been subjected to silicone release treatment at room temperature so that the thickness after curing was 50 m, and cured at 130 ° C for 3 minutes to adhere. An agent layer was formed. Next, on the cured adhesive layer, a moisture-permeable polyurethane sheet (DSU—214—CDB, SO ^ m) (basis weight: 35 g / m ² ) manufactured by Seadam Co., Ltd. (basis weight: 35 g / m ² ) as a support is 5 kg / cm. ^2. Lamination was performed at a speed of 2 m / min. In this way, a transdermal absorption preparation was prepared.

 [0118] (Comparative Example 1)

100 parts by weight of an acrylic copolymer obtained by copolymerizing 65 parts by weight of 2-ethylhexyl acrylate, 30 parts by weight of 2-methoxyethyl acrylate, and 5 parts by weight of acrylic acid was dissolved in 200 parts by weight of toluene. A uniform pressure-sensitive adhesive solution was prepared. This solution was mixed so that 0.03 part by weight of ubiquinone per 100 parts by weight of the acrylic copolymer was applied to the release sheet after the release treatment so that the thickness after drying was 50 m. 110 ° C for 3 minutes After drying, the product was transferred to a moisture-permeable polyurethane sheet (same as in the above example) as a support to obtain a percutaneous absorption preparation.

 [0119] (Comparative Example 2)

 4 parts by weight of stearyl alcohol, 8 parts by weight of oleic acid, 6 parts by weight of octyl stearate, 2 parts by weight of sorbitan monooleate, 5 parts by weight of propylene glycol, 0.2 part by weight of benzoic acid, 0.4 part by weight of potassium hydroxide, 70.4 parts by weight of purified water was added to 0.03 parts by weight of ubiquinone and stirred with a homogenizer to obtain an O / W type cream.

 [0120] Example 1 and Comparative Examples 1 and 2 were affixed to the skin of the hands of three volunteers and reapplied or smeared every 24 hours. Table 1 shows the results of observing these conditions.

 [0121] (Evaluation of wrinkle improvement)

 Evaluation criteria: ○: The wrinkles are visually improved before and after application.

 [0122] △: The wrinkles were slightly improved visually before and after application.

 [0123] X: There is no change in the wrinkles before and after application.

 [0124] (Skin irritation)

 A transdermal absorption preparation cut to a width of 20 mm was affixed to the back of a volunteer, and a lkg-weight roller was reciprocated once and pressed. After 6 hours, the percutaneously absorbable preparation was peeled off, and the exfoliated percutaneously absorbable preparation was used to measure the amount of exfoliated corneum. In other words, the skin exfoliated from the volunteer's back is immersed in keratin staining solution (Gentian Violetl%, Brilliant GreenO. 5%, distilled water 98.5%) manufactured by Wako Pure Chemical Industries, Ltd. for about 30 minutes to stain skin keratin. I did. Thereafter, the sample was thoroughly washed with distilled water and then dried for 24 hours. The pressure-sensitive adhesive layer surface of the sample after drying was observed using a microscope, image analysis was performed, and the keratin exfoliation area ratio was obtained.

 [0125] [Table 1] Evaluation of wrinkle improvement Skin irritation (%)

Polantia A Β c ABC Example 1 O ○ △ 5 8 7 Comparative Example 1 Δ to XX Δ to 55 45 50 Comparative Example 2 XXX--- [0126] From the above results, the present invention can contain a sufficient amount of a physiologically active substance that is less irritating to the skin than conventional adhesives and creams, and is capable of releasing the physiologically active substance. It is clear to provide a good transdermal absorption formulation.

 [0127] (Example 2)

2.3 parts by weight of compound (B) per 100 parts by weight of polymer (A) platinum 1,3-divinyl-1,1,3,3-tetramethyldisiloxane complex (3 parts by weight) as a hydrosilylation catalyst _^0/0 platinum isopropanol solution) 0.1 part by weight, to give dimethyl 0.03 parts by weight of maleic acid, myristyl phosphate isopropyl 30 parts by weight, the estradiol 1 part by weight were mixed thoroughly adhesive composition. This pressure-sensitive adhesive composition was applied on a polyester film (thickness 25 m) so that the thickness after curing was 50 inches, and then heated at 130 ° C for 5 minutes to obtain the transdermal absorption preparation of the present invention. It was.

 [Example 3]

Polymer (A) 4.2 parts by weight of compound (B) per 100 parts by weight of platinum 1,3-divinyl-1,1,3,3-tetramethyldisiloxane complex (3 parts by weight) as a hydrosilylation catalyst _^0/0 platinum isopropanol solution) 0.1 part by weight, to give dimethyl 0.03 parts by weight of maleic acid, myristyl phosphate isopropyl 30 parts by weight, the estradiol 1 part by weight were mixed thoroughly adhesive composition. This pressure-sensitive adhesive composition was applied on a polyester film (thickness 25 m) so that the thickness after curing was 50 inches, and then heated at 130 ° C for 5 minutes to obtain the transdermal absorption preparation of the present invention. It was.

 [Example 4]

 10.7 parts by weight of the compound (B) per 100 parts by weight of the polymer (A), platinum 1,3-divinyl-1,1,3,3-tetramethyldisiloxane complex (3 parts by weight) as a hydrosilylation catalyst % Platinum isopropanol solution) 0.1 parts by weight, 0.03 parts by weight of dimethyl maleate, 30 parts by weight of isopropyl myristate, and 1 part by weight of estradiol were sufficiently mixed to obtain a pressure-sensitive adhesive composition. This pressure-sensitive adhesive composition was applied on a polyester film (thickness 25 m) so that the thickness after curing was 50 inches, and then heated at 130 ° C for 5 minutes to obtain the transdermal absorption preparation of the present invention. It was.

[0130] (Example 5) 10.7 parts by weight of the compound (B) per 100 parts by weight of the polymer (A), platinum 1,3-divinyl-1,1,3,3-tetramethyldisiloxane complex (3 parts by weight) as a hydrosilylation catalyst % Platinum isopropanol solution) 0.1 part by weight, 0.03 part by weight of dimethyl maleate and 1 part by weight of estradiol were sufficiently mixed to obtain an adhesive composition. This pressure-sensitive adhesive composition was applied on a polyester film (thickness 25 μm) so that the thickness after curing was 50 μm, and then heated at 130 ° C. for 5 minutes to obtain the transdermally absorbable preparation of the present invention. Obtained. Table 2 shows the results of adhesion tests on the examples and comparative examples.

 [0131] (Adhesion test)

 Each strip-shaped preparation sample cut to a width of 25 mm was affixed to a SUS304 plate, and a rubber roller weighing 2 kg was brought into close contact by reciprocating at a speed of 2 m / min, and then left for 1 hour. The adhesive strength was measured by peeling the tape at a 180 ° angle at a speed of 300 mm / min.

 [0132] [Table 2]

[0133] From the above results, the present invention can contain a sufficient amount of a physiologically active substance, and the adhesive strength is controlled by adding an organic liquid component, resulting in low skin irritation! /, An adhesive sheet It is clear that it provides.

 [Example 6]

2.3 parts by weight of compound (B) per 100 parts by weight of polymer (A) platinum 1,3-divinyl-1,1,3,3-tetramethyldisiloxane complex (3 parts by weight) as a hydrosilylation catalyst _^0/0 platinum isopropanol solution) 0.1 part by weight, dimethyl 0.03 parts by weight of maleic acid, Tetorao maleic acid polyoxyethylene sorbit 20 parts by weight, in addition to so that such the estradiol 2.5 weight _^0/0, sufficient To obtain a pressure-sensitive adhesive composition. This pressure-sensitive adhesive composition was applied onto a polyester film (thickness 25 μm) so that the thickness after curing was 50 μm, and then heated at 130 ° C. for 5 minutes to obtain the transdermally absorbable preparation of the present invention. It was. [Example 7]

2.3 parts by weight of compound (B) per 100 parts by weight of polymer (A) platinum 1,3-divinyl-1,1,3,3-tetramethyldisiloxane complex (3 parts by weight) as a hydrosilylation catalyst _^0/0 platinum isopropanol solution) 0.1 part by weight, dimethyl 0.03 parts by weight of maleic acid, in addition to estradiol is 2. becomes 5 wt%, to obtain a pressure-sensitive adhesive composition was mixed thoroughly. The pressure-sensitive adhesive composition was applied onto a polyester film (thickness 25, 1 m) so that the thickness after curing was 50, 1 m, and then heated at 130 ° C for 5 minutes to obtain the transdermal absorption preparation of the present invention. Got. Table 3 shows the results of a bioactive substance release test for each of the resulting preparations.

 [0136] (Bioactive substance release test)

 The release test was performed using a Franz diffusion cell. As a permeable membrane, a 25111-thick urethane film cut into a circle having a diameter of 3 cm was used, and a 50% ethanol solution was used as a reservoir solution. The sample was cut into a circle with a diameter of 1 cm and used. Using a Franz diffusion cell, the concentration of the physiologically active substance released from the sample into the reservoir solution was quantified by liquid chromatography. The results are shown in Table 3.

 [0137] [Table 3]

[0138] From the above results, the present invention can provide a transdermal absorption preparation having a release characteristic of a physiologically active substance and further having excellent release characteristics by using a transdermal absorption enhancer. Clear power.

 [Example 8]

2.3 parts by weight of compound (B) per 100 parts by weight of polymer (A) platinum 1,3-divinyl-1,1,3,3-tetramethyldisiloxane complex (3 parts by weight) as a hydrosilylation catalyst _^0/0 platinum isopropanol solution) 0.1 part by weight, with respect to dimethyl maleate 0.03 parts by weight, a full Noreno Levi fenoprofen, added Caro as content is 2-5 wt% with respect to the pressure-sensitive adhesive composition Shi Then, it was sufficiently mixed to obtain a pressure-sensitive adhesive composition. This pressure-sensitive adhesive composition was applied onto a polyester film (thickness 25, 1 m) so that the thickness after curing was 50, 1 m, and then heated at 130 ° C for 5 minutes to obtain the transdermal structure of the present invention. An absorption formulation was obtained.

 [0140] (Example 9)

2.3 parts by weight of compound (B) per 100 parts by weight of polymer (A) platinum 1,3-divinyl-1,1,3,3-tetramethyldisiloxane complex (3 parts by weight) as a hydrosilylation catalyst _^0/0 platinum isopropanol solution) 0.1 part by weight, dimethyl 0.03 parts by weight of maleic acid, to myristyl phosphate isopropyl 30 parts by weight, the amount of content for the pressure-sensitive adhesive composition is 2.5 wt% and Do that amount of Flurbiprofen was made into the above-mentioned isopropyl myristate solution, and then thoroughly mixed to obtain a pressure-sensitive adhesive composition. This pressure-sensitive adhesive composition was applied on a polyester film (thickness 25, 1 m) so that the thickness after curing was 50, 1 m, and then heated at 130 ° C for 5 minutes to obtain the transdermally absorbable preparation of the present invention. Got.

 [0141] (Example 10)

2.3 parts by weight of compound (B) per 100 parts by weight of polymer (A) platinum 1,3-divinyl-1,1,3,3-tetramethyldisiloxane complex (3 parts by weight) as a hydrosilylation catalyst _^0/0 platinum isopropanol solution) 0.1 part by weight, dimethyl 0.03 parts by weight of maleic acid, to Tetorao maleic acid polyoxyethylene sorbit 20 parts by weight, flurbiprofen, content for the pressure-sensitive adhesive composition 2 After adding 5% by weight, the mixture was mixed well to obtain an adhesive composition. This pressure-sensitive adhesive composition was applied on a polyester film (thickness 25 m) so that the thickness after curing was 50 m, and then heated at 130 ° C. for 5 minutes to obtain the skin-absorbing preparation of the present invention. .

 [0142] (Example 11)

2.3 parts by weight of compound (B) per 100 parts by weight of polymer (A) platinum 1,3-divinyl-1,1,3,3-tetramethyldisiloxane complex (3 parts by weight) as a hydrosilylation catalyst _^0/0 platinum isopropanol solution) 0.1 part by weight, with respect to dimethyl maleate 0.03 parts by weight, the Ke Topurofen, after the amount of contained for pressure-sensitive adhesive composition was added to a 0% 5. sufficiently To obtain a pressure-sensitive adhesive composition. After applying this pressure-sensitive adhesive composition on a polyester film (thickness 25, 1 m) so that the thickness after curing is 50, 1 m, it is at 130 ° C for 5 minutes. Heated to obtain a transdermally absorbable preparation of the present invention.

 [0143] (Comparative Example 3)

 DURO- TAK387- 2052 (acrylic adhesive, manufactured by NSC) After adding 100 parts by weight of fluorenorebiprofen so that the content of the adhesive composition is 2.5% by weight And sufficiently mixed to obtain a pressure-sensitive adhesive composition. This pressure-sensitive adhesive composition was applied on a polyester film (thickness 25, 1 m) to a thickness of 50, 1 m, and then heated at 130 ° C for 5 minutes to obtain a transdermal absorption preparation.

 [0144] (Comparative Example 4)

 MD7-4502 (silicone adhesive, manufactured by Toray Dow Cowing Silicone) 100 parts by weight Flurbiprofen was added so that the content of the adhesive composition was 2.5% by weight. Adhesive composition was obtained by mixing thoroughly. This pressure-sensitive adhesive composition was applied on a polyester film (thickness 25 Hm) to a thickness of 50 Hm and then heated at 130 ° C for 5 minutes. Flurbiprofen precipitated in a crystalline state. A uniform formulation could not be obtained.

 [0145] (Comparative Example 5)

 DURO- TAK387- 2052 (acrylic adhesive, manufactured by NSC) To 100 parts by weight, ketoprofen was added so that the content of the adhesive composition was 5.0% by weight, and then mixed well. Thus, a pressure-sensitive adhesive composition was obtained. This pressure-sensitive adhesive composition was applied on a polyester film (thickness 25 m) to a thickness of 50 m, and then heated at 130 ° C. for 5 minutes to obtain a skin-absorbing preparation.

 [0146] (Comparative Example 6)

 MD7-4502 (silicone adhesive, manufactured by Toray Dow Cowing Silicone Co., Ltd.) To 100 parts by weight, ketoprofen was added so that the content of the adhesive composition was 5.0% by weight, and then mixed thoroughly Thus, a pressure-sensitive adhesive composition was obtained. After applying this pressure-sensitive adhesive composition on a polyester film (thickness 25 Hm) to a thickness of 50 Hm, the force heated at 130 ° C for 5 minutes caused flurbiprofen to precipitate in the crystalline state. A uniform formulation could not be obtained.

[0147] (Judgment of solubility of physiologically active substance) The percutaneously absorbable preparations obtained in Examples 8 to 11 and Comparative Examples 3 to 6 were visually determined as follows.

[0148] ○: The physiologically active substance is uniformly dispersed.

[0149] Δ: The physiologically active substance is uniformly dispersed but is opaque.

[0150] X: The dispersion of the physiologically active substance is poor and uneven.

[0151] (Bioactive substance release test)

 The above method was used.

[0152] (Adhesion test)

 The above method was used.

[0153] (Skin irritation)

 Each band-shaped preparation sample cut to a width of 5 mm was affixed to the skin, and a rubber roller having a weight of 2 kg was brought into close contact by reciprocating at a speed of 2 m / min, and then left for 72 hours. Each tape was peeled from the skin at a speed of 300 mm / min at an angle of 180 °, and then the condition of the skin was observed and evaluated as follows.

[0154] ○: No change with surrounding skin.

 [0155] X: Compared with surrounding skin, the color changes to red, and peeling of the skin is observed.

[0156] [Table 4]

上記結果より、本発明が、これまでの粘着剤に比較して皮膚刺激性が小さぐ十分 な量の生理活性物質を含有させることが出来、かつ生理活性物質の放出性の良い 経皮吸収製剤を提供することが明らかである _n

From the above results, the present invention can contain a sufficient amount of a physiologically active substance that is less irritating to the skin than conventional adhesives, and has a good release of the physiologically active substance. It is clear to provide _n

Claims

The scope of the claims  [1] In a skin patch having a pressure-sensitive adhesive composition layer formed on a support, the pressure-sensitive adhesive composition layer is made of a polyether polymer having a siloxane bond, and the pressure-sensitive adhesive composition layer A transdermally absorbable preparation characterized in that at least one layer contains a physiologically active substance.  [2] In a percutaneous absorption preparation having a pressure-sensitive adhesive composition layer formed on a support, the pressure-sensitive adhesive composition layer is  (A) a polyether polymer having at least one alkenyl group at its end;  (B) a compound having 10 to 10 hydrosilyl groups in the molecule;  (C) Hydrosilylation catalyst  2. The transdermally absorbable preparation according to claim 1, which is obtained by curing a strong pressure-sensitive adhesive composition, and contains a physiologically active substance in at least one layer of the pressure-sensitive adhesive composition layer. [3] The transdermally absorbable preparation according to claim 1 or 2, wherein the pressure-sensitive adhesive composition layer contains (D) an organic liquid component.  [4] The percutaneous absorption preparation according to any one of claims 1 to 3, wherein the pressure-sensitive adhesive composition layer contains a transdermal absorption enhancer. [5] The percutaneous absorption preparation according to any one of claims 1 to 4, wherein the polyether polymer of the polymer (A) is polyoxypropylene. [6] The power according to any one of claims 1 to 5, wherein the bioactive substance is dissolved in the polymer (A), mixed with the compound (B) and the catalyst (C), and then cured. 2. A method for producing a transdermal absorption preparation according to item 1.  [7] The bioactive substance is dissolved in the organic liquid component (D), and then mixed with the polymer (A), the compound (B) and the catalyst (C), and then cured. Item 6. A method for producing a transdermally absorbable preparation according to any one of Items 3 to 5.  [8] A pressure-sensitive adhesive sheet for skin application having a pressure-sensitive adhesive composition layer formed on a support, wherein the pressure-sensitive adhesive composition layer is  (A) a polyether polymer having at least one alkenyl group at its terminal  (B) a compound having in the molecule;! -10 hydrosilyl groups (C) Hydrosilylation catalyst (D) Organic liquid component  A pressure-sensitive adhesive sheet for application to the skin, which is obtained by curing a mixture of force. [9] The total amount of hydroxyl groups in the compound (B) in the adhesive sheet for skin application in which the pressure-sensitive adhesive composition layer is formed on the support, the total amount of alkenyl groups in the polymer (A) is 0 per mole. The pressure-sensitive adhesive sheet according to claim 8, which has 4 to 4 moles of hydrosilyl group. Yes  [10] The pressure-sensitive adhesive sheet according to claim 8 or 9, wherein the polyether polymer of the polymer (A) is polyoxypropylene. [11] The pressure-sensitive adhesive sheet according to any one of claims 8 to 10, wherein the hydrosilylation catalyst (C) is a platinum monobutylsiloxane complex. [12] The pressure-sensitive adhesive sheet according to any one of [8] to [11], wherein the organic liquid component (D) is a fatty acid ester. [13] The content of the polymer (A) and the organic liquid component (D) is 1.0: 0.001; 1.0: 1.5, or any one of claims 8 to 12, Or the pressure-sensitive adhesive sheet according to item 1.