JP3461401B2 - Transdermal tape - Google Patents

Description

Detailed Description of the Invention

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a percutaneous tape preparation for transdermal administration in which side effects such as rash are remarkably reduced in the tape preparation for percutaneous administration, and more specifically, transdermal administration containing trehalose or a trehalose derivative. Tape agent.

[0002]

2. Description of the Related Art As a means for administering a transdermal drug,
Conventionally, preparation forms such as poultices, ointments and tapes containing various drugs have been widely used. However, these preparations often cause skin irritation due to excessive irritation of the drug or irritation of the base. Further, in recent years, a therapy called ODT therapy has been performed in which the skin surface is sealed with a tape or the like to swell the stratum corneum of the skin and reduce the barrier function to perform percutaneous absorption. However, since this also seals the skin for a long period of time, serious side effects such as redness, edema, and rash occur due to water stains, contact with a base, and the like. Further, in recent years, for the purpose of treating angina and hypertension, treatment and prevention have been attempted by transdermally absorbing a systemic drug. These cover the skin with a tape, patch, etc. composed of a drug impermeable film and a drug-containing adhesive layer,
The idea is to control the release of the drug so that it can be absorbed through the skin. However, these gradually release and absorb the drug and try to maintain the effective blood concentration for a long time, so that the application time is inevitably prolonged. Therefore, it has been unavoidable that serious side effects such as redness, edema, and rash occur due to skin irritation caused by bases, adhesives, and the like, as compared with conventional topical patches. on the other hand,
For the purpose of preventing these skin rashes on the external patch,
Conventionally, various antifoggants have been blended and used. For example, 0.01 to 1.0% by weight of a drug having an antihistamine action or an antiallergic action such as diphenhydramine hydrochloride, chlorpheniramine maleate, diphenhydramine salicylate, ammonium glycyrrhizinate, or glycyrrhetinic acid is used. However, these antifoggants described above have poor stability in the base material and their effects are insufficient. Therefore, it has been attempted to blend a large amount of the anti-fogging agent, but the side effect of the anti-fogging agent itself appears, which has an adverse effect on the skin, and is also a cause of rash. That is, at present, the effect of the conventional antifoggants is insufficient.

Next, conventional techniques of trehalose and derivatives will be described. Trehalose has a molecular weight of 342.3.
One of the disaccharides represented by 1, which has a structure in which two molecules of D-glucose are bound with their reducing groups,
There are three types of isomers of natural α, α-bond (mycose), α, β-bond (neotrehalose), β, β-bond (isotrehalose) in the binding mode. Known trehalose derivatives include, for example, trehalose fatty acid ester, sulfated trehalose, 4-hydroxyphenyltrehalose, trehalose alkyl ester and the like. Conventionally, trehalose has been known as a cell dry-protecting substance, and its application as a new preservative for foods and pharmaceuticals is being studied. Recently, trehalose and its derivatives have been under development for cosmetic use. For example, in JP-A-61-110052, a carrier consisting of trehalose-containing cream, lotion, ointment and milk suppresses skin dryness due to skin moisturizing. Then, the disclosure has been made.
Japanese Patent Application Laid-Open No. 4-290808 discloses that trehalose is excellent in improving skin conditions such as rough skin, lack of gloss and fine wrinkles, and moisturizing by retaining skin moisture. JP-A-5-24920 discloses 6,6-bis-0- [9- [4-methoxy-, which is a derivative of trehalose.
Topical administration of 2,3,6-trimethylphenyl] -3,7-dimethyl-2,4,6,8-nonatetraenoyl] -D-trehalose in the treatment of acne and psoriasis and in inflammation and allergic dermatitis It is disclosed that it is effective. Japanese Unexamined Patent Publication (Kokai) No. 6-12262 discloses the use of a moisturizing agent, a mucopolysaccharide compounding agent, as an anti-sticking agent. Japanese Patent Application Laid-Open No. 6-92858 discloses a trehalosue 4
-It is disclosed that the hydroxyphenyl derivative suppresses melanin production and has an excellent whitening effect. Japanese Unexamined Patent Publication (Kokai) No. 6-122614 discloses use as a hair cosmetic composition which is excellent in moisturizing effect and less sticky. Japanese Unexamined Patent Publication (Kokai) No. 6-122618 discloses the use of a skin roughening preventive agent in combination with an ultraviolet preventive agent.
Japanese Unexamined Patent Publication (Kokai) No. 6-128136 discloses a synergist of allantoin and glycyrrhetinic acid as an anti-inflammatory effect. Japanese Patent Application Laid-Open No. 6-239717 discloses the application of trehalose fatty acid monoester as a surfactant with less skin irritation. Further, JP-A-6-256
Japanese Patent No. 219 discloses as an irritation reducing agent for transmucosal administration by ointment, cream, gel cream, lotion, aerosol, liquid, suppository and the like.

[0004]

However, in the above-mentioned conventional methods, even if a drug having an antihistamine action or an antiallergic action is compounded, the rash is not sufficiently reduced. Further, there is no description or suggestion of a tape preparation for transdermal administration of trehalose or its derivative used in cosmetics or transmucosal preparations. Furthermore, the fact is that no consideration has been given to the prescription of tapes. Therefore, the present invention relates to the development of the most suitable anti-foggant agent for transdermal administration tape preparations, the study of tape formulation, and the development of the tape agent for the purpose of preventing anti-fog on the transdermal skin.

[0005]

In order to achieve this object, the tape preparation for transdermal application of the present invention has the following constitution. That is, the tape preparation for transdermal administration of the present invention is composed of a tape preparation for reducing rash which is prepared by blending trehalose or a trehalose derivative as an essential component for reducing rash. The tape preparation for transdermal administration of the present invention comprises the antifoggant tape preparation containing a medicinal component, an adhesive and trehalose or a trehalose derivative as essential components. The tape preparation for transdermal administration of the present invention comprises a tackifier and / or
Alternatively, it comprises the antifoggant tape agent containing a softening agent. The tape preparation for transdermal administration of the present invention comprises the above-mentioned antifoggant tape preparation containing 0.01 to 10% by weight of trehalose or a trehalose derivative.

An absorption promoter, a drug dissolving agent, an inorganic filler, and an antioxidant can be added to the tape agent, if necessary. Here, the antifoggant is trehalose, that is, trehalose containing three isomers of α, α-bond (mycose), α, β-bond (neotrehalose) and β, β-bond (isotrehalose). The trehalose may be used alone or in the form of a mixture. Further, trehalose means anhydrous or hydrous trehalose. In the present invention, these isomers are collectively referred to as trehalose. Further, as a trehalose derivative, a trehalose fatty acid ester (for example, the trehalose fatty acid ester used in the present invention is an ester of trehalose and a fatty acid or a fatty acid derivative, in which the fatty acid residue, the acyl group, is a straight chain having 8 to 22 carbon atoms. Or, those having a branched saturated alkyl group or alkenyl group are preferable.Specific examples include trehalose monocaprylate, trehalose monononanoate, trehalose monocaprate, trehalose monoundecanoate, trehalose monolaurate, trehalose monomyristate. Trehalose monopalmitate, trehalose monostearate, trehalose monoarachiate, trehalose monobehenate, trehalose monoundecylenate, trehalose monooleate, monolino Acid trehalose, monolinolenic acid trehalose, monoisostearic acid trehalose, monohydroxystearic acid trehalose, monoricinoleic acid trehalose, etc. These trehalose fatty acid monoesters can be used alone or in combination of two or more.) Sulfuric acid It is selected from trehalose derivatives such as derivatized trehalose, 4-hydroxyphenyltrehalose, trehalose alkyl ester and the like, and these may be used alone or in combination of two or more kinds. The blending amount of trehalose or trehalose derivative is 0.01 to 10% by weight, preferably 0.1 to 5% by weight,
More preferably, it is used at 0.5 to 5% by weight. As the blending amount becomes 0.01% by weight or less, the absorption of moisture such as sweat and lipids from the skin on the surface to be adhered is reduced, and the antifoggant action is not exhibited. If it is contained in an amount of 10% by weight or more, more moisture such as perspiration and lipids than the skin on the surface to be adhered is increased, rather the adhesive strength is lowered and peeling easily occurs. Moreover, the suppression rate of the anti-fogging effect is not improved.

Next, the amount of the medicinal component used in the patch for external use of the present invention is 0.01 to 20% by weight, preferably 0.1 to 15% by weight, more preferably 0.5 to 1%.
0% by weight is compounded. When the amount is less than 0.01% by weight, the pharmacological action becomes weak and sufficient medicinal effect cannot be obtained. Again 20
Formulation with more than wt% does not increase the cost of the preparation and does not show any further medicinal effect. There is no particular limitation on the medicinal component, and any medicinal component can be selected from conventionally known medicinal components and used. Examples of such medicinal components include methyl salicylate, glycol salicylate, 1-menthol, camphor, peppermint oil, nicotinic acid benzyl ester, capsicum extract, and a cooling agent such as capsaicin.
Warming agents, prednisolone, dexamethasone, hydrocortisone, fluocinolone acetonide, betamethasone valerate, betamethasone dipropionate, clobetasone butyrate,
Steroidal anti-inflammatory agents such as prednisolone succinate, indomethacin, diclofenac, ibuprofen, ketoprofen, flufenamic acid, ketorolac, flurbiprofen, felbinac, suprofen, planoprofen, thiaprofen, loxoprofen, tenidap, aspirin, actarit, mizoribine, oxaprozin, oxaprozin. , Auranofin, indomethacin farnesyl, oxaprozin, mofezolac, etodolac, non-steroidal anti-inflammatory agents such as meloxicam, lornoxicam and its ester derivatives, tranilast, azelastine, ketotifen, mequitazine, ibudilast, oxatomide, anti-allergic agents such as emedastine, epinastine, etc. , Chlorpheniramine, promethazine, tripelenami Antihistamines etc., chlorpromazine, nitrazepam, diazepam, phenol Nipah ruby tar, central nervous agents such as reserpine, insulin, testosterone, norethisterone, hormonal agents such as methyl testosterone, progesterone, estradiol, clonidine, reserpine, guanethidine sulfate,
Antihypertensive agents such as efonidipine, carvedilol hydrochloride, bevantolol hydrochloride, bopindolol malonate, cardiotonic agents such as digitoxin and digoxin, antiarrhythmic agents such as propranolol hydrochloride, coronary vasodilators such as nitroglycerin, isosorbide dinitrate, papaverine hydrochloride, nifedipine ,
Local anesthetics such as lidocaine, benzocaine, procaine hydrochloride, tetracaine, morphine, buprenorphine hydrochloride, fentanyl citrate, pentazocine, eptazosin hydrobromide, aspirin, codeine, acetanilide, analgesics such as aminopyrine, eperisone, tizanidine, tolperisone, Skeletal muscle relaxants such as inaperisone, pridinol and dantrolene, acetophenylamine, nitrofurazone, pentamycin, naphthomate, miconazole, omoconazole, clotrimazole, butenafine hydrochloride, bifonazole, amorolfine hydrochloride, lanoconazole, liranaphthate, terbinafine hydrochloride and other antifungal agents , 5-Fluorouracil, Busulfan, Actinomycin, Pleomycin, Mitomycin and other anti-neoplastic agents, Bamikami , Clenbuterol hydrochloride, osaterone acetate, mepartricin, telolizine hydrochloride, oxybutynin hydrochloride, tamsulosin hydrochloride, etc., dysuria, antiepileptics such as nitrazepam, meprobamate, antiparkinsonian agents such as chlorzoxazone, lepodopa, nicotine etc. , Anti-emetics such as timiperone, bemperidol, fluoropipamide, fanisone,
Vitamins (eg vitamin E), prostaglandins (eg PGE ₁ , PGF ₂ α, PGE ₂ , PGI)
₂ ), interferons, angiotensin converting enzyme inhibitors, Ca antagonists, diuretics, and their medically acceptable inorganic salts or organic salts, but of course not limited to these.

Next, as the pressure-sensitive adhesive, an acrylic pressure-sensitive adhesive, a rubber-based pressure-sensitive adhesive, a silicone-based pressure-sensitive adhesive, etc. are used in consideration of skin safety, release of medicinal components, adhesion to the skin and the like. The content of these adhesives is 3 to 99% by weight,
Preferably 10-98% by weight, more preferably 15-9
7% by weight is blended. If it is less than 3% by weight, the adhesive strength will be insufficient and the tape will be easily peeled off, and a sufficient tape preparation cannot be obtained. On the other hand, if the amount is 99% by weight or more, the adhesive strength will be too strong, which will lead to adverse effects such as damage to the skin during peeling or side effects such as rash, rash and edema on the skin.
As the acrylic pressure-sensitive adhesive, in particular, a homopolymer or copolymer of a (meth) acrylic acid alkyl ester having an alkyl group having 4 to 18 carbon atoms, or the above (meth) acrylic acid alkyl ester and another functional monomer The copolymer of is preferably used. Examples of the (meth) acrylic acid ester include butyl acrylate, isobutyl acrylate, hexyl acrylate, octyl acrylate, 2-ethylhexyl acrylate, isooctyl acrylate,
Decyl acrylate, isodecyl acrylate, lauryl acrylate, stearyl acrylate, isobutyl methacrylate, ethyl methacrylate, butyl methacrylate, isobutyl methacrylate, 2-ethylhexyl methacrylate, isooctyl methacrylate, decyl methacrylate,
Examples include isodecyl methacrylate, lauryl methacrylate, stearyl methacrylate, and the like.

Examples of the functional monomer include a monomer having a hydroxyl group, a monomer having a carboxyl group,
Examples thereof include amide group-containing molymers, amino group-containing monomers, and pyrrolidone ring-containing monomers. Examples of the monomer having a hydroxyl group include hydroxyalkyl (meth) acrylates such as 2-hydroxyethyl (meth) acrylate and hydroxypropyl (meth) acrylate. Examples of monomers having a carboxyl group include α, β such as acrylic acid and methacrylic acid.
-Unsaturated carboxylic acid: maleic acid monoalkyl ester such as butyl maleate: maleic acid: fumaric acid: crotonic acid. Maleic anhydride also gives the same copolymerization components as maleic acid. Examples of the monomer having an amide group include alkyl (meth) acrylamides such as acrylamide, dimethyl acrylamide and diethyl acrylamide, N-butoxymethyl acrylamide, N
-N-alkoxylmethyl (meth) acrylamides such as ethoxymethylacrylamide, diacetone acrylamide, etc. are exemplified. Examples of the monomer having an amino group include dimethylaminoethyl acrylate. Examples of the monomer having a pyrrolidone ring include N-vinyl-2-pyrrolidone.

As the rubber-based adhesive, natural rubber, synthetic isoprene rubber, polyisobutylene, polyvinyl ether, polyeletin, polyisoprene, polybutadiene,
Examples thereof include a styrene-butadiene copolymer, a styrene-isoprene copolymer, a styrene-isoprene-styrene block copolymer (SIS block copolymer) and the like.
As the silicone-based pressure-sensitive adhesive, those containing polyorganosiloxane or polydimethylsiloxane as a main component are used.

Among these pressure-sensitive adhesives, a styrene-isoprene-styrene copolymer is preferable, and its compounding amount is 3-45% by weight, preferably 10-40% by weight, more preferably 15-35% by weight. It If it is less than 3% by weight, the shape retention cannot be maintained and a tape preparation cannot be obtained. Again 45
If the content is more than 10% by weight, the pressure-sensitive adhesive is too hard to be molded, and even if it is formed, the pressure-sensitive adhesive strength is insufficient and peeling easily occurs, and a sufficient tape agent cannot be obtained. In addition, a tackifier and / or a softening agent is appropriately used for the tape preparation comprising the above-mentioned base components so as to obtain a good preparation according to the tape preparation.

The tackifier is a rosin-based rosin and hydrogenated, disproportionated, polymerized, esterified rosin derivative: terpene resin such as α-pinene and β-pinene: terpene-phenol resin: fat Family-based, aromatic-based,
Alicyclic and copolymer petroleum resins and alkyl-phenyl resins: xylene resins and the like are used. The blending amount thereof is 5 to 50% by weight, preferably 10 to 45% by weight, more preferably 15 to 40% by weight. If it is 5% by weight or less, no increase in adhesive strength can be expected, and it tends to peel off during application. On the other hand, when the amount is 50% by weight or more, the adhesive strength is increased too much, and side effects such as rash, rash and edema due to application tend to be remarkable. Further, the possibility of causing damage to the skin at the time of peeling increases, which is not preferable.

The emollient is one that plasticizes and softens the base polymer to maintain proper adhesion to the skin. As this softening agent, polybutene, liquid paraffin, liquid isoprene rubber, polyisobutylene, higher fatty acid esters such as isopropyl myristate, and vegetable oils such as silicone oil and almond oil, olive oil, camellia oil, persic oil, and peanut oil are used. To be done. The blending amount is 60% by weight or less, preferably 55% by weight or less,
More preferably, the content is 50% by weight or less. In some cases, the softening agent is not used when the acrylic adhesive is used as the main base. Also natural rubber or S
When an elastic body such as an IS block copolymer is used as a main base, it is added in an amount of 5 to 50% by weight, preferably 10 to 45% by weight, more preferably 15 to 40% by weight. If it is less than 5% by weight, the workability of the elastic body is deteriorated and the adhesion is influenced. On the other hand, if it is 50% by weight or more, the base material becomes too soft, resulting in sagging of the base material or deterioration of the adhesiveness, and a good tape preparation cannot be obtained. Incidentally, as the absorption promoter or drug dissolving agent which can be appropriately blended with the base component of the present invention as necessary, 1-menthol, peppermint oil, limonene, crotamiton, pyrothiodecane, isopropyl myristate,
Isopropyl palmitate, lactic acid, malic acid, fumaric acid, maleic acid, oleic acid, salicylic acid, glycol salicylate, diethyl sebacate, polyethylene glycol, diethylene glycol, propylene glycol,
Examples thereof include surfactants. Examples of the inorganic filler include zinc oxide, crystalline calcium sulfate, bentonite, titanium oxide, calcium carbide, anhydrous silicon, talc and the like. Further, it is not particularly limited as long as it can prevent deterioration with time due to oxidation. For example, 2,6 di-t-butyl-p-
Examples include cresol and the like. As the support of the tape agent, one that does not affect the release of the medicinal component is desirable, and a stretchable or non-stretchable one is used. For example,
As the synthetic resin film, a film or sheet of polyethylene, polypropylene, polybutadiene, ethylene vinyl acetate copolymer, polyvinyl chloride, polyester, nylon, polyurethane or the like, or a laminate of these, a porous film,
It is selected from foam, paper, cloth and non-woven fabric.

This tape agent can be easily produced by a conventionally known production method. For example, in the case of a synthetic rubber tape, a mixer such as a kneader or a mixer is used,
The adhesive base, the softening agent and the tackifier are heated and mixed at 120 to 160 ° C., and then the medicinally active ingredient and trehalose are added and mixed and directly spread on a polypropylene or polyester film, or once subjected to a release treatment. Alternatively, the desired support may be covered with a desired paper after being spread on a paper or a film and transferred by pressure. In the case of an acrylic tape, an adhesive base, a drug and trehalose and, if necessary, a compounding agent are dissolved or dispersed in an appropriate solvent, and the resulting solution or dispersion is directly applied to the surface of the support and dried to give a thickness of 30. A patch of ˜200 μm is formed. Further, this solution or dispersion may be coated on a protective release paper, and the adhesive layer obtained after drying may be brought into close contact with the support. The solvent used in this production method is not particularly limited as long as it is an organic solvent that is compatible with the compounding components such as the adhesive base and the drug, but is, for example, aromatic hydrocarbons such as toluene, benzene and xylene, ethyl acetate. And halogenated hydrocarbons such as carbon tetrachloride, chloroform and methylene chloride.

[0015]

The tape preparation of the present invention is one in which trehalose mixed as an antifoggant absorbs moisture such as sweat and lipids in the skin and stays on the skin site without irritating the skin and exhibits antifoggant effect. Is.

[0016]

EXAMPLES The present invention will be described in more detail with reference to the following examples and test examples. The term "central part" in the text means% by weight. Example 1 2-Ethylhexyl Acrylate / Vinyl Acetate Copolymer (Solid Type) 96.0 parts Indomethacin 3.0 parts Trehalose 1.0 part The above components are added to an ethylene-vinyl acetate copolymer sheet 5
It was spread to a thickness of 0 μm, cut into a desired size, and used as the tape preparation of the present invention.

Example 2 Styrene-isoprene-styrene block copolymer 20.0 parts Rosin-modified resin 25.0 parts Liquid paraffin 43.0 parts Glycol salicylate 5.0 parts l-Menthol 5.0 parts Trehalose 2.0 parts The above components were spread on a silicone-treated polyester liner to a thickness of 150 μm, covered with a foamed polybutadiene sheet, pressure-transferred, cut into a desired size, and the tape preparation of the present invention was obtained. did.

Example 3 Natural rubber 30.0 parts Rosin resin 27.0 parts Polybutene 12.0 parts Zinc oxide 18.0 parts Methyl salicylate 6.0 parts l-Menthol 5.5 parts Trehalose (hydrated) 1.5 parts The above components were spread on a non-woven fabric so as to have a thickness of 200 μm, cut into a desired size, and used as the tape preparation of the present invention.

Example 4 Styrene-isoprene-styrene block copolymer 25.0 parts Alicyclic petroleum resin 31.9 parts Liquid paraffin 35.0 parts Clonidine 8.0 parts Trehalose 0.1 part Polyester containing the above components It was spread on a film so as to have a thickness of 100 μm, cut into a desired size, and used as a tape preparation of the present invention.

Example 5 Acrylic acid-2-ethylbutyl acrylate (solid content) 88.0 parts Isosorbide dinitrate 10.0 parts Trehalose 2.0 parts The above components were spread on a polyester film to a thickness of 60 μm. The tape was rolled and cut into a desired size to obtain the tape preparation of the present invention.

Example 6 Styrene-isoprene-styrene block copolymer 18.0 parts Polyisobutylene 10.0 parts Rosin modified resin 16.0 parts Liquid paraffin 50.0 parts 1-menthol 3.0 parts Ketoprofen 2.0 parts Trehalose 1.0 part The above components are spread on a silicone-treated polyester liner to a thickness of 150 μm, covered with a polyester cloth, transferred under pressure, transferred to a desired size, and cut into a tape of the present invention. I used it as an agent.

Example 7 Styrene-isoprene-styrene block copolymer 20.0 parts Polyisobutylene 8.5 parts Aliphatic saturated hydrocarbon resin 22.5 parts Liquid paraffin 37.0 parts Glycol salicylate 5.0 parts 1- Menthol 5.0 parts 6-myristylate-trehalose 2.0 parts The above components are spread on a silicone-treated polyester liner to a thickness of 200 μm, covered with a polyester non-woven fabric, and transferred under pressure to obtain the desired product. After cutting to a size, the tape preparation of the present invention was obtained.

Example 8 Styrene-isoprene-styrene block copolymer 18.5 parts Polyisobutylene 10.0 parts Rosin modified resin 30.5 parts Liquid paraffin 33.5 parts Estradiol 1.0 parts Crotamiton 5.0 parts Sulfation Trehalose 1.5 parts The above components are spread on a silicone-treated polyester liner so as to have a thickness of 100 μm, covered with a polyester film, pressure-transferred and cut into a desired size. It was used as a tape.

Example 9 Styrene-isoprene-styrene block copolymer 33.0 parts Liquid paraffin 40.0 parts Rosin-modified resin 20.0 parts Estradiol 1.0 parts Crotamiton 5.0 parts Trehalose 1.0 parts The above components Was spread on a polyester liner treated with silicone so as to have a thickness of 100 μm, covered with a vinyl chloride / polyester composite film, pressure-transferred, cut into a desired size, and used as the tape preparation of the present invention. .

Example 10 Styrene-isoprene-styrene block copolymer 25.0 parts Polyisobutylene 8.0 parts Liquid paraffin 36.0 parts Rosin modified resin 25.0 parts Pridinol 2.0 parts Trehalose 4.0 parts The above The components were spread on a polyolefin film so as to have a thickness of 150 μm, cut into a desired size, and used as a tape preparation of the present invention.

Example 11 Styrene-isoprene-styrene block copolymer 25.50 parts Liquid paraffin 34.49 parts Rosin modified resin 32.50 parts Norethisterone 2.50 parts Crotamiton 5.00 parts Trehalose 0.01 parts The above components Was spread on a polyester film to a thickness of 100 μm, cut into a desired size, and used as the tape preparation of the present invention.

Comparative Example 1     2-ethylhexyl acrylate / vinyl acetate copolymer (solid content)                                                               97.0 copies     Indomethacin 3.0 parts The above components were treated as in Example 1 to give Comparative Example 1.

Comparative Example 2 Styrene-isoprene-styrene block copolymer 30.0 parts Rosin-modified resin 25.0 parts Liquid paraffin 35.0 parts Glycol salicylate 5.0 parts l-Menthol 5.0 parts The above components were carried out. It processed like Example 2 and it was set as the comparative example 2.

Comparative Example 3     2-ethylhexyl acrylate / vinyl acetate copolymer (solid content)                                                           96.995 copies     Indomethacin 3.0 parts     Trehalose 0.005 parts The above components were treated as in Example 1 to give Comparative Example 3.

Comparative Example 4     Styrene-isoprene-styrene block copolymer 25.0 parts     Rosin-modified resin 21.0 parts     Liquid paraffin 28.0 parts     Glycol salicylate 5.5 parts     l-menthol 5.5 parts     Trehalose 15.0 parts The above components were treated as in Example 2 to give Comparative Example 4.

Reference Example 1     2-ethylhexyl acrylate / vinyl acetate copolymer (solid content)                                                               96.0 copies     Indomethacin 3.0 parts     Diphenhydramine hydrochloride 1.0 part The above components were treated as in Example 1 to give Reference Example 1.

Reference example 2     Styrene-isoprene-styrene block copolymer 30.0 parts     Rosin-modified resin 25.0 parts     Liquid paraffin 34.0 parts     Glycol salicylate 5.0 parts     l-menthol 5.0 parts     Glycyrrhetinic acid 1.0 part The above components were treated as in Example 2 to give Reference Example 2.

Test Example 1 Skin Irritation Test Examples 1 and 2 of the present invention, Comparative Examples 1 to 4, and Reference Example 1,
A skin irritation test with human skin was performed using each of the tape preparations of 2. The test method is as follows. Test subjects: 40 adult males (aged 26 to 35 years old) Test method: Each test sample was punched out into a circle with a diameter of 20 mm, attached to the upper back of the subject, and covered with 3M Micropore Tape from the top for 48 hours. I did a closed patch. The skin was peeled off after 48 hours, and after 1 hour and 24 hours, the degree of skin change was observed to determine the degree of skin irritation. The test results are shown in Table 1. (Criteria and calculation methods are as follows) Skin irritation criteria Criteria Score No change; -0.0 Weak redness; ± 0.5 Clear redness; +1.0 Papules, edema; ++ 2. 0

[0034]

[Table 1] As is clear from the results shown in Table 1, the tape preparation of the present invention showed higher fog than those containing no trehalose and those containing a known antifoggant.

Test Example 2 Adhesive Strength Test An adhesive strength test and a change in adhesive strength with time were carried out using the tape preparations of Examples 1, 2 and Comparative Example 4. (180 degree peeling test method) Each test sample adjusted to a surface having a width of 2 cm and a length of 25 cm was attached to a bakelite plate with a constant load, and then peeled by 180 degrees using a tensile tester to measure the adhesive force. . The test results are shown in FIG. As is clear from the figure, Comparative Example 4 containing 15% trehalose
In comparison with, it is shown that the tape preparations of Examples 1 and 2 of the present invention are excellent in remarkable adhesive strength stability.

[0036]

EFFECTS OF THE INVENTION The tape preparation for transdermal administration of the present invention has a remarkable anti-fogging effect and is excellent in qualitativeness as is clear from the above-mentioned test examples, and is very useful as a medical tape preparation. It is a thing.

[Brief description of drawings]

FIG. 1 is a graph showing the results of a 180 ° peel test in Test Example 2. The vertical axis represents the 180 ° peeling force (g / 2 cm), and the horizontal axis represents the initial products of Examples 1 and 2 and Comparative Example 4 at 50 ° C. for 3 months.
(Initial value is white, shaded area is 50 ° C for 3 months)

[Explanation of symbols]

[A]: Tape preparation of Example 1 [B]: Tape agent of Example 2 [C]: Tape agent of Comparative Example 4

─────────────────────────────────────────────────── ─── Continuation of the front page (56) Reference JP-A-8-53339 (JP, A) (58) Fields investigated (Int.Cl. ⁷ , DB name) A61K 47/26 A61K 9/70

Claims (4)

(57) [Claims] 1. A tape preparation for transdermal administration with reduced rash, which comprises trehalose or a trehalose derivative as an antifoggant . 2. A mosquito according to claim 1, which comprises a medicinal component, an adhesive and trehalose or a trehalose derivative.
A transdermal tape preparation with reduced blurring . 3. A pressure-sensitive adhesive imparting agents and / or softening agent for transdermal administration tape preparation rash is reduced according to claim 2, wherein by blending a. 4. The tape preparation for transdermal administration according to claim 1, 2 or 3, which comprises 0.01 to 10% by weight of trehalose or a trehalose derivative.