JP2638635B2 - Transdermal formulation - Google Patents
Transdermal formulationInfo
- Publication number
- JP2638635B2 JP2638635B2 JP1023074A JP2307489A JP2638635B2 JP 2638635 B2 JP2638635 B2 JP 2638635B2 JP 1023074 A JP1023074 A JP 1023074A JP 2307489 A JP2307489 A JP 2307489A JP 2638635 B2 JP2638635 B2 JP 2638635B2
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- Japan
- Prior art keywords
- drug
- absorption
- preparation
- group
- patch
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
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- Materials For Medical Uses (AREA)
Description
【発明の詳細な説明】 （産業上の利用分野） 本発明は薬物を含有する経皮投与形製剤に関する。本
発明は，特に，該薬物の形皮吸収性を高めた経皮吸収製
剤に関する。Description: TECHNICAL FIELD The present invention relates to a drug-containing transdermal dosage form. The present invention particularly relates to a percutaneous absorption preparation in which the percutaneous absorption of the drug is enhanced.
（従来の技術） 全身もしくは局部での薬効を得るために，経皮投与経
製剤を用い，薬物（生理活性物質）を皮膚を介して吸収
させることが行われている。この経皮投与法は，従来の
経口投与法に比べて利点が多い。例えば，薬物を経口投
与すると，腸で吸収された薬物は肝臓へ循環して代謝を
受けるため，その薬効を発揮する前にかなりの量が分解
されてしまう。これに対して，経皮投与法では，吸収さ
れた薬物は体内の初回循環時に肝臓を通過しない。その
ため，肝臓での代謝により薬効が大幅に減じるというこ
とがあに。非ステロイド系抗炎症剤を経口投与すると胃
腸障害を生じやすいが，経皮投与法ではこのような胃腸
障害が生じにくい。薬物の吸収性をコントロールすれ
ば，薬物が短時間に大量に吸収されるために起こる副作
用を軽減することが可能となる。長時間にわたり一定の
薬物血中濃度を維持できれば薬物の投与回数を減らすこ
ともできる。(Prior Art) In order to obtain a systemic or local drug effect, a drug (bioactive substance) is absorbed through the skin using a transdermal administration preparation. This transdermal administration method has many advantages over the conventional oral administration method. For example, when a drug is orally administered, the drug absorbed in the intestine circulates to the liver and is metabolized, so that a considerable amount of the drug is degraded before exerting its medicinal effect. In contrast, in transdermal administration, the absorbed drug does not pass through the liver during the first circulation in the body. For that reason, the metabolism in the liver greatly reduces the medicinal effect. Oral administration of nonsteroidal anti-inflammatory drugs tends to cause gastrointestinal disorders, but transdermal administration is unlikely to cause such gastrointestinal disorders. Controlling the absorption of a drug can reduce the side effects caused by the absorption of a large amount of the drug in a short time. If a constant drug blood concentration can be maintained over a long period of time, the number of drug administrations can be reduced.
しかし，経皮吸収製剤を用いて薬物を投与しても，該
薬物が皮膚を投下しにくく生体利用率（バイオアベイラ
ビリティ）が低くなる場合が多い。特に，皮膚表面には
角質層が存在し，この角質層は体内へ異物が侵入するの
を防ぐバリアー機能を有するため，薬理効果を発揮しう
るに充分な量の薬物が皮膚を通して吸収されない場合が
多い。However, even when a drug is administered using a transdermal absorption preparation, it is often difficult for the drug to drop onto the skin, and the bioavailability often decreases. In particular, there is a stratum corneum on the skin surface, and since this stratum corneum has a barrier function to prevent invasion of foreign substances into the body, a sufficient amount of drug that can exert a pharmacological effect may not be absorbed through the skin. Many.
角質層のバリアー機能を弱めて充分な量の薬物を吸収
させるべく吸収促進剤を含有させた製剤が製造されてい
る。例えば，特開昭57−9714号公報，特公昭58−43368
号公報，特開昭58−52216号公報，特開昭58−79918号公
報，特開昭60−13720号公報および特開昭60−11431号公
報には，吸収促進剤を粘着剤層に含有させた貼付剤など
が開示されている。Preparations containing an absorption enhancer to reduce the barrier function of the stratum corneum and absorb a sufficient amount of the drug have been manufactured. For example, JP-A-57-9714, JP-B-58-43368.
JP-A-58-52216, JP-A-58-79918, JP-A-60-13720 and JP-A-60-11431 disclose an absorption accelerator contained in an adhesive layer. An adhesive patch and the like are disclosed.
上記吸収促進剤のうち，例えば，サリチル酸，尿素，
ジメチルスルホキシドは角質を溶解することが知られて
いるが，これらを添加しても薬物の経皮吸収性は必ずし
も良好でない。プロピレングリコール，グリセリン，ピ
ロリドンカルボン酸ソーダなどは角質層に水分を保持さ
せ得るが，薬物吸収促進効果がほとんど認められない。
ジメチルスルホキシドなどは，皮膚を刺激して紅斑やか
ぶれを生じやすい。アジピン酸ジイソプロピルなどのジ
カルボン酸エステルや脂肪酸エステルを粘着剤層に含有
させてテープ製剤とすると，粘着剤と薬物との相溶性が
低下するため，薬物が粘着剤から析出しやすく，粘着性
が低下することもある。チオグリコール酸カルシウムな
どのイオウ含有化合物は悪臭の原因ともなる。上記化合
物の他，ミリスチン酸エステル，アジピン酸エステル，
ラウリル硫酸エステル，ポリオキシエチレンアルキルエ
ーテルなども開示されているが，これらの吸収促進剤を
用いても皮膚を通しての薬物の吸収量は必ずしも充分で
あるとはいえない。このように，薬物を効果的に吸収さ
せうる経皮吸収製剤はいまだ得られていないのが現状で
ある。Among the above-mentioned absorption promoters, for example, salicylic acid, urea,
Dimethyl sulfoxide is known to dissolve stratum corneum, but the percutaneous absorption of the drug is not always good even if it is added. Propylene glycol, glycerin, sodium pyrrolidone carboxylate and the like can retain water in the stratum corneum, but have little effect on promoting drug absorption.
Dimethyl sulfoxide and the like tend to irritate the skin and cause erythema and rash. When a tape preparation is prepared by incorporating a dicarboxylic acid ester such as diisopropyl adipate or a fatty acid ester into the adhesive layer, the compatibility between the adhesive and the drug is reduced, so that the drug is easily precipitated from the adhesive and the adhesive property is reduced. Sometimes. Sulfur-containing compounds such as calcium thioglycolate also cause malodor. In addition to the above compounds, myristic esters, adipates,
Lauryl sulfate, polyoxyethylene alkyl ether and the like are also disclosed, but even if these absorption enhancers are used, the amount of drug absorbed through the skin is not always sufficient. As described above, at present, a transdermal absorption preparation that can effectively absorb a drug has not yet been obtained.
（発明が解決しようとする問題点） 本発明は上記従来の欠点を解決するものであり，その
目的とするところは，含有する薬物を効果的に皮膚を通
じて吸収させうる製剤を提供することにある。本発明の
他の目的は，含有される薬物の経皮吸収性を高め，かつ
皮膚に対する刺激性がなく生体に対して安全な吸収促進
剤を含有する経皮吸収製剤を提供することにある。本発
明のさらに他の目的は，基剤の性質を変化させることが
なく，しかも，薬物が析出することがなく，かつ含有さ
れる薬物の変性が生じることのない吸収促進剤を含有す
る経皮吸収製剤を提供することにある。(Problems to be solved by the invention) The present invention solves the above-mentioned conventional disadvantages, and an object of the present invention is to provide a preparation capable of effectively absorbing a drug contained therein through the skin. . Another object of the present invention is to provide a percutaneous absorption preparation which contains a permeation enhancer which enhances the percutaneous absorption of a drug contained therein and has no irritation to the skin and is safe for a living body. Still another object of the present invention is to provide a transdermal preparation containing an absorption enhancer which does not change the properties of the base, does not precipitate the drug, and does not cause the drug to be denatured. It is to provide an absorption preparation.
（問題点を解決するための手段） 本発明の経皮吸収製剤は，支持体の片面に薬物および
該薬物の吸収促進剤を含有する粘着剤層が設けられた経
皮吸収製剤であって、該薬物が硝酸イソソルビドであ
り，該粘着剤層の粘着基剤がアクリル酸２エチルヘキシ
ルおよびビニルピロリドンからなる共重合体であり，該
吸収促進剤が没食子酸アルキルエステルであり，該没食
子酸アルキルエステルのアルキル基の炭素数が１〜18で
あり，そのことにより上記目的が達成される。(Means for Solving the Problems) The percutaneous absorption preparation of the present invention is a percutaneous absorption preparation in which a pressure-sensitive adhesive layer containing a drug and an absorption promoter for the drug is provided on one surface of a support, The drug is isosorbide dinitrate, the adhesive base of the adhesive layer is a copolymer of 2-ethylhexyl acrylate and vinylpyrrolidone, the absorption enhancer is an alkyl gallate, and the absorption enhancer is an alkyl gallate. The alkyl group has 1 to 18 carbon atoms, thereby achieving the above object.
本発明に用いられる吸収促進剤は，下記式で示される
没食子酸アルキルエステル（3,4,5−トリヒドロキシ安
息香酸アルキルエステル）である： ここでＲは炭素数１〜18のアルキル基である。上記没
食子アルキルエステルのアルキル基としては，メチル
基，エチル基,n−プロピル基,iso−プロピル基,n−ブチ
ル基,iso−ブチル基,sec−ブチル基,tert−ブチル基,n
−アミノ基,iso−アミル基,sec−アミル基,tert−アミ
ル基，ネオペンチル基，ヘキシル基，ヘプチル基，オク
チル基,2エチルヘキシル基，ノニル基，デシル基，ラウ
リル基，セチル基，ステアリル基，アリル基などが挙げ
られる。このような没食子酸アルキルエステルは製剤中
に0.5〜30重量％の割合で含有される。この割合は，薬
物含有層（粘着剤層）に対する含有量を示す。後述の薬
物含有量についても同様である。吸収促進剤の量が過少
であると薬物の吸収促進効果が得られない。過剰であっ
ても薬物の吸収性はそれ以上向上しないばかりか，粘着
物性が低下し，粘着剤との相溶性が悪化する。The absorption enhancer used in the present invention is an alkyl gallate (alkyl 3,4,5-trihydroxybenzoate) represented by the following formula: Here, R is an alkyl group having 1 to 18 carbon atoms. Examples of the alkyl group of the gallic alkyl ester include a methyl group, an ethyl group, a n-propyl group, an isopropyl group, a n-butyl group, an iso-butyl group, a sec-butyl group, a tert-butyl group, and a
-Amino group, iso-amyl group, sec-amyl group, tert-amyl group, neopentyl group, hexyl group, heptyl group, octyl group, 2-ethylhexyl group, nonyl group, decyl group, lauryl group, cetyl group, stearyl group, Allyl groups and the like. Such a gallic acid alkyl ester is contained in the preparation at a ratio of 0.5 to 30% by weight. This ratio indicates the content relative to the drug-containing layer (adhesive layer). The same applies to the drug content described below. If the amount of the absorption promoter is too small, the effect of promoting absorption of the drug cannot be obtained. Even if it is excessive, not only does the absorbability of the drug not improve any more, but also the adhesive properties decrease, and the compatibility with the adhesive deteriorates.
使用される薬物（生理活性物質）は，硝酸イソソルビ
ドに限定される。The drug (bioactive substance) used is limited to isosorbide dinitrate.
硝酸イソソルビドの配合量は，製剤の使用目的により
異なるが，通常，薬物含有層（粘着剤層）中に0.1〜30
重量％の割合で含有される。The amount of isosorbide dinitrate varies depending on the intended use of the preparation, but is usually 0.1 to 30% in the drug-containing layer (adhesive layer).
% By weight.
本発明の経皮吸収製剤としては，テープ製剤，パッチ
剤などがある。The transdermal absorption preparation of the present invention includes a tape preparation, a patch and the like.
本発明の経皮吸収製剤は，支持体の片面に薬物と吸収
促進剤とを含有する粘着剤層が形成されている。本発明
の経皮吸収製剤の基剤（粘着剤）は該製剤を常温で皮膚
方面に長時間固定しうる粘着力が必要であり，アクリル
酸２エチルヘキシルおよびビニルピロリドンからなる共
重合体が用いられる。The transdermal preparation of the present invention has a pressure-sensitive adhesive layer containing a drug and an absorption enhancer formed on one surface of a support. The base (adhesive) of the percutaneous absorption preparation of the present invention needs to have an adhesive force capable of fixing the preparation to the skin at room temperature for a long time, and a copolymer composed of 2-ethylhexyl acrylate and vinylpyrrolidone is used. .
上記粘着剤中には必要に応じて各種配合剤，例えばロ
ジン系樹脂，ポリテルペン樹脂，クマロン−インデン樹
脂，石油系樹脂，テルペンフェノール樹脂などの粘着性
付与剤；液状ポリブテン，鉱油，ラノリン，液状ポリイ
ソプレン，液状ポリアクリレートなどの可塑剤；充填
剤；老化防止剤；が添加される。In the above-mentioned pressure-sensitive adhesive, if necessary, various compounding agents such as rosin resin, polyterpene resin, cumarone-indene resin, petroleum resin, terpene phenol resin, etc .; liquid polybutene, mineral oil, lanolin, liquid poly Plasticizers such as isoprene and liquid polyacrylate; fillers; antioxidants;
本発明の経皮吸収製剤に用いられる支持体としては，
貼付剤に通常利用される支持体が用いられる。このよう
な支持体の素材としては，酢酸セルロース，エチルセル
ロース，ポリエチレンテレフタレート，可塑化酢酸ビニ
ル−塩化ビニル共重合体，ナイロン，エチレン−酢酸ビ
ニル共重合体，可塑化ポリ塩化ビニル，ポリウレタン，
ポリエチレン，ポリ塩化ビニリデン，アルミニウムなど
がある。これらは，例えば，単層のシート（フィルム）
や二枚以上の積層（ラミネート）体として用いられる。
アルミニウム以外の素材は織布や不織布として利用して
もよい。The support used in the transdermal absorption preparation of the present invention includes:
A support usually used for a patch is used. Materials for such a support include cellulose acetate, ethyl cellulose, polyethylene terephthalate, plasticized vinyl acetate-vinyl chloride copolymer, nylon, ethylene-vinyl acetate copolymer, plasticized polyvinyl chloride, polyurethane,
Examples include polyethylene, polyvinylidene chloride, and aluminum. These are, for example, single-layer sheets (films)
Or as a laminate of two or more sheets.
Materials other than aluminum may be used as a woven or nonwoven fabric.
上記支持体表面に薬物と吸収促進剤とを含有する薬物
含有（粘着剤）層が形成されてテープ製剤やパッチ剤が
得られる。粘着剤層を形成するには，溶剤塗工法，ホッ
トメルト塗工法，電子線硬化エマルジョン塗工法など種
々の塗工法が用いられうる。なかでも溶剤塗工法が好適
に用いられる。溶塗工法で粘着剤層を形成するには，例
えば，粘着剤を適当な溶媒で稀釈し，これに薬物，吸収
促進剤，さらに必要に応じて配合剤を加えて均一に混合
し，得られた溶液を支持体表面に塗布・乾燥する。溶液
を直接支持体表面に塗布せずにシリコーン樹脂などをコ
ーティングした剥離紙上に塗布し，乾燥後に支持体と密
着させてもよい。このような剥離紙は，使用時まで貼付
剤の粘着剤層表面を保護するために用いられる。溶剤塗
工法以外の塗工法においても粘着剤層形成後，粘着剤層
表面保護のために剥離紙を配することが推奨される。粘
着剤層の厚みも使用目的により異なるが，通常,30〜200
μｍである。30μｍを下まわると必要量の薬物を含有す
ることができず，粘着性も不充分である。200μｍを上
まわると支持体付近の粘着剤層に含有される薬物が充分
に拡散せず，薬物及び放出性が低下する。A drug-containing (adhesive) layer containing a drug and an absorption promoter is formed on the surface of the support to obtain a tape preparation or a patch. In order to form the pressure-sensitive adhesive layer, various coating methods such as a solvent coating method, a hot melt coating method, and an electron beam curing emulsion coating method can be used. Among them, a solvent coating method is suitably used. To form a pressure-sensitive adhesive layer by the melt coating method, for example, the pressure-sensitive adhesive is diluted with an appropriate solvent, and the drug, absorption enhancer, and if necessary, compounding agents are added, and the mixture is mixed uniformly. The solution is applied to the surface of the support and dried. Instead of applying the solution directly to the surface of the support, the solution may be applied to a release paper coated with a silicone resin or the like, and then dried and then brought into close contact with the support. Such a release paper is used to protect the surface of the adhesive layer of the patch until use. In coating methods other than the solvent coating method, it is recommended that a release paper be provided after the formation of the pressure-sensitive adhesive layer to protect the surface of the pressure-sensitive adhesive layer. The thickness of the adhesive layer also varies depending on the purpose of use, but it is usually 30 to 200
μm. If the thickness is less than 30 μm, the required amount of drug cannot be contained, and the adhesiveness is insufficient. When the thickness exceeds 200 μm, the drug contained in the pressure-sensitive adhesive layer near the support is not sufficiently diffused, and the drug and the release property are reduced.
（作用） 本発明の経皮吸収製剤を皮膚に密着させると含有され
る薬物が容易に皮膚を通して吸収される。その詳細な機
構は不明であるが，吸収促進剤が皮膚に作用し，その蛋
白質を変性させ，含水率を上昇させて軟化させるためと
考えられる。そのため，通常，薬物を投下しにくい皮膚
表面の角質層も軟化して含有される薬物が容易に皮膚を
通して吸収されると考えられる。(Action) When the transdermal absorption preparation of the present invention is brought into close contact with the skin, the contained drug is easily absorbed through the skin. Although the detailed mechanism is unknown, it is considered that the absorption enhancer acts on the skin, denaturing the protein, increasing the water content and softening the protein. Therefore, it is considered that the stratum corneum on the skin surface, which is usually hard to drop the drug, is also softened and the contained drug is easily absorbed through the skin.
必要な薬効を得るのに充分な量の薬物が容易に吸収さ
れるため，従来のように大量の薬物を製剤中に含有させ
る必要がない。つまり，薬物のバイオアペイラビリティ
が高い。このような経皮吸収促進効果は吸収促進剤を用
いたときよりもはるかに高い。さらに，本発明に用いる
吸収促進剤は皮膚に対する刺激性がなく安全性が高い。
吸収促進剤自体が副作用を生じることもない。含有され
る薬物を変性させることもない。基剤との相溶性にも優
れる。薬物と基剤との相溶性に変化を与えないため，調
製後の製剤から薬物が析出することもない。吸収促進剤
自体が粘着剤の粘着機能を低下させるなど粘着剤の物性
に悪影響をおよぼすこともない。Since a sufficient amount of the drug is easily absorbed to obtain the required medicinal effect, it is not necessary to incorporate a large amount of the drug into the preparation as in the related art. In other words, the bioavailability of the drug is high. Such a transdermal absorption promoting effect is much higher than when an absorption enhancer is used. Furthermore, the absorption enhancer used in the present invention has no irritation to the skin and has high safety.
The absorption enhancer itself does not cause any side effects. It does not denature the contained drug. Excellent compatibility with base. Since the compatibility between the drug and the base does not change, the drug does not precipitate from the prepared preparation. The absorption promoter itself does not adversely affect the physical properties of the pressure-sensitive adhesive, such as reducing the pressure-sensitive adhesive function of the pressure-sensitive adhesive.
（実施例） 以下に本発明を実施例について説明する。(Example) Hereinafter, the present invention will be described with reference to examples.
実施例１ （Ａ）貼付剤（テープ製剤）の調製：アクリル酸２エチ
ルヘキシル85重量部およびビニルピロリドン15重量部か
らなる共重合体を20重量％の割合で含有する酢酸エチル
溶液を調製した。この溶液100重量部に対して，薬物と
して硝酸イソソルビド（ISDN）３重量部，経皮吸収促進
剤として没食子酸ｎ−プロピル１重量部を添加し，ディ
ゾルバーで充分に撹拌して均一な溶液を得た。これを片
面が離型処理された厚さ45μｍのポリエチレンテレフタ
レート（PET）フィルム上に乾燥後の厚さが40μｍとな
るように塗布し,65℃のギアオーブンで20分間乾燥し
た。得られた粘着剤層表面に支持体として厚さ10μｍの
PETフィルムをラミネートした。この貼付剤の粘着剤層
中の薬物濃度は12.5重量％，そして吸収促進剤の濃度は
4.2重量％である。Example 1 (A) Preparation of Patch (Tape Preparation): An ethyl acetate solution containing a copolymer consisting of 85 parts by weight of 2-ethylhexyl acrylate and 15 parts by weight of vinylpyrrolidone at a ratio of 20% by weight was prepared. To 100 parts by weight of this solution, 3 parts by weight of isosorbide dinitrate (ISDN) as a drug and 1 part by weight of n-propyl gallate as a percutaneous absorption enhancer were added, and sufficiently stirred with a dissolver to obtain a uniform solution. Was. This was applied on a 45 μm-thick polyethylene terephthalate (PET) film having a mold release treatment on one side so that the thickness after drying was 40 μm, and dried in a gear oven at 65 ° C. for 20 minutes. 10 μm thick as a support on the surface of the obtained pressure-sensitive adhesive layer
The PET film was laminated. The drug concentration in the adhesive layer of this patch was 12.5% by weight, and the concentration of the absorption enhancer was
4.2% by weight.
（Ｂ）貼付剤の性能評価：（Ａ）項で得られた貼付剤を
10cm2の大きさに裁断し，これを日本白色家兎の脱毛し
た背部の皮膚表面に貼付した。0.5時間後,1時間後,2時
間後,4時間後,6時間後,10時間後および24時間後に家兎
の耳介静脈から採血し，遠心分離を行って血漿を得た。
これをヘキサンで抽出し,Ni63ECDガスクロマトグラフィ
ーにかけ薬物濃度を測定した。その結果を表１に示す。
24時間後に貼付剤を剥離したが，皮膚表面に発赤，かぶ
れなどの障害は認められなかった。(B) Performance evaluation of patch: The patch obtained in section (A)
It was cut into a size of 10 cm 2 and this was affixed to the skin surface of the depilated back of a Japanese white rabbit. 0.5 hours, 1 hour, 2 hours, 4 hours, 6 hours, 10 hours and 24 hours later, blood was collected from the auricular vein of rabbits and centrifuged to obtain plasma.
This was extracted with hexane and subjected to Ni 63 ECD gas chromatography to determine the drug concentration. Table 1 shows the results.
The patch was peeled off 24 hours later, but no redness or rash was observed on the skin surface.
比較例１ （Ａ）貼付剤（テープ製剤）の調製：吸収促進剤を加え
なかったこと以外は実施例１（Ａ）項と同様である。Comparative Example 1 (A) Preparation of Patch (Tape Preparation): Same as Example 1 (A) except that no absorption promoter was added.
（Ｂ）貼付剤の性能評価：本比較例（Ａ）項で得られた
貼付剤を用い，実施例１（Ｂ）項と同様に行った。その
結果を表１に示す。24時間後に貼付剤を剥離したが，皮
膚表面に発赤，かぶれなどの障害は認められなかった。(B) Performance evaluation of patch: Using the patch obtained in this comparative example (A), the same procedure as in Example 1 (B) was carried out. Table 1 shows the results. The patch was peeled off 24 hours later, but no redness or rash was observed on the skin surface.
比較例２ （Ａ）貼付剤（テープ製剤）の調製：吸収促進剤として
サリチル酸１重量部を用いたこと以外は実施例１と同様
である。Comparative Example 2 (A) Preparation of Patch (Tape Preparation): Same as Example 1 except that 1 part by weight of salicylic acid was used as an absorption promoter.
（Ｂ）貼付剤（テープ製剤）の性能評価：本比較例
（Ａ）項で得られた貼付剤を用い，実施例１（Ｂ）項と
同様に行った。その結果を表１に示す。24時間後に貼付
剤を剥離したところ，皮膚表面にわずかな発赤が認めら
れた。(B) Performance evaluation of patch (tape preparation): The same procedure as in Example 1 (B) was carried out using the patch obtained in this comparative example (A). Table 1 shows the results. After 24 hours, the patch was peeled off, and slight redness was observed on the skin surface.
（発明の効果） 本発明によれば，このように，没食子酸アルキルエス
テルを吸収促進剤として製剤中に含有させることによ
り，薬物の経皮吸収性を極めて優れた製剤が得られる。
薬物の吸収性が優れているため，必要な薬理効果を得る
ために従来のような大量の薬物を製剤中に含有させる必
要がない。用いられる吸収促進剤は皮膚に対する刺激性
がないため，長時間貼付してもかぶれが生じない。吸収
促進剤自体が吸収されて副作用を示すこともない。薬物
を変質させることもない。さらに，吸収促進剤が原因と
なって薬物が析出したり，粘着性が低下することもな
い。このような製剤では，硝酸イソソルビドを経皮吸収
させることができ，該製剤を用いたときの治療効果も高
い。 (Effect of the Invention) According to the present invention, a preparation having extremely excellent transdermal absorbability of a drug can be obtained by including an alkyl gallate in a preparation as an absorption enhancer.
Because of the excellent drug absorption, it is not necessary to incorporate a large amount of the drug into the preparation as in the past in order to obtain the necessary pharmacological effect. Since the absorption enhancer used is not irritating to the skin, it does not cause rash even when applied for a long time. The absorption enhancer itself is not absorbed and shows no side effects. It does not alter the drug. In addition, there is no precipitation of the drug or a decrease in the adhesiveness due to the absorption enhancer. In such a preparation, isosorbide dinitrate can be absorbed transdermally, and the therapeutic effect when the preparation is used is high.
Claims (3)
進剤を含有する粘着剤層が設けられた経皮吸収製剤であ
って， 該薬物が硝酸イソソルビドであり， 該粘着剤層の粘着基剤がアクリル酸２エチルヘキシルお
よびビニルピロリドンからなる共重合体であり， 該吸収促進剤が没食子酸アルキルエステルであり， 該没食子酸アルキルエステルのアルキル基の炭素数が１
〜18である， 経皮吸収製剤。1. A transdermal absorption preparation comprising a support and a pressure-sensitive adhesive layer containing a drug and an absorption enhancer for the drug provided on one surface of the support, wherein the drug is isosorbide dinitrate, The base is a copolymer comprising 2-ethylhexyl acrylate and vinylpyrrolidone; the absorption promoter is an alkyl gallate; and the alkyl group of the alkyl gallate has 1 carbon atom.
Percutaneously absorbable preparation.
含有する特許請求の範囲第１項に記載の経皮吸収製剤。2. The percutaneous absorption preparation according to claim 1, wherein said absorption enhancer is contained in a ratio of 0.5 to 30% by weight.
記載の経皮吸収製剤。3. The transdermally absorbable preparation according to claim 1, which is a tape preparation.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP1023074A JP2638635B2 (en) | 1989-01-31 | 1989-01-31 | Transdermal formulation |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP1023074A JP2638635B2 (en) | 1989-01-31 | 1989-01-31 | Transdermal formulation |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPH02202813A JPH02202813A (en) | 1990-08-10 |
| JP2638635B2 true JP2638635B2 (en) | 1997-08-06 |
Family
ID=12100256
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP1023074A Expired - Fee Related JP2638635B2 (en) | 1989-01-31 | 1989-01-31 | Transdermal formulation |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JP2638635B2 (en) |
Families Citing this family (19)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0601058A4 (en) * | 1991-08-27 | 1995-05-31 | Cygnus Therapeutic Systems | Transdermal formulations for administering prazosin. |
| FR2719770A1 (en) * | 1994-05-11 | 1995-11-17 | Lhd Lab Hygiene Dietetique | Matrix system for transdermal delivery of ibuprofen and method of preparation |
| WO1998008547A1 (en) * | 1996-08-29 | 1998-03-05 | Sekisui Kagaku Kogyo Kabushiki Kaisha | Stanozolol-containing percutaneously absorbable preparation |
| US5962522A (en) * | 1997-09-05 | 1999-10-05 | Avmax, Inc. | Propyl gallate to increase bioavailability of orally administered pharmaceutical compounds |
| US6193996B1 (en) | 1998-04-02 | 2001-02-27 | 3M Innovative Properties Company | Device for the transdermal delivery of diclofenac |
| JP4880813B2 (en) * | 2000-10-26 | 2012-02-22 | 第一三共株式会社 | Anti-inflammatory analgesic composition for external use |
| NO20014746D0 (en) | 2001-09-28 | 2001-09-28 | Clas M Kjoelberg | Pain reliever |
| WO2004084920A2 (en) * | 2003-03-27 | 2004-10-07 | Santosolve As | Anti-inflammatory treatment based on strontium compounds |
| ATE448828T1 (en) | 2003-10-27 | 2009-12-15 | Univ Basel | TRANSDERMAL DRUG DELIVERY SYSTEM |
| US8252321B2 (en) | 2004-09-13 | 2012-08-28 | Chrono Therapeutics, Inc. | Biosynchronous transdermal drug delivery for longevity, anti-aging, fatigue management, obesity, weight loss, weight management, delivery of nutraceuticals, and the treatment of hyperglycemia, alzheimer's disease, sleep disorders, parkinson's disease, aids, epilepsy, attention deficit disorder, nicotine addiction, cancer, headache and pain control, asthma, angina, hypertension, depression, cold, flu and the like |
| AU2005284908B2 (en) | 2004-09-13 | 2011-12-08 | Morningside Venture Investments Limited | Biosynchronous transdermal drug delivery |
| WO2006127905A2 (en) | 2005-05-24 | 2006-11-30 | Chrono Therapeutics, Inc. | Portable drug delivery device |
| EP2729148A4 (en) | 2011-07-06 | 2015-04-22 | Parkinson S Inst | Compositions and methods for treatment of symptoms in parkinson's disease patients |
| US10105487B2 (en) | 2013-01-24 | 2018-10-23 | Chrono Therapeutics Inc. | Optimized bio-synchronous bioactive agent delivery system |
| JP2018511355A (en) | 2015-01-28 | 2018-04-26 | クロノ セラピューティクス インコーポレイテッドＣｈｒｏｎｏ Ｔｈｅｒａｐｅｕｔｉｃｓ Ｉｎｃ． | Drug delivery method and system |
| EP3267875A4 (en) | 2015-03-12 | 2018-12-05 | Chrono Therapeutics Inc. | Craving input and support system |
| JP2020503950A (en) | 2017-01-06 | 2020-02-06 | クロノ セラピューティクス インコーポレイテッドＣｈｒｏｎｏ Ｔｈｅｒａｐｅｕｔｉｃｓ Ｉｎｃ． | Device and method for transdermal drug delivery |
| AU2019279884A1 (en) | 2018-05-29 | 2020-12-10 | Morningside Venture Investments Limited | Drug delivery methods and systems |
| JP7197238B2 (en) * | 2018-12-13 | 2022-12-27 | 株式会社ブリヂストン | Additive for rubber, additive composition for rubber, rubber composition for tire, crosslinked rubber composition for tire, rubber product for tire, and tire |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS63313723A (en) * | 1987-06-16 | 1988-12-21 | Nitto Electric Ind Co Ltd | External cataplasm |
-
1989
- 1989-01-31 JP JP1023074A patent/JP2638635B2/en not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| JPH02202813A (en) | 1990-08-10 |
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