【発明の詳細な説明】 〔産業上の利用分野〕 本発明は有効成分として塩酸クロルプレナリンを含有す
る気管支拡張用貼付剤及びその製法に関する。TECHNICAL FIELD The present invention relates to a patch for bronchodilation containing chlorprenaline hydrochloride as an active ingredient and a method for producing the same.
従来、塩酸クロルプレナリン（以下、CPと略称する）
は、気管支平滑筋刺激作用を有するため、気管支喘息、
肺気腫、気管支炎等の治療に経口剤として、錠剤、吸収
液及び顆粒剤の形で使用されている。Conventionally, chlorprenaline hydrochloride (hereinafter abbreviated as CP)
Has bronchial smooth muscle stimulating action, so bronchial asthma,
It is used as an oral preparation in the form of tablets, absorption solutions and granules for the treatment of emphysema, bronchitis and the like.
しかしCPは、経口投与した場合極めて速やかに代謝さ
れ、薬効の持続時間が短かく、満足すべき薬効が得られ
ないことが知られている。However, CP is known to be metabolized very rapidly when administered orally, and has a short duration of drug effect, so that a satisfactory drug effect cannot be obtained.
一方、近年、CP等の薬物を含水ゲルに含有せしめて貼付
剤の形とすることが報告された（特開昭59−25320号公
報参照）。しかしながら、当然特許公開公報の記載に従
つてCPを配合した貼付剤を製造し、その効果を試験した
ところ、このものの経皮吸収は不十分で目的とする薬理
効果を得ることができず、実用に供し得ないことが判明
した。On the other hand, in recent years, it has been reported that a drug such as CP is contained in a hydrous gel to form a patch (see JP-A-59-25320). However, of course, when a patch containing CP was manufactured according to the description of the patent publication and its effect was tested, the transdermal absorption of this product was insufficient and the desired pharmacological effect could not be obtained, and it was practically used. It turned out that it could not be used for.
本発明者等は、持続性の高いCP製剤が開発されれば気管
支炎、喘息等の患者の発作の予防に極めて有用なことか
ら、CPの外用による投与につき種々検討を重ねたとこ
ろ、CPは水溶性が高く、通常の外用剤形態ではほとんど
経皮吸収されないことが明らかとなつた。The present inventors, after development of a highly durable CP preparation, is extremely useful for preventing seizures in patients with bronchitis, asthma, etc. It was revealed that it is highly water-soluble and is hardly percutaneously absorbed in the usual external preparation form.
従つて、CPを安定し保持し、基剤からの放出性が良く、
経皮吸収させることの可能な製剤が望まれていた。Therefore, it keeps CP stable and has good release from the base,
A formulation capable of percutaneous absorption has been desired.
本発明者等は、CPの物理化学的性質及び各種外用剤基剤
からの放出性につき鋭意研究を重ねた結果、基剤からの
CPの放出を促進する物質を見い出し、更に製剤全体のpH
を８〜10に調整すれば、CPを経費的に吸収させることが
可能になることを見い出し、本発明を完成した。The inventors of the present invention have conducted extensive studies on the physicochemical properties of CP and the release properties from various external preparation bases, and as a result,
We found a substance that accelerates the release of CP,
It was found that the CP can be absorbed cost-effectively by adjusting 8 to 8 to 10 and the present invention has been completed.
すなわち本発明は、次の（１）〜（３） （１）塩酸クロルプレナリン 0.1〜10重量％ （２）プロピレグリコール、ブチレングリコール、ベン
ジルアルコール、ミリスチン酸イソプロピル、セバシン
酸ジエチル、ジエチルトルアミド及びシクロデキストリ
ンからなる群より選ばれる１種又は２種以上の放出改善
剤 １〜10重量％ （３）貼付剤用基剤 全量が100重量％になる量 よりなり、かつpH8〜10に調整した気管支拡張用含水貼
付剤及びその製法を提供するものである。That is, the present invention provides the following (1) to (3) (1) chlorprenaline hydrochloride 0.1 to 10% by weight (2) propylene glycol, butylene glycol, benzyl alcohol, isopropyl myristate, diethyl sebacate, diethyl toluamide. And 1 or 2 or more release-improving agents selected from the group consisting of cyclodextrin 1 to 10% by weight (3) The amount of the base for patches is 100% by weight, and the pH is adjusted to 8 to 10 A water-containing patch for bronchodilation and a method for producing the same.
本発明で用いるCPの放出改善剤とは、基剤からのCPの放
出を促進する性質を有する物質であつて、貼付剤用基剤
に含有させることが可能なものであり、用いる基剤成分
との相溶性を考慮して、プロピレングリコール、ブチレ
ングリコール、ベンジルアルコール、ミリスチン酸イソ
プロピル、セバシン酸ジエチル、ジエチルトリアミド及
びシクロデキストリンから１種又は２種以上を適宜選択
して使用することができる。The CP release-improving agent used in the present invention is a substance having a property of accelerating the release of CP from the base, which can be contained in the base for patch, and is a base component used. In consideration of the compatibility with propylene glycol, butylene glycol, benzyl alcohol, isopropyl myristate, diethyl sebacate, diethyltriamide and cyclodextrin, one kind or two kinds or more can be appropriately selected and used.
放出改善剤は、CPの放出能を示す濃度であれば良く、１
〜20重量％（以下、％で示す）の範囲で使用できるが、
基剤との相溶性、製剤全体の安定性、使用感等を考慮す
るならば、１〜10％、更に好ましくは、３〜８％で添加
できる。The release-improving agent may be any concentration as long as it exhibits CP-releasing ability.
It can be used in the range of up to 20% by weight (hereinafter referred to as%),
Considering the compatibility with the base, the stability of the whole preparation, the feeling of use, etc., it can be added at 1 to 10%, more preferably 3 to 8%.
主剤であるCPは、薬効量、即ち有効血中濃度が得られる
量を基剤中に含有させれば良く、放出改善剤あるいは基
剤とのバランス、製剤全体の安定性、使用感等を考慮し
て決められるが、通常0.1〜10％の範囲、好ましくは１
〜５％の範囲で含有させることができる。CP, which is the main ingredient, should be contained in the base in a medicinal amount, that is, an amount that provides an effective blood concentration.Consideration of the balance with the release-improving agent or the base, stability of the whole formulation, feeling of use, etc. However, it is usually in the range of 0.1 to 10%, preferably 1
It can be contained in the range of up to 5%.
CPの投与量としては、１回５〜50mgの範囲、特に10〜30
mgとなるように設定するのが好ましい。The dose of CP is in the range of 5 to 50 mg, especially 10 to 30
It is preferable to set it to be mg.
また、本発明で用いる貼付剤用基剤としては、通常貼付
剤に使用されるものであればいずれも使用でき、例えば
ゼラチン、キサンタンガム、カラギナン、寒天、アルギ
ン酸ナトリウム、アルギン酸プロピレングリコール、カ
ゼイン、カゼインナトリウム、メチルセルロース、カル
ボキシメチルセルロース、ハイドロキシプロピルセルロ
ース、ポリビニルアルコール、ポリアクリル酸ナトリウ
ムなどの水溶性高分子化合物；ポリブテン、ポリイソプ
レン、流動パラフインなどの油溶性化合物；アクリル酸
デンプンなどの高分子架橋体；グリセリン、ソルビトー
ルなどの多価アルコール類；カオリン、ベントナイト、
酸化チタン、酸化亜鉛、タルク、水酸化アルミニウムな
どの水不溶性の粉末；ソルビタン脂肪酸エステル、モノ
オレイン酸ポリオキシエチレンソルビタン、モノラウリ
ル酸ポリオキシエチレンソルビタンなどの乳化剤；パラ
オキシ安息香酸エステル類；塩化ベンザルコニウム、安
息香酸ナトリウムなどの防腐剤などが挙げられる。Moreover, as the patch base used in the present invention, any of those usually used for patches can be used, for example, gelatin, xanthan gum, carrageenan, agar, sodium alginate, propylene glycol alginate, casein, sodium caseinate. , Water-soluble polymer compounds such as methyl cellulose, carboxymethyl cellulose, hydroxypropyl cellulose, polyvinyl alcohol and sodium polyacrylate; oil-soluble compounds such as polybutene, polyisoprene and liquid paraffin; polymer cross-linked products such as acrylate starch; glycerin, Polyhydric alcohols such as sorbitol; kaolin, bentonite,
Water-insoluble powders of titanium oxide, zinc oxide, talc, aluminum hydroxide, etc .; Emulsifiers such as sorbitan fatty acid ester, polyoxyethylene sorbitan monooleate, polyoxyethylene sorbitan monolaurate; paraoxybenzoic acid esters; benzalco chloride Preservatives such as sodium and sodium benzoate are listed.
本発明の貼付剤において、CP及び放出改善剤を含有する
製剤全体のpHを８〜10に調整するためのpH調整剤は、貼
付剤の種類により適宜選択できる。例えば貼付剤基剤の
pH値により、酸又は塩基が用いられる。また貼付剤基剤
の特性も考慮して、有機性あるいは無機性の酸あるいは
塩基が用いられる。例えば塩酸、リン酸などの無機酸；
マレイン酸、クエン酸、酒石酸、グルコン酸、乳酸など
の有機酸；水酸化ナトリウム、水酸化カリウムなどの無
機塩基；トリエタノールアミン、ジイソプロパノールア
ミン、ジエタノールアミン、トリイソプロパノールアミ
ンなどの有機塩基；更に炭酸ナトリウム、炭酸カルシウ
ム、炭酸水素ナトリウム、ピロリン酸ナトリウム、メタ
リン酸ナトリウムなどの無機塩；無水マレイン酸、グル
コノデルタラクトンなど水溶液中で反応して、酸又は塩
基の働きをする化合物などが用いられる。In the patch of the present invention, the pH adjusting agent for adjusting the pH of the entire preparation containing CP and the release improving agent to 8 to 10 can be appropriately selected depending on the type of patch. For example of the patch base
Depending on the pH value, acids or bases are used. An organic or inorganic acid or base is used in consideration of the characteristics of the patch base. Inorganic acids such as hydrochloric acid and phosphoric acid;
Organic acids such as maleic acid, citric acid, tartaric acid, gluconic acid and lactic acid; inorganic bases such as sodium hydroxide and potassium hydroxide; organic bases such as triethanolamine, diisopropanolamine, diethanolamine and triisopropanolamine; sodium carbonate Inorganic salts such as calcium carbonate, sodium hydrogencarbonate, sodium pyrophosphate, and sodium metaphosphate; and compounds such as maleic anhydride and gluconodeltalactone that react in an aqueous solution to act as an acid or a base are used.
本発明貼付剤は、例えばCP、放出改善剤及び貼付剤用基
剤を均一に混合した泥状物のpHを８〜10に調整し、必要
に応じてこれを支持体に遅延することにより製造され
る。更に具体的には、例えば基剤成分中の水溶性高分子
化合物、多価アルコールなどの水可溶性成分及びCPを水
に溶解し、更にCP放出改善剤、乳化剤などを添加して練
合し、最後にpH調整剤を加えてpHを８〜10に調整して練
合して均質な膏体を製し、必要に応じてこれを不織布な
どの支持体に遅延し、ライナーを貼り合わせるなどの方
法により製造される。本発明貼付剤の製法は、基剤の組
み合わせにより、最適の方法を選択することができ、例
示した方法に限定されるものではない。The patch of the present invention is produced, for example, by adjusting the pH of a mud-like substance in which CP, a release-improving agent and a patch base are uniformly mixed to 8 to 10, and delaying this to a support, if necessary. To be done. More specifically, for example, a water-soluble polymer compound in the base component, a water-soluble component such as a polyhydric alcohol and CP are dissolved in water, and further a CP release-improving agent, an emulsifier, etc. are added and kneaded, Finally, add a pH adjuster to adjust the pH to 8-10 and knead to make a homogeneous plaster, delay it to a non-woven fabric support, and attach a liner if necessary. Manufactured by the method. The production method of the patch of the present invention can be selected as an optimum method depending on the combination of bases, and is not limited to the exemplified method.
〔作用〕 本発明貼付剤に使用される放出改善剤は、後記試験例か
らも明らかな如く、水溶性の高いCPを基剤から放出させ
る作用を有する。そして、かかる作用は、製剤のpHが８
以上のときに特に顕著である。[Action] The release-improving agent used in the patch of the present invention has the action of releasing highly water-soluble CP from the base, as is clear from the test examples below. And, such action has the effect that the pH of the preparation is 8
It is particularly remarkable in the above cases.
本発明貼付剤は、CP放出性が高くCPを経皮吸収させるこ
とが可能であり、薬効が持続することから、喘息等の夜
間ないし早期の発作の予防に特に有用である。INDUSTRIAL APPLICABILITY The patch of the present invention has a high CP-releasing property and is capable of transdermally absorbing CP, and since the drug effect continues, it is particularly useful for preventing nighttime or early attacks such as asthma.
なお、貼付部位としては、気管支、肺に近い部位が特に
好ましい。It should be noted that a site near the bronchus or lungs is particularly preferred as the site of application.
次に試験例及び実施例を挙げて説明する。 Next, test examples and examples will be described.
試験例１ インビトロ放出試験： 第１図に示す装置を用いた。３は円筒セルで、その一端
にラツト腹部皮膚２を張り、その内面に後記実施例１で
得られた貼付剤に用いた膏体を塗布した。これをリン酸
緩衝液（pH7.4、37℃）４に浸漬し液を撹拌子５により
撹拌した。５時間後、この放出液系に存在する塩酸クロ
ルプレナリンの濃度をガスクロマトグラフ法を用いて測
定した。Test Example 1 In vitro release test: The device shown in FIG. 1 was used. 3 is a cylindrical cell, the rat abdominal skin 2 was attached to one end thereof, and the plaster used in the patch obtained in Example 1 below was applied to the inner surface thereof. This was immersed in a phosphate buffer solution (pH 7.4, 37 ° C.) 4 and the solution was stirred by a stirrer 5. After 5 hours, the concentration of chlorprenaline hydrochloride present in this release liquid system was measured by gas chromatography.
結果を表‐１に示した。The results are shown in Table-1.
試験例２ 放出量のpH依存性： 後記実施例２で得た貼付剤（本発明品４）の膏体を用
い、放出液のpHを５〜10の範囲で変えた以外は試験例１
と同様にして放出試験を行なつた。 Test Example 2 pH Dependence of Release Amount: Test Example 1 except that the plaster of the patch (invention product 4) obtained in Example 2 below was used and the pH of the release liquid was changed within the range of 5 to 10.
A release test was conducted in the same manner as in.
結果を表‐２を示した。The results are shown in Table-2.
尚、pHが10を超えるものは、皮膚刺激が強く実用に供し
得ないものであつた。 Those having a pH of more than 10 had strong skin irritation and could not be put to practical use.
試験例３ 各種放出改善剤の効果： 後記実施例２及び３で得た各種放出改善剤を含有する貼
付剤の膏体を用い、試験例１と同様にして放出試験を行
なつた。なお、いずれの膏体もpH8に調整した。Test Example 3 Effect of various release-improving agents: Using the plasters of patches containing the various release-improving agents obtained in Examples 2 and 3 below, a release test was conducted in the same manner as in Test Example 1. In addition, all plasters were adjusted to pH 8.
結果を表‐３に示した。The results are shown in Table-3.
実施例１ 次の表‐４に示す組成の貼付剤膏体を下記方法により調
製し貼付剤を製造した。 Example 1 An adhesive patch having the composition shown in Table 4 below was prepared by the following method to produce an adhesive patch.
（製法） 水35部に50〜60℃でゼラチン３重量部（以下、単に部と
いう）、アルギン酸ナトリウム３部を加えて撹拌、溶解
し、塩酸クロルプレナリン0.1部、安息香酸ナトリウム
0.2部を加えて溶かす。次いで水６部にカルボキシルビ
ニルポリマー0.3部を溶解させた液を加えた後、ポリア
クリル酸ナトリウム7.5部をグリセリン30部に分散させ
た液を加えて練合し、更にミリスチン酸イソプロピル10
部とポリソルベート80 0.2部を混合した液を加えた
後、グルコノデルタラクトンを適量加えてpH8.0に調整
し、全量が100部となるように水を加えてよく練合し膏
体を調製する。得られた膏体を不織布面上に均一に展延
し、膏体面にプラステツクフイルムを貼り合わせた後、
所要の面積に裁断し貼付剤（本発明品１）を得た。 (Production method) 3 parts by weight of gelatin (hereinafter referred to as "parts") and 3 parts of sodium alginate are added to 35 parts of water at 50 to 60 ° C, stirred and dissolved, and 0.1 part of chlorprenaline hydrochloride and sodium benzoate are added.
Add 0.2 parts to dissolve. Next, a solution prepared by dissolving 0.3 part of carboxyl vinyl polymer in 6 parts of water was added, and then a solution prepared by dispersing 7.5 parts of sodium polyacrylate in 30 parts of glycerin was added and kneaded. Further, 10 parts of isopropyl myristate were added.
Parts and polysorbate 80 0.2 parts were mixed, then gluconodeltalactone was added in an appropriate amount to adjust the pH to 8.0, and water was added so that the total amount became 100 parts, and the mixture was well kneaded to prepare a paste. To do. After uniformly spreading the obtained plaster on the non-woven fabric surface, after laminating the plastic film to the plaster surface,
The patch was cut into a required area to obtain a patch (product 1 of the present invention).
また、本発明品１と同様にして本発明品２、３及び比較
品１を得た。Further, the present invention products 2 and 3 and the comparative product 1 were obtained in the same manner as the present invention product 1.
かくして得られる貼付剤の塩酸クロルプレナリン添加量
は、例えば膏体100gを1,000cm2の面積に展延し、100cm2
の面積に裁断した場合、貼付剤１枚当り10mgとなる。Thus hydrochloride clorprenaline amount of the adhesive agent obtained, for example by spreading the plaster 100g to an area of 1,000 cm2, 100 cm2
When cut to the area of, the amount of patch is 10 mg per patch.
実施例２ 70℃の水43.9部にゼラチン３部を加え、ゼラチンが完全
に溶解するまで撹拌を続ける。この液にグルコノデルタ
ラクトン0.4部を加えて撹拌して溶解させる。次いでこ
の液にグリセリン30部にポリアクリル酸ナトリウム５
部、アルギン酸ナトリウム２部を加えて撹拌して分散さ
せた液を撹拌しながら徐々に加え、更に水10部に塩酸ク
ロルプレナリン0.5部を溶解した液を加えて練合する。
次にミリスチン酸イソプロピル2.5部、N,N-ジエチル‐m
-トルアミド2.5部にニツコールTL-10（日光ケミカルズ
製）0.2部を加えて混合した液を加え、全体が均一にな
るまで練合し、膏体を調製する。得られた膏体を不織布
面上に厚さ1mmで均一に展延し、膏体面にプラスチック
フイルムを貼合わせた後、所要の面積に裁断して貼付剤
（本発明品４）を得た。Example 2 3 parts of gelatin was added to 43.9 parts of water at 70 ° C., and stirring was continued until the gelatin was completely dissolved. 0.4 parts of glucono delta lactone is added to this liquid and stirred to dissolve. Then add 30 parts of glycerin to 5 parts of sodium polyacrylate.
Part, and 2 parts of sodium alginate are added and stirred to disperse the liquid, and the mixture is gradually added with stirring. Further, a solution in which 0.5 part of chlorprenaline hydrochloride is dissolved in 10 parts of water is added and kneaded.
Then 2.5 parts of isopropyl myristate, N, N-diethyl-m
-To 2.5 parts of toluamide, 0.2 parts of Niitsukol TL-10 (manufactured by Nikko Chemicals Co., Ltd.) was added and mixed, and the mixture was kneaded until the whole became uniform to prepare a plaster. The obtained plaster was uniformly spread on the non-woven fabric surface in a thickness of 1 mm, a plastic film was stuck on the plaster surface, and then cut into a required area to obtain a plaster (Product 4 of the present invention).
また、本発明品４において、ミリスチン酸イソプロピル
（IPM）2.5部及びN,N−ジエチル−ｍ−トルアミド（DET
A）2.5部の代りに放出改善剤としてIPM2.5部＋ベンジル
アルコール（BzOH）2.5部（本発明品５）、DETA2.5部＋
BzOH2.5部（本発明品６）、DETA5部（本発明品７）、IP
M5部（本発明品８）、無添加（比較品２）を用いる以外
は本発明品４と同様にして貼付剤を得た。Further, in the product 4 of the present invention, 2.5 parts of isopropyl myristate (IPM) and N, N-diethyl-m-toluamide (DET
A) 2.5 parts of IPM as a release improver in place of 2.5 parts + 2.5 parts of benzyl alcohol (BzOH) (invention product 5), 2.5 parts of DETA +
BzOH 2.5 parts (invention product 6), DETA5 parts (invention product 7), IP
A patch was obtained in the same manner as in the product 4 of the present invention except that M5 part (product 8 of the present invention) and no additive (comparative product 2) were used.
実施例３ 70℃の水29.7部にゼラチン６部を加え、ゼラチンが完全
に溶解するまで撹拌を続ける。液の温度が50℃以下にな
らないよう保温しながら、カルボキシビニルポリマー0.
6部を水12部に溶解し、一夜放置した液を加えて撹拌し
均一な液とする。この液にカルボキシメチルセルロース
ナトリウム６部をグリセリン20部に加えて分散させた液
を加えて撹拌し溶解させる。更に、これに保温しながら
ポリビニルアルコール２部を90℃の水10部に溶解させ一
夜放置した。液を加え撹拌する。撹拌しながら、トリエ
タノールアミン３部、水５部に塩酸クロルプレナリン0.
5部を溶解させた液を順次加える。最後にベンジルアル
コール５部とニツコールTO-10（日光ケミカルズ製）0.2
部を混合した液を加え全体が均一になるまで練合する。
以下実施例１と同様に操作し貼付剤（本発明品９）を製
する。Example 3 6 parts of gelatin was added to 29.7 parts of water at 70 ° C., and stirring was continued until the gelatin was completely dissolved. Carboxyvinyl polymer 0 while keeping the temperature of the liquid below 50 ° C.
Dissolve 6 parts in 12 parts water, add the solution left overnight, and stir to make a uniform solution. A solution prepared by adding 6 parts of sodium carboxymethyl cellulose to 20 parts of glycerin and dispersing the solution is added and stirred to dissolve. Further, 2 parts of polyvinyl alcohol was dissolved in 10 parts of water at 90 ° C. while keeping it warm and left overnight. Add liquid and stir. Chlorprenaline hydrochloride (3 parts) and water (5 parts) with stirring.
A solution in which 5 parts are dissolved is sequentially added. Finally, 5 parts of benzyl alcohol and Nitzkor TO-10 (Nikko Chemicals) 0.2
Add the mixed solution and knead until the whole is uniform.
Then, the same operation as in Example 1 is carried out to produce a patch (product 9 of the present invention).
また、本発明品９において、ベンジルアルコール５部の
代りに放出改善剤としてセバシン酸ジエチル５部（本発
明品10）、β‐シクロデキストリン１部（本発明品1
1）、プロピレングリコール５部（本発明品12）、ブチ
ルグリコール５部（本発明品13）を用いる以外は本発明
品９と同様にして貼付剤を得た。Further, in the product 9 of the present invention, 5 parts of diethyl sebacate (the product 10 of the present invention) and 1 part of β-cyclodextrin (the product 1 of the present invention) were used as the release improving agent in place of the 5 parts of benzyl alcohol.
A patch was obtained in the same manner as in Product 9 of the present invention except that 1), 5 parts of Propylene glycol (Product 12 of the present invention) and 5 parts of butyl glycol (Product 13 of the present invention) were used.
第１図は、試験例１においてCPのインビトロ放出試験に
使用した装置の概略説明図である。FIG. 1 is a schematic explanatory view of an apparatus used for an in vitro release test of CP in Test Example 1.
───────────────────────────────────────────────────── フロントページの続き (51)Int.Cl.5 識別記号 庁内整理番号 ＦＩ 技術表示箇所 Ａ６１Ｋ 47/14 Ｎ 7433−4Ｃ 47/16 Ｎ 7433−4Ｃ 47/40 Ｎ 7433−4Ｃ (72)発明者 村松 豊二郎 埼玉県狭山市狭山台１−４―９ (56)参考文献 特開 昭59−25320（ＪＰ，Ａ) 特開 昭57−4917（ＪＰ，Ａ) 特開 昭60−156607（ＪＰ，Ａ) 特開 昭55−143912（ＪＰ，Ａ) 特開 昭56−142209（ＪＰ，Ａ) 特開 昭60−174716（ＪＰ，Ａ) 特開 昭60−16917（ＪＰ，Ａ) 特開 昭60−36422（ＪＰ，Ａ) 特開 昭62−53933（ＪＰ，Ａ) 特開 昭61−17513（ＪＰ，Ａ)─────────────────────────────────────────────────── ─── Continuation of the front page (51) Int.Cl.5 Identification code Office reference number FI Technical display location A61K 47/14 N 7433-4C 47/16 N 7433-4C 47/40 N 7433-4C (72) Inventor Toyojiro Muramatsu 1-4-9 Sayamadai, Sayama City, Saitama Prefecture (56) Reference JP 59-25320 (JP, A) JP 57-4917 (JP, A) JP 60-156607 ( JP, A) JP 55-143912 (JP, A) JP 56-142209 (JP, A) JP 60-174716 (JP, A) JP 60-16917 (JP, A) JP JP-A-60-36422 (JP, A) JP-A-62-53933 (JP, A) JP-A-61-17513 (JP, A)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP60245020AJPH0667825B2 (en) | 1985-10-31 | 1985-10-31 | Water-containing patch for bronchodilation and method for producing the same |
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP60245020AJPH0667825B2 (en) | 1985-10-31 | 1985-10-31 | Water-containing patch for bronchodilation and method for producing the same |
| Publication Number | Publication Date |
|---|---|
| JPS62106014A JPS62106014A (en) | 1987-05-16 |
| JPH0667825B2true JPH0667825B2 (en) | 1994-08-31 |
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP60245020AExpired - Fee RelatedJPH0667825B2 (en) | 1985-10-31 | 1985-10-31 | Water-containing patch for bronchodilation and method for producing the same |
| Country | Link |
|---|---|
| JP (1) | JPH0667825B2 (en) |
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2933944B2 (en)* | 1989-03-29 | 1999-08-16 | 日東電工株式会社 | Medical patch |
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS55143912A (en)* | 1980-01-28 | 1980-11-10 | Sumitomo Chem Co Ltd | Useful preparation comprising bencyclane fumarate |
| ZA811288B (en)* | 1980-03-06 | 1982-03-31 | Merck & Co Inc | N,n-diethyl-m-toluamide for enhancing skin permeation of bio-affecting agents |
| JPS574917A (en)* | 1980-06-12 | 1982-01-11 | Nitto Electric Ind Co Ltd | Material for medical purpose |
| JPS5925320A (en)* | 1982-08-02 | 1984-02-09 | Watanabe Yakuhin Kogyo Kk | Plaster for drug administration |
| US4557934A (en)* | 1983-06-21 | 1985-12-10 | The Procter & Gamble Company | Penetrating topical pharmaceutical compositions containing 1-dodecyl-azacycloheptan-2-one |
| JPS6016917A (en)* | 1983-07-08 | 1985-01-28 | Yamanouchi Pharmaceut Co Ltd | Ointment of nicardipine hydrochloride or nifedipine |
| JPS60156607A (en)* | 1984-01-25 | 1985-08-16 | Fujisawa Pharmaceut Co Ltd | Percutaneous absorption pharmaceutical containing 2- nitroxymethyl-6-chloropyridine or beta-cyclodextrin clathrate compound therefof |
| JPS60174716A (en)* | 1984-02-21 | 1985-09-09 | Yamanouchi Pharmaceut Co Ltd | Medicinal patch |
| ZA853488B (en)* | 1984-05-10 | 1986-12-30 | American Home Prod | Transdermal dosage form |
| JPS6253933A (en)* | 1985-09-02 | 1987-03-09 | Nitto Electric Ind Co Ltd | Composition for exodermal administration |
| Publication number | Publication date |
|---|---|
| JPS62106014A (en) | 1987-05-16 |
| Publication | Publication Date | Title |
|---|---|---|
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| Date | Code | Title | Description |
|---|---|---|---|
| R250 | Receipt of annual fees | Free format text:JAPANESE INTERMEDIATE CODE: R250 | |
| LAPS | Cancellation because of no payment of annual fees |