JP5307309B2 - External preparation containing prednisolone valerate acetate and basic local anesthetic - Google Patents
External preparation containing prednisolone valerate acetate and basic local anesthetic Download PDFInfo
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Description
本発明は、吉草酸酢酸プレドニゾロン及び塩基性局所麻酔薬を配合してなる外用剤に関し、詳しくは、吉草酸酢酸プレドニゾロンを長期間安定に配合することのできる、吉草酸酢酸プレドニゾロン及び塩基性局所麻酔薬を配合した外用剤に関する。 The present invention relates to an external preparation comprising prednisolone valerate acetate and a basic local anesthetic, and more specifically, prednisolone valerate acetate and basic local anesthesia capable of stably containing prednisolone valerate for a long period of time. The present invention relates to an external preparation containing a medicine.
近年、アトピー性皮膚炎に代表される皮膚疾患が蔓延し、その治療薬の研究も急速に進歩している。これらの炎症を伴う皮膚疾患にはステロイド薬が適用されている。
吉草酸酢酸プレドニゾロンは、皮膚表面の患部で抗炎症効果の高いステロイドとして働き、体内に吸収されると分解されその副作用が弱くなる、所謂アンテドラッグステロイド薬として湿疹、皮膚炎、かぶれ、あせも、ただれ、蕁麻疹などの外用治療薬として汎用されている。
また、患部の痛み、かゆみ、ほてり等を抑えることを目的として局所麻酔薬が外用剤に配合され使用されている。
アトピー性皮膚炎に代表される皮膚疾患の治療薬としては、湿疹、皮膚炎、かぶれ、あせも、ただれ、蕁麻疹などの皮膚疾患に加え、患部の痛み、かゆみ、ほてりなどを伴う疾患を１剤で治療できる外用剤が望まれており、ステロイド薬と局所麻酔薬を同時に配合した外用剤の調製が試みられているが、吉草酸酢酸プレドニゾロンと塩基性局所麻酔薬とを同時に配合した外用剤は今まで知られていなかった。In recent years, skin diseases typified by atopic dermatitis have spread, and research on therapeutic agents has been rapidly progressing. Steroid drugs have been applied to these inflammatory skin diseases.
Prednisolone valerate acts as a highly anti-inflammatory steroid in the affected area of the skin surface, and when it is absorbed into the body, its side effects are weakened. So-called ante-drug steroid drugs such as eczema, dermatitis, rash, and rashes It is widely used as an external treatment for urticaria.
Moreover, a local anesthetic is blended and used in an external preparation for the purpose of suppressing pain, itchiness, hot flashes and the like in the affected area.
As a therapeutic agent for skin diseases represented by atopic dermatitis, in addition to skin diseases such as eczema, dermatitis, rash, dry skin, urticaria, urticaria, etc., one drug that causes pain, itching, hot flashes, etc. However, the preparation of an external preparation containing a steroid and a local anesthetic at the same time has been attempted, but an external preparation containing prednisolone valerate and a basic local anesthetic is used at the same time. It was not known until now.
しかしながら、吉草酸酢酸プレドニゾロンと塩基性局所麻酔薬とを同時に配合した外用剤を調製した場合、製剤中の吉草酸酢酸プレドニゾロンが経時的に不安定となり、特に剤形を製剤中の水分含量が比較的高いクリーム剤、乳剤等とした場合に顕著に経時的に不安定となるため、吉草酸酢酸プレドニゾロンと塩基性局所麻酔薬とを同時に配合した安定な外用剤の調製は極めて困難であった。 However, when an external preparation containing prednisolone valerate acetate and a basic local anesthetic was prepared at the same time, prednisolone valerate acetate in the preparation became unstable over time. Therefore, it is extremely difficult to prepare a stable external preparation containing prednisolone valerate acetate and a basic local anesthetic at the same time.
本発明者は、上記事実に鑑み鋭意検討した結果、吉草酸酢酸プレドニゾロンと塩基性局所麻酔薬を配合した外用剤を特定のｐＨに調整することにより、外用剤中の吉草酸酢酸プレドニゾロンを経時的に安定化できることを見出し、本発明を完成した。 As a result of intensive studies in view of the above facts, the present inventor adjusted prednisolone valerate acetate in an external preparation over time by adjusting the external preparation containing prednisolone valerate acetate and a basic local anesthetic to a specific pH. The present invention has been completed.
即ち、本発明は、吉草酸酢酸プレドニゾロン及び塩基性局所麻酔薬を同時に配合した外用剤を精製水で１０倍に希釈したときの懸濁液のｐＨを３〜７の範囲とすることによって、吉草酸酢酸プレドニゾロンを安定化した外用剤及びその安定化方法を提供するものである。本発明の外用剤は吉草酸酢酸プレドニゾロンのもつ湿疹、皮膚炎、かぶれ、あせも、ただれ、蕁麻疹などの皮膚疾患治療作用及び局所麻酔薬のもつ患部の痛み、かゆみ、ほてりなどを伴う疾患の治療作用を併せ持つ、長期間保存が可能な外用剤として有用である。 That is, the present invention provides a solution having a pH of 3 to 7 when the external preparation containing simultaneously prednisolone valerate acetate and a basic local anesthetic is diluted 10 times with purified water. It is intended to provide an external preparation stabilized with prednisolone valerate and a method for stabilizing the same. The topical preparation of the present invention is used to treat skin diseases such as eczema, dermatitis, rash, rash, sores, urticaria, etc. with prednisolone valerate and treatment of diseases associated with pain, itching, hot flashes, etc. It is useful as an external preparation that has an action and can be stored for a long period of time.
本発明の外用剤は、軟膏剤、乳剤、クリーム剤があげられ、水中油型製剤、油中水型製剤のいずれも含む。この中でも特にクリーム剤、乳剤が好ましい。 The external preparation of the present invention includes ointments, emulsions and creams, and includes both oil-in-water preparations and water-in-oil preparations. Of these, creams and emulsions are particularly preferred.
本発明の外用剤に使用される塩基性局所麻酔薬は、リドカイン、ジブカイン、テトラカイン、オキシジブカイン、ブピバカイン、メピバカイン、プロピトカイン、パラブチルアミノ安息香酸ジエチルアミノエチルなどであり、その中でもリドカイン、ジブカイン、テトラカインが好ましく、特に好ましいのはリドカインである。 Examples of the basic local anesthetic used in the external preparation of the present invention include lidocaine, dibucaine, tetracaine, oxydibucaine, bupivacaine, mepivacaine, propitocaine, diethylaminoethyl parabutylaminobenzoate, and the like, among which lidocaine, dibucaine, tetra Caine is preferred, and lidocaine is particularly preferred.
本発明の外用剤に使用される基剤は、ワセリン、プラスチベース、パラフィン、流動パラフィン、軽質流動パラフィン、サラシミツロウ、ベヘニルアルコール、ステアリルアルコール、セタノール、ステアリン酸、ベヘニン酸、シリコーン油などの油脂性基剤；水、マクロゴール、エタノール、メチルエチルケトン、綿実油、オリーブ油、落花生油などの溶剤；ポリオキシエチレン硬化ヒマシ油、ポリオキシエチレンソルビタン脂肪酸エステル、グリセリン脂肪酸エステル、ポリオキシエチレン脂肪酸エステル、ポリオキシエチレンアルキルエーテル、ソルビタン脂肪酸エステル、ポリオキシエチレンポリオキシプロピレングリコールなどの非イオン性界面活性剤又はラウリル硫酸ナトリウム、セチル硫酸ナトリウムなどのイオン性界面活性剤などの乳化剤；ポリビニルピロリドン、カルボキシメチルセルロース、コロイド性含水ケイ酸アルミニウム、キサンタンガム、ローカストビーンガム、トラガントガム、グアーガム、ゼラチン、アラビアゴム、アルギン酸、アルブミンなどの増粘剤；オキシベンゾン、ジブチルヒドロキシトルエン、エデト酸ナトリウムなどの安定化剤；ヒアルロン酸ナトリウム、コンドロイチン硫酸ナトリウム、グリセリン、１，３−ブチレングリコール、プロピレングリコール、尿素、ショ糖、エリスリトール、ソルビトールなどの保湿剤；パラオキシ安息香酸メチル、パラオキシ安息香酸エチル、パラオキシ安息香酸プロピル、パラオキシ安息香酸ブチル、デヒドロ酢酸ナトリウム、ｐ−クレゾールなどの防腐剤であり、剤形に応じて適宜選択して使用する。 The base used in the external preparation of the present invention is an oily base such as petrolatum, plastibase, paraffin, liquid paraffin, light liquid paraffin, white beeswax, behenyl alcohol, stearyl alcohol, cetanol, stearic acid, behenic acid, silicone oil, etc. Solvents such as water, macrogol, ethanol, methyl ethyl ketone, cottonseed oil, olive oil, peanut oil; polyoxyethylene hydrogenated castor oil, polyoxyethylene sorbitan fatty acid ester, glycerin fatty acid ester, polyoxyethylene fatty acid ester, polyoxyethylene alkyl ether, Nonionic surfactants such as sorbitan fatty acid ester and polyoxyethylene polyoxypropylene glycol or ionic surfactants such as sodium lauryl sulfate and sodium cetyl sulfate Emulsifiers such as polyvinylpyrrolidone, carboxymethylcellulose, colloidal hydrous aluminum silicate, xanthan gum, locust bean gum, tragacanth gum, guar gum, gelatin, gum arabic, alginic acid, albumin, etc .; oxybenzone, dibutylhydroxytoluene, sodium edetate Stabilizers such as sodium hyaluronate, sodium chondroitin sulfate, glycerin, 1,3-butylene glycol, propylene glycol, urea, sucrose, erythritol, sorbitol, etc .; methyl paraoxybenzoate, ethyl paraoxybenzoate, paraoxy Preservatives such as propyl benzoate, butyl paraoxybenzoate, sodium dehydroacetate, p-cresol, etc. To.
本発明の外用剤は精製水で１０倍に希釈したときの懸濁液がｐＨ３〜７であるように調整することができるが、ｐＨ調整するためには、クエン酸、乳酸、リン酸、リンゴ酸、酒石酸、酢酸、ソルビン酸、塩酸などの酸又はそれらのナトリウム塩、カリウム塩、カルシウム塩などの水溶性の酸又はそれらの塩の１種又は２種以上を使用する。好ましくはクエン酸、乳酸、リンゴ酸である。酸又はそれらの塩の配合量は、本発明の目的を達成できる量であればよく、外用剤全組成物に対して０．０１〜１０重量％が好ましく、特に０．１〜５重量％が好ましい。 The external preparation of the present invention can be adjusted so that the suspension when diluted 10 times with purified water has a pH of 3 to 7, but in order to adjust the pH, citric acid, lactic acid, phosphoric acid, apple One or two or more of acids such as acid, tartaric acid, acetic acid, sorbic acid and hydrochloric acid, or water-soluble acids such as sodium salt, potassium salt and calcium salt, or salts thereof are used. Citric acid, lactic acid and malic acid are preferred. The compounding amount of the acid or a salt thereof may be an amount that can achieve the object of the present invention, and is preferably 0.01 to 10% by weight, particularly 0.1 to 5% by weight based on the total composition of the external preparation. preferable.
吉草酸酢酸プレドニゾロンと塩基性局所麻酔薬の配合比率は、吉草酸酢酸プレドニゾロン１重量部に対して塩基性局所麻酔薬０．１〜１００重量部、好ましくは３〜２０重量部である。 The mixing ratio of prednisolone valerate and basic local anesthetic is 0.1 to 100 parts by weight, preferably 3 to 20 parts by weight, based on 1 part by weight of prednisolone acetate valerate.
本発明の外用剤は、次の通り調製される。 The external preparation of the present invention is prepared as follows.
例えば、クリーム剤又は乳剤は、吉草酸酢酸プレドニゾロン、リドカインなどの親油性成分及びクエン酸、乳酸、リンゴ酸などの親水性成分を適当な基剤に別々に加温溶解し、後者を前者に添加し、ホモミキサーなどを用いて攪拌しながら乳化し、それを常温まで冷却して製する。 For example, for creams or emulsions, lipophilic components such as prednisolone valerate and lidocaine and hydrophilic components such as citric acid, lactic acid and malic acid are separately heated and dissolved in a suitable base, and the latter is added to the former Then, the mixture is emulsified with stirring using a homomixer or the like, and cooled to room temperature.
本発明の外用剤には吉草酸酢酸プレドニゾロンと塩基性局所麻酔薬のほか次の薬効成分を配合することができる。例えば、ブフェキサマク、ジクロフェナック、ケトプロフェン、インドメタシン、グリチルレチン酸などの消炎鎮痛剤；塩酸ジフェンヒドラミン、塩酸ジフェニルピラリン、マレイン酸クロルフェニラミンなどの抗ヒスタミン剤；酸化亜鉛などの収斂剤；イソプロピルメチルフェノール、塩酸クロルヘキシジンなどの殺菌剤；アスコルビン酸ナトリウム、塩酸ピリドキシン、トコフェロール、酢酸トコフェロールなどのビタミン剤；クロタミトンなどの鎮痒剤；トルナフタート、ビホナゾール、硝酸ミコナゾールなどの抗真菌剤；塩酸ナファゾリンなどの血管収縮剤；アラントインなどの創傷治癒剤；メントール、ボルネオール、カンフル、ハッカ油などの清涼化剤などが挙げられるが、これらに限定されるものではない。 In addition to prednisolone valerate acetate and a basic local anesthetic, the following pharmaceutical ingredients can be blended in the external preparation of the present invention. For example, anti-inflammatory analgesics such as bufexamac, diclofenac, ketoprofen, indomethacin, glycyrrhetinic acid; antihistamines such as diphenhydramine hydrochloride, diphenylpyraline hydrochloride, chlorpheniramine maleate; astringents such as zinc oxide; Agents; vitamins such as sodium ascorbate, pyridoxine hydrochloride, tocopherol and tocopherol acetate; antipruritic agents such as crotamiton; antifungal agents such as tolnaftate, bifonazole and miconazole nitrate; vasoconstrictors such as naphazoline hydrochloride; wound healing agents such as allantoin A cooling agent such as menthol, borneol, camphor, mint oil and the like, but is not limited thereto.
かくして得られた本発明の外用剤は、優れた経時的安定性を有するため、長期間の保存でも製剤中の吉草酸酢酸プレドニゾロンが不安定とならず、安定な吉草酸酢酸プレドニゾロン及び塩基性局所麻酔薬を配合した製剤を提供することが可能である。 Since the external preparation of the present invention thus obtained has excellent temporal stability, prednisolone valerate acetate in the preparation does not become unstable even during long-term storage, and stable prednisolone acetate valerate and basic topical It is possible to provide a preparation containing an anesthetic.
以下に実施例及び比較例を挙げて本発明を詳細に説明するが、本発明はこれらに限定されるものではない。 Hereinafter, the present invention will be described in detail with reference to Examples and Comparative Examples, but the present invention is not limited thereto.
実施例１
吉草酸酢酸プレドニゾロン０．１５ｇ、リドカイン２ｇ、パラオキシ安息香酸プロピル０．１ｇ、ポリオキシエチレン（２）セチルエーテル３．９ｇ、ポリオキシエチレン（２３）セチルエーテル３．１ｇ、セタノール９ｇ、パラフィン８ｇ、軽質流動パラフィン２．５ｇ及びラノリン３．５ｇを加温して溶解した。この溶液に、クエン酸１．５ｇ、エデト酸ナトリウム０．５ｇ及びキサンタンガム０．３ｇを溶解した熱水を加えて１００ｇとし、次いでホモミキサーを用いて乳化し、常温まで冷却してクリーム剤（水中油型）を得た。なお、本クリーム剤を精製水で１０倍に希釈し、攪拌した懸濁液のｐＨは４．３であった。Example 1
Prednisolone valerate 0.15 g, lidocaine 2 g, propyl paraoxybenzoate 0.1 g, polyoxyethylene (2) cetyl ether 3.9 g, polyoxyethylene (23) cetyl ether 3.1 g, cetanol 9 g, paraffin 8 g, light Liquid paraffin 2.5g and lanolin 3.5g were heated and dissolved. To this solution was added hot water in which 1.5 g of citric acid, 0.5 g of sodium edetate and 0.3 g of xanthan gum were dissolved to make 100 g, then emulsified using a homomixer, cooled to room temperature, and then a cream (in water Oil type) was obtained. The cream was diluted 10 times with purified water, and the pH of the stirred suspension was 4.3.
実施例２
吉草酸酢酸プレドニゾロン０．１５ｇ、リドカイン１ｇ、パラオキシ安息香酸メチル０．１ｇ、パラオキシ安息香酸プロピル０．１ｇ、白色ワセリン２５ｇ、ステアリルアルコール２０ｇ、ポリオキシエチレン（６０）硬化ヒマシ油４ｇ及びモノステアリン酸グリセリン１ｇを加温して溶解した。この溶液に、９０％乳酸０．６ｇ、アラントイン１ｇ、エデト酸ナトリウム０．５ｇ及びプロピレングリコール１２ｇを溶解した熱水を加えて１００ｇとし、次いで実施例１と同様の操作を行いクリーム剤（水中油型）を得た。なお、本クリーム剤を精製水で１０倍に希釈し、攪拌した懸濁液のｐＨは５．４であった。Example 2
0.15 g prednisolone valerate acetate, 1 g lidocaine, 0.1 g methyl paraoxybenzoate, 0.1 g propyl paraoxybenzoate, 25 g white petrolatum, 20 g stearyl alcohol, 4 g polyoxyethylene (60) hydrogenated castor oil and glyceryl monostearate 1 g was dissolved by heating. To this solution was added 100 g of hot water in which 0.6 g of 90% lactic acid, 1 g of allantoin, 0.5 g of sodium edetate and 12 g of propylene glycol were dissolved. Type). The cream was diluted 10 times with purified water, and the pH of the stirred suspension was 5.4.
実施例３
吉草酸酢酸プレドニゾロン０．１５ｇ、リドカイン０．５ｇ、パラオキシ安息香酸メチル０．０２５ｇ、パラオキシ安息香酸プロピル０．０１５ｇ、ステアリルアルコール２．５ｇ及び軽質流動パラフィン２５ｇを加温して溶解した。この溶液に、リンゴ酸０．３ｇ、エデト酸ナトリウム０．５ｇ、ラウリル硫酸ナトリウム１ｇ及びグリセリン１０ｇを溶解した熱水を加えて１００ｇとし、次いでホモミキサーを用いて乳化し、常温まで冷却して乳剤（水中油型）を得た。なお、本乳剤を精製水で１０倍に希釈し、攪拌した懸濁液のｐＨは６．０であった。Example 3
Prednisolone valerate acetate 0.15 g, lidocaine 0.5 g, methyl paraoxybenzoate 0.025 g, propyl paraoxybenzoate 0.015 g, stearyl alcohol 2.5 g and light liquid paraffin 25 g were heated and dissolved. To this solution was added hot water in which 0.3 g of malic acid, 0.5 g of sodium edetate, 1 g of sodium lauryl sulfate and 10 g of glycerin were dissolved to make 100 g, and then emulsified using a homomixer, cooled to room temperature, and emulsion (Oil-in-water type) was obtained. The emulsion was diluted 10-fold with purified water, and the pH of the stirred suspension was 6.0.
実施例４
吉草酸酢酸プレドニゾロン０．１５ｇ、リドカイン３ｇ、酢酸トコフェロール０．５ｇ、パラオキシ安息香酸エチル０．１ｇ、パラオキシ安息香酸ブチル０．１ｇ、白色ワセリン４０ｇ、セタノール１０ｇ、サラシミツロウ５ｇ、セスキオレイン酸ソルビタン（ソルビタンセスキオレイン酸エステル）５ｇ及びラウロマクロゴール（ポリオキシエチレン（８）ラウリルエーテル）０．５ｇを加温して溶解した。この溶液に、クエン酸１ｇ、リンゴ酸０．７ｇ及びエデト酸ナトリウム０．５ｇを溶解した熱水を加えて１００ｇとし、次いで実施例１と同様の操作を行いクリーム剤（油中水型）を得た。なお、本クリーム剤を精製水で１０倍に希釈し、攪拌した懸濁液のｐＨは４．０であった。Example 4
Prednisolone valerate 0.15 g, lidocaine 3 g, tocopherol acetate 0.5 g, ethyl paraoxybenzoate 0.1 g, butyl paraoxybenzoate 0.1 g, white petrolatum 40 g, cetanol 10 g, white beeswax 5 g, sesquioleate sorbitan (sorbitan 5 g of sesquioleate and 0.5 g of lauromacrogol (polyoxyethylene (8) lauryl ether) were heated and dissolved. To this solution was added 100 g of hot water in which 1 g of citric acid, 0.7 g of malic acid and 0.5 g of sodium edetate were dissolved, and then the same operation as in Example 1 was performed to obtain a cream (water-in-oil type). Obtained. The cream was diluted 10 times with purified water, and the pH of the stirred suspension was 4.0.
比較例
実施例１〜４において、各クリーム剤及び乳剤のｐＨを変動させた製剤を製造し、それを比較例とした。Comparative Example In Examples 1 to 4, preparations were prepared in which the pH of each cream and emulsion was varied, and this was used as a comparative example.
比較例１
実施例１において、クエン酸を添加しないこと以外は同様の操作を行い、精製水で１０倍に希釈し、攪拌した懸濁液のｐＨが８．８であるクリーム剤を得た。Comparative Example 1
In Example 1, the same operation was carried out except that citric acid was not added, and the mixture was diluted 10 times with purified water to obtain a cream having a stirred suspension pH of 8.8.
比較例２
実施例２において、９０％乳酸を添加しないこと以外は同様の操作を行い、精製水で１０倍に希釈し、攪拌した懸濁液のｐＨが８．５であるクリーム剤を得た。Comparative Example 2
In Example 2, the same operation was performed except that 90% lactic acid was not added, and the mixture was diluted 10-fold with purified water to obtain a cream having a stirred suspension pH of 8.5.
比較例３
実施例３において、リンゴ酸を添加しないこと以外は同様の操作を行い、精製水で１０倍に希釈し、攪拌した懸濁液のｐＨが８．２である乳剤を得た。Comparative Example 3
In Example 3, the same operation was performed except that malic acid was not added, and the emulsion was diluted 10 times with purified water, and the pH of the stirred suspension was 8.2.
比較例４
実施例４において、クエン酸及びリンゴ酸を添加しないこと以外は同様の操作を行い、精製水で１０倍に希釈し、攪拌した懸濁液のｐＨが９．０であるクリーム剤を得た。Comparative Example 4
In Example 4, the same operation was performed except that citric acid and malic acid were not added, and the mixture was diluted 10-fold with purified water to obtain a cream having a pH of 9.0 after stirring.
吉草酸酢酸プレドニゾロンの安定性試験
各実施例及び比較例で製造した製剤を５０℃及び４０℃相対湿度７５％にて、それぞれ一定期間保存し、吉草酸酢酸プレドニゾロンの定量を行った。試験結果を表１及び表２に示した。Stability test of prednisolone valerate acetate The preparations prepared in each Example and Comparative Example were stored for a certain period of time at 50 ° C. and 40 ° C. and a relative humidity of 75%, respectively, and prednisolone acetate valerate was quantified. The test results are shown in Tables 1 and 2.
なお、吉草酸酢酸プレドニゾロンの定量は下記に示す条件の高速液体クロマトグラフ法によって実施した。
検出器：紫外吸光光度計（測定波長：２４３ｎｍ）
カラム：ＴＳＫゲルＯＤＳ−８０ＴＳ（東ソー（株）製）
移動相：メタノール・水（１０：３）混液In addition, quantification of prednisolone valerate was carried out by a high performance liquid chromatography method under the following conditions.
Detector: UV absorptiometer (measurement wavelength: 243 nm)
Column: TSK gel ODS-80TS (manufactured by Tosoh Corporation)
Mobile phase: Methanol / water (10: 3) mixture
表１及び表２から明らかなように、実施例の製剤は比較例の製剤よりも製剤中の吉草酸酢酸プレドニゾロンが安定であることが確認された。 As is clear from Tables 1 and 2, it was confirmed that prednisolone valerate acetate in the preparations of Examples was more stable than the preparations of Comparative Examples.
本発明の外用剤は、吉草酸酢酸プレドニゾロンのもつ湿疹、皮膚炎、かぶれ、あせも、ただれ、蕁麻疹などの皮膚疾患治療作用及び局所麻酔薬のもつ患部の痛み、かゆみ、ほてりなどを伴う疾患の治療作用を併せ持つ、長期間の保存が可能な外用剤として有用である。 The topical preparation of the present invention is used for the treatment of skin diseases such as eczema, dermatitis, rash, rashes, sores, urticaria, etc., and pains, itching, hot flashes, etc. of local anesthetics with prednisolone acetate valerate. It is useful as an external preparation that has a therapeutic action and can be stored for a long time.
Claims (2)
A cream or emulsion comprising prednisolone valerate acetate, a basic local anesthetic selected from lidocaine, dibucaine and tetracaine, and citric acid, lactic acid, malic acid or a salt thereof, and the cream or pH of the suspension when the diluted 10-fold with purified water emulsion Ri der 4.0 to 6.0, the mixing ratio of the prednisolone valerate acetate and basic local anesthetics, prednisolone valerate acetate 1 A cream or emulsion comprising 3 to 20 parts by weight of a basic local anesthetic with respect to parts by weight .
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| JP24942399A JP5307309B2 (en) | 1999-09-03 | 1999-09-03 | External preparation containing prednisolone valerate acetate and basic local anesthetic |
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| JP4500013B2 (en) * | 2003-06-20 | 2010-07-14 | 天藤製薬株式会社 | Local anesthetic composition |
| JP2005320282A (en) * | 2004-05-10 | 2005-11-17 | Shiseido Co Ltd | Skin care preparation for external use for local anaesthesis |
| JP2005350379A (en) * | 2004-06-09 | 2005-12-22 | Ikeda Mohandou:Kk | Method for stabilizing prednisolone valerate acetate and excellently stable skin care preparation for external use comprising prednisolone valerate acetate |
| CN101340916A (en) * | 2005-12-22 | 2009-01-07 | 兴和株式会社 | Preparation for external use having improved temporal stability of steroid |
| JP5849550B2 (en) * | 2011-09-08 | 2016-01-27 | 大正製薬株式会社 | External preparation containing steroidal anti-inflammatory drug |
| JP6543945B2 (en) * | 2014-02-12 | 2019-07-17 | 大正製薬株式会社 | Emulsified composition |
| FR3085848B1 (en) * | 2018-09-17 | 2020-09-18 | Soc Dexploitation De Produits Pour Les Industries Chimiques Seppic | PHARMACEUTICAL COMPOSITION FOR TOPICAL USE INCLUDING AT LEAST ONE LOCAL ANESTHESIS SUBSTANCE |
| JP7139206B2 (en) | 2018-09-21 | 2022-09-20 | 小林製薬株式会社 | Pharmaceutical composition |
| WO2020251017A1 (en) * | 2019-06-14 | 2020-12-17 | ゼリア新薬工業株式会社 | Composition for external application |
| JP7465066B2 (en) | 2019-06-17 | 2024-04-10 | 小林製薬株式会社 | Emulsion stabilizer |
| WO2023154047A1 (en) * | 2022-02-10 | 2023-08-17 | Glaxosmithkline Consumer Healthcare Holdings (Us) Llc | Rapid relief spray |
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| JPS59139315A (en) * | 1983-01-31 | 1984-08-10 | Taisho Pharmaceut Co Ltd | Cream agent |
| JPH0236572B2 (en) * | 1984-11-13 | 1990-08-17 | Hokuriku Pharmaceutical | SUTEROIDOO177MONOESUTERUGANJUKURIIMUZAI |
| JPH05286860A (en) * | 1992-04-03 | 1993-11-02 | Kowa Co | Gel ointment |
| JP3593716B2 (en) * | 1993-07-12 | 2004-11-24 | 大正製薬株式会社 | Hemorrhoid treatment composition |
| JP2860748B2 (en) * | 1993-12-24 | 1999-02-24 | エスエス製薬株式会社 | Stable hydrocortisone butyrate-containing cream |
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