JP6545933B2 - Composition for external use - Google Patents
Composition for external use Download PDFInfo
- Publication number
- JP6545933B2 JP6545933B2 JP2014124440A JP2014124440A JP6545933B2 JP 6545933 B2 JP6545933 B2 JP 6545933B2 JP 2014124440 A JP2014124440 A JP 2014124440A JP 2014124440 A JP2014124440 A JP 2014124440A JP 6545933 B2 JP6545933 B2 JP 6545933B2
- Authority
- JP
- Japan
- Prior art keywords
- weight
- acid
- parts
- composition
- malassezia
- 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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Landscapes
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Description
本発明は、Malassezia restricta(M.restrictaと略称される)及びMalassezia globosa(M.globosaと略称される)からなる群より選択される少なくとも1種のマラセチア属真菌に対する増殖抑制効果を発揮できる外用組成物に関する。 The present invention is an external composition capable of exerting a growth inhibitory effect on at least one Malassezia fungus selected from the group consisting of Malassezia restricta (abbreviated as M. restricta) and Malassezia globosa (abbreviated as M. globosa) Related to things.
頭皮湿疹は、フケや痒みを生じさせるため、日常生活に支障をきたすことも多い。また、清潔志向の高まりからも、改善することが望まれる症状である。そして近年、このような頭皮で起こる脂漏性湿疹は、頭部や髪の生え際で生じる特定真菌の過剰増殖が原因であることが研究で明らかになりつつある(非特許文献1)。 Because scalp eczema causes dandruff and itching, it often affects daily life. In addition, it is a symptom that it is desirable to improve from the rise of cleanliness preference. In recent years, it has been clarified by research that such seborrhoeic eczema that occurs in the scalp is caused by the overgrowth of a specific fungus that occurs at the hairline of the head and hair (Non-patent Document 1).
マラセチア属真菌(Malassezia)は、人体の皮膚に常在する酵母様の真菌であることが知られており、マラセチア属真菌は現在13の菌種に分類されている。マラセチア属真菌が関与すると考えられている各種皮膚疾患は、癜風、マラセチア毛包炎、脂漏性湿疹(脂漏性皮膚炎とも言う)、脂漏性角化症、アトピー性皮膚炎、外耳炎等があり、これらの疾患毎に関与するマラセチア属真菌の種類が異なることが明らかになってきている。 Malassezia fungus (Malassezia) is known to be a yeast-like fungus that is permanently present in human skin, and Malassezia fungus is currently classified into 13 species. Various skin diseases considered to be associated with Malassezia fungi include scabies, Malassezia folliculitis, seborrheic eczema (also called seborrheic dermatitis), seborrhoea keratosis, atopic dermatitis, outer ear It is becoming clear that there are fires and so on, and the type of Malassezia fungus involved in each of these diseases is different.
ここで脂漏性湿疹は、脂漏部位や間擦部位に紅斑や鱗屑(フケ)を生じる頭皮湿疹の一種であるが、マラセチア属真菌のうち、主にM.restrictaとM.globosaの過剰増殖が関与していることが示唆されている(非特許文献2)。 Here, seborrhoeic eczema is a type of scalp eczema that causes erythema and scaling (dandruff) at seborrhoea sites and interfacial sites. restricta and M. It has been suggested that the overgrowth of globosa is involved (Non-patent Document 2).
その他の皮膚疾患について、胸部や背部に褐色斑が生じる癜風又は慢性の湿疹性病変を生じるアトピー性皮膚炎でも、主にM.restrictaとM.globosaの関与が示唆されている(非特許文献1及び2)。 With regard to other skin diseases, atopic dermatitis that causes rheumatic plaques or chronic eczematous lesions that cause brown spots on the chest and back also mainly includes M. tuberculosis. restricta and M. The involvement of globosa has been suggested (non-patent documents 1 and 2).
しかしながら、マラセチア属真菌に直接的に増殖抑制効果を有する薬剤は多くは報告されていない状況である。 However, many drugs having a direct growth inhibitory effect on Malassezia fungi have not been reported.
そこで、マラセチア属真菌の関与する疾患や症状を治療、予防、又は改善することができる外用組成物、なかでも脂漏性湿疹に代表される頭皮湿疹を効果的に治療、予防、改善できる外用組成物の開発が求められている。 Therefore, an external composition capable of treating, preventing or ameliorating a disease or condition involving Malassezia fungus, particularly an external composition capable of effectively treating, preventing or improving scalp eczema represented by seborrheic eczema There is a need for the development of goods.
本発明は、上記に鑑みてなされたものであり、脂漏性湿疹等の主たる原因菌とされているマラセチア属真菌の増殖を抑制できる有用な外用組成物を提供することを目的とする。 The present invention is made in view of the above, and an object of the present invention is to provide a useful external composition which can suppress the growth of Malassezia fungus which is considered to be a main cause bacteria such as seborrhoeic eczema.
本発明者は前記課題に鑑み、鋭意検討を行った結果、ステロイド系抗炎症薬単独では、マラセチア属真菌の増殖抑制に効果が認められない場合であっても、2重量%以上のモノテルペンを組み合わせて配合させることにより、マラセチア属真菌の中でもM.restricta及び/又はM.globosaの増殖を抑制できることを見出し、本発明を完成するに至った。 As a result of intensive studies conducted by the inventor in view of the above-mentioned problems, the steroid anti-inflammatory drug alone has a monoterpene content of 2% by weight or more even when no effect is observed in suppressing the growth of Malassezia fungus. Among the Malassezia fungi, M. aeruginosa can be obtained by combining them. restricta and / or M. It has been found that the growth of globosa can be suppressed, and the present invention has been completed.
すなわち、本発明は、ステロイド系抗炎症薬及び2重量%以上のモノテルペンを含有する、M.restricta及びM.globosaからなる群より選択される少なくとも1種のマラセチア属真菌の増殖を抑制するために用いられる外用組成物に関する。 That is, the present invention relates to M. S. et al., Which comprises a steroidal anti-inflammatory drug and 2% by weight or more of a monoterpene. restricta and M. The present invention relates to an external composition used to inhibit the growth of at least one Malassezia fungus selected from the group consisting of globosa.
上記外用組成物において、上記ステロイド系抗炎症薬は、プレドニゾロン、ヒドロコルチゾン、コルチゾン、デキサメタゾン、ベタメタゾン、トリアムシノロン、トリアムシノロンアセトニド、ジフルプレドナード、モメタゾン、ジフルコルトロン、フルオニシド、ベクロムタゾン、デプロドン、クロベタゾン、アルクロメタゾン、フルメタゾン、及びこれらの誘導体、並びにこれらの塩からなる群より選択される少なくとも1種であり得る。 In the above composition for external use, the above-mentioned steroidal anti-inflammatory drug is prednisolone, hydrocortisone, cortisone, dexamethasone, betamethasone, triamcinolone, triamcinolone, triamcinolone acetonide, diflupredonad, mometasone, diflucortorone, fluoniside, beclotazone, deprodone, clobetasone, alclomethasone, It may be at least one selected from the group consisting of flumethasone, and derivatives thereof, and salts thereof.
上記外用組成物において、上記モノテルペンは、メントール、カンフル、ボルネオール、オイゲノール、シネオール、チモール、リモネン、ピネン、アネトール、シメン、テルピネオール、カンフェン、イソボルネオール、フェンチェン、ゲラニオール、ネロール、ミルセン、ミルセノール、リナロール、酢酸リナロール、及びラバンジュロールからなる群より選択される少なくとも1種であり得る。 In the composition for external use, the monoterpene is menthol, camphor, borneol, eugenol, cineole, thymol, limonene, pinene, anethole, cymene, terpineol, camphene, isoborneol, phenchen, geraniol, nerol, myrcene, myrcenol, linalool And at least one selected from the group consisting of linalool acetate, and lavandurol.
また、本発明において、上記マラセチア属真菌は、Malassezia globosaとすることができる。 In the present invention, the Malassezia genus fungus can be Malassezia globosa.
本発明において、上記外用組成物は、頭皮に対して用いられ得る。 In the present invention, the composition for external use may be used on the scalp.
また、本発明は、ステロイド系抗炎症薬及び2重量%以上のモノテルペンを含有する、Malassezia restricta及びMalassezia globosaからなる群より選択される少なくとも1種のマラセチア属真菌性の皮膚疾患又は皮膚症状の予防及び/又は治療剤に関する。 The present invention is also directed to at least one Malassezia fungal skin disease or skin condition selected from the group consisting of Malassezia restricta and Malassezia globosa containing a steroidal anti-inflammatory drug and 2% by weight or more of monoterpenes. It relates to a preventive and / or therapeutic agent.
また、本発明により、ステロイド系抗炎症薬及び2重量%以上のモノテルペンを含有する組成物を用いることによる、Malassezia restricta及びMalassezia globosaからなる群より選択される少なくとも1種のマラセチア属真菌の増殖抑制方法を提供することも可能である。このような方法には、医師による医療行為は含まないとすることができる。 Further, according to the present invention, growth of at least one Malassezia fungus selected from the group consisting of Malassezia restricta and Malassezia globosa by using a composition containing a steroidal anti-inflammatory drug and 2% by weight or more of monoterpenes. It is also possible to provide a suppression method. Such methods may not include medical practices by a physician.
本発明によれば、マラセチア属真菌(特にM.restricta及び/又はM.globosa)の増殖を直接的に抑制することができるようになり、これらのマラセチア属真菌の関与する疾患や症状を治療、予防、又は改善することができる外用組成物を提供することができる。 According to the present invention, it becomes possible to directly suppress the growth of Malassezia genus fungi (in particular, M. restricta and / or M. globosa), and to treat diseases and conditions involving these Malassezia genus fungi, An external composition which can be prevented or improved can be provided.
本発明の外用組成物は、ステロイド系抗炎症薬及び2重量%以上のモノテルペンを含有する。 The topical composition of the present invention contains a steroidal anti-inflammatory drug and 2% by weight or more of a monoterpene.
本明細書において、ステロイド系抗炎症薬とは、ステロイド核を有するステロイドホルモン又はそれに由来する構造を有する薬物であって、抗炎症作用、免疫抑制作用、抗アレルギー作用等を有するものである。ステロイドホルモンは、糖質コルチコイド、鉱質コルチコイド、性ホルモン等に分類されるが、抗炎症薬としては、主に糖質コルチコイドが用いられている。また、本明細書において、ステロイド系抗炎症薬には、その誘導体やこれらの薬学的に許容される塩も含まれる。ステロイド系抗炎症薬は、公知の方法により合成して使用しても、市販の薬剤を入手して使用してもよい。 In the present specification, a steroidal anti-inflammatory drug is a steroid hormone having a steroid nucleus or a drug having a structure derived therefrom, and having an anti-inflammatory action, an immunosuppressive action, an antiallergic action and the like. Steroid hormones are classified into glucocorticoids, mineralocorticoids, sex hormones and the like, but glucocorticoids are mainly used as anti-inflammatory agents. Also, as used herein, steroidal anti-inflammatory agents include their derivatives and their pharmaceutically acceptable salts. The steroidal anti-inflammatory drug may be synthesized and used by known methods, or a commercially available drug may be obtained and used.
本発明の外用組成物において、ステロイド系抗炎症薬の誘導体とは、本発明の効果を損なわない範囲において、ステロイド系抗炎症薬の有する官能基の一部を化学修飾したもの、官能基の一部に保護基を付加したもの等をいい、異性体を含むものである。限定はされないが、例えば、ステロイド系抗炎症薬におけるステロイド核の一つ又はそれ以上の水素原子が、ヒドロキシル基、アミノ基、クロロ基、ブロモ基、ヨード基、フルオロ基、トリフルオロ基、ニトロ基、シアノ基、カルボキシル基、炭素数1〜6のアルキル基、炭素数2〜6のアセチル基、炭素数6〜10のアリール基、炭素数2〜6のアルキニル基、炭素数2〜6のアルケニル基、炭素数1〜6のアルコキシル基、炭素数1〜6のアルキルアミノ基等に置換されたものや、有機酸(例えば、吉草酸、酢酸、酪酸、プロピオン酸、フランカルボン酸等)でエステル化されたもの、保護基が外れることによりステロイド系抗炎症薬としての活性を有するように修飾された前駆体等が挙げられる。より高い本発明の効果が期待できるという観点から、好ましくは、有機酸でエステル化された誘導体であり、より好ましくは、吉草酸、酢酸、酪酸、プロピオン酸及び/又はフランカルボン酸でエステル化された誘導体であり、更に好ましくは吉草酸、酢酸、酪酸及び/又はプロピオン酸でエステル化された誘導体である。エステル化誘導体はモノエステル、ジエステル、トリエステル等の任意のエステル化誘導体であってよく、例えば、プレドニゾロン吉草酸エステル酢酸エステル(吉草酸酢酸プレドニゾロンともいう)等のように、2種以上の有機酸でエステル化された誘導体であってもよい。 In the composition for external use of the present invention, the derivative of a steroidal anti-inflammatory drug refers to a derivative of the steroid-based anti-inflammatory drug having a portion thereof chemically modified, or a functional group within the range not impairing the effects of the present invention. It is a compound in which a protective group is added to a moiety, etc., and contains an isomer. For example, although not limited thereto, one or more hydrogen atoms of a steroid nucleus in a steroidal anti-inflammatory drug may be hydroxyl group, amino group, chloro group, bromo group, iodo group, fluoro group, trifluoro group, nitro group Cyano, carboxyl, alkyl having 1 to 6 carbons, acetyl having 2 to 6 carbons, aryl having 6 to 10 carbons, alkynyl having 2 to 6 carbons, alkenyl having 2 to 6 carbons Substituted with an alkoxy group having 1 to 6 carbon atoms, an alkylamino group having 1 to 6 carbon atoms, or an organic acid (eg, valeric acid, acetic acid, butyric acid, propionic acid, furan carboxylic acid, etc.) And a precursor modified to have activity as a steroidal anti-inflammatory drug when the protective group is removed. From the viewpoint that higher effects of the present invention can be expected, it is preferably a derivative esterified with an organic acid, more preferably esterified with valeric acid, acetic acid, butyric acid, propionic acid and / or furan carboxylic acid Derivatives, more preferably derivatives esterified with valeric acid, acetic acid, butyric acid and / or propionic acid. The esterified derivative may be any esterified derivative such as monoester, diester, triester, etc. For example, two or more organic acids such as prednisolone valerate ester acetate (also referred to as valerate acetic acid prednisolone) etc. It may be an esterified derivative of
本発明の外用組成物において、ステロイド系抗炎症薬又はその誘導体の「薬学的に許容される塩」としては、限定はされないが、例えば、アルカリ金属塩、アルカリ土類金属塩、有機塩基等との塩が例示され、ナトリウム、カリウム、カルシウム、マグネシウム、アンモニウム、又はジエタノールアミン、エチレンジアミン等との塩が挙げられる。さらには、アンモニア、メチルアミン、ジメチルアミン、トリメチルアミン、ジシクロヘキシルアミン、トリス(ヒドロキシメチル)アミノメタン、N,N−ビス(ヒドロキシエチル)ピペラジン、2−アミノ−2−メチル−1−プロパノール、エタノールアミン、N−メチルグルカミン、L−グルカミン等のアミンの塩;又はリジン、δ−ヒドロキシリジン、アルギニンなどの塩基性アミノ酸との塩などが挙げられる。また、例えば、塩酸、臭化水素酸、硫酸、硝酸、リン酸等の鉱酸の塩;メタンスルホン酸、ベンゼンスルホン酸、パラトルエンスルホン酸、酢酸、プロピオン酸、酒石酸、フマル酸、マレイン酸、リンゴ酸、シュウ酸、コハク酸、吉草酸、クエン酸、安息香酸、マンデル酸、ケイ皮酸、乳酸、グリコール酸、グルクロン酸、アスコルビン酸、ニコチン酸、サリチル酸等の有機酸との塩;又はアスパラギン酸、グルタミン酸などの酸性アミノ酸との塩なども挙げられる。「薬学的に許容される塩」には、塩の溶媒和物又は水和物を含んでいてもよい。 In the composition for external use of the present invention, the “pharmaceutically acceptable salt” of the steroidal anti-inflammatory drug or the derivative thereof is not limited, but, for example, an alkali metal salt, an alkaline earth metal salt, an organic base and the like And salts thereof with sodium, potassium, calcium, magnesium, ammonium or diethanolamine, ethylene diamine and the like. Furthermore, ammonia, methylamine, dimethylamine, trimethylamine, dicyclohexylamine, tris (hydroxymethyl) aminomethane, N, N-bis (hydroxyethyl) piperazine, 2-amino-2-methyl-1-propanol, ethanolamine, Examples thereof include salts of amines such as N-methylglucamine and L-glucamine; and salts of basic amino acids such as lysine, δ-hydroxylysine and arginine. Also, for example, salts of mineral acids such as hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, phosphoric acid; methanesulfonic acid, benzenesulfonic acid, p-toluenesulfonic acid, acetic acid, propionic acid, tartaric acid, fumaric acid, maleic acid, Malic acid, oxalic acid, succinic acid, valeric acid, citric acid, benzoic acid, mandelic acid, mandelic acid, cinnamic acid, lactic acid, glycolic acid, glucuronic acid, ascorbic acid, salts with organic acids such as nicotinic acid, salicylic acid; or asparagine Acids, salts with acidic amino acids such as glutamic acid, and the like can also be mentioned. "Pharmaceutically acceptable salt" may include a solvate or hydrate of a salt.
外用組成物に使用できるステロイド系抗炎症薬であれば、限定はされないが、具体的には、プレドニゾロン、ヒドロコルチゾン、コルチゾン、デキサメタゾン、ベタメタゾン、トリアムシノロン、トリアムシノロンアセトニド、ジフルプレドナード、モメタゾン、ジフルコルトロン、フルオニシド、ベクロムタゾン、デプロドン、クロベタゾン、アルクロメタゾン、フルメタゾン及びこれらの誘導体、並びにこれらの塩等が挙げられ、これらの中でも、マラセチア属真菌の増殖を効果的に抑制する観点から、好ましくは、プレドニゾロン、ヒドロコルチゾン、ジフルプレドナード、コルチゾン、デキサメタゾン、ベタメタゾン、トリアムシノロン、トリアムシノロンアセトニド、及びこれらの誘導体、並びにこれらの塩であり、より好ましくはプレドニゾロン、ヒドロコルチゾン、ジフルプレドナード、及びこれらの誘導体、並びにこれらの塩であり、更に好ましくは、プレドニゾロン及びこの誘導体、並びにこれらの塩である。本発明において、ステロイド系抗炎症薬は、単独でも、2種類以上を組み合わせて配合してもよい。 The steroidal anti-inflammatory drug which can be used for the composition for external use includes, but is not limited to, prednisolone, hydrocortisone, cortisone, dexamethasone, betamethasone, triamcinolone, triamcinolone acetonide, diflupredonad, mometasone, diflucortorone. And fluonisone, deprodone, clobetasone, alclomethasone, flumethasone and derivatives thereof, salts thereof and the like, and among them, from the viewpoint of effectively suppressing the growth of Malassezia genus fungus, preferably prednisolone, hydrocortisone , Diflupredonad, cortisone, dexamethasone, betamethasone, triamcinolone, triamcinolone acetonide, and derivatives thereof, and salts thereof, more preferably Prednisolone, hydrocortisone, a difluprednate donor de, and their derivatives, and salts thereof, more preferably prednisolone and derivatives thereof, and salts thereof. In the present invention, the steroidal anti-inflammatory drug may be used alone or in combination of two or more.
現在、ステロイド系抗炎症薬は、ステロイドの強さによって5段階(強い薬物から順に、ストロンゲスト、ベリーストロング、ストロング、ミディアム、ウィーク)に分類されており、本発明にはそのいずれもが用いられ得るが、好ましくは、人体への作用は比較的緩和でありながら、モノテルペンと共存することでM.restricta及び/又はM.globosaに対しては効果的な増殖抑制効果を発揮することが期待できるストロング、ミディアム、ウィークに分類されるステロイド系抗炎症薬が用いられる。具体的に、ステロイド系抗炎症薬としては、プロピオン酸クロベタゾール、プロピオン酸ハロベタゾール、酢酸ジフロラゾン、ジプロピオン酸ベタメタゾン、吉草酸ジフルコルトロン、フランカルボン酸モメタゾン、ジプロピオン酸ベタメタゾン、アムシノニド、プロピオン酸デキサメタゾン、ジフルプレドナート、フルオニシド、酪酸プロピオン酸ヒドロコルチゾン、吉草酸酢酸プレドニゾロン、ジプロピオン酸ベタメタゾン、プレドニゾロン、ベクロメタゾンジプロピオネート、プロピオン酸ベクロメタゾン、吉草酸デキサメタゾン、吉草酸ベタメタゾン、フルオシノロンアセトニド、トリアムシノロンアセトニド、酪酸ヒドロコルチゾン、酢酸ヒドロコルチゾン、酢酸クロベタゾン、プロピオン酸アルクロメタゾン、デキサメタゾン、ヒドロコルチゾン、ベタメタゾン、酢酸デキサメタゾン、ヒドロコルチゾン、酢酸コルチゾン、酢酸プレドニゾロン等が挙げられる。モノテルペンと共存することでM.restricta及び/又はM.globosaの増殖を効果的に抑制する観点から、好ましくは、吉草酸酢酸プレドニゾロン、ジプロピオン酸ベタメタゾン、プレドニゾロン、ベクロメタゾンジプロピオネート、プロピオン酸ベクロメタゾン、吉草酸デキサメタゾン、吉草酸ベタメタゾン、フルオシノロンアセトニド、トリアムシノロンアセトニド、酪酸ヒドロコルチゾン、酢酸ヒドロコルチゾン、酢酸クロベタゾン、プロピオン酸アルクロメタゾン、デキサメタゾン、ヒドロコルチゾン、ベタメタゾン、酢酸デキサメタゾン、ヒドロコルチゾン、酢酸コルチゾン、酢酸プレドニゾロン等が挙げられる。特には、塗布した患部で薬理活性を示し、体内で低活性な物質に代謝される、吉草酸酢酸プレドニゾロン、酪酸ヒドロコルチゾン、酪酸プロピオン酸ヒドロコルチゾン、ジフルプレドナート、プロピオン酸ベクロメタゾン等のアンテドラッグステロイドが好適に用いられ、なかでも吉草酸酢酸プレドニゾロン(プレドニゾロン吉草酸エステル酢酸エステルともいう)、酪酸ヒドロコルチゾン(ヒドロコルチゾン酪酸エステルともいう)、プロピオン酸ベクロメタゾン(ベクロメタゾンプロピオン酸エステルともいう)等のアンテドラッグステロイドが好適である。 At present, steroidal anti-inflammatory drugs are classified into five levels (strong drugs, in order from strong drugs, strong guests, very strong, strong, medium, weak) according to the strength of steroids, and any of them is used in the present invention. Although it is preferable, preferably, the action on the human body is relatively moderated, but in the presence of monoterpenes M. restricta and / or M. Steroidal anti-inflammatory drugs classified into strong, medium and weak that can be expected to exert an effective growth inhibitory effect against globosa are used. Specifically, as steroidal anti-inflammatory agents, clobetasol propionate, halobetasol propionate, diflorazone acetate, betamethasone dipropionate, diflucortorone valerate, mometasone furoate, betamethasone dipropionate, amcinonide, dexamethasone propionate, Difluprednate, fluoniside, hydrocortisone butyrate propionate, prednisolone acetate valerate, betamethasone dipropionate, prednisolone dipropionate, beclomethasone dipropionate, beclomethasone propionate, dexamethasone valerate, betamethasone valerate, fluocinolone acetonide, triamcinolone acetonide, Hydrocortisone butyrate, hydrocortisone acetate, clobetasone acetate, alclomethasone propionate, dexamethasone, Fludrocortisone, betamethasone, dexamethasone acetate, hydrocortisone, cortisone acetate, prednisolone acetate, and the like. By coexistence with monoterpenes, M. restricta and / or M. From the viewpoint of effectively suppressing the growth of globosa, preferably, prednisolone acetate valerate, betamethasone dipropionate, prednisolone, beclomethasone dipropionate, beclomethasone propionate, dexamethasone valerate, betamethasone valerate, fluocinolone acetonide, Triamcinolone acetonide, hydrocortisone butyrate, hydrocortisone acetate, clobetasone acetate, alclomethasone propionate, dexamethasone propionate, dexamethasone, hydrocortisone, betamethasone, dexamethasone acetate, hydrocortisone, cortisone acetate, prednisolone acetate and the like. In particular, antedrug steroids such as prednisolone valerate acetate, hydrocortisone butyrate, hydrocortisone butyrate butyrate, diflupredonato, beclomethasone propionate and the like which exhibit pharmacological activity in the affected affected area and which are metabolized to low active substances in the body are preferable. Antedrug steroids such as prednisolone valeric acid acetate (also referred to as prednisolone valerate ester acetate ester), hydrocortisone butyric acid (also referred to hydrocortisone butyrate ester), and beclomethasone propionate (also referred to as beclomethasone propionate ester) are particularly preferred. is there.
本発明の外用組成物において、ステロイド系抗炎症薬の含有量は、マラセチア属真菌の増殖を効果的に抑制する観点から、組成物の全量に対して、一般的には約0.01重量%以上とすることができ、約0.025重量%以上が好ましく、約0.05重量%以上がより好ましい。また、ステロイド系抗炎症薬の含有量は、モノテルペンと共存することでM.restricta及び/又はM.globosaの増殖を効果的に抑制する観点から、組成物の全量に対して、一般的には約1重量%以下とすることができ、約0.7重量%以下が好ましく、約0.5重量%以下がより好ましい。上記範囲であれば、マラセチア属真菌の増殖を抑制する効果を発揮することができ、液剤、ゲル剤、クリーム剤、軟膏剤、エアゾール剤等の製剤を調製するにあたり、効果的な製剤を得ることができる。 In the composition for external use of the present invention, the content of the steroidal anti-inflammatory drug is generally about 0.01% by weight based on the total amount of the composition, from the viewpoint of effectively suppressing the growth of Malassezia fungus. It can be made into the above, about 0.025 weight% or more is preferable, and about 0.05 weight% or more is more preferable. In addition, the content of the steroidal anti-inflammatory drug is determined by coexistence with monoterpenes. restricta and / or M. From the viewpoint of effectively suppressing the growth of globosa, the total amount of the composition can generally be about 1% by weight or less, preferably about 0.7% by weight or less, about 0.5% by weight % Or less is more preferable. If it is the said range, the effect which suppresses the growth of Malassezia genus fungus can be exhibited, and when preparing formulations, such as a liquid, a gel, a cream, an ointment, and an aerosol agent, an effective formulation is obtained. Can.
本明細書において、モノテルペンとは、二個のイソプレン単位からなる構造を有し、清涼化剤等として公知の化合物である。本発明に用いられるモノテルペンは、医薬上又は生理学的に使用され得るものである限り、特に制限されない。また、モノテルペンは、d体、l体又はdl体の何れであってもよい。 In the present specification, a monoterpene is a compound having a structure consisting of two isoprene units and known as a refreshing agent and the like. The monoterpene used in the present invention is not particularly limited as long as it can be used pharmaceutically or physiologically. The monoterpene may be any of d-form, l-form or dl-form.
具体的には、モノテルペンとして、例えば、メントール、オイゲノール、チモール、リモネン、アネトール、シメン、テルピネオールのような単環式モノテルペン;カンフル、ボルネオール、シネオール、ピネン、カンフェン、イソボルネオール、フェンチェンのような二環式モノテルペン;ゲラニオール、ネロール、ミルセン、ミルセノール、リナロール、酢酸リナロール、ラバンジュロールのような非環式モノテルペン;などが挙げられる。これらの中でも、ステロイド系抗炎症薬と共存することでM.restricta及び/又はM.globosaの増殖を効果的に抑制する観点から好ましくは、メントール、カンフル、ボルネオール、オイゲノール、シネオール、チモール、リモネン、ピネン、アネトール、シメン、テルピネオール、カンフェン、イソボルネオール、フェンチェン、ゲラニオール、ネロール、ミルセン、ミルセノール、リナロール、酢酸リナロール、ラバンジュロールであり、より好ましくは、メントール、カンフル、オイゲノール、ゲラニオール、及びボルネオールであり、好ましくは、メントール、カンフルであり、特に好ましくはメントールである。これらのモノテルペンは、1種を単独で使用してもよく、また2種以上を任意に組み合わせて使用してもよい。 Specifically, monoterpenes such as menthol, eugenol, thymol, limonene, anethole, cymene, monocyclic monoterpenes such as terpineol; such as camphor, borneol, cineole, pinene, camphene, isoborneol, phenchene And acyclic monoterpenes such as geraniol, nerol, myrcene, myrisenol, linalool, linalool acetate, lavandurol and the like. Among these, M. S. et al. restricta and / or M. From the viewpoint of effectively suppressing the growth of globosa, menthol, camphor, borneol, eugenol, cineole, thymol, limonene, pinene, anethole, cymene, terpineol, camphene, isoborneol, phenchen, geraniol, nerol, myrcene, Myrsenol, linalool, linalool acetate, lavandurol are more preferable, and menthol, camphor, eugenol, geraniol and borneol are preferable, menthol and camphor are preferable, and menthol is particularly preferable. These monoterpenes may be used alone or in any combination of two or more.
さらに、モノテルペンとしては、それを含む精油を用いてもよい。このような精油としては、クールミント油、ペパーミント油、ハッカ油、ユーカリ油、ベルガモット油、スペアミント油、ローズ油、樟脳油などが挙げられる。例えば、メントールやカンフルを含む精油としては、クールミント油、ペパーミント油、ハッカ油、樟脳油などを挙げることができる。これらの精油は、植物から、公知の方法で採取することができる。このような公知の精油採油方法として、水蒸気蒸留法、脱臭した動物油脂に植物を添加して精油を吸着させた後、エタノールで精油を抽出する油脂吸着法、植物をヘキサンやベンゼンのような有機溶媒又は超臨界流体で抽出し、抽出溶媒をエタノールに溶解させた後、エタノールを蒸発させて残渣を採取する溶剤抽出法、圧搾法などが挙げられる。モノテルペンは、精油から、各種クロマトグラフィーにより回収することもできる。 Furthermore, as the monoterpene, an essential oil containing it may be used. Such essential oils include cool mint oil, peppermint oil, peppermint oil, eucalyptus oil, bergamot oil, spearmint oil, rose oil, camphor oil and the like. For example, as an essential oil containing menthol and camphor, cool mint oil, peppermint oil, peppermint oil, camphor oil and the like can be mentioned. These essential oils can be collected from plants by known methods. As such a known essential oil production method, a steam distillation method, a plant is added to deodorized animal oil and fat to adsorb the essential oil, and then the oil and fat adsorption method to extract the essential oil with ethanol, the plant is organic such as hexane or benzene After extracting with a solvent or a supercritical fluid, dissolving the extraction solvent in ethanol, the solvent extraction method of evaporating ethanol and collecting a residue, a pressing method, etc. may be mentioned. Monoterpenes can also be recovered from essential oils by various chromatography.
本発明の外用組成物において、モノテルペンの含有量は、組成物全体に対して、2重量%以上であれば、モノテルペンの種類に応じて適宜設定することができるが、マラセチア属真菌の増殖を効果的に抑制する観点から、組成物全体に対して、約2重量%以上とすることができ、約2.5重量%以上が好ましく、約3重量%以上がより好ましく、約3.5重量%以上が更に好ましい。また、モノテルペンの含有量は、マラセチア属真菌の増殖を効果的に抑制する観点から、組成物全体に対して、一般的には約15重量%以下とすることができ、約13重量%以下が好ましく、約10重量%以下がより好ましい。上記範囲であれば、ステロイド系抗炎症薬と共存することでM.restricta及び/又はM.globosaの増殖を抑制する効果を発揮することができ、液剤、ゲル剤、クリーム剤、軟膏剤、エアゾール剤等の製剤を調製するにあたり、効果的な製剤を得ることができる。モノテルペンを含む精油を用いる場合には、配合される精油中のモノテルペン含有量が上記範囲を満たすように設定される。 In the composition for external use of the present invention, the content of monoterpene can be appropriately set according to the kind of monoterpene if it is 2% by weight or more with respect to the whole composition, but the growth of Malassezia genus fungus From the viewpoint of effectively suppressing this, the content can be about 2% by weight or more, preferably about 2.5% by weight or more, and more preferably about 3% by weight or more, with respect to the whole composition. % Or more is more preferable. In addition, the content of the monoterpene can be generally about 15% by weight or less, and about 13% by weight or less, based on the whole composition, from the viewpoint of effectively suppressing the growth of Malassezia fungus. Is preferred, and about 10% by weight or less is more preferred. If it is the said range, it will be M. by coexistence with a steroid type anti-inflammatory drug. restricta and / or M. The effect of suppressing the growth of globosa can be exhibited, and an effective preparation can be obtained in preparing a preparation such as a solution, a gel, a cream, an ointment, and an aerosol. When an essential oil containing monoterpene is used, the content of monoterpene in the essential oil to be blended is set to satisfy the above range.
本発明の外用組成物において、ステロイド系抗炎症薬に対するモノテルペンの配合比率は、ステロイド系抗炎症薬1重量部に対して、約1重量部以上が好ましく、約7重量部以上がより好ましく、約10重量部以上がさらに好ましく、約20重量部以上がとりわけ好ましい。配合比率の上限も、本発明の効果を損なわない限り特に限定はされないが、一例として、ステロイド系抗炎症薬1重量部に対して、約1500重量部以下が好ましく、約1000重量部以下がより好ましく、約500重量部以下がさらに好ましく、約200重量部以下がとりわけ好ましい。 In the composition for external use of the present invention, the blending ratio of monoterpene to steroidal anti-inflammatory drug is preferably about 1 part by weight or more, more preferably about 7 parts by weight or more, with respect to 1 part by weight of steroidal anti-inflammatory drug. About 10 parts by weight or more is more preferable, and about 20 parts by weight or more is particularly preferable. The upper limit of the compounding ratio is not particularly limited as long as the effects of the present invention are not impaired, but as an example, it is preferably about 1500 parts by weight or less and more preferably about 1000 parts by weight or less with respect to 1 part by weight of a steroid antiinflammatory drug Preferably, about 500 parts by weight or less is more preferable, and about 200 parts by weight or less is particularly preferable.
本発明の外用組成物は、M.restricta及びM.globosaからなる群より選択される少なくとも1種のマラセチア属真菌の増殖を抑制するために用いられる。 The composition for external use of the present invention is M.I. restricta and M. It is used to inhibit the growth of at least one Malassezia fungus selected from the group consisting of globosa.
マラセチア属真菌は、種々の皮膚疾患への関与が報告されており、癜風、マラセチア毛包炎、脂漏性湿疹(脂漏性皮膚炎とも言う)、脂漏性角化症、アトピー性皮膚炎、外耳炎等の原因又は増悪因子として知られている。多種のマラセチア属真菌が知られているなかで、特にM.restrictaとM.globosaは、頭皮湿疹の主な原因である脂漏性湿疹(脂漏性皮膚炎)への関与、又はアトピー性皮膚炎等への関与が示唆されている。本発明の外用組成物は、なかでもM.globosaの増殖を抑制するために有益に用いられる。M.globosaは、マラセチア属真菌のなかでも特にリパーゼ活性が高く、皮脂分解を促進して、皮膚刺激を誘発する遊離脂肪酸を生じさせやすい傾向があることが知られている。 Malassezia fungus has been reported to be involved in various skin diseases, and it is known that scabies, Malassezia folliculitis, seborrheic eczema (also called seborrheic dermatitis), seborrhoea keratosis, atopic skin It is known as a cause or exacerbation factor such as inflammation and otitis externa. Among various types of Malassezia fungi known, especially M. restricta and M. It has been suggested that globosa is involved in seborrheic eczema (seborrhoeic dermatitis), which is the main cause of scalp eczema, or in atopic dermatitis and the like. The composition for external use of the present invention is, among others, M.I. It is used beneficially to control the growth of globosa. M. It is known that globosa is particularly high in lipase activity among Malassezia fungi, and tends to promote sebum degradation and to generate free fatty acids that induce skin irritation.
本明細書において、「マラセチア属真菌の増殖を抑制する」とは、マラセチア属真菌の生育を抑えることをいい、マラセチア属真菌の生菌数を増加させないことや減少させること、マラセチア属真菌を殺菌することを含む。 In the present specification, "suppressing the growth of Malassezia fungus" refers to suppressing the growth of Malassezia fungus, not increasing or decreasing the viable count of Malassezia fungus, and killing Malassezia fungus To do.
本発明の外用組成物のpHは、生理学的又は薬学的に許容できる範囲であれば制限されないが、例えば、pHが3〜9、好ましくは3.5〜8.5、より好ましくは4〜8、さらに好ましくは4.5〜7とすることができる。 The pH of the composition for external use of the present invention is not limited as long as it is in a physiologically or pharmaceutically acceptable range, but for example, the pH is 3 to 9, preferably 3.5 to 8.5, more preferably 4 to 8 More preferably, it can be 4.5-7.
本発明の外用組成物は、医薬品、医薬部外品又は化粧品として公知の形態であれば、特に限定されないが、例えば、液剤、懸濁剤、乳剤、クリーム剤、軟膏剤、ゲル剤、リニメント剤、ローション剤、エアゾール剤、パウダー剤、不織布等のシートに外用組成物を含浸させたシート剤等の形態により、公知の方法で製剤化することができる。このような形態に製剤化することにより、マラセチア属真菌の増殖を抑制する効果を十分に発揮することができる。 The composition for external use according to the present invention is not particularly limited as long as it is a form known as pharmaceuticals, quasi-drugs or cosmetics, for example, solutions, suspensions, emulsions, creams, ointments, gels, liniments It can be formulated by a known method in the form of a sheet agent or the like in which the composition for external use is impregnated into a sheet such as a lotion, an aerosol, a powder or a non-woven fabric. By formulating in such a form, the effect of suppressing the growth of Malassezia fungus can be sufficiently exhibited.
液剤、懸濁剤、乳剤、クリーム剤、軟膏剤、ゲル剤、ローション剤等の形態で外用組成物を液状又は半固形状に製剤化した場合、限定はされないが、ノズル付き容器に収容することにより、本発明の外用組成物を、紅斑、湿疹、痒み、かぶれ又は炎症を引き起こしている患部に直接的に塗布することができる。ノズルは、患部の狭い範囲に塗布できるように、先細に設計することも可能であり、患部の広い範囲に塗布できるよう孔径の大きなノズルを用いることも可能である。また、本発明の外用組成物を頭髪の間から患部に直接的に塗布できるように、長いノズルを用いることも可能であり、伸縮性のノズルを用いることも可能である。また、ノズルの先端にロール又はボール等の回転体を用いることにより、本発明の外用組成物を患部に均一に塗布するよう設計することも可能である。患部に本発明の外用組成物を塗布した後に、不織布や指等により、塗り拡げて用いることも可能である。また別の態様として、液剤、懸濁剤、乳剤、クリーム剤、ゲル剤、ローション剤等の形態で外用組成物を液状に製剤化した場合、限定はされないが、スプレー容器に収容することにより、本発明の外用組成物を、紅斑、湿疹、痒み、かぶれ又は炎症を引き起こしている患部に直接的に噴霧して使用することもできる。噴霧した後に、不織布や指等により、塗り拡げて用いることも可能である。 When the composition for external use is formulated in liquid or semi-solid form in the form of liquid, suspension, emulsion, cream, ointment, gel, lotion, etc., it is not limited, but housed in a container with a nozzle Thus, the composition for external use of the present invention can be applied directly to the affected area causing erythema, eczema, itching, rash or inflammation. The nozzle can be designed to be tapered so that it can be applied to a narrow area of the affected area, or a nozzle with a large pore diameter can be used to apply to a wide area of the affected area. In addition, a long nozzle can be used so that the composition for external use of the present invention can be applied directly to the affected area from between the hairs, and a stretchable nozzle can also be used. Moreover, it is also possible to design so that the composition for external use of this invention may be uniformly apply | coated to an affected part by using rotary bodies, such as a roll or a ball, at the front-end | tip of a nozzle. After the composition for external use of the present invention is applied to the affected area, it may be spread and used with a non-woven fabric, a finger or the like. In another embodiment, when the composition for external use is formulated in the form of liquid, suspension, emulsion, cream, gel, lotion, etc., it is not limited, but by containing it in a spray container, The composition for external use of the present invention can also be used by directly spraying the affected area causing erythema, eczema, itching, rash or inflammation. After spraying, it is also possible to spread and use it with a non-woven fabric, a finger or the like.
本発明の外用組成物の適用部位は、紅斑、湿疹、痒み、かぶれ、炎症等のマラセチア属真菌による症状が生じている部位であれば限定はされないが、頭皮(頭部、髪の毛の生え際等)、胸の上部や背中の皮膚、ニキビ様の発疹が生じている部位等が例示される。なかでも、M.restrictaやM.globosaがフケや痒み等の耐え難い症状を発生させやすく、症状が現れた場合にすばやく治療、改善することが望まれることが多い頭皮湿疹(具体的には、頭皮における脂漏性湿疹)を治療、改善、又は予防するために、頭皮に対して用いられることが好ましい。 The application site of the composition for external use of the present invention is not limited as long as it is a site where a symptom caused by Malassezia fungus such as erythema, eczema, itching, rash, inflammation occurs, but scalp (hair on hair, head, etc.) , The upper chest and back skin, the site where acne-like rash has occurred, etc. are exemplified. Among them, M. restricta and M. globosa is easy to develop intolerable symptoms such as dandruff and itching, and it is desirable to treat and improve scalp eczema (specifically, seborrheic eczema on the scalp), which is often desired to be treated and improved promptly when symptoms occur. It is preferably used on the scalp to improve or prevent.
本発明の外用組成物の有効投与量は、配合成分の種類及び含有量、該外用組成物の用途や製剤形態に応じて適宜設定され得るが、頭皮やその他の皮膚に塗布する場合には、1日数回又は痒み等の症状が現れた際に、単位面積あたり1回、約20〜60mg/cm2程度である。 The effective dose of the composition for external use of the present invention may be appropriately set according to the type and content of the compounding ingredients, the application of the composition for external use, and the form of preparation, but when applied to the scalp or other skin, When symptoms such as itching several times a day appear, it is about 20 to 60 mg / cm 2 once per unit area.
本発明の外用組成物を頭皮やその他の皮膚に適用することにより、M.restricta及び/又はM.globosaの増殖が抑制され、紅斑、湿疹、鱗屑等の症状が改善され、これらのマラセチア属真菌が関与すると考えられている各種皮膚疾患(癜風、マラセチア毛包炎、脂漏性湿疹(脂漏性皮膚炎とも言う)、脂漏性角化症、アトピー性皮膚炎、外耳炎等)が予防又は治療される。 By applying the topical composition of the present invention to the scalp and other skin, M. restricta and / or M. Growth of globosa is suppressed, symptoms such as erythema, eczema, scaling are improved, and various skin diseases that are considered to be related to these Malassezia fungi (Bulleze, Malassezia folliculitis, seborrhoeic eczema (seborrhea (Also referred to as atopic dermatitis), seborrheic keratosis, atopic dermatitis, otitis externa etc. are prevented or treated.
本発明の外用組成物は、公知の方法により製造することができる。必要に応じて、滅菌工程を含めることができる。本発明の外用組成物を製剤化することにより、マラセチア属真菌性の皮膚疾患又は皮膚症状の予防及び/又は治療剤として用いることができる。具体的には、マラセチア属真菌、特には、M.restricta及び/又はM.globosaが関与する脂漏性湿疹の予防及び/又は治療剤(例えば、皮脂を原因とする頭皮湿疹の予防及び/又は治療剤)、癜風の予防及び/又は治療剤、脂漏性角化症の予防及び/又は治療剤、アトピー性皮膚炎の予防及び/又は治療剤、外耳炎の予防及び/又は治療剤、毛包炎の予防及び/又は治療剤等として用いることができる。 The composition for external use of the present invention can be produced by a known method. Optionally, a sterilization step can be included. By formulating the composition for external use of the present invention, it can be used as an agent for preventing and / or treating Malassezia fungal skin disease or skin condition. Specifically, Malassezia fungi, especially M. restricta and / or M. An agent for preventing and / or treating seborrheic eczema involving globosa (eg, an agent for preventing and / or treating scalp eczema caused by sebum), an agent for preventing and / or treating blight, seborrhoea keratosis The agent can be used as an agent for preventing and / or treating atopic dermatitis, an agent for preventing and / or treating atopic dermatitis, an agent for preventing and / or treating otitis externa, an agent for preventing and / or treating folliculitis, and the like.
本発明の外用組成物は、本発明の効果を損なわない範囲で、医薬品、医薬部外品、化粧品等として用いられ得る、公知の基剤又は担体と共に混合して製剤化することができる。その他に、本発明の外用組成物には、例えば、界面活性剤、油分、アルコール類、増粘剤、防腐剤、抗酸化剤、酸化防止剤、保存剤、キレート剤、pH調整剤、安定化剤、溶解補助剤、懸濁化剤、等張化剤、緩衝剤、無痛化剤、分散剤、香料、着色剤、色素、水等の添加剤を配合することができる。これらの添加剤は、1種を単独で又は2種以上を組み合わせて使用できる。 The composition for external use of the present invention can be formulated by mixing with a known base or carrier that can be used as a medicine, quasi-drug, cosmetic, etc., as long as the effects of the present invention are not impaired. In addition, the composition for external use of the present invention includes, for example, surfactants, oils, alcohols, thickeners, preservatives, antioxidants, antioxidants, preservatives, chelating agents, pH adjusters, and stabilization. Additives such as agents, solubilizers, suspending agents, tonicity agents, buffers, soothing agents, dispersants, perfumes, colorants, dyes, water and the like can be blended. These additives may be used alone or in combination of two or more.
基剤又は担体としては、流動パラフィン、スクワラン、ゲル化炭化水素(プラスチベースなど)、オゾケライト、α−オレフィンオリゴマー、軽質流動パラフィンのような炭化水素;メチルポリシロキサン、架橋型メチルポリシロキサン、高重合メチルポリシロキサン、環状シリコーン、アルキル変性シリコーン、架橋型アルキル変性シリコーン、アミノ変性シリコーン、ポリエーテル変性シリコーン、ポリグリセリン変性シリコーン、架橋型ポリエーテル変性シリコーン、架橋型アルキルポリエーテル変性シリコーン、シリコーン・アルキル鎖共変性ポリエーテル変性シリコーン、シリコーン・アルキル鎖共変性ポリグリセリン変性シリコーン、ポリエーテル変性分岐シリコーン、ポリグリセリン変性分岐シリコーン、アクリルシリコン、フェニル変性シリコーン、シリコーンレジンのようなシリコーン油;ポリエチレングリコール;ジオキサン;ミリスチン酸イソプロピル、ミリスチン酸オクチルドデシル、パルミチン酸イソプロピル、パルミチン酸セチル、イソノナン酸イソノニル、テトラ2−エチルヘキサン酸ペンタエリスリットのようなエステル類;エタノール、イソプロパノールのような低級アルコール;ジエチレングリコールモノメチルエーテル、ジエチレングリコールモノエチルエーテルのようなグリコールエーテル;ポリエチレングリコール、プロピレングリコール、1,3-ブチレングリコール、グリセリン、イソプレングリコールなどの多価アルコール;水などの水系基剤などが挙げられる。 As a base or carrier, liquid paraffin, squalane, gelled hydrocarbon (such as plastibase), ozokerite, α-olefin oligomer, hydrocarbon such as light liquid paraffin; methylpolysiloxane, crosslinked methylpolysiloxane, highly-polymerized methyl Polysiloxane, cyclic silicone, alkyl modified silicone, crosslinked alkyl modified silicone, amino modified silicone, polyether modified silicone, polyglycerin modified silicone, crosslinked polyether modified silicone, crosslinked alkyl polyether modified silicone, silicone / alkyl chain co-modified silicone Modified polyether modified silicone, silicone / alkyl chain co-modified polyglycerin modified silicone, polyether modified branched silicone, polyglycerin modified branched silicone, acrylic silicone, Silicones such as henyl modified silicones, silicone resins; polyethylene glycol; dioxane; isopropyl myristate, octyldodecyl myristate, isopropyl palmitate, cetyl palmitate, isononyl isononanoate, pentaerisyl tetra 2-ethylhexanoate Esters; Lower alcohols such as ethanol and isopropanol; glycol ethers such as diethylene glycol monomethyl ether and diethylene glycol monoethyl ether; polyhydric alcohols such as polyethylene glycol, propylene glycol, 1,3-butylene glycol, glycerin and isoprene glycol; water And water-based bases.
基剤又は担体は、1種を単独で又は2種以上を組み合わせて使用できる。 The base or carrier can be used alone or in combination of two or more.
界面活性剤としては、例えば、ソルビタンモノイソステアレート、ソルビタンモノラウレート、ソルビタンモノパルミテート、ソルビタンモノステアレート、ペンタ−2−エチルヘキシル酸ジグリセロールソルビタン、テトラ−2−エチルヘキシル酸ジグリセロールソルビタンのようなソルビタン脂肪酸エステル類;モノステアリン酸プロピレングリコールのようなプロピレングリコール脂肪酸エステル類;ポリオキシエチレン硬化ヒマシ油40(HCO−40)、ポリオキシエチレン硬化ヒマシ油50(HCO−50)、ポリオキシエチレン硬化ヒマシ油60(HCO−60)、ポリオキシエチレン硬化ヒマシ油80などの硬化ヒマシ油誘導体;モノラウリル酸ポリオキシエチレン(20)ソルビタン(ポリソルベート20)、モノステアリン酸ポリオキシエチレン(20)ソルビタン(ポリソルベート60)、モノオレイン酸ポリオキシエチレン(20)ソルビタン(ポリソルベート80)、イソステアリン酸ポリオキシエチレン(20)ソルビタンのようなポリオキシエチレンソルビタン脂肪酸エステル類;ポリオキシエチレンモノヤシ油脂肪酸グリセリル;グリセリンアルキルエーテル;アルキルグルコシド;ポリオキシエチレンセチルエーテルのようなポリオキシアルキレンアルキルエーテル;ステアリルアミン、オレイルアミンのようなアミン類;ポリオキシエチレン・メチルポリシロキサン共重合体、ラウリルPEG−9ポリジメチルシロキシエチルジメチコン、PEG−9ポリジメチルシロキシエチルジメチコンのようなシリコーン系界面活性剤;ラウリン酸塩、パルミチン酸塩、ココイルグルタミン酸塩、ヤシ油メチルアラニン塩、アシルメチルタウリン塩、ポリオキシエチレンラウリル硫酸塩のようなアニオン性界面活性剤、ラウリルジアミノエチルグリシン塩、ヤシ油脂肪酸ベタイン塩などの両性界面活性剤、ポリオキシエチレンラウリルアルコールエーテルなどの非イオン性界面活性剤などが挙げられる。 Examples of surfactants include sorbitan monoisostearate, sorbitan monolaurate, sorbitan monopalmitate, sorbitan monostearate, diglycerol sorbitan penta-2-ethylhexylate, diglycerol sorbitan tetra-2-ethylhexylate Sorbitan fatty acid esters; propylene glycol fatty acid esters such as propylene glycol monostearate; polyoxyethylene hydrogenated castor oil 40 (HCO-40), polyoxyethylene hydrogenated castor oil 50 (HCO-50), polyoxyethylene cured Hydrogenated castor oil derivatives such as castor oil 60 (HCO-60), polyoxyethylene hydrogenated castor oil 80; monolauric acid polyoxyethylene (20) sorbitan (polysorbate 20) monostearate Polyoxyethylene sorbitan fatty acid esters such as polyoxyethylene (20) sorbitan (polysorbate 60), monooleate polyoxyethylene (20) sorbitan (polysorbate 80), and isostearic acid polyoxyethylene (20) sorbitan; Glyceryl alkyl ether; alkyl glucoside; polyoxyalkylene alkyl ether such as polyoxyethylene cetyl ether; amines such as stearylamine, oleylamine; polyoxyethylene / methylpolysiloxane copolymer, Silicone surfactants such as lauryl PEG-9 polydimethylsiloxyethyl dimethicone, PEG-9 polydimethylsiloxyethyl dimethicone; laurate, Amphoteric surfactants such as lumitic acid salt, cocoyl glutamate, coconut oil methylalanine salt, acylmethyltaurine salt, anionic surfactants such as polyoxyethylene lauryl sulfate, lauryldiaminoethylglycine salt, coconut oil fatty acid betaine salt, etc. Agents, nonionic surfactants such as polyoxyethylene lauryl alcohol ether, and the like.
油分としては、天然動植物油脂類、炭化水素油、エステル油、シリコーン油、高級アルコール、高級脂肪酸、動植物や合成の精油などが挙げられる。 Examples of the oil include natural animal and vegetable oils and fats, hydrocarbon oils, ester oils, silicone oils, higher alcohols, higher fatty acids, and essential oils of animals and plants.
天然動植物油脂類としては、例えば、アボガド油、アマニ油、アーモンド油、オリーブ油、カカオ油、牛脂、キリ油、小麦胚芽油、ゴマ油、米胚芽油、米糠油、サフラワー油、大豆油、月見草油、ツバキ油、トウモロコシ油、ナタネ油、馬脂、パーシック油、パーム油、パーム核油、ヒマシ油、ヒマワリ油、豚脂、ブドウ油、ホホバ油、マカデミアナッツ油、ミンク油、綿実油、モクロウ、ヤシ油、硬化ヤシ油、落花生油、ラノリン、卵黄油、ローズヒップ油等が挙げられる。 Natural animal and vegetable oils and fats include, for example, avocado oil, linseed oil, almond oil, olive oil, cacao oil, beef tallow, tung oil, wheat germ oil, sesame oil, rice germ oil, rice bran oil, safflower oil, soybean oil, evening primrose oil , Camellia oil, corn oil, rapeseed oil, horse oil, persic oil, palm oil, palm kernel oil, castor oil, sunflower oil, pork oil, pork oil, jojoba oil, macadamia nut oil, mink oil, cotton seed oil, cottonseed oil, coconut oil, coconut oil And hardened coconut oil, peanut oil, lanolin, egg yolk oil, rosehip oil and the like.
炭化水素油としては、パラフィン系炭化水素、オレフィン系炭化水素が用いられ、例えば、スクワラン、スクワレン、セレシン、パラフィン、プリスタン、マイクロクリスタリンワックス、流動パラフィン、ワセリン等が挙げられる。 As hydrocarbon oil, paraffin type hydrocarbon and olefin type hydrocarbon are used, for example, squalane, squalene, ceresin, paraffin, pristane, microcrystalline wax, liquid paraffin, vaseline and the like can be mentioned.
エステル油としては、合成エステル類、高級アルコールと高級脂肪酸とのエステル類が用いられ、例えば、アジピン酸ジイソブチル、アジピン酸2−ヘキシルデシル、アジピン酸ジ−2−ヘプチルウンデシル、イソステアリン酸イソステアリル、トリイソステアリン酸トリメチロールプロパン、2−エチルヘキサン酸セチル、ジ−2−エチルヘキサン酸ネオペンチルグリコール、トリ−2−エチルヘキサン酸トリメチロールプロパン、テトラ−2−エチルヘキサン酸ペンタエリスリトール、オクタン酸セチル、オレイン酸オレイル、オレイン酸オクチルドデシル、オレイン酸デシル、ジカプリン酸ネオペンチルグリコール、コハク酸2−エチルヘキシル、ステアリン酸イソセチル、ステアリン酸ブチル、セバシン酸ジイソプロピル、乳酸セチル、乳酸テトラデシル、ミリスチン酸イソプリピル、ミリスチン酸オクチルドデシル、ミリスチン酸セチル、ミリスチン酸ミリスチル、パルミチン酸オクチル、パルミチン酸2−エチルヘキシル、パルミチン酸2−ヘキシルデシル、パルミチン酸2−ヘプチルウンデシル、12−ヒドロキシステアリン酸コレステリル、オレイン酸フィトステリル、リンゴ酸ジイソステアリル、パラメトキシケイ皮酸エステル、テトラロジン酸ペンタエリスリット等が挙げられる。 As the ester oil, synthetic esters, esters of higher alcohols and higher fatty acids are used, for example, diisobutyl adipate, 2-hexyldecyl adipate, di-2-heptylundecyl adipate, isostearyl isostearate, Trimethylolpropane triisostearate, cetyl 2-ethylhexanoate, neopentyl glycol di-2-ethylhexanoate, trimethylolpropane tri-2-ethylhexanoate, pentaerythritol tetra-2-ethylhexanoate, cetyl octanoate, Oleyl oleate, octyldodecyl oleate, decyl oleate, neopentyl glycol dicaprate, 2-ethylhexyl succinate, isocetyl stearate, butyl stearate, diisopropyl sebacate, secetyl lactate , Tetradecyl lactate, isopipyr myristate, octyldodecyl myristate, cetyl myristate, myristyl myristate, octyl palmitate, 2-ethylhexyl palmitate, 2-hexyldecyl palmitate, 2-heptylundecyl palmitate, 12-hydroxystearin Examples thereof include cholesteryl acid, phytosteryl oleate, diisostearyl malate, paramethoxycinnamate, pentaerysylate tetrarosinate, and the like.
シリコーン油としては、例えば、ジメチルポリシロキサン、高重合メチルポリシロキサン、メチルフェニルポリシロキサン、メチルハイドロジェンポリシロキサン、オクタメチルシクロテトラシロキサン、オクタメチルシクロペンタシロキサン、デカメチルシクロヘキサシロキサン、ステアロキシシリコーン等の高級アルコキシ変性シリコーン、アルキル変性シリコーン、高級脂肪酸エステル変性シリコーン等が挙げられる。 As silicone oil, for example, dimethylpolysiloxane, highly polymerized methylpolysiloxane, methylphenylpolysiloxane, methylhydrogenpolysiloxane, octamethylcyclotetrasiloxane, octamethylcyclopentasiloxane, decamethylcyclohexasiloxane, stearoxysilicone etc. And higher alkoxy-modified silicones, alkyl-modified silicones, higher fatty acid ester-modified silicones, and the like.
高級アルコールとしては、例えば、オクチルドデカノール、イソステアリルアルコール、オレイルアルコール、ステアリルアルコール、セタノール、ベヘニルアルコール等が挙げられる。 Examples of higher alcohols include octyl dodecanol, isostearyl alcohol, oleyl alcohol, stearyl alcohol, cetanol, behenyl alcohol and the like.
高級脂肪酸としては、飽和又は不飽和の直鎖もしくは分岐鎖の炭素数12〜22の脂肪酸を用いることができ、例えば、イソステアリン酸、オキシステアリン酸、オレイン酸、ステアリン酸、パルミチン酸、ベヘニン酸、ミリスチン酸、ラウリン酸、ラノリン酸、リノール酸、リノレン酸等が挙げられる。 As the higher fatty acid, a saturated or unsaturated linear or branched fatty acid having 12 to 22 carbon atoms can be used. For example, isostearic acid, oxystearic acid, oleic acid, stearic acid, palmitic acid, behenic acid, Myristic acid, lauric acid, lanolinic acid, linoleic acid, linolenic acid and the like can be mentioned.
増粘剤としては、例えば、グアーガム、ローカストビーンガム、カラギーナン、キサンタンガム、カルボキシメチルセルロース、ヒドロキシメチルセルロース、ヒドロキシエチルセルロース、ヒドロキシプロピルセルロース、ヒドロキシプロピルメチルセルロース、疎水化ヒドロキシプロピルメチルセルロース、ポリビニルアルコール、ポリビニルピロリドン、カルボキシビニルポリマー、アクリル酸メタクリル酸アルキル共重合体、ポリエチレングリコール、ベントナイト、(アクリル酸ヒドロキシエチル/アクリロイルジメチルタウリンNa)コポリマー、(アクリロイルジメチルタウリンアンモニウム/ビニルピロリドン)コポリマーなどが挙げられる。 As a thickener, for example, guar gum, locust bean gum, carrageenan, xanthan gum, carboxymethylcellulose, hydroxymethylcellulose, hydroxyethylcellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose, hydrophobized hydroxypropylmethylcellulose, polyvinyl alcohol, polyvinylpyrrolidone, carboxyvinyl polymer And acrylic acid methacrylic acid alkyl methacrylate copolymer, polyethylene glycol, bentonite, (hydroxyethyl acrylate / acryloyl dimethyl taurine Na) copolymer, (acryloyl dimethyl taurine ammonium / vinyl pyrrolidone) copolymer and the like.
防腐剤の好適な例としては、例えばパラオキシ安息香酸エステル類、クロロブタノール、ベンジルアルコール、フェネチルアルコール、デヒドロ酢酸、ソルビン酸などが挙げられる。 Preferred examples of preservatives include, for example, p-hydroxybenzoic acid esters, chlorobutanol, benzyl alcohol, phenethyl alcohol, dehydroacetic acid, sorbic acid and the like.
抗酸化剤の好適な例としては、例えば亜硫酸塩、アスコルビン酸などが挙げられる。 Preferred examples of the antioxidant include, for example, sulfite, ascorbic acid and the like.
酸化防止剤としては、ジブチルヒドロキシトルエン(BHT)、ブチルヒドロキシアニソール、ソルビン酸、亜硫酸ナトリウム、アスコルビン酸、エリソルビン酸、L−システイン塩酸塩などが挙げられる。 Examples of the antioxidant include dibutyl hydroxytoluene (BHT), butyl hydroxyanisole, sorbic acid, sodium sulfite, ascorbic acid, erythorbic acid, L-cysteine hydrochloride and the like.
保存剤としては、安息香酸、安息香酸ナトリウム、デヒドロ酢酸、デヒドロ酢酸ナトリウム、パラオキシ安息香酸イソブチル、パラオキシ安息香酸イソプロピル、パラオキシ安息香酸ブチル、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ベンジル、パラオキシ安息香酸メチル、フェノキシエタノールなどが挙げられる。 As preservatives, benzoic acid, sodium benzoate, dehydroacetic acid, sodium dehydroacetate, isobutyl p-hydroxybenzoate, isopropyl p-hydroxybenzoate, butyl p-hydroxybenzoate, ethyl p-hydroxybenzoate, propyl p-hydroxybenzoate, benzyl p-hydroxybenzoate, p-hydroxybenzoate Methyl benzoate, phenoxyethanol and the like can be mentioned.
キレート剤としては、EDTA・2ナトリウム塩、EDTA・カルシウム・2ナトリウム塩などが挙げられる。 As a chelating agent, EDTA · disodium salt, EDTA · calcium · disodium salt and the like can be mentioned.
pH調整剤としては、無機酸(塩酸、硫酸など)、有機酸(乳酸、乳酸ナトリウム、クエン酸、クエン酸ナトリウム、コハク酸、コハク酸ナトリウムなど)、無機塩基(水酸化カリウム、水酸化ナトリウムなど)、有機塩基(トリエタノールアミン、ジイソプロパノールアミン、トリイソプロパノールアミンなど)などが挙げられる。 pH adjusters include inorganic acids (such as hydrochloric acid and sulfuric acid), organic acids (such as lactic acid, sodium lactate, citric acid, sodium citrate, sodium citrate, succinic acid, sodium succinate), inorganic bases (such as potassium hydroxide and sodium hydroxide) And organic bases (triethanolamine, diisopropanolamine, triisopropanolamine etc.) and the like.
安定化剤としては、ポリアクリル酸ナトリウム、ジブチルヒドロキシトルエン、ブチルヒドロキシアニソールなどが挙げられる。 As the stabilizer, sodium polyacrylate, dibutylhydroxytoluene, butylhydroxyanisole and the like can be mentioned.
溶解補助剤の好適な例としては、例えばポリエチレングリコール、プロピレングリコール、D−マンニトール、安息香酸ベンジル、エタノール、トリスアミノメタン、コレステロール、トリエタノールアミン、炭酸ナトリウム、クエン酸ナトリウムなどが挙げられる。 Preferred examples of solubilizers include polyethylene glycol, propylene glycol, D-mannitol, benzyl benzoate, ethanol, trisaminomethane, cholesterol, triethanolamine, sodium carbonate, sodium citrate and the like.
懸濁化剤の好適な例としては、例えばステアリルトリエタノールアミン、ラウリル硫酸ナトリウム、ラウリルアミノプロピオン酸、レシチン、塩化ベンザルコニウム、塩化ベンゼトニウム、モノステアリン酸グリセリンなどの界面活性剤;例えばポリビニルアルコール、ポリビニルピロリドン、カルボキシメチルセルロースナトリウム、メチルセルロース、ヒドロキシメチルセルロース、ヒドロキシエチルセルロース、ヒドロキシプロピルセルロースなどの親水性高分子などが挙げられる。 Preferred examples of suspending agents include surfactants such as stearyl triethanolamine, sodium lauryl sulfate, lauryl aminopropionic acid, lecithin, benzalkonium chloride, benzethonium chloride, glyceryl monostearate, etc .; eg polyvinyl alcohol, Examples thereof include hydrophilic polymers such as polyvinyl pyrrolidone, sodium carboxymethyl cellulose, methyl cellulose, hydroxymethyl cellulose, hydroxyethyl cellulose and hydroxypropyl cellulose.
等張化剤の好適な例としては、例えば塩化ナトリウム、グリセリン、D−マンニトールなどが挙げられる。 Preferred examples of the tonicity agent include sodium chloride, glycerin, D-mannitol and the like.
緩衝剤の好適な例としては、例えばリン酸塩、酢酸塩、炭酸塩、クエン酸塩などの緩衝液などが挙げられる。 Preferred examples of the buffer include buffers such as phosphate, acetate, carbonate, citrate and the like.
無痛化剤の好適な例としては、例えばベンジルアルコールなどが挙げられる。 Preferred examples of the soothing agent include benzyl alcohol and the like.
分散剤としては、例えば、ピロリン酸ナトリウム、ヘキサメタリン酸ナトリウム、ポリビニルアルコール、ポリビニルピロリドン、メチルビニルエーテル/無水マレイン酸架橋コポリマー、有機酸等が挙げられる。 Examples of the dispersant include sodium pyrophosphate, sodium hexametaphosphate, polyvinyl alcohol, polyvinyl pyrrolidone, methyl vinyl ether / maleic anhydride cross-linked copolymer, organic acid and the like.
着色剤としては、無機顔料、天然色素などが挙げられる。 As a coloring agent, an inorganic pigment, a natural pigment, etc. are mentioned.
本発明の外用組成物は、本発明の効果を損なわない範囲で、その他の有効成分を含むことができる。有効成分の具体例としては、例えば、保湿成分、パール光沢付与剤、コンディショニング剤、スクラブ剤、血行促進成分、収斂成分、紫外線吸収成分、紫外線散乱成分、洗浄成分、抗菌成分、抗炎症剤、鎮痒成分、ビタミン類、ペプチド又はその誘導体、アミノ酸又はその誘導体、細胞賦活化成分などが挙げられる。 The composition for external use of the present invention can contain other active ingredients as long as the effects of the present invention are not impaired. Specific examples of the active ingredient include, for example, moisturizing ingredients, pearl luster imparting agents, conditioning agents, scrub agents, blood circulation promoting ingredients, astringent ingredients, ultraviolet light absorbing ingredients, ultraviolet light scattering ingredients, cleansing ingredients, antibacterial ingredients, anti-inflammatory agents, antipruritic agents Components, vitamins, peptides or derivatives thereof, amino acids or derivatives thereof, cell activation components and the like can be mentioned.
保湿成分としては、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、ポリエチレングリコール、ジグリセリンのような多価アルコール;トレハロース、キシリトール、オリゴ糖のような糖類;ヒアルロン酸ナトリウム、ヘパリン類似物質、コンドロイチン硫酸ナトリウム、コラーゲン、エラスチン、ケラチン、キチン、キトサンのような高分子化合物;グリシン、アスパラギン酸、アルギニンのようなアミノ酸;乳酸ナトリウム、尿素、ピロリドンカルボン酸ナトリウムのような天然保湿因子;セラミド、コレステロール、リン脂質のような脂質;カミツレエキス、ハマメリスエキス、チャエキス、シソエキスのような植物抽出エキスなどが挙げられる。 Moisturizing ingredients include glycerin, 1,3-butylene glycol, propylene glycol, polyethylene glycol, polyhydric alcohols such as diglycerin; saccharides such as trehalose, xylitol and oligosaccharides; sodium hyaluronate, heparin analogue, chondroitin sulfate Polymer compounds such as sodium, collagen, elastin, keratin, chitin and chitosan; amino acids such as glycine, aspartic acid and arginine; natural moisturizing factors such as sodium lactate, urea and pyrrolidone carboxylate; ceramide, cholesterol and phosphorus Lipids such as lipids; plant extracts such as chamomile extract, hamamelis extract, tea extract, perilla extract and the like.
パール光沢付与剤としては、例えば、ジステアリン酸エチレングリコール、モノステアリン酸エチレングリコール、ジステアリン酸トリエチレングリコールなどが挙げられる。 Examples of pearlescent agents include ethylene glycol distearate, ethylene glycol monostearate, triethylene glycol distearate and the like.
コンディショニング剤としては、例えば、カチオン化セルロース、カチオン化澱粉、カチオン化フェヌグリークガム、カチオン化グアーガム、カチオン化タラガム、カチオン化ローカストビーンガム、カチオン化キサンタンガム、ジアリル四級アンモニウム塩/アクリルアミド共重合物、ポリクオタニウム、ビニルイミダゾリウムトリクロライド/ビニルピロリドン共重合体、ヒドロキシエチルセルロース/ジメチルジアリルアンモニウムクロライド共重合体、ビニルピロリドン/四級化ジメチルアミノエチルメタクリレート共重合体、ポリビニルピロリドン/アルキルアミノアクリレート共重合体、ポリビニルピロリドン/アルキルアミノアクリレート/ビニルカプロラクタム共重合体、ビニルピロリドン/メタクリルアミドプロピル塩化トリメチルアンモニウム共重合体、アルキルアクリルアミド/アクリレート/アルキルアミノアルキルアクリルアミド/ポリエチレングリコールメタクリレート共重合体、アジピン酸/ジメチルアミノヒドロキシプロピルエチレントリアミン共重合体等が挙げられる。 As the conditioning agent, for example, cationized cellulose, cationized starch, cationized fenugreek gum, cationized guar gum, cationized cod gum, cationized locust bean gum, cationized xanthan gum, diallyl quaternary ammonium salt / acrylamide copolymer, polyquaternium , Vinylimidazolium trichloride / vinylpyrrolidone copolymer, hydroxyethyl cellulose / dimethyldiallyl ammonium chloride copolymer, vinylpyrrolidone / quaternized dimethylaminoethyl methacrylate copolymer, polyvinylpyrrolidone / alkylamino acrylate copolymer, polyvinylpyrrolidone / Alkylamino acrylate / vinylcaprolactam copolymer, vinyl pyrrolidone / methacrylamidopropyl chloride Trimethyl ammonium copolymer, alkyl acrylamide / acrylate / alkylaminoalkyl acrylamide / polyethylene glycol methacrylate copolymers, adipic acid / dimethylaminohydroxypropyl ethylene triamine copolymer.
スクラブ剤としては、例えば、アプリコット核粉末、アーモンド殻粉末、アンズ核粉末、塩化ナトリウム粒、オリーブ核粉末、海水乾燥物粒、キャンデリラワックス、くるみ殻粉末、さくらんぼ核粉末、サンゴ粉末、炭粉末、はしばみ殻粉末、ポリエチレン末、無水ケイ酸等が挙げられる。 As a scrub agent, for example, apricot kernel powder, almond shell powder, apricot kernel powder, sodium chloride particles, olive kernel powder, dried seawater particles, candelilla wax, walnut shell powder, cherry kernel powder, coral powder, charcoal powder, There may be mentioned rice husk powder, polyethylene powder, anhydrous silicic acid and the like.
血行促進剤としては、例えば、アセチルコリン、イクタモール、カフェイン、カプサイシン、カンタリスチンキ、ガンマーオリザノール、ショオウキョウチンキ、ジンゲロン、セファランチン、センブリエキス、タンニン酸、トウガラシチンキ、トラゾリン、ニコチン酸トコフェロール、ニコチン酸ベンジルエステル等が挙げられる。 As a blood circulation promoter, for example, acetylcholine, ictamol, caffeine, capsaicin, cantaristinki, gamma-oryzanol, pink oyster tincture, zingerone, cepharantin, semen extract, tannic acid, chili pepper, trazoline, tocopherol nicotinate, benzyl nicotinate Ester etc. are mentioned.
収斂成分としては、酸化亜鉛、硫酸亜鉛、アラントインヒドロキシアルミニウム、塩化アルミニウム、スルホ石炭酸亜鉛及びタンニン酸等が挙げられる。 Examples of the astringent component include zinc oxide, zinc sulfate, allantoin hydroxyaluminum, aluminum chloride, zinc sulfocarbonate and tannic acid.
紫外線吸収成分としては、オクチルトリアゾン、ジエチルアミノヒドロキシベンゾイル安息香酸ヘキシル、ジメトキシベンジリデンジオキソイミダゾリジンプロピオン酸オクチル、パラメトキシケイ皮酸2−エチルヘキシル、t−ブチルメトキシジベンゾイルメタン、フェニルベンズイミダゾールスルホン酸、メトキシケイヒ酸オクチル、メトキシケイヒ酸エチルヘキシルなどが挙げられる。 As an ultraviolet absorbing component, octyl triazone, hexyl diethylaminohydroxybenzoyl benzoate, dimethoxybenzylidene dioxoimidazolidine octylate, 2-ethylhexyl paramethoxycinnamate, t-butyl methoxy dibenzoyl methane, phenyl benzimidazole sulfonic acid, Examples thereof include octyl methoxycinnamate and ethylhexyl methoxycinnamate.
紫外線散乱成分としては、含水ケイ酸、ケイ酸亜鉛、ケイ酸セリウム、ケイ酸チタン、酸化亜鉛、酸化ジルコニウム、酸化セリウム、酸化チタン、酸化鉄、無水ケイ酸等の無機化合物、それらの無機化合物を含水ケイ酸、水酸化アルミニウム、マイカやタルク等の無機粉体で被覆したり、ポリアミド、ポリエチレン、ポリエステル、ポリスチレン、ナイロン等の樹脂粉体に複合化したもの、さらにシリコン油や脂肪酸アルミニウム塩等で処理したものなどが挙げられる。 As the ultraviolet light scattering component, inorganic compounds such as hydrous silicic acid, zinc silicate, cerium silicate, titanium silicate, zinc oxide, zirconium oxide, cerium oxide, titanium oxide, iron oxide, anhydrous silicic acid and the like, and inorganic compounds thereof Those coated with inorganic powder such as hydrous silicic acid, aluminum hydroxide, mica and talc, compounded with resin powder such as polyamide, polyethylene, polyester, polystyrene, nylon, etc., and silicone oil or fatty acid aluminum salt etc. What was processed etc. are mentioned.
洗浄成分としては、ラウリン酸カリウム、ミリスチン酸カリウム、パルミチン酸カリウム又はステアリン酸カリウムなどのアルカリ金属塩、アルカノールアミド塩又はアミノ酸塩などの石けん類、ココイルグルタミン酸ナトリウム、ココイルメチルタウリンナトリウムなどのアミノ酸系界面活性剤、ラウレス硫酸ナトリウムなどのエーテル硫酸エステル塩、ラウリルエーテル酢酸ナトリウムなどのエーテルカルボン酸塩、アルキススルホコハク酸エステルナトリウムなどのスルホコハク酸エステル塩、ヤシ油脂肪酸モノエタノールアミド、ヤシ油脂肪酸時エタノールアミドなどの脂肪酸アルカノールアミド、ラウリルリン酸ナトリウム、ポリオキシエチレンラウリルエーテルリン酸ナトリウムなどのモノアルキルリン酸エステル塩、ヤシ油脂肪酸アミドプロピルジメチルアミノ酢酸ベタイン、ラウリルジメチルアミノ酢酸ベタイン、2−アルキル−N−カルボキシメチル−N−ヒドロキシエチルイミダゾリニウムベタイン、ラウリルヒドロキシスルホベタイン及びラウロイルアミドエチルヒドロキシエチルカルボキシメチルベタインヒドロキシプロピルリン酸ナトリウムなどのベタイン型両性界面活性剤、ラウリルアミノプロピオン酸ナトリウムなどのアミノ酸型両性界面活性剤などが挙げられる。 Examples of cleaning components include alkali metal salts such as potassium laurate, potassium myristate, potassium palmitate or potassium stearate, soaps such as alkanolamide salts or amino acid salts, amino acid based interfaces such as sodium cocoyl glutamate and sodium cocoyl methyl taurine Activators, ether sulfates such as sodium laureth sulfate, ether carboxylates such as sodium lauryl ether acetate, sulfosuccinates such as sodium alkys sulfosuccinate, coconut oil fatty acid monoethanolamide, coconut oil fatty acid ethanolamide Fatty acid alkanolamide such as sodium lauryl phosphate, monoalkyl phosphate ester salt such as polyoxyethylene lauryl ether sodium phosphate, coconut oil Acid amidopropyl dimethylamino acetic acid betaine, lauryl dimethylamino acetic acid betaine, 2-alkyl-N-carboxymethyl-N-hydroxyethyl imidazolinium betaine, lauryl hydroxy sulfobetaine and lauroyl amidoethyl hydroxyethyl carboxymethyl betaine sodium hydroxypropyl phosphate And betaine-type amphoteric surfactants, amino acid-type amphoteric surfactants such as sodium lauryl aminopropionate, and the like.
抗菌成分としては、クロルヘキシジン、サリチル酸、塩化ベンザルコニウム、アクリノール、エタノール、塩化ベンゼトニウム、クレゾール、グルコン酸及びその誘導体、ポピドンヨード、ヨウ化カリウム、ヨウ素、イソプロピルメチルフェノール、トリクロカルバン、トリクロサン、感光素101号、感光素201号、パラベン、フェノキシエタノール、1,2−ペンタンジオール、塩酸アルキルジアミノグリシン、ピロクトオラミン、ミコナゾールなどが挙げられる。 As an antimicrobial component, chlorhexidine, salicylic acid, benzalkonium chloride, acrinol, ethanol, benzethonium chloride, cresol, gluconic acid and derivatives thereof, popidone iodine, potassium iodide, iodine, isopropylmethylphenol, triclocarban, triclosan, photosensitizer 101 Sensitizer No. 201, paraben, phenoxyethanol, 1,2-pentanediol, alkyldiaminoglycine hydrochloride, pyroctoramine, miconazole and the like.
抗炎症剤としては、前記のステロイド系抗炎症薬の他、非ステロイド系抗炎症剤を用いることができる。非ステロイド系抗炎症剤としては、湿疹、皮膚炎等に用いられるものであれば特に限定されないが、具体的には、ケトプロフェン、インドメタシン、ブフェキサマック、イブプロフェン、イブプロフェンピコノール、ウフェナマート、ピロキシカム、スプロフェン、ケトチフェン、フルルビプロフェン、ナプロキセン、ロキソプロフェン、フェルビナク、チアプロフェン酸、カルプロフェン、ベノキサプロフェン、フェンブフェン、ジクロフェナック、フェノプロフェン、イブフェナック、ピメプロフェン、ベンダザック、テノキシカム、グリチルレチン酸、グリチルリチン酸、メフェナム酸、アラントイン、サリチル酸メチル、サリチル酸グリコール、及びそれらの薬学的に許容される塩等が例示されるが、これに限定されない。 As the anti-inflammatory agent, in addition to the above-mentioned steroidal anti-inflammatory drug, non-steroidal anti-inflammatory drug can be used. Non-steroidal anti-inflammatory agents are not particularly limited as long as they are used for eczema, dermatitis etc. Specifically, ketoprofen, indomethacin, bufexamac, ibuprofen, ibuprofen piconol, ufenamate, piroxicam, suprofen , Ketotifen, flurbiprofen, naproxen, loxoprofen, ferbinac, thiaprofenic acid, carprofen, benoxaprofen, fenbufen, diclofenac, fenoprofen, ibufenac, pimeprofen, bendazac, tenoxicam, glycyrrhetinic acid, glycyrrhizinic acid, mefenamic acid, Examples include, but are not limited to, allantoin, methyl salicylate, glycol salicylate, and pharmaceutically acceptable salts thereof, and the like.
鎮痒成分としては、クロタミトン、イクタモール、モクタモール、チモール酸、ジフェンヒドラミン、クロルフェニラミンおよびその薬理学的に許容される塩(例えば、ジフェンヒドラミン塩酸塩、クロルフェニラミンマレイン酸塩等)などが挙げられる。 As an antipruritic ingredient, crotamiton, ictamol, moctamol, thymolic acid, diphenhydramine, chlorpheniramine and pharmaceutically acceptable salts thereof (eg, diphenhydramine hydrochloride, chlorpheniramine maleate etc.) and the like can be mentioned.
ビタミン類としては、dl−α−トコフェロール、酢酸dl−α−トコフェロール、コハク酸dl−α−トコフェロール、コハク酸dl−α−トコフェロールカルシウム等のビタミンE類;リボフラビン、フラビンモノヌクレオチド、フラビンアデニンジヌクレオチド、リボフラビン酪酸エステル、リボフラビンテトラ酪酸エステル、リボフラビン5’−リン酸エステルナトリウム、リボフラビンテトラニコチン酸エステル等のビタミンB2類;ニコチン酸dl−α−トコフェロール、ニコチン酸ベンジル、ニコチン酸メチル、ニコチン酸β−ブトキシエチル、ニコチン酸1−(4−メチルフェニル)エチル等のニコチン酸類;アスコルビゲン−A、アスコルビン酸ステアリン酸エステル、アスコルビン酸パルミチン酸エステル、ジパルミチン酸L−アスコルビルなどのビタミンC類;メチルヘスペリジン、エルゴカルシフェロール、コレカルシフェロールなどのビタミンD類;フィロキノン、ファルノキノン等のビタミンK類、γ−オリザノール、ジベンゾイルチアミン、ジベンゾイルチアミン塩酸塩;チアミン塩酸塩、チアミンセチル塩酸塩、チアミンチオシアン酸塩、チアミンラウリル塩酸塩、チアミン硝酸塩、チアミンモノリン酸塩、チアミンリジン塩、チアミントリリン酸塩、チアミンモノリン酸エステルリン酸塩、チアミンモノリン酸エステル、チアミンジリン酸エステル、チアミンジリン酸エステル塩酸塩、チアミントリリン酸エステル、チアミントリリン酸エステルモノリン酸塩等のビタミンB1類;塩酸ピリドキシン、酢酸ピリドキシン、塩酸ピリドキサール、5’−リン酸ピリドキサール、塩酸ピリドキサミン等のビタミンB6類;シアノコバラミン、ヒドロキソコバラミン、デオキシアデノシルコバラミン等のビタミンB12類;葉酸、プテロイルグルタミン酸等の葉酸類;ニコチン酸、ニコチン酸アミドなどのニコチン酸類;パントテン酸、パントテン酸カルシウム、パントテニルアルコール(パンテノール)、D−パンテサイン、D−パンテチン、補酵素A、パントテニルエチルエーテル等のパントテン酸類;ビオチン、ビオチシン等のビオチン類;アスコルビン酸、アスコルビン酸ナトリウム、デヒドロアスコルビン酸、アスコルビン酸リン酸エステルナトリウム、アスコルビン酸リン酸エステルマグネシウム等のアスコルビン酸誘導体であるビタミンC類;カルニチン、フェルラ酸、α−リポ酸、オロット酸等のビタミン様作用因子などが挙げられる。 Vitamins include vitamin E such as dl-α-tocopherol, dl-α-tocopherol acetate, dl-α-tocopherol succinate, dl-α-tocopherol calcium succinate, etc .; riboflavin, flavin mononucleotide, flavin adenine dinucleotide Vitamin B2s such as riboflavin butyrate, riboflavin tetrabutyrate, riboflavin 5'-phosphate sodium, riboflavin tetranicotinate; nicotinate dl-α-tocopherol, nicotinate benzyl, nicotinate methyl, nicotinate β- Nicotinic acids such as butoxyethyl and nicotinic acid 1- (4-methylphenyl) ethyl; Ascorbigen-A, ascorbic acid stearic acid ester, ascorbic acid palmitic acid ester, dipalmitic acid acid -Vitamin C such as ascorbyl; Vitamin D such as methyl hesperidin, ergocalciferol, cholecalciferol, vitamin K such as phylloquinone, farnoquinone etc., γ- oryzanol, dibenzoyl thiamine, dibenzoyl thiamine hydrochloride; thiamine hydrochloride , Thiamine cetyl hydrochloride, thiamine thiocyanate, thiamine lauryl hydrochloride, thiamine nitrate, thiamine monophosphate, thiamine lysine salt, thiamine triphosphate, thiamine monophosphate phosphate, thiamine monophosphate, thiamine diphosphate , Thiamine diphosphate hydrochloride, thiamine triphosphate, thiamine triphosphate monophosphate etc., vitamin B1s; pyridoxine hydrochloride, pyridoxine acetate, pyridoxal hydrochloride, 5'- Vitamin B6s such as pyridoxal phosphate and pyridoxamine hydrochloride; Vitamin B12s such as cyanocobalamin, hydroxocobalamin, deoxyadenosyl cobalamin; folic acids such as folic acid and pteroyl glutamic acid; nicotinic acids such as nicotinic acid and nicotinic acid amide; pantothenic acid , Pantothenic acid calcium, Pantothenyl alcohol (Panthenol), D-Pantethein, D-Pantethin, Co-enzyme A, Pantothenic acid such as Pantothenylethylether; Biotins such as Biotin, Bioticin; Ascorbic acid, Sodium ascorbate, Vitamin C which is an ascorbic acid derivative such as dehydroascorbic acid, sodium ascorbate phosphate, magnesium ascorbate phosphate, carnitine, ferulic acid, α-lipoic acid Such as vitamin-like effect factors such as orotic acid, and the like.
ペプチド又はその誘導体としては、ケラチン分解ペプチド、加水分解ケラチン、コラーゲン、魚由来コラーゲン、アテロコラーゲン、ゼラチン、エラスチン、エラスチン分解ペプチド、コラーゲン分解ペプチド、加水分解コラーゲン、塩化ヒドロキシプロピルアンモニウム加水分解コラーゲン、エラスチン分解ペプチド、コンキオリン分解ペプチド、加水分解コンキオリン、シルク蛋白分解ペプチド、加水分解シルク、ラウロイル加水分解シルクナトリウム、大豆蛋白分解ペプチド、加水分解大豆蛋白、小麦蛋白、小麦蛋白分解ペプチド、加水分解小麦蛋白、カゼイン分解ペプチド、アシル化ペプチド(パルミトイルオリゴペプチド、パルミトイルペンタペプチド、パルミトイルテトラペプチド等)などが挙げられる。 As peptides or derivatives thereof, keratinolytic peptides, hydrolyzed keratin, collagen, fish-derived collagen, atelocollagen, gelatin, elastin, elastin degrading peptides, collagenolytic peptides, hydrolyzed collagen, hydroxypropyl ammonium chloride hydrolyzed collagen, elastin degrading peptides , Conchiolin degrading peptide, hydrolyzing conchiolin, silk proteolytic peptide, hydrolyzing silk, lauroyl hydrolyzing silk sodium, soybean proteolytic peptide, hydrolyzing soybean protein, wheat protein, wheat proteolytic peptide, hydrolyzing wheat protein, caseinolytic peptide And acylated peptides (palmitoyl oligopeptide, palmitoyl pentapeptide, palmitoyl tetrapeptide, etc.) and the like.
アミノ酸又はその誘導体としては、ベタイン(トリメチルグリシン)、プロリン、ヒドロキシプロリン、アルギニン、リジン、セリン、グリシン、アラニン、フェニルアラニン、β−アラニン、スレオニン、グルタミン酸、グルタミン、アスパラギン、アスパラギン酸、システイン、シスチン、メチオニン、ロイシン、イソロイシン、バリン、ヒスチジン、タウリン、γ−アミノ酪酸、γ−アミノ−β−ヒドロキシ酪酸、カルニチン、カルノシン、クレアチン等が挙げられる。 As amino acids or derivatives thereof, betaine (trimethylglycine), proline, hydroxyproline, arginine, lysine, serine, glycine, glycine, alanine, phenylalanine, β-alanine, threonine, glutamic acid, glutamine, asparagine, aspartic acid, cysteine, cystine, methionine Leucine, isoleucine, valine, histidine, taurine, γ-aminobutyric acid, γ-amino-β-hydroxybutyric acid, carnitine, carnosine, creatine and the like.
細胞賦活化成分としては、γ-アミノ酪酸、ε-アミノカプロン酸などのアミノ酸類、レチノール、チアミン、リボフラビン、塩酸ピリドキシン、パントテン酸類などのビタミン類、グリコール酸、乳酸などのα-ヒドロキシ酸類、タンニン、フラボノイド、サポニン、アラントイン、感光素301号などが挙げられる。 Cell activation components include amino acids such as γ-aminobutyric acid and ε-aminocaproic acid, vitamins such as retinol, thiamine, riboflavin, pyridoxine hydrochloride and pantothenic acids, α-hydroxy acids such as glycolic acid and lactic acid, tannin, Flavonoid, saponin, allantoin, photosensitive element No. 301 and the like can be mentioned.
本発明の外用組成物において、ステロイド系抗炎症薬とモノテルペンとを配合する場合は、その組み合わせは特に限定されず、他の配合成分の種類及び含有量、製剤形態、使用方法等に応じて適宜設定される。限定はされないが、ステロイド系抗炎症薬とモノテルペンとの組み合わせを以下の表1に例示する。 When the steroidal anti-inflammatory drug and the monoterpene are blended in the composition for external use of the present invention, the combination thereof is not particularly limited, and depending on the type and content of other blending components, the form of formulation, the method of use, etc. It is set appropriately. Without limitation, combinations of steroidal anti-inflammatory agents and monoterpenes are exemplified in Table 1 below.
次に、実施例や試験例により本発明を具体的に説明するが、本発明は以下の実施例や試験例に限定されるものではない。 Next, the present invention will be specifically described by way of examples and test examples, but the present invention is not limited to the following examples and test examples.
試験例1.マラセチア属真菌に対する増殖抑制試験
マラセチア属真菌(M.globosa、M.restricta)に対する増殖抑制効果を評価するために、以下の試験を行った。先ず、上記2種のマラセチア真菌(M.globosa(ATCC:MYA−4612)、M.restricta(ATCC:MYA−4611))を用意し、各菌液を約106CFU/mL接種したMLNA培地(modified Leeming and Notman Agar培地)を作製した。滅菌済みの穿孔カッター(TOYOBO製、バイオプシーパンチ8mm、ステンレス製)で直径8mmの穴を開けた。穴内一杯(約0.1mL)に下記表2に示す各種被験試料を注入した。その後、M.restricta又はM.globosaを接種したMLNA培地は8日間30℃好気条件下で培養した。培養期間終了後、それぞれの阻止円の直径(大きさ)を測定し、マラセチア真菌種毎に平均値を算出した。この結果を以下の表2に示す。
Test Example 1 Growth Inhibition Test on Malassezia Fungus The following test was conducted to evaluate the growth inhibitory effect on Malassezia fungus (M. globosa, M. restricta). First, an MLNA medium (M. globosa (M. globosa (ATCC: MYA-4612), M. restricta (ATCC: MYA-4611)) was prepared, and each bacterial solution was inoculated at about 10 6 CFU / mL (MLNA medium) A modified Leeming and Notman Agar medium was prepared. A hole of 8 mm in diameter was drilled with a sterile perforated cutter (TOYOBO, biopsy punch 8 mm, stainless steel). The various test samples shown in Table 2 below were injected into the entire hole (about 0.1 mL). Then, M. restricta or M. The MLNA medium inoculated with globosa was cultured under aerobic conditions at 30 ° C. for 8 days. After completion of the culture period, the diameter (size) of each inhibition circle was measured, and the average value was calculated for each Malassezia fungal species. The results are shown in Table 2 below.
上記の結果に示されるように、比較例1において、吉草酸酢酸プレドニゾロン自体にはマラセチア属真菌(M.globosa、M.restricta)に対する増殖抑制効果は認められなかった。また、比較例2において、吉草酸酢酸プレドニゾロンに1.0重量%メントールを組み合わせて使用した場合にも、マラセチア属真菌(M.globosa、M.restricta)に対する増殖抑制効果は認められなかった。一方、実施例1において、全く予想外なことに、吉草酸酢酸プレドニゾロンに3.5重量%メントールを組み合わせた場合には、高い増殖抑制効果が発揮されることが明らかになった。 As shown in the above results, in Comparative Example 1, the prednisolone acetate valerate itself has no growth inhibitory effect on Malassezia fungus (M. globosa, M. restricta). In addition, in Comparative Example 2, even when prednisolone acetate valerate was used in combination with 1.0% by weight menthol, no growth inhibitory effect on Malassezia fungus (M. globosa, M. restricta) was observed. On the other hand, it was revealed that, in Example 1, when a combination of 3.5% by weight menthol with prednisolone valerate acetate was totally unexpected, a high growth inhibitory effect was exhibited.
参考試験例1.メントール自体によるマラセチア属真菌に対する増殖抑制試験
上記実施例1で認められた、吉草酸酢酸プレドニゾロン及び3.5重量%のメントールを組み合わせることにより発揮されるマラセチア属真菌に対する増殖抑制効果がメントール自体による効果か否かを確認するために、以下の試験を行った。具体的には、上記試験例1と実質的に同様の手順で、拡散法により3.5重量%メントールのみを含有する被験試料を調製して試験を行った。この結果を以下の表3に示す。
Reference Test Example 1 Growth inhibition test against Malassezia fungus by menthol itself Growth inhibitory effect against Malassezia fungus exerted by combining prednisolone valerate acetate and 3.5% by weight of menthol observed in Example 1 above is the effect by menthol itself The following tests were conducted to confirm whether or not it was. Specifically, a test sample containing only 3.5% by weight menthol was prepared and tested by the diffusion method in substantially the same manner as in Test Example 1 above. The results are shown in Table 3 below.
上記の結果に示されるように、M.globosaに対しては3.5重量%メントールのみを含む被験製剤を使用してもマラセチア属真菌(M.globosa)に対する増殖抑制効果は認められないことが明らかとなった。従って、上記実施例1で認められたマラセチア属真菌(M.globosa)に対する増殖抑制効果が、吉草酸酢酸プレドニゾロンと3.5重量%メントールとを組み合わせることによって初めて得られる相乗効果であることが認められた。 As shown in the results above, M.S. It was revealed that the use of a test preparation containing only 3.5% by weight menthol against globosa does not show any growth inhibitory effect against Malassezia fungus (M. globosa). Therefore, it is recognized that the growth inhibitory effect against Malassezia genus fungus (M. globosa) observed in Example 1 above is a synergistic effect obtained by combining prednisolone valerate acetate and 3.5% by weight menthol. It was done.
以下、本発明の外用組成物の製剤処方例を示す。 Hereinafter, formulation examples of the composition for external use of the present invention will be shown.
(製剤処方例1:クリーム剤(水中油型))
(1)イオン交換水 残余
(2)プレドニゾロン吉草酸エステル酢酸エステル 0.15重量%
(3)l−メントール 2.0重量%
(4)ステアリン酸 3.0重量%
(5)セタノール 3.0重量%
(6)ミツロウ 3.0重量%
(7)固形パラフィン 3.0重量%
(8)流動パラフィン 10重量%
(9)パラベン 0.15重量%
(10)ポリオキシエチレンヤシ油脂肪酸ソルビタン 2.0重量%
(11)ステアリン酸グリセリル 1.0重量%
(12)1,3-ブチレングリコール 5.0重量%
Formulation Example 1: Cream (oil-in-water type)
(1) Ion-exchanged water residue (2) Prednisolone valerate ester acetate 0.15% by weight
(3) l-menthol 2.0% by weight
(4) stearic acid 3.0% by weight
(5) Settanol 3.0% by weight
(6) Beeswax 3.0% by weight
(7) Solid paraffin 3.0% by weight
(8) Liquid paraffin 10% by weight
(9) Paraben 0.15% by weight
(10) Polyoxyethylene coconut oil fatty acid sorbitan 2.0% by weight
(11) glyceryl stearate 1.0% by weight
(12) 1,3-butylene glycol 5.0% by weight
(製剤処方例2:クリーム剤(水中油型))
(1)イオン交換水 残余
(2)プレドニゾロン吉草酸エステル酢酸エステル 0.15重量%
(3)l−メントール 5.0重量%
(4)グリセリン 10重量%
(5)1,3−ブチレングリコール 5重量%
(6)パラベン 0.2重量%
(7)エデト酸2ナトリウム 0.05重量%
(8)カルボキシビニルポリマー 0.5重量%
(9)トリエタノールアミン 0.4重量%
(10)ステアリン酸ソルビタン 1.0重量%
(11)ポリソルベート60 1.0重量%
(12)スクワラン 8.0重量%
(13)パルミチン酸イソプロピル 5.0重量%
(14)ベヘニルアルコール 5.0重量%
Formulation Example 2: Cream (oil-in-water type)
(1) Ion-exchanged water residue (2) Prednisolone valerate ester acetate 0.15% by weight
(3) l-menthol 5.0% by weight
(4) Glycerin 10% by weight
(5) 5% by weight of 1,3-butylene glycol
(6) Paraben 0.2% by weight
(7) Edetate disodium 0.05% by weight
(8) Carboxyvinyl polymer 0.5% by weight
(9) 0.4% by weight of triethanolamine
(10) 1.0% by weight of sorbitan stearate
(11) Polysorbate 60 1.0% by weight
(12) Squaran 8.0% by weight
(13) 5.0% by weight of isopropyl palmitate
(14) Behenyl alcohol 5.0% by weight
(製剤処方例3:液剤)
(1)イオン交換水 残余
(2)無水エタノール 45重量%
(3)プレドニゾロン吉草酸エステル酢酸エステル 0.15重量%
(4)l−メントール 3.5重量%
(5)1,3−ブチレングリコール 8.0重量%
(6)カラギーナン 0.01重量%
(7)トリエタノールアミン 0.1重量%
(Formulation example 3: Solution)
(1) Ion-exchanged water residue (2) Absolute ethanol 45% by weight
(3) Prednisolone valerate ester acetate 0.15% by weight
(4) l-menthol 3.5% by weight
(5) 1,3-butylene glycol 8.0% by weight
(6) carrageenan 0.01% by weight
(7) 0.1% by weight of triethanolamine
Claims (5)
該ステロイド系抗炎症薬が、吉草酸酢酸プレドニゾロンである、
Malassezia restricta及びMalassezia globosaからなる群より選択される少なくとも1種のマラセチア属真菌の増殖を抑制するために用いられる外用組成物
(但し、下記組成物を除く:
(1)0.05〜0.1重量%のデキサメタゾン、0.5〜1.5重量%のカンフル、及び0.5〜1.5重量%のメントールを含有する組成物;
(2)0.5〜1重量部の酢酸デキサメタゾン、5〜15重量部のカンフル、5〜15重量部のメントール、100〜320重量部のプロピレングリコール、5〜50重量部の無水エタノール、60〜600重量部のポリソルベート80、2〜20重量部のヒプロメロース、4〜40重量部のカルボマー、及び1.5〜5.5重量部のトリエタノールアミンを含有する組成物;並びに
(3)90〜100gのボルネオール、80〜110gのホウ酸、1000〜1500mlの水、5〜100gのクロラムフェニコール注射剤、5〜100gのプロメタジン注射剤、5〜100mlのデキサメタゾン注射剤、及び95〜150mlのアルコールを含有するかゆみ止め組成物)。 Contains steroidal anti-inflammatory drug and 3% by weight or more of menthol,
The steroidal anti-inflammatory drug, a valeric acid prednisolone,
An externally applied composition used to inhibit the growth of at least one Malassezia fungus selected from the group consisting of Malassezia restricta and Malassezia globosa (except for the following compositions:
(1) a composition containing 0.05 to 0.1% by weight of dexamethasone, 0.5 to 1.5% by weight of camphor, and 0.5 to 1.5% by weight of menthol;
(2) 0.5 to 1 part by weight of dexamethasone acetate, 5 to 15 parts by weight of camphor, 5 to 15 parts by weight of menthol, 100 to 320 parts by weight of propylene glycol, 5 to 50 parts by weight of absolute ethanol, 60 to A composition comprising 600 parts by weight of polysorbate 80, 2 to 20 parts by weight of hypromellose, 4 to 40 parts by weight of carbomer, and 1.5 to 5.5 parts by weight of triethanolamine; and (3) 90 to 100 g. Borneol, 80-110 g boric acid, 1000-1500 ml water, 5-100 g chloramphenicol injection, 5-100 g promethazine injection, 5-100 ml dexamethasone injection, and 95-150 ml alcohol Containing composition for preventing itching).
該ステロイド系抗炎症薬が、吉草酸酢酸プレドニゾロンである、
Malassezia restricta及びMalassezia globosaからなる群より選択される少なくとも1種のマラセチア属真菌性の皮膚疾患又は皮膚症状の予防及び/又は治療剤(但し、下記組成物を除く:
(1)0.05〜0.1重量%のデキサメタゾン、0.5〜1.5重量%のカンフル、及び0.5〜1.5重量%のメントールを含有する組成物;
(2)0.5〜1重量部の酢酸デキサメタゾン、5〜15重量部のカンフル、5〜15重量部のメントール、100〜320重量部のプロピレングリコール、5〜50重量部の無水エタノール、60〜600重量部のポリソルベート80、2〜20重量部のヒプロメロース、4〜40重量部のカルボマー、及び1.5〜5.5重量部のトリエタノールアミンを含有する組成物;並びに
(3)90〜100gのボルネオール、80〜110gのホウ酸、1000〜1500mlの水、5〜100gのクロラムフェニコール注射剤、5〜100gのプロメタジン注射剤、5〜100mlのデキサメタゾン注射剤、及び95〜150mlのアルコールを含有するかゆみ止め組成物)。 Contains steroidal anti-inflammatory drug and 3% by weight or more of menthol,
The steroidal anti-inflammatory drug, a valeric acid prednisolone,
A preventive and / or therapeutic agent for at least one Malassezia fungal skin disease or skin condition selected from the group consisting of Malassezia restricta and Malassezia globosa (except the following composition:
(1) a composition containing 0.05 to 0.1% by weight of dexamethasone, 0.5 to 1.5% by weight of camphor, and 0.5 to 1.5% by weight of menthol;
(2) 0.5 to 1 part by weight of dexamethasone acetate, 5 to 15 parts by weight of camphor, 5 to 15 parts by weight of menthol, 100 to 320 parts by weight of propylene glycol, 5 to 50 parts by weight of absolute ethanol, 60 to A composition comprising 600 parts by weight of polysorbate 80, 2 to 20 parts by weight of hypromellose, 4 to 40 parts by weight of carbomer, and 1.5 to 5.5 parts by weight of triethanolamine; and (3) 90 to 100 g. Borneol, 80-110 g boric acid, 1000-1500 ml water, 5-100 g chloramphenicol injection, 5-100 g promethazine injection, 5-100 ml dexamethasone injection, and 95-150 ml alcohol Containing composition for preventing itching).
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CN107510773A (en) * | 2017-09-05 | 2017-12-26 | 肇庆高新区国专科技有限公司 | A kind of pure plant extract solution and preparation method thereof |
CN112826831A (en) * | 2021-01-28 | 2021-05-25 | 梁潇艺 | Traditional Chinese medicine composition for treating skin diseases, preparation method and application |
KR102606763B1 (en) * | 2022-11-02 | 2023-11-29 | 연세대학교 산학협력단 | A Composition for Improving or Alleviating Stress-related Disorders Comprising Nerol Compound |
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CN101874805B (en) * | 2009-04-30 | 2012-09-05 | 三九医药股份有限公司 | Compound dexamethasone acetate gel and preparation method thereof |
CN102366437A (en) * | 2011-07-15 | 2012-03-07 | 吉林敖东集团大连药业股份有限公司 | Compound dexamethasone ointment and preparation method thereof |
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CN103055179B (en) * | 2013-01-10 | 2015-06-17 | 刘倩 | Traditional Chinese medicine solution for diminishing inflammation and relieving itching |
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