JP3193483B2 - External composition for skin - Google Patents
External composition for skinInfo
- Publication number
- JP3193483B2 JP3193483B2 JP30188492A JP30188492A JP3193483B2 JP 3193483 B2 JP3193483 B2 JP 3193483B2 JP 30188492 A JP30188492 A JP 30188492A JP 30188492 A JP30188492 A JP 30188492A JP 3193483 B2 JP3193483 B2 JP 3193483B2
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- Japan
- Prior art keywords
- skin
- present
- composition
- physiologically active
- effect
- 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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Description
【０００１】[0001]
【産業上の利用分野】本発明は、生理活性物質の皮膚吸
収性に優れた新規な皮膚外用組成物に関する。BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a novel composition for external use on skin which is excellent in skin absorbability of physiologically active substances.
【０００２】[0002]
【従来の技術および発明が解決しようとする課題】近
年、生理活性物質の投与経路として経皮投与が注目され
ている。これは、静脈内投与や経口投与が痛みを伴った
り、消化管障害を引き起こしたり、血中濃度を維持する
のに一日に何度も投与する必要が有ったり、また肝臓で
初回通過効果により代謝されてしまう等の問題点がある
のに対し、経皮投与ではこれらの問題点が回避されるた
めである。2. Description of the Related Art In recent years, transdermal administration has attracted attention as an administration route of a physiologically active substance. This is because intravenous and oral administration can be painful, cause gastrointestinal problems, need to be administered multiple times a day to maintain blood levels, and have a first-pass effect in the liver. This is because, while there are problems such as metabolism by transdermal administration, these problems are avoided by transdermal administration.
【０００３】皮膚は、紫外線や温度変化等の環境因子及
び外部化学物質の侵入に抗する優れたバリヤーの性質を
持つ。外部化学物質に対する浸透抵抗性は表皮の外層即
ち角質層が最も強く、その下層部は比較的抵抗性が低
い。従って、生理活性物質を経皮投与する場合、角質層
を透過させることが最も重要になる。[0003] The skin has an excellent barrier property against the invasion of environmental factors such as ultraviolet rays and temperature changes and external chemicals. The penetration resistance to external chemicals is strongest in the outer layer of the epidermis, that is, the stratum corneum, and the lower layer has relatively low resistance. Therefore, when a physiologically active substance is transdermally administered, it is most important to penetrate the stratum corneum.
【０００４】そこで、角質層の透過性を高める目的で、
レシチン、オレイン酸、界面活性剤、ＡＺＯＮ、モノテ
ルペン類等の経皮吸収促進剤が検討されている。これら
の経皮吸収促進剤の中で、モノテルペン類は水溶性及び
油溶性物質の何れをも透過させやすくする、作用が一過
性で投与を中止すれば角質層のバリヤー能がすぐに復帰
する等の利点があることから有用である。Therefore, in order to increase the permeability of the stratum corneum,
Transdermal absorption enhancers such as lecithin, oleic acid, surfactants, AZON, and monoterpenes have been studied. Among these percutaneous absorption enhancers, monoterpenes make it easy to penetrate both water-soluble and oil-soluble substances. The action is transient, and if the administration is stopped, the barrier function of the stratum corneum is immediately restored. This is useful because it has advantages such as doing.
【０００５】モノテルペン類の中でも構造上水酸基，カ
ルボキシル基を有さない炭化水素系モノテルペンが最も
有用であることが報告されている（Ｄｒｕｇ Ｄｅｓｉ
ｇｎａｎｄ Ｄｅｌｉｖｅｒｙ，４巻，３１３頁，１９
８９年）。しかし、炭化水素系モノテルペン類は揮発性
が高いため、パップ剤等の閉塞投与型の剤形では有効で
あるが、クリーム，軟膏，液剤など開放系で皮膚塗布す
る製剤に適用した場合、十分な効果を示さない。It has been reported that among the monoterpenes, hydrocarbon monoterpenes having no hydroxyl group or carboxyl group in structure are most useful (Drug Design).
gand Delivery, 4, 313, 19
1989). However, since hydrocarbon monoterpenes are highly volatile, they are effective in occlusive dosage forms such as cataplasms. However, when applied to preparations to be applied to the skin in an open system such as creams, ointments and liquids, they are not sufficiently effective. Does not show any significant effect.
【０００６】また、特公平３−６５３２３号公報には、
炭素数が７〜２０で、且つ融点が４０℃以下の脂肪族ア
ルコール、モノテルペン系アルコール、セスキテルペン
系アルコールから選ばれた少なくとも一種のアルコール
成分、及びジメチルスルホキシドを必須成分とする外用
製剤用基剤および外用製剤が提案され、更に、特開平３
−６３２３３号公報には、含有する薬物成分を経皮から
吸収させる外用剤において薬物成分の経皮吸収を促進す
べくテルペン類（Ｃ5 Ｈ8 ）ｎの分子式を有するととも
に分子骨格中に酸素原子を含まない経皮吸収促進物質が
提案されている。[0006] In addition, in JP-public flat 3-65323,
A group for an external preparation containing at least one alcohol component selected from aliphatic alcohols having a carbon number of 7 to 20 and a melting point of 40 ° C. or lower, monoterpene alcohols, and sesquiterpene alcohols, and dimethyl sulfoxide as essential components. Preparations and external preparations have been proposed.
JP-A-63233 discloses a terpene (C5H8) n having a molecular formula of a terpene (C5H8) n in order to promote the transdermal absorption of a drug component in an external preparation for absorbing the drug component through the skin, and containing an oxygen atom in the molecular skeleton. No transdermal absorption enhancers have been proposed.
【０００７】前者のうちセスキテルペンアルコール類と
ジメチルスルホキシドとの組み合わせは、開放系で用い
た場合にも若干の促進効果を発現するが、ジメチルスル
ホキシドに起因する皮膚刺激が問題となる。[0007] Of the former, the combination of sesquiterpene alcohols and dimethylsulfoxide exhibits a slight accelerating effect when used in an open system, but there is a problem of skin irritation caused by dimethylsulfoxide.
【０００８】後者の発明は、モノテルペン類およびセス
キテルペン類を用いる場合、前述の論文と同様に閉鎖系
では効果を有するが、開放系では殆ど効果がない。ま
た、ジテルペン以上の化合物は揮発性はそれほど顕著で
はないが、経皮吸収促進効果がない。In the latter invention, when monoterpenes and sesquiterpenes are used, they have an effect in a closed system as in the above-mentioned article, but have little effect in an open system. Compounds of diterpene or higher do not have a remarkable volatility, but have no transdermal absorption promoting effect.
【０００９】係る状況に鑑み検討した結果、経皮吸収促
進効果を有し、比較的揮発性の少ないセスキテルペンで
ある、ビサボレン、ベルガモテン、カリオフィレン、イ
ロンから選ばれる一種以上と水溶性多価アルコールを組
み合わせることにより、開放系でも顕著な経皮吸収促進
効果が得られることを見出し、本発明を完成するに至っ
た。As a result of an examination in view of the above situation, it is found that bisabolene, bergamoten, caryophyllene, and i, which are sesquiterpenes having a transdermal absorption promoting effect and having relatively low volatility.
It has been found that a combination of at least one of Ron and a water-soluble polyhydric alcohol can provide a remarkable transdermal absorption promoting effect even in an open system, and have completed the present invention.
【００１０】[0010]
【課題を解決するための手段】本発明は、少なくとも一
種の生理活性物質と、ビサボレン、ベルガモテン、カリ
オフィレン、イロンから選ばれる一種以上と、水溶性多
価アルコール１．０〜 ７０重量％とを配合してなる皮膚
外用組成物である。SUMMARY OF THE INVENTION The present invention provides at least one physiologically active substance , bisabolene, bergamoten, and potassium.
One or more selected from offylene and iron, and water-soluble
It is a composition for external use on the skin, which comprises 1.0 to 70% by weight of a polyhydric alcohol .
【００１１】以下、本発明の構成の詳細について説明す
る。本発明に用いられる生理活性物質は、皮膚適用薬及
び全身作用薬に大別され、その配合量は各々局所効果及
び全身効果が発現される量が使用される。Hereinafter, the configuration of the present invention will be described in detail. The physiologically active substance used in the present invention is roughly classified into a drug for skin application and a drug for systemic action, and the compounding amount thereof is such that a local effect and a systemic effect are exhibited, respectively.
【００１２】本発明は、種々の生理活性物質の皮膚透過
速度を増大させるための組成物を与える物であり、本発
明の組成物を利用することにより、皮膚下部組織に吸収
される皮膚適用薬の量及び全身血流中に移行する全身作
用薬の量が増大する。The present invention provides a composition for increasing the rate of penetration of various physiologically active substances into the skin. The composition of the present invention is used to absorb a drug for skin application to the lower skin tissue. And the amount of systemic agent that migrates into the systemic bloodstream is increased.
【００１３】以下本発明に用いられる生理活性物質の例
を挙げるが、本発明はそれらに限定される物ではない。
抗菌剤、抗真菌剤、にきび治療剤または抗ウイルス剤と
してリンコマイシン、テトラサイクリン、エリスロマイ
シン、ペニシリンＧ、セファレキシン、クロロヘキシジ
ン、ストレプトマイシン、アンホテリシンＢ等が挙げら
れる。Examples of the physiologically active substance used in the present invention are described below, but the present invention is not limited thereto.
Examples of antibacterial agents, antifungal agents, acne therapeutic agents or antiviral agents include lincomycin, tetracycline, erythromycin, penicillin G, cephalexin, chlorohexidine, streptomycin, amphotericin B and the like.
【００１４】代謝拮抗物質として、５−フルオロウラシ
ル、６メルカプトプリン、メトトレキセート等が挙げら
れる。抗炎症剤としてステロイド系の酢酸コルチゾン、
吉草酸ベタメサゾン、ハイドロコルチゾンシクロペンチ
ルプロピオネート等が、非ステロイド系のインドメタシ
ン、イブプロフェン、メフェナム酸、グリチルリチン酸
ナトリウム、グリチルレチン酸カリウム等が挙げられ
る。Examples of antimetabolites include 5-fluorouracil, 6-mercaptopurine, methotrexate and the like. Steroidal cortisone acetate as an anti-inflammatory agent,
Non-steroidal indomethacin, ibuprofen, mefenamic acid, sodium glycyrrhizinate, potassium glycyrrhetinate, and the like, such as betamethasone valerate and hydrocortisone cyclopentyl propionate.
【００１５】局所麻酔剤としてジブカイン、プロカイ
ン、リドカイン等が挙げられる。ホルモンおよびその誘
導体として、エストラジオール、テストステロン、エチ
ニルエストラジオール、プロゲステロン等が挙げられ
る。[0015] Examples of local anesthetics include dibucaine, procaine, lidocaine and the like. Hormones and their derivatives include estradiol, testosterone, ethinylestradiol, progesterone and the like.
【００１６】その他の皮膚適用剤としてハイドロキノ
ン、アルブチン、アスコルビン酸、アスコルビン酸リン
酸エステルマグネシウム塩、ジイソプロピルアミンジク
ロロアセテート、γ−アミノ酪酸、トコフェロール、ニ
コチン酸トコフェロール、酢酸トコフェロール等が挙げ
られる。Other skin-applying agents include hydroquinone, arbutin, ascorbic acid, magnesium ascorbic acid phosphate, diisopropylamine dichloroacetate, γ-aminobutyric acid, tocopherol, tocopherol nicotinate, tocopherol acetate.
【００１７】本発明に用いられるビサボレン、ベルガモ
テン、カリオフィレン、イロンから選ばれる一種以上の
配合量は、最終組成物の重量を基準に、０．０１％〜２
０％が好ましい。０．０１％未満では促進効果が顕著で
ない。また、２０％を超えて配合しても配合量に見合っ
た効果が期待できず、また、製剤化が困難になる。 Bisabolene and Bergamo used in the present invention
The compounding amount of one or more selected from ten, caryophyllene and iron is 0.01% to 2% based on the weight of the final composition.
0% is preferred. If less than 0.01%, the accelerating effect is not remarkable. In addition, even if the content exceeds 20%, an effect commensurate with the compounding amount cannot be expected, and it becomes difficult to formulate the preparation.
【００１８】本発明に用いられる水溶性多価アルコール
としては、グリセリン、プロピレングリコール、ジプロ
ピレングリコール、１，３−ブチレングリコール、ジグ
リセリン、ヘキサグリセリン、ポリグリセリン、ポリエ
チレングリコール等が挙げられる。The water-soluble polyhydric alcohol used in the present invention includes glycerin, propylene glycol, dipropylene glycol, 1,3-butylene glycol, diglycerin, hexaglycerin, polyglycerin, polyethylene glycol and the like.
【００１９】その配合量は、最終組成物の重量を基準
に、１．０％〜７０％である。１．０％未満では促進効
果が顕著でなく、７０％を超えて配合しても配合量に見
合った効果が期待できない。The compounding amount is 1.0% to 70% based on the weight of the final composition. If it is less than 1.0%, the accelerating effect is not remarkable, and even if it exceeds 70%, an effect commensurate with the compounding amount cannot be expected.
【００２０】本発明が適用される製剤としては、軟膏、
クリーム、リニメント剤、酒精剤、エアゾール剤、乳
液、ローション、パック等が挙げられる。The preparations to which the present invention is applied include ointments,
Creams, liniments, spirits, aerosols, emulsions, lotions, packs and the like can be mentioned.
【００２１】本発明の皮膚外用組成物には、必須構成成
分の他に、上記製剤を形成するため、本発明の効果を損
なわない範囲で、該製剤に応じた基剤を配合することが
できる。The composition for external use on the skin of the present invention may contain, in addition to the essential constituents, a base according to the preparation so as not to impair the effects of the present invention in order to form the above preparation. .
【００２２】[0022]
【実施例】以下実施例により本発明を更に詳細に説明す
る。尚、以下における％表示は、特に指定しない限り、
重量％を示す。The present invention will be described in more detail with reference to the following examples. Unless otherwise specified, the percentages shown below are
Indicates the weight%.
【００２３】実施例中の経皮吸収性試験は以下の通りで
ある。フランツ型拡散セルにヘアレスラットの腹部皮膚
を装着し、上側のセル（開放系）に皮膚外用組成物（１
０ｍｇ／ｃｍ 2 ）を、下側のセルに生理食塩水（生理活
性物質が油溶性の場合は０．１％ポリオキシエチレンソ
ルビタンモノオレエート含有、生理食塩水）（１７．５
ｍｌ）をいれ、経時的に下側のセルから生理食塩水をサ
ンプリングし、下側のセルに移行した生理活性物質の濃
度を定量し、上側セルからの移行率（％）を求めた。The transdermal absorption test in the examples is as follows. The abdominal skin of a hairless rat was attached to a Franz diffusion cell, and the skin external composition (1) was placed in the upper cell (open system).
0 mg / cm 2 ) was placed in a physiological saline (17.5% polyoxyethylene sorbitan monooleate-containing physiological saline when the physiologically active substance was oil-soluble) (17.5).
ml), physiological saline was sampled from the lower cell over time, the concentration of the physiologically active substance transferred to the lower cell was quantified, and the transfer rate (%) from the upper cell was determined.
【００２４】実施例１（ローション）Example 1 (Lotion)
【００２５】[0025]
【表１】 [Table 1]
【００２６】上記組成の通り、本発明のローションを常
法に従って調製し、経皮吸収性試験を実施した。According to the above composition, the lotion of the present invention was prepared according to a conventional method, and a transdermal absorption test was conducted.
【００２７】比較例１（ローション）Comparative Example 1 (Lotion)
【００２８】[0028]
【表２】 [Table 2]
【００２９】上記組成の通り、比較用のローションを常
法に従って調製し、経皮吸収性試験を実施した。A lotion for comparison was prepared according to a conventional method as in the above composition, and a transdermal absorption test was carried out.
【００３０】比較例２（ローション）Comparative Example 2 (Lotion)
【００３１】[0031]
【表３】 [Table 3]
【００３２】上記組成の通り、比較用のローションを常
法に従って調製し、経皮吸収性試験を実施した。According to the above composition, a lotion for comparison was prepared according to a conventional method, and a transdermal absorption test was carried out.
【００３３】[0033]
【表４】 [Table 4]
【００３４】表４の結果より明かな如く、本発明の実施
例１は吸収促進剤としてビサボレンのみを配合した比較
例１及び吸収促進剤を配合しない比較例２に比べ各時間
とも著しく移行率が高くなっていることが判る。As is clear from the results shown in Table 4, Example 1 of the present invention showed a remarkably higher migration rate at each time than Comparative Example 1 in which only bisabolene was blended as an absorption promoter and Comparative Example 2 in which no absorption promoter was blended. You can see that it is higher.
【００３５】実施例２ ハイドロコルチゾン０．０３ｇをベルガモテン１．９７
ｇに分散溶解し、更に、グリセリン１．０ｇに分散しハ
イドロコルチゾンの１％溶液を調製した。この溶液１０
０ｍｇと市販のハイドロコルチゾン製剤（ハイドロコル
チゾン含有量１％）について上記経皮吸収性試験を実施
した。その結果を表５に示す。EXAMPLE 2 0.03 g of hydrocortisone was added to bergamoten 1.97.
g, and then dispersed in 1.0 g of glycerin to prepare a 1% solution of hydrocortisone. This solution 10
The transdermal absorption test was performed on 0 mg and a commercially available hydrocortisone preparation (hydrocortisone content 1%). Table 5 shows the results.
【００３６】[0036]
【表５】 [Table 5]
【００３７】実施例３（親水軟膏）Example 3 (Hydrophilic ointment)
【００３８】[0038]
【表６】 [Table 6]
【００３９】上記組成の通り本発明のテトラサイクリン
含有親水軟膏を調製し、上記の経皮吸収性試験を実施し
た結果、既存のカリオフィレンを配合しないで同様に調
製した物と比較し著しく皮膚吸収性に優れていた。As a result of preparing the tetracycline-containing hydrophilic ointment of the present invention according to the above-mentioned composition and conducting the above-mentioned percutaneous absorption test, the skin occlusion was remarkably improved as compared with the existing preparation prepared without caryophyllene. It was excellent.
【００４０】実施例４（化粧水）Example 4 (Lotion)
【００４１】[0041]
【表７】 [Table 7]
【００４２】上記組成の通り常法に従い本発明の化粧水
を調製し、上記経皮吸収試験を実施した結果、ニコチン
酸トコフェロール及びグリチルリチン酸ジカリウムの皮
膚吸収性は、イロンを配合せずに調製した化粧水に比較
し著しく向上していた。A lotion of the present invention was prepared according to a conventional method as described above, and the above-mentioned percutaneous absorption test was carried out. As a result, the skin absorbability of tocopherol nicotinate and dipotassium glycyrrhizinate was adjusted without adding iron. It was significantly improved compared to lotion.
【００４３】[0043]
【発明の効果】以上記載の如く、本発明の皮膚外用組成
物が広範囲の生理活性物質の皮膚吸収性を向上させるこ
とは明かである。As described above, it is clear that the composition for external use of the skin of the present invention improves skin absorbability of a wide range of physiologically active substances.
───────────────────────────────────────────────────── フロントページの続き (58)調査した分野(Int.Cl.7，ＤＢ名) A61K 47/06,47/08,47/10 A61K 7/00,7/48 ──────────────────────────────────────────────────続 き Continued on the front page (58) Field surveyed (Int.Cl. 7 , DB name) A61K 47 / 06,47 / 08,47 / 10 A61K 7 / 00,7 / 48
Claims (1)
ボレン、ベルガモテン、カリオフィレン、イロンから選
ばれる一種以上と、水溶性多価アルコール１．０〜７０
重量％とを配合してなる皮膚外用組成物。At least one physiologically active substance and a visa
Choose from Boren, Bergamoten, Kalliophyllen, and Iron
One or more water soluble polyhydric alcohols 1.0 to 70
% By weight of the composition for external use on the skin.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP30188492A JP3193483B2 (en) | 1992-10-13 | 1992-10-13 | External composition for skin |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP30188492A JP3193483B2 (en) | 1992-10-13 | 1992-10-13 | External composition for skin |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPH06128120A JPH06128120A (en) | 1994-05-10 |
| JP3193483B2 true JP3193483B2 (en) | 2001-07-30 |
Family
ID=17902302
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP30188492A Expired - Lifetime JP3193483B2 (en) | 1992-10-13 | 1992-10-13 | External composition for skin |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JP3193483B2 (en) |
Families Citing this family (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP3967471B2 (en) * | 1998-08-20 | 2007-08-29 | ポーラ化成工業株式会社 | Skin external preparation suitable for whitening |
| US6284802B1 (en) | 1999-04-19 | 2001-09-04 | The Procter & Gamble Company | Methods for regulating the condition of mammalian keratinous tissue |
| US6444647B1 (en) | 1999-04-19 | 2002-09-03 | The Procter & Gamble Company | Skin care compositions containing combination of skin care actives |
| EP1206932A4 (en) * | 1999-08-24 | 2005-09-14 | Kao Corp | Cosmetics |
-
1992
- 1992-10-13 JP JP30188492A patent/JP3193483B2/en not_active Expired - Lifetime
Also Published As
| Publication number | Publication date |
|---|---|
| JPH06128120A (en) | 1994-05-10 |
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