JP4246980B2 - Topical skin preparation - Google Patents

Description

【００１０】
セドロールは、一般にマツ科ヒマラヤスギ属、ヒノキ科ネズミサシ属、ビャクシン属、クロベ属等の植物の精油に含まれる香料成分として知られている。また、シダーウッド油、ヒバ油等の精油から蒸留等により精製して得ることができるし、合成によっても得られる。本発明において使用するセドロールは上記精油精製品、合成品のいずれを使用してもよく、市販品を用いてもよい。
【００１１】
セドロールは、本発明の皮膚外用剤中に０．００１〜１０重量％、特に０．１〜５重量％含有させると、抗炎症、抗アレルギー作用を効果的に発揮できるので好ましい。
【００１２】
本発明の皮膚外用剤に使用する成分（Ｂ）のアニオン界面活性剤としては、リン酸エステル基、アシルアミノ基、カルボン酸基、スルホン酸基、硫酸エステル基等を有するもの及びそれらの塩が挙げられる。
リン酸エステル基を有するものとしては、アルキルリン酸塩、アルキルエーテルリン酸塩等；アシルアミノ基を有するものとしては、アシルサルコシン塩、アシルグルタミン酸塩、アシルメチルタウリン塩、アシルアルギニン塩、アシルメチルアラニン塩等；カルボン酸基を有するものとしては、脂肪酸石鹸、エーテルカルボン酸又はその塩等；スルホン酸基を有するものとしては、アルキルスルホン酸塩、スルホコハク酸塩、エステルスルホン酸塩、アルキルアリールスルホン酸塩等；硫酸エステル基を有するものとしては、硫酸化油、エステル硫酸塩、アルキル硫酸塩、エーテル硫酸塩、アルキルアリール硫酸塩等が挙げられる。ここで、塩としては、ナトリウム、カリウム等のアルカリ金属塩、カルシウム、マグネシウム等のアルカリ土類金属塩、アルギニン等のアミノ酸塩、アンモニウム塩、モノエタノールアミン塩、ジエタノールアミン塩などが挙げられ、特にアルカリ金属塩が好ましい。また、上記アルキル基、アシル基を含む置換基のうち、単独で用いられるときは、アルキル基は炭素数１２以上、アシル基は炭素数１４以上が好ましい。
【００１３】
成分（Ｂ）としては、特にリン酸エステル基を有するアニオン界面活性剤及び炭素数１４以上のアシル基を持つアシルアミノ基を有するアニオン界面活性剤が、皮膚の刺激もなく、使用感の点で、更に経皮吸収効果の点で好ましい。
【００１４】
リン酸エステル基を有するアニオン界面活性剤としては、モノ又はジ（Ｃ₆〜Ｃ₂₄）アルキル又はアルケニルリン酸エステル塩、モノ又はジ（ポリオキシエチレン（２〜２０）Ｃ₆〜Ｃ₂₄アルキル又はアルケニル）リン酸エステル塩が挙げられる。具体例としては、モノラウリルリン酸ナトリウム、イソステアリルリン酸ナトリウム、２−ヘキシルデシルリン酸アルギニン、２−ヘプチルウンデシルリン酸カリウム、ポリオキシエチレン（４〜１０）ラウリルエーテルリン酸ナトリウム、モノセチルリン酸ナトリウム、モノミリスチルリン酸アルギニン、モノオレイルリン酸ナトリウム、ポリオキシエチレン（２〜１０）ラウリルエーテルリン酸カリウム、ジオクチルリン酸ナトリウム等が挙げられる。
【００１５】
炭素数１４以上のアシル基を持つアシルアミノ基を有するアニオン界面活性剤としては、Ｎ−Ｃ₁₄〜Ｃ₂₄アシルサルコシン塩、Ｎ−Ｃ₁₄〜Ｃ₂₄アシルメチルタウリン塩、Ｎ−Ｃ₁₄〜Ｃ₂₄アシルグルタミン酸塩、Ｎ−Ｃ₁₄〜Ｃ₂₄アシルアルギニン塩、Ｎ−Ｃ₁₄〜Ｃ₂₄アシルメチルアラニン塩等が挙げられる。具体例としては、ミリストイルメチルタウリンナトリウム、パルミトイルメチルタウリンナトリウム、ステアロイルメチルタウリンナトリウム、Ｎ−ステアロイルグルタミン酸ナトリウム、Ｎ−パルミトイルグルタミン酸カリウム、Ｎ−パルミトイル−β−アラニンアルギニン、パルミトイルサルコシンナトリウム等が挙げられる。
【００１６】
本発明の皮膚外用剤には、アニオン界面活性剤は２種以上を併用してもよい。アニオン界面活性剤は、効果、安定性の点で、膚外用剤中に０．００１〜１０重量％、特に０．１〜５重量％含有するのが好ましい。
【００１７】
本発明の皮膚外用剤は、上記成分（Ａ）及び（Ｂ）の他に、通常医薬品、医薬部外品、化粧品等の皮膚外用剤に用いられる成分、例えば、美白剤、保湿剤、酸化防止剤、紫外線吸収剤、非イオン界面活性剤（ポリオキシエチレン硬化ヒマシ油等）、油性成分（スクワラン、オリーブ油、高級アルコール、高級脂肪酸等）、増粘剤（ヒドロキシエチルセルロース、キサンタンガム、カルボキシビニルポリマー等）、アルコール類（グリセリン、１，３−ブチレングリコール、エタノール等）、有機酸類（クエン酸、コハク酸、アジピン酸、乳酸）、pH調整剤（水酸化ナトリウム、水酸化カリウム等）、粉末成分、色剤、水性成分、防腐剤、酸化防止剤、香料、キレート剤、水、各種皮膚栄養剤、生薬、エキス等を必要に応じて適宜配合することができる。
【００１８】
本発明の皮膚外用剤は、通常の方法に従って製造することができ、例えばクリーム、乳液、ローション、ジェル等の形態にすることができる。
【００１９】
【実施例】
実施例１
次の皮膚外用剤を常法により調製し、経皮吸収性、刺激性及び使用感について評価した。結果を表１に示す。
組成：セドロール ０．１（重量％）
界面活性剤 （表１）
モノステアリン酸ソルビタン １
グリセリン ５
オリーブ油 １
１，３−ブチレングリコール ５
精製水 残量
【００２０】
次の評価法を用いた。
＜経皮吸収性＞
パネラー（１０名）の上腕部に、開孔径１６mmの孔のあいたパッチテスト用バンソウ膏を貼った後、試料２００μＬを塗布した。塗布後、６時間でバンソウ膏をはがし、次いで塗布部をセロハンテープで１０回テープストリップピングを行い、セロハンテープに密着した角層中のセドロール量を測定した。
セドロールの定量は、１０枚のセロハンテープからのエタノール抽出物をガスクロマトグラフィーで測定した。下記式により経皮吸収率を求め、判定基準により判定した。
【００２１】
【数１】

【００２２】
経皮吸収性判定基準：１；経皮吸収率 １％未満。
２；経皮吸収率 １％以上２％未満。
３；経皮吸収率 ２％以上３％未満。
４；経皮吸収率 ３％以上。
【００２３】
＜刺激性＞
敏感肌パネラー（１０名）に石鹸で洗顔後、各皮膚外用剤を塗布し、１分後の肌の状態を次の判定基準で判定した。表１の結果中、カッコ内はセドロールを配合しない場合の刺激性である。
刺激性判定基準：Ａ；少しでも刺激感を感じた人数 ０名。
Ｂ；少しでも刺激感を感じた人数 １〜２名。
Ｃ；少しでも刺激感を感じた人数 ３〜５名。
Ｄ；少しでも刺激感を感じた人数 ６〜１０名。
【００２４】
＜使用感＞
美容専門パネラー（１０名）が、各皮膚化粧料を使用した際の使用感を次の評価基準で評価し、判定基準により判定した。
評価基準：１；べたつかない。
２；わずかにべたつく。
３；べたつく。
４；著しくべたつく。
使用感判定基準：Ａ；平均評価点 １．５未満。
Ｂ；平均評価点 １．５以上２．５未満。
Ｃ；平均評価点 ２．５以上３．５未満。
Ｄ；平均評価点 ３．５以上。
【００２５】
【表１】

【００２６】
本発明品１〜４はいずれも、経皮吸収性が向上し、刺激性もなくまた使用感に優れていた。
【００２７】
実施例２ （乳液）

【００２８】
実施例３ （ジェル）

【００２９】
実施例４ （ローション）

【００３０】
実施例５ （クリーム）

【００３１】
実施例２〜５の皮膚外用剤は、いずれもセドロールの経皮吸収性に優れ、抗炎症作用、抗アレルギー（ＩＬ４産生抑制）作用、刺激緩和作用が優れ、使用感も良好である。
【００３２】
【発明の効果】
本発明の皮膚外用剤は、セドロールの経皮吸収性が向上し、抗炎症作用、抗アレルギー（ＩＬ４産生抑制）作用、刺激緩和作用に優れ、使用感も良好である。[0001]
BACKGROUND OF THE INVENTION
The present invention relates to a topical skin preparation with improved transdermal absorbability of cedrol and excellent anti-inflammatory action, anti-allergy (IL4 production suppression) action, and irritation mitigating action.
[0002]
[Prior art]
Examples of drug administration methods include oral administration, mucosal administration, injection administration, and the like in which the drug is administered directly into the body. Recently, external preparations containing these drugs by transdermal administration have been developed because of their few side effects.
In general, the surface of the skin (skin) is covered with a stratum corneum, and has a structure that prevents foreign substances from entering the body. Simply applying an external preparation containing active ingredients to the epidermis is sufficient for transdermal absorption. Cannot be obtained. Therefore, in order to improve the direct absorption from the epidermis, a transdermal absorption enhancer such as dimethyl sulfoxide, dimethylformamide, dimethylacetamide has been proposed (Patent Document 1).
[0003]
On the other hand, the inventors have found that cedrol has excellent anti-inflammatory action and anti-allergic action (Patent Document 2) due to IL4 production inhibitory action, but is a water-insoluble substance and cedrol into the stratum corneum. In many cases, the percutaneous absorption was not sufficient.
[0004]
[Patent Document 1]
JP-A-61-33129 [Patent Document 2]
JP 2000-309528 A
[Problems to be solved by the invention]
An object of the present invention is to provide a skin external preparation capable of improving the transdermal absorbability of cedrol and sufficiently exhibiting the effects of cedrol (anti-inflammatory action, anti-allergic action, irritation mitigating action).
[0006]
[Means for Solving the Problems]
The present inventor has improved the transdermal absorbability by efficiently retaining cedrol in the stratum corneum by utilizing the softening action of the anionic surfactant and the compatibility between the anionic surfactant and cedrol. It has been found that an external preparation for skin can be obtained. In addition, by using one or more anionic surfactants having a phosphate ester group or an acylamino group as an anionic surfactant that is satisfactory in terms of safety and usability, the transdermal absorbability of cedrol is achieved. It has been found that an external preparation for skin can be obtained which is excellent in the anti-inflammatory action, anti-allergy (IL4 production suppression) action and stimulation alleviation action of cedrol itself.
[0007]
The present invention includes the following components (A) and (B):
(A) cedrol,
(B) An external preparation for skin containing an anionic surfactant is provided.
[0008]
DETAILED DESCRIPTION OF THE INVENTION
The cedrol of component (A) used in the external preparation for skin of the present invention is one of sesquiterpene alcohols and has optical isomers, but is generally a (d) isomer represented by the formula (1). Exists. The cedrol, which is an active ingredient of the antiallergic action of the present invention, is preferably the (d) isomer, but the (l) isomer that is an optical isomer or the form in which the (d) and (l) isomers are mixed. But there is no problem with effectiveness.
[0009]
[Chemical 1]

[0010]
Cedrol is generally known as a perfume component contained in essential oils of plants such as the pine family Cedar genus, cypress family Sera genus, juniper genus, and black genus. Moreover, it can obtain by refine | purifying by distillation etc. from essential oils, such as a cedarwood oil and a hiba oil, and can also be obtained by a synthesis | combination. As the cedrol used in the present invention, either the above-mentioned essential oil refined product or synthetic product may be used, or a commercially available product may be used.
[0011]
Cedrol is preferably contained in the external preparation for skin of the present invention in an amount of 0.001 to 10% by weight, particularly 0.1 to 5% by weight, because it can effectively exert anti-inflammatory and antiallergic effects.
[0012]
Examples of the component (B) anionic surfactant used in the external preparation for skin of the present invention include those having a phosphate ester group, an acylamino group, a carboxylic acid group, a sulfonic acid group, a sulfate ester group, and salts thereof. It is done.
Those having a phosphate group include alkyl phosphates, alkyl ether phosphates, etc .; those having an acylamino group include acyl sarcosine salts, acyl glutamates, acylmethyl taurine salts, acyl arginine salts, acyl methyl alanine Salts, etc .; those having carboxylic acid groups, fatty acid soaps, ether carboxylic acids or salts thereof; those having sulfonic acid groups, alkyl sulfonates, sulfosuccinates, ester sulfonates, alkylaryl sulfonic acids Salts and the like; those having a sulfate group include sulfated oils, ester sulfates, alkyl sulfates, ether sulfates, alkylaryl sulfates and the like. Here, examples of the salt include alkali metal salts such as sodium and potassium, alkaline earth metal salts such as calcium and magnesium, amino acid salts such as arginine, ammonium salts, monoethanolamine salts, diethanolamine salts, and the like. Metal salts are preferred. Moreover, among the substituents containing the alkyl group and acyl group, when used alone, the alkyl group preferably has 12 or more carbon atoms, and the acyl group preferably has 14 or more carbon atoms.
[0013]
As the component (B), an anionic surfactant having a phosphate ester group and an anionic surfactant having an acylamino group having an acyl group having 14 or more carbon atoms can be used without causing irritation to the skin. Furthermore, it is preferable in terms of transdermal absorption effect.
[0014]
Examples of the anionic surfactant having a phosphate ester group include mono- or di (C ₆ -C ₂₄ ) alkyl or alkenyl phosphate ester salt, mono- or di (polyoxyethylene (2-20) C ₆ -C ₂₄ alkyl, or Alkenyl) phosphate ester salts. Specific examples include sodium monolauryl phosphate, sodium isostearyl phosphate, arginine 2-hexyldecyl phosphate, potassium 2-heptylundecyl phosphate, polyoxyethylene (4-10) sodium lauryl ether phosphate, monocetyl phosphate Examples thereof include sodium, arginine monomyristyl phosphate, sodium monooleyl phosphate, polyoxyethylene (2 to 10) potassium lauryl ether phosphate, sodium dioctyl phosphate, and the like.
[0015]
Examples of the anionic surfactant having an acylamino group having an acyl group having 14 or more carbon atoms include N—C _{14 to} C ₂₄ acyl sarcosine salts, N—C _{14 to} C ₂₄ acylmethyl taurine salts, and N—C _{14 to} C _24. Examples include acyl glutamate, N—C _{14 to} C ₂₄ acyl arginine salt, and N—C _{14 to} C ₂₄ acylmethylalanine salt. Specific examples include myristoyl methyl taurine sodium, palmitoyl methyl taurine sodium, stearoyl methyl taurine sodium, N-stearoyl glutamate sodium, N-palmitoyl glutamate potassium, N-palmitoyl-β-alanine arginine, palmitoyl sarcosine sodium and the like.
[0016]
In the external preparation for skin of the present invention, two or more anionic surfactants may be used in combination. The anionic surfactant is preferably contained in an amount of 0.001 to 10% by weight, particularly 0.1 to 5% by weight, in the skin external preparation, in terms of effects and stability.
[0017]
In addition to the above components (A) and (B), the external preparation for skin of the present invention is usually used for external preparations for skin such as pharmaceuticals, quasi-drugs, and cosmetics, such as whitening agents, moisturizing agents, and antioxidants. Agent, ultraviolet absorber, nonionic surfactant (polyoxyethylene hydrogenated castor oil, etc.), oil component (squalane, olive oil, higher alcohol, higher fatty acid, etc.), thickener (hydroxyethyl cellulose, xanthan gum, carboxyvinyl polymer, etc.) , Alcohols (glycerin, 1,3-butylene glycol, ethanol, etc.), organic acids (citric acid, succinic acid, adipic acid, lactic acid), pH adjusters (sodium hydroxide, potassium hydroxide, etc.), powder components, color Add appropriate ingredients such as additives, aqueous components, preservatives, antioxidants, fragrances, chelating agents, water, various skin nutrients, herbal medicines, extracts, etc. It can be.
[0018]
The external preparation for skin of the present invention can be produced according to an ordinary method, and can be in the form of a cream, emulsion, lotion, gel or the like.
[0019]
【Example】
Example 1
The following external preparations for skin were prepared by a conventional method and evaluated for percutaneous absorbability, irritation and feeling of use. The results are shown in Table 1.
Composition: Cedrol 0.1 (% by weight)
Surfactant (Table 1)
Sorbitan monostearate 1
Glycerin 5
Olive oil 1
1,3-butylene glycol 5
Purified water remaining [0020]
The following evaluation method was used.
<Transdermal absorption>
A patch test banso plaster having a hole diameter of 16 mm was applied to the upper arm of a panel (10 persons), and then 200 μL of a sample was applied. After application, the bansou was peeled off in 6 hours, and then the applied part was subjected to tape stripping 10 times with a cellophane tape, and the amount of cedrol in the stratum corneum adhered to the cellophane tape was measured.
Cedrol was quantified by gas chromatography of ethanol extracts from 10 cellophane tapes. The percutaneous absorption rate was determined according to the following formula and judged according to the criteria.
[0021]
[Expression 1]

[0022]
Transdermal absorbability criteria: 1; Percutaneous absorption rate is less than 1%.
2: Percutaneous absorption rate is 1% or more and less than 2%.
3: Percutaneous absorption rate of 2% or more and less than 3%.
4; Percutaneous absorption rate of 3% or more.
[0023]
<Irritation>
After washing face with soap on sensitive skin panelists (10 persons), each skin external preparation was applied, and the skin condition after 1 minute was judged according to the following criteria. In the results of Table 1, the parentheses indicate irritation when no cedrol is added.
Criteria for determining irritation: A: Number of people who felt a little irritation 0 people.
B: Number of people who felt a sense of stimulation 1-2 people.
C: Number of people who felt a sense of stimulation 3 to 5 people.
D: 6-10 people who felt a sense of stimulation even a little.
[0024]
<Usage>
Beauty panelists (10 persons) evaluated the feeling of use when each skin cosmetic was used according to the following evaluation criteria, and determined based on the determination criteria.
Evaluation criteria: 1;
2; Slightly sticky.
3; Sticky.
4; Remarkably sticky.
Usability criteria: A; Average evaluation score <1.5.
B: Average evaluation score of 1.5 or more and less than 2.5.
C: Average evaluation score of 2.5 or more and less than 3.5.
D: Average evaluation score 3.5 or more.
[0025]
[Table 1]

[0026]
All of the products 1 to 4 of the present invention have improved transdermal absorbability, no irritation, and excellent usability.
[0027]
Example 2 (Emulsion)

[0028]
Example 3 (Gel)

[0029]
Example 4 (Lotion)

[0030]
Example 5 (Cream)

[0031]
The skin external preparations of Examples 2 to 5 are all excellent in transdermal absorbability of cedrol, excellent in anti-inflammatory action, anti-allergy (IL4 production suppression) action, irritation mitigating action, and good in use feeling.
[0032]
【The invention's effect】
The external preparation for skin of the present invention improves the transdermal absorbability of cedrol, is excellent in anti-inflammatory action, anti-allergy (IL4 production suppression) action, irritation mitigating action, and has a good feeling in use.

Claims (3)

The following components (A) and (B):
(A) cedrol,
(B) A skin external preparation containing an anionic surfactant selected from an anionic surfactant having a phosphate ester group and an anionic surfactant having an acylamino group having an acyl group having 14 or more carbon atoms . Component (B) is mono or di (polyoxyethylene (2-20) C ₆ ~ C _{twenty four} Alkyl or alkenyl) phosphate ester salt, N-C ₁₄ ~ C _{twenty four} Acyl sarcosine salt, N-C ₁₄ ~ C _{twenty four} Acylmethyl taurate, N-C ₁₄ ~ C _{twenty four} Acyl glutamate and N-C ₁₄ ~ C _{twenty four} The skin external preparation according to claim 1, which is an anionic surfactant selected from acylmethylalanine salts. Component (A) of 0.001 to 10 wt%, skin external preparation according to claim 1, comprising components (B) 0.001 to 10 wt%.